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Sample records for melanocyte stimulating hormone

  1. alpha-Melanocyte-stimulating-hormone precursors in the pig pituitary

    DEFF Research Database (Denmark)

    Fenger, M

    1986-01-01

    The occurrence of intermediates from the processing of ACTH-(1-39) [adrenocorticotropic hormone-(1-39)] to alpha-melanocyte-stimulating hormone was investigated in normal pig pituitaries by the use of sensitive and specific radioimmunoassays for ACTH-(1-13), ACTH-(1-14), ACTH-(1-13)-NH2 and ACTH-(1...

  2. [Effect of Tribulus terrestris extract on melanocyte-stimulating hormone expression in mouse hair follicles].

    Science.gov (United States)

    Yang, Liu; Lu, Jian-wei; An, Jing; Jiang, Xuan

    2006-12-01

    To observe the effect of Tribulus terrestris extract on melanocyte stimulating hormone (MSH) expression in C57BL/6J mouse hair follicles, and investigate the role of Tribulus terrestris extract in activation, proliferation, epidermal migration of dormant hair follicle melanocytes. The aqueous extract of Tribulus terrestris was administered orally in specific pathogen-free C57BL/6J mouse at the daily dose equivalent to 1 g/1 kg in adult human, and the expression and distribution of MSH in the mouse hair follicles was observed with immunohistochemistry. The positivity rate of MSH expression in the hair follicle melanocytes was 75% in mice treated with the extract, significantly higher than the rate of only 18.75% in the control group (PTribulus terrestris can significantly increase MSH expression in the hair follicle melanocytes by activating tyrosinase activity and promoting melanocyte proliferation, melanine synthesis, and epidermal migration of dormant melanocytes.

  3. Mammalian tyrosinase: biosynthesis, processing, and modulation by melanocyte-stimulating hormone.

    Science.gov (United States)

    Jiménez, M; Kameyama, K; Maloy, W L; Tomita, Y; Hearing, V J

    1988-01-01

    We have examined the rate of synthesis and degradation of tyrosinase (monophenol, 3,4-dihydroxyphenylalanine:oxygen oxidoreductase, EC 1.14.18.1), the critical enzyme involved in mammalian pigmentation, using pulse-chase metabolic labeling of murine melanoma cells and immunoprecipitation of protein extracts with antibodies directed specifically against the enzyme. We have found that tyrosinase is synthesized and glycosylated within melanocytes rapidly, since significant quantities of pulse-labeled enzyme could be detected within 30 min. The maximum amount of enzyme was processed within 4 hr, and the t1/2 of tyrosinase in vivo was 10 hr (compared to 120 hr with purified enzyme), suggesting that tyrosinase activity in melanocytes is at least in part regulated by rapid synthesis and active degradation. We also have examined the melanogenic stimulation caused by melanocyte-stimulating hormone, using metabolic labeling, radiometric assays, and immunofluorescence techniques; responding cells increased their melanogenic potential more than 7-fold within 4 days without increasing their levels of tyrosinase synthesis. The results demonstrate that a pool of inactive tyrosinase exists in melanocytes and that rapid increases in enzyme activity elicited by melanocyte-stimulating hormone reflect an alteration in the activity of a preexisting pool of intracellular tyrosinase. Images PMID:3131764

  4. Re-evaluation of Adrenocorticotropic Hormone and Melanocyte Stimulating Hormone Activation of GPR139 in Vitro

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    Diane Nepomuceno

    2018-03-01

    Full Text Available It is now well established that GPR139, a G-protein coupled receptor exclusively expressed in the brain and pituitary, is activated by the essential amino acids L-tryptophan (L-Trp and L-phenylalanine (L-Phe via Gαq-coupling. The in vitro affinity and potency values of L-Trp and L-Phe are within the physiological concentration ranges of L-Trp and L-Phe. A recent paper suggests that adrenocorticotropic hormone (ACTH, α and β melanocyte stimulating hormones (α-MSH and β-MSH and derivatives α-MSH1-9/α-MSH1-10 can also activate GPR139 in vitro. We tested this hypothesis using guanosine 5′-O-(3-[35S]thio-triphosphate binding (GTPγS, calcium mobilization and [3H]JNJ-63533054 radioligand binding assays. In the GTPγS binding assay, α-MSH, α-MSH1-9/α-MSH1-10, and β-MSH had no effect on [35S]GTPγS incorporation in cell membranes expressing GPR139 up to 30 μM in contrast to the concentration dependent activation produced by L-Trp, JNJ-63533054, and TC-09311 (two small molecule GPR139 agonists. ACTH slightly decreased the basal level of [35S]GTPγS incorporation at 30 μM. In the GPR139 radioligand binding assay, a moderate displacement of [3H]JNJ-63533054 binding by ACTH and β-MSH was observed at 30 μM (40 and 30%, respectively; α-MSH, α-MSH1-9/α-MSH1-10 did not displace any specific binding at 30 μM. In three different host cell lines stably expressing GPR139, α-MSH, and β-MSH did not stimulate calcium mobilization in contrast to L-Trp, JNJ-63533054, and TC-09311. ACTH, α-MSH1-9/α-MSH1-10 only weakly stimulated calcium mobilization at 30 μM (<50% of EC100. We then co-transfected GPR139 with the three melanocortin (MC receptors (MC3R, MC4R, and MC5R to test the hypothesis that ACTH, α-MSH, and β-MSH might stimulate calcium mobilization through a MCR/GPR139 interaction. All three MC peptides stimulated calcium response in cells co-transfected with GPR139 and MC3R, MC4R, or MC5R. The MC peptides did not stimulate calcium

  5. The neuropeptide alpha-melanocyte-stimulating hormone is critically involved in the development of cytotoxic CD8+ T cells in mice and humans.

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    Karin Loser

    Full Text Available BACKGROUND: The neuropeptide alpha-melanocyte-stimulating hormone is well known as a mediator of skin pigmentation. More recently, it has been shown that alpha-melanocyte-stimulating hormone also plays pivotal roles in energy homeostasis, sexual function, and inflammation or immunomodulation. Alpha-melanocyte-stimulating hormone exerts its antiinflammatory and immunomodulatory effects by binding to the melanocortin-1 receptor, and since T cells are important effectors during immune responses, we investigated the effects of alpha-melanocyte-stimulating hormone on T cell function. METHODOLOGY/PRINCIPAL FINDINGS: T cells were treated with alpha-melanocyte-stimulating hormone, and subsequently, their phenotype and function was analyzed in a contact allergy as well as a melanoma model. Furthermore, the relevance of alpha-melanocyte-stimulating hormone-mediated signaling for the induction of cytotoxicity was assessed in CD8(+ T cells from melanoma patients with functional and nonfunctional melanocortin-1 receptors. Here we demonstrate that the melanocortin-1 receptor is expressed by murine as well as human CD8(+ T cells, and we furthermore show that alpha-melanocyte-stimulating hormone/melanocortin-1 receptor-mediated signaling is critical for the induction of cytotoxicity in human and murine CD8(+ T cells. Upon adoptive transfer, alpha-melanocyte-stimulating hormone-treated murine CD8(+ T cells significantly reduced contact allergy responses in recipient mice. Additionally, the presented data indicate that alpha-melanocyte-stimulating hormone via signaling through a functional melanocortin-1 receptor augmented antitumoral immunity by up-regulating the expression of cytotoxic genes and enhancing the cytolytic activity in tumor-specific CD8(+ T cells. CONCLUSIONS/SIGNIFICANCE: Together, these results point to an important role of alpha-melanocyte-stimulating hormone in MHC class I-restricted cytotoxicity. Therefore, treatment of contact allergies or

  6. Nitric oxide enhances the sensitivity of alpaca melanocytes to respond to {alpha}-melanocyte-stimulating hormone by up-regulating melanocortin-1 receptor

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    Dong, Yanjun; Cao, Jing; Wang, Haidong; Zhang, Jie; Zhu, Zhiwei; Bai, Rui; Hao, HuanQing; He, Xiaoyan; Fan, Ruiwen [College of Animal Science and Technology, Shanxi Agricultural University, 030801 Taigu, Shanxi (China); Dong, Changsheng, E-mail: cs_dong@sxau.edu.cn [College of Animal Science and Technology, Shanxi Agricultural University, 030801 Taigu, Shanxi (China)

    2010-06-11

    Nitric oxide (NO) and {alpha}-melanocyte-stimulating hormone ({alpha}-MSH) have been correlated with the synthesis of melanin. The NO-dependent signaling of cellular response to activate the hypothalamopituitary proopiomelanocortin system, thereby enhances the hypophysial secretion of {alpha}-MSH to stimulate {alpha}-MSH-receptor responsive cells. In this study we investigated whether an NO-induced pathway can enhance the ability of the melanocyte to respond to {alpha}-MSH on melanogenesis in alpaca skin melanocytes in vitro. It is important for us to know how to enhance the coat color of alpaca. We set up three groups for experiments using the third passage number of alpaca melanocytes: the control cultures were allowed a total of 5 days growth; the UV group cultures like the control group but the melanocytes were then irradiated everyday (once) with 312 mJ/cm{sup 2} of UVB; the UV + L-NAME group is the same as group UV but has the addition of 300 {mu}M L-NAME (every 6 h). To determine the inhibited effect of NO produce, NO produces were measured. To determine the effect of the NO to the key protein and gene of {alpha}-MSH pathway on melanogenesis, the key gene and protein of the {alpha}-MSH pathway were measured by quantitative real-time PCR and Western immunoblotting. The results provide exciting new evidence that NO can enhance {alpha}-MSH pathway in alpaca skin melanocytes by elevated MC1R. And we suggest that the NO pathway may more rapidly cause the synthesis of melanin in alpaca skin under UV, which at that time elevates the expression of MC1R and stimulates the keratinocytes to secrete {alpha}-MSH to enhance the {alpha}-MSH pathway on melanogenesis. This process will be of considerable interest in future studies.

  7. The Alpha-Melanocyte Stimulating Hormone Induces Conversion of Effector T Cells into Treg Cells

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    Andrew W. Taylor

    2011-01-01

    Full Text Available The neuropeptide alpha-melanocyte stimulating hormone (α-MSH has an important role in modulating immunity and homeostasis. The production of IFN-γ by effector T cells is suppressed by α-MSH, while TGF-β production is promoted in the same cells. Such α-MSH-treated T cells have immune regulatory activity and suppress hypersensitivity, autoimmune diseases, and graft rejection. Previous characterizations of the α-MSH-induced Treg cells showed that the cells are CD4+ T cells expressing the same levels of CD25 as effector T cells. Therefore, we further analyzed the α-MSH-induced Treg cells for expression of effector and regulatory T-cell markers. Also, we examined the potential for α-MSH-induced Treg cells to be from the effector T-cell population. We found that the α-MSH-induced Treg cells are CD25+  CD4+ T cells that share similar surface markers as effector T cells, except that they express on their surface LAP. Also, the α-MSH treatment augments FoxP3 message in the effector T cells, and α-MSH induction of regulatory activity was limited to the effector CD25+ T-cell population. Therefore, α-MSH converts effector T cells into Treg cells, which suppress immunity targeting specific antigens and tissues.

  8. Inhibition of systemic inflammation by central action of the neuropeptide alpha-melanocyte- stimulating hormone.

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    Delgado Hernàndez, R; Demitri, M T; Carlin, A; Meazza, C; Villa, P; Ghezzi, P; Lipton, J M; Catania, A

    1999-01-01

    The neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) reduces fever and acute inflammation in the skin when administered centrally. The aim of the present research was to determine whether central alpha-MSH can also reduce signs of systemic inflammation in mice with endotoxemia. Increases in serum tumor necrosis factor-alpha and nitric oxide, induced by intraperitoneal administration of endotoxin, were modulated by central injection of a small concentration of alpha-MSH. Inducible nitric oxide synthase (iNOS) activity and iNOS mRNA in lungs and liver were likewise modulated by central alpha-MSH. Lung myeloperoxidase activity, a marker of neutrophil infiltration, was increased in endotoxemic mice; the increase was significantly less in lungs of mice treated with central alpha-MSH. Intraperitoneal administration of the small dose of alpha-MSH that was effective centrally did not alter any of the markers of inflammation. In experiments using immunoneutralization of central alpha-MSH, we tested the idea that endogenous peptide induced within the brain during systemic inflammation modulates host responses to endotoxic challenge in peripheral tissues. The data showed that proinflammatory agents induced by endotoxin in the circulation, lungs, and liver were significantly greater after blockade of central alpha-MSH. The results suggest that anti-inflammatory influences of neural origin that are triggered by alpha-MSH could be used to treat systemic inflammation.

  9. Combination of alpha-melanocyte stimulating hormone with conventional antibiotics against methicillin resistant Staphylococcus aureus.

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    Madhuri Singh

    Full Text Available Our previous studies revealed that alpha-melanocyte stimulating hormone (α-MSH is strongly active against Staphylococcus aureus (S. aureus including methicillin resistant S. aureus (MRSA. Killing due to α-MSH occurred by perturbation of the bacterial membrane. In the present study, we investigated the in vitro synergistic potential of α-MSH with five selected conventional antibiotics viz., oxacillin (OX, ciprofloxacin (CF, tetracycline (TC, gentamicin (GM and rifampicin (RF against a clinical MRSA strain which carried a type III staphylococcal cassette chromosome mec (SCCmec element and belonged to the sequence type (ST 239. The strain was found to be highly resistant to OX (minimum inhibitory concentration (MIC = 1024 µg/ml as well as to other selected antimicrobial agents including α-MSH. The possibility of the existence of intracellular target sites of α-MSH was evaluated by examining the DNA, RNA and protein synthesis pathways. We observed a synergistic potential of α-MSH with GM, CF and TC. Remarkably, the supplementation of α-MSH with GM, CF and TC resulted in ≥ 64-, 8- and 4-fold reductions in their minimum bactericidal concentrations (MBCs, respectively. Apart from membrane perturbation, in this study we found that α-MSH inhibited ≈ 53% and ≈ 47% DNA and protein synthesis, respectively, but not RNA synthesis. Thus, the mechanistic analogy between α-MSH and CF or GM or TC appears to be the reason for the observed synergy between them. In contrast, α-MSH did not act synergistically with RF which may be due to its inability to inhibit RNA synthesis (<10%. Nevertheless, the combination of α-MSH with RF and OX showed an enhanced killing by ≈ 45% and ≈ 70%, respectively, perhaps due to the membrane disrupting properties of α-MSH. The synergistic activity of α-MSH with antibiotics is encouraging, and promises to restore the lost potency of discarded antibiotics.

  10. Melanoma Therapy with Rhenium-Cyclized Alpha Melanocyte Stimulating Hormone Peptide Analogs

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    Thomas P Quinn

    2005-11-22

    Malignant melanoma is the 6th most commonly diagnosed cancer with increasing incidence in the United States. It is estimated that 54,200 cases of malignant melanoma will be newly diagnosed and 7,600 cases of death will occur in the United States in the year 2003 (1). At the present time, more than 1.3% of Americans will develop malignant melanoma during their lifetime (2). The average survival for patients with metastatic melanoma is about 6-9 months (3). Moreover, metastatic melanoma deposits are resistant to conventional chemotherapy and external beam radiation therapy (3). Systematic chemotherapy is the primary therapeutic approach to treat patients with metastatic melanoma. Dacarbazine is the only single chemotherapy agent approved by FDA for metastatic melanoma treatment (5). However, the response rate to Dacarbazine is only approximately 20% (6). Therefore, there is a great need to develop novel treatment approaches for metastatic melanoma. The global goal of this research program is the rational design, characterization and validation of melanoma imaging and therapeutic radiopharmaceuticals. Significant progress has been made in the design and characterization of metal-cyclized radiolabeled alpha-melanocyte stimulating hormone peptides. Therapy studies with {sup 188}Re-CCMSH demonstrated the therapeutic efficacy of the receptor-targeted treatment in murine and human melanoma bearing mice (previous progress report). Dosimetry calculations, based on biodistribution data, indicated that a significant dose was delivered to the tumor. However, {sup 188}Re is a very energetic beta-particle emitter. The longer-range beta-particles theoretically would be better for larger tumors. In the treatment of melanoma, the larger primary tumor is usually surgically removed leaving metastatic disease as the focus of targeted radiotherapy. Isotopes with lower beta-energies and/or shorter particle lengths should be better suited for targeting metastases. The {sup 177}Lu

  11. Melanome Therapy with Rhenium Cyclized Alpha Melanocyte Stimulating Hormone Peptide Analogs. Final report

    International Nuclear Information System (INIS)

    Quinn, Thomas P.

    2005-01-01

    Malignant melanoma is the 6th most commonly diagnosed cancer with increasing incidence in the United States. It is estimated that 54,200 cases of malignant melanoma will be newly diagnosed and 7,600 cases of death will occur in the United States in the year 2003 (1). At the present time, more than 1.3% of Americans will develop malignant melanoma during their lifetime (2). The average survival for patients with metastatic melanoma is about 6-9 months (3). Moreover, metastatic melanoma deposits are resistant to conventional chemotherapy and external beam radiation therapy (3). Systematic chemotherapy is the primary therapeutic approach to treat patients with metastatic melanoma. Dacarbazine is the only single chemotherapy agent approved by FDA for metastatic melanoma treatment (5). However, the response rate to Dacarbazine is only approximately 20% (6). Therefore, there is a great need to develop novel treatment approaches for metastatic melanoma. The global goal of this research program is the rational design, characterization and validation of melanoma imaging and therapeutic radiopharmaceuticals. Significant progress has been made in the design and characterization of metal-cyclized radiolabeled alpha-melanocyte stimulating hormone peptides. Therapy studies with 188 Re-CCMSH demonstrated the therapeutic efficacy of the receptor-targeted treatment in murine and human melanoma bearing mice (previous progress report). Dosimetry calculations, based on biodistribution data, indicated that a significant dose was delivered to the tumor. However, 188 Re is a very energetic beta-particle emitter. The longer-range beta-particles theoretically would be better for larger tumors. In the treatment of melanoma, the larger primary tumor is usually surgically removed leaving metastatic disease as the focus of targeted radiotherapy. Isotopes with lower beta-energies and/or shorter particle lengths should be better suited for targeting metastases. The 177 Lu-DOTA-Re(Arg11)CCMSH and

  12. Plasma concentrations of alpha-melanocyte-stimulating hormone are elevated in patients on chronic haemodialysis.

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    Airaghi, L; Garofalo, L; Cutuli, M G; Delgado, R; Carlin, A; Demitri, M T; Badalamenti, S; Graziani, G; Lipton, J M; Catania, A

    2000-08-01

    Clinical and/or laboratory signs of systemic inflammation occur frequently in patients undergoing long-term haemodialysis. It is likely, therefore, that a compensatory release of endogenous anti-inflammatory molecules occurs to limit host reactions. The aim of the present research was to determine if the potent anti-inflammatory peptide alpha-melanocyte-stimulating hormone (alpha-MSH), a pro-opiomelanocortin derivative, is increased in plasma of haemodialysis patients. Because endotoxin and cytokines induce alpha-MSH in vivo and in vitro, we also measured plasma concentrations of endotoxin, interleukin-6 (IL-6), and tumour necrosis factor alpha (TNF-alpha), and the two circulating products of activated monocytes, nitric oxide (NO) and neopterin. Thirty-five chronic haemodialysis patients, 20 patients with chronic renal failure not yet on dialysis, and 35 normal controls were included in the study. In the haemodialysis group, blood samples were obtained before and at the end of a dialysis session. Plasma alpha-MSH was measured using a double antibody radioimmunoassay, and IL-6, TNF-alpha, and neopterin using specific enzyme-linked immunosorbent assays. Plasma nitrites were determined by a colorimetric method, and endotoxin with the quantitative chromogenic LAL (limulus amoebocyte lysate) method. Mean plasma alpha-MSH was higher in haemodialysis patients than in control subjects, with the peptide concentrations being particularly elevated in dialysed patients with detectable endotoxin. High alpha-MSH concentrations were observed in the pre-dialysis samples, with no substantial change at the end of the dialysis session. Plasma concentrations of IL-6, TNF-alpha, neopterin, and NO were generally elevated in chronic haemodialysis patients and there was a negative correlation between circulating alpha-MSH and IL-6. In patients with renal failure not yet on dialysis, mean plasma alpha-MSH was similar to that of normal subjects. alpha-MSH is increased in the circulation of

  13. Pro-opiomelanocortin-derived peptides in the pig pituitary: alpha- and gamma 1-melanocyte-stimulating hormones and their glycine-extended forms

    DEFF Research Database (Denmark)

    Fenger, M

    1988-01-01

    to the neurointermediate lobe (19.8 nmol POMC/anterior lobe vs 7.0 nmol/neurointermediate lobe). In the neurointermediate lobe 93% of POMC was processed to alpha-melanocyte-stimulating hormone (alpha-MSH) and analogs exclusively of low molecular weight. Most of the remaining adrenocorticotropic hormone (ACTH...

  14. In vivo multiplex quantitative analysis of 3 forms of alpha melanocyte stimulating hormone in pituitary of prolyl endopeptidase deficient mice

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    Perroud Bertrand

    2009-06-01

    Full Text Available Abstract Background In vitro reactions are useful to identify putative enzyme substrates, but in vivo validation is required to identify actual enzyme substrates that have biological meaning. To investigate in vivo effects of prolyl endopeptidase (PREP, a serine protease, on alpha melanocyte stimulating hormone (α-MSH, we developed a new mass spectrometry based technique to quantitate, in multiplex, the various forms of α-MSH. Methods Using Multiple Reaction Monitoring (MRM, we analyzed peptide transitions to quantify three different forms of α-MSH. Transitions were first confirmed using standard peptides. Samples were then analyzed by mass spectrometry using a triple quadrupole mass spectrometer, after elution from a reverse phase C18 column by a gradient of acetonitrile. Results We first demonstrate in vitro that PREP digests biological active alpha melanocyte stimulating hormone (α-MSH1–13, by cleaving the terminal amidated valine and releasing a truncated alpha melanocyte stimulating hormone (α-MSH1–12 product – the 12 residues α-MSH form. We then use the technique in vivo to analyze the MRM transitions of the three different forms of α-MSH: the deacetylated α-MSH1–13, the acetylated α-MSH1–13 and the truncated form α-MSH1–12. For this experiment, we used a mouse model (PREP-GT in which the serine protease, prolyl endopeptidase, is deficient due to a genetrap insertion. Here we report that the ratio between acetylated α-MSH1–13 and α-MSH1–12 is significantly increased (P-value = 0.015, N = 6 in the pituitaries of PREP-GT mice when compared to wild type littermates. In addition no significant changes were revealed in the relative level of α-MSH1–13 versus the deacetylated α-MSH1–13. These results combined with the demonstration that PREP digests α-MSH1–13 in vitro, strongly suggest that α-MSH1–13 is an in vivo substrate of PREP. Conclusion The multiplex targeted quantitative peptidomics technique we

  15. Ultraviolet B, melanin and mitochondrial DNA: Photo-damage in human epidermal keratinocytes and melanocytes modulated by alpha-melanocyte-stimulating hormone [version 1; referees: 2 approved

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    Markus Böhm

    2016-05-01

    Full Text Available Alpha-melanocyte-stimulating hormone (alpha-MSH increases melanogenesis and protects from UV-induced DNA damage. However, its effect on mitochondrial DNA (mtDNA damage is unknown. We have addressed this issue in a pilot study using human epidermal keratinocytes and melanocytes incubated with alpha-MSH and irradiated with UVB. Real-time touchdown PCR was used to quantify total and deleted mtDNA. The deletion detected encompassed the common deletion but was more sensitive to detection. There were 4.4 times more mtDNA copies in keratinocytes than in melanocytes. Irradiation alone did not affect copy numbers. Alpha-MSH slightly increased copy numbers in both cell types in the absence of UVB and caused a similar small decrease in copy number with dose in both cell types. Deleted copies were nearly twice as frequent in keratinocytes as in melanocytes. Alpha-MSH reduced the frequency of deleted copies by half in keratinocytes but not in melanocytes. UVB dose dependently led to an increase in the deleted copy number in alpha-MSH-treated melanocytes. UVB irradiation had little effect on deleted copy number in alpha-MSH-treated keratinocytes. In summary, alpha-MSH enhances mtDNA damage in melanocytes presumably by increased melanogenesis, while α-MSH is protective in keratinocytes, the more so in the absence of irradiation.

  16. Recent advances in the understanding of how neuropeptide Y and α-melanocyte stimulating hormone function in adipose physiology

    Science.gov (United States)

    Shipp, Steven L.; Cline, Mark A.; Gilbert, Elizabeth R.

    2016-01-01

    ABSTRACT Communication between the brain and the adipose tissue has been the focus of many studies in recent years, with the “brain-fat axis” identified as a system that orchestrates the assimilation and usage of energy to maintain body mass and adequate fat stores. It is now well-known that appetite-regulating peptides that were studied as neurotransmitters in the central nervous system can act both on the hypothalamus to regulate feeding behavior and also on the adipose tissue to modulate the storage of energy. Energy balance is thus partly controlled by factors that can alter both energy intake and storage/expenditure. Two such factors involved in these processes are neuropeptide Y (NPY) and α-melanocyte stimulating hormone (α-MSH). NPY, an orexigenic factor, is associated with promoting adipogenesis in both mammals and chickens, while α-MSH, an anorexigenic factor, stimulates lipolysis in rodents. There is also evidence of interaction between the 2 peptides. This review aims to summarize recent advances in the study of NPY and α-MSH regarding their role in adipose tissue physiology, with an emphasis on the cellular and molecular mechanisms. A greater understanding of the brain-fat axis and regulation of adiposity by bioactive peptides may provide insights on strategies to prevent or treat obesity and also enhance nutrient utilization efficiency in agriculturally-important species. PMID:27994947

  17. Recent advances in the understanding of how neuropeptide Y andα-melanocyte stimulating hormone function in adipose physiology.

    Science.gov (United States)

    Shipp, Steven L; Cline, Mark A; Gilbert, Elizabeth R

    2016-01-01

    Communication between the brain and the adipose tissue has been the focus of many studies in recent years, with the "brain-fat axis" identified as a system that orchestrates the assimilation and usage of energy to maintain body mass and adequate fat stores. It is now well-known that appetite-regulating peptides that were studied as neurotransmitters in the central nervous system can act both on the hypothalamus to regulate feeding behavior and also on the adipose tissue to modulate the storage of energy. Energy balance is thus partly controlled by factors that can alter both energy intake and storage/expenditure. Two such factors involved in these processes are neuropeptide Y (NPY) and α-melanocyte stimulating hormone (α-MSH). NPY, an orexigenic factor, is associated with promoting adipogenesis in both mammals and chickens, while α-MSH, an anorexigenic factor, stimulates lipolysis in rodents. There is also evidence of interaction between the 2 peptides. This review aims to summarize recent advances in the study of NPY and α-MSH regarding their role in adipose tissue physiology, with an emphasis on the cellular and molecular mechanisms. A greater understanding of the brain-fat axis and regulation of adiposity by bioactive peptides may provide insights on strategies to prevent or treat obesity and also enhance nutrient utilization efficiency in agriculturally-important species.

  18. Comparative Functional Alanine Positional Scanning of the α-Melanocyte Stimulating Hormone and NDP-Melanocyte Stimulating Hormone Demonstrates Differential Structure-Activity Relationships at the Mouse Melanocortin Receptors.

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    Todorovic, Aleksandar; Ericson, Mark D; Palusak, Ryan D; Sorensen, Nicholas B; Wood, Michael S; Xiang, Zhimin; Haskell-Luevano, Carrie

    2016-07-20

    The melanocortin system has been implicated in the regulation of various physiological functions including melanogenesis, steroidogenesis, energy homeostasis, and feeding behavior. Five melanocortin receptors have been identified to date and belong to the family of G protein-coupled receptors (GPCR). Post-translational modification of the proopiomelanocortin (POMC) prohormone leads to the biosynthesis of the endogenous melanocortin agonists, including α-melanocyte stimulating hormone (α-MSH), β-MSH, γ-MSH, and adrenocorticotropic hormone (ACTH). All the melanocortin agonists derived from the POMC prohormone contain a His-Phe-Arg-Trp tetrapeptide sequence that has been implicated in eliciting the pharmacological responses at the melanocortin receptors. Herein, an alanine (Ala) positional scan is reported for the endogenous α-MSH ligand and the synthetic, more potent, NDP-MSH peptide (Ac-Ser(1)-Tyr(2)-Ser(3)-Nle(4)-Glu(5)-His(6)-DPhe(7)-Arg(8)-Trp(9)-Gly(10)-Lys(11)-Pro(12)-Val(13)-NH2) at the cloned mouse melanocortin receptors to test the assumption that the structure-activity relationships of one ligand would apply to the other. Several residues outside of the postulated pharmacophore altered potency at the melanocortin receptors, most notably the 1560-, 37-, and 15-fold potency loss when the Glu(5) position of α-MSH was substituted with Ala at the mMC1R, mMC3R, and mMC4R, respectively. Importantly, the altered potencies due to Ala substitutions in α-MSH did not necessarily correlate with equivalent Ala substitutions in NDP-MSH, indicating that structural modifications and corresponding biological activities in one of these melanocortin ligands may not be predictive for the other agonist.

  19. Fluorine-18-labeled [Nle4,D-Phe7]-α-MSH, an α-melanocyte stimulating hormone analogue

    International Nuclear Information System (INIS)

    Vaidyanathan, Ganesan; Zalutsky, Michael R.

    1997-01-01

    The α-melanocyte stimulating hormone (α-MSH) analogue [N1e 4 ,D-Phe 7 ]-α-MSH was labeled with 18 F using N-succinimidyl 4-[ 18 F]fluorobenzoate ([ 18 F]SFB) in >80% radiochemical yield. The IC 50 values of [N1e 4 ,D-Phe 7 ]-α-MSH and para-fluorobenzoyl-[N1e 4 ,D-Phe 7 ]-α-MSH ([N1e 4 ,D-Phe 7 ,Lys 11 -( 18 F)PFB]-α-MSH) for inhibiting the binding of meta-[ 131 I]iodobenzoyl-[N1e 4 ,D-Phe 7 ]-α-MSH ([N1e 4 ,D-Phe 7 ,Lys 11 -( 131 I)MIB]-α-MSH) to B16-F1 murine melanoma cells were 89 ± 9 pM and 112 ± 22 pM, respectively, suggesting that addition of 4-fluorobenzoate did not compromise α-MSH receptor binding affinity. Binding of [N1e 4 ,D-Phe 7 ,Lys 11 -( 18 F)PFB]-α-MSH was influenced by the specific activity of the preparation (400-1000 Ci/mmol). The normal tissue clearance of [N1e 4 ,D-Phe 7 ,Lys 11 -( 18 F)PFB]-α-MSH in mice was quite rapid, with little evidence for defluorination

  20. Prostaglandin D2 production in FM55 melanoma cells is regulated by α-melanocyte-stimulating hormone and is not related to melanin production

    Science.gov (United States)

    Masoodi, Mojgan; Nicolaou, Anna; Gledhill, Karl; Rhodes, Lesley E; Tobin, Desmond J; Thody, Anthony J

    2010-01-01

    This study shows that prostaglandins in human FM55 melanoma cells and epidermal melanocytes are produced by COX-1. Prostaglandin production in FM55 melanoma cells was unrelated to that of melanin suggesting that the two processes can occur independently. α-Melanocyte-stimulating hormone, which had no effect on melanin production in FM55 cells, stimulated PGD2 production in these cells without affecting PGE2. While cAMP pathways may be involved in regulating PGD2 production, our results suggest that α-MSH acts independently of cAMP, possibly by regulating the activity of lipocalin-type PGD synthase. This α-MSH-mediated effect may be associated with its role as an immune modulator. PMID:20482620

  1. Alpha-Melanocyte Stimulating Hormone Protects against Cytokine-Induced Barrier Damage in Caco-2 Intestinal Epithelial Monolayers.

    Directory of Open Access Journals (Sweden)

    Judit Váradi

    Full Text Available Alpha-melanocyte-stimulating hormone (α-MSH is a potent anti-inflammatory peptide with cytoprotective effect in various tissues. The present investigation demonstrates the ability of α-MSH to interact with intestinal epithelial cell monolayers and mitigate inflammatory processes of the epithelial barrier. The protective effect of α-MSH was studied on Caco-2 human intestinal epithelial monolayers, which were disrupted by exposure to tumor necrosis factor-α and interleukin-1β. The barrier integrity was assessed by measuring transepithelial electric resistance (TEER and permeability for marker molecules. Caco-2 monolayers were evaluated by immunohistochemistry for expression of melanocortin-1 receptor and tight junction proteins ZO-1 and claudin-4. The activation of nuclear factor kappa beta (NF-κB was detected by fluorescence microscopy and inflammatory cytokine expression was assessed by flow cytometric bead array cytokine assay. Exposure of Caco-2 monolayers to proinflammatory cytokines lowered TEER and increased permeability for fluorescein and albumin, which was accompanied by changes in ZO-1 and claudin-4 immunostaining. α-MSH was able to prevent inflammation-associated decrease of TEER in a dose-dependent manner and reduce the increased permeability for paracellular marker fluorescein. Further immunohistochemistry analysis revealed proinflammatory cytokine induced translocation of the NF-κB p65 subunit into Caco-2 cell nuclei, which was inhibited by α-MSH. As a result the IL-6 and IL-8 production of Caco-2 monolayers were also decreased with different patterns by the addition of α-MSH to the culture medium. In conclusion, Caco-2 cells showed a positive immunostaining for melanocortin-1 receptor and α-MSH protected Caco-2 cells against inflammatory barrier dysfunction and inflammatory activation induced by tumor necrosis factor-α and interleukin-1β cytokines.

  2. Alpha-Melanocyte Stimulating Hormone Protects against Cytokine-Induced Barrier Damage in Caco-2 Intestinal Epithelial Monolayers

    Science.gov (United States)

    Váradi, Judit; Harazin, András; Fenyvesi, Ferenc; Réti-Nagy, Katalin; Gogolák, Péter; Vámosi, György; Bácskay, Ildikó; Fehér, Pálma; Ujhelyi, Zoltán; Vasvári, Gábor; Róka, Eszter; Haines, David; Deli, Mária A.; Vecsernyés, Miklós

    2017-01-01

    Alpha-melanocyte-stimulating hormone (α-MSH) is a potent anti-inflammatory peptide with cytoprotective effect in various tissues. The present investigation demonstrates the ability of α-MSH to interact with intestinal epithelial cell monolayers and mitigate inflammatory processes of the epithelial barrier. The protective effect of α-MSH was studied on Caco-2 human intestinal epithelial monolayers, which were disrupted by exposure to tumor necrosis factor-α and interleukin-1β. The barrier integrity was assessed by measuring transepithelial electric resistance (TEER) and permeability for marker molecules. Caco-2 monolayers were evaluated by immunohistochemistry for expression of melanocortin-1 receptor and tight junction proteins ZO-1 and claudin-4. The activation of nuclear factor kappa beta (NF-κB) was detected by fluorescence microscopy and inflammatory cytokine expression was assessed by flow cytometric bead array cytokine assay. Exposure of Caco-2 monolayers to proinflammatory cytokines lowered TEER and increased permeability for fluorescein and albumin, which was accompanied by changes in ZO-1 and claudin-4 immunostaining. α-MSH was able to prevent inflammation-associated decrease of TEER in a dose-dependent manner and reduce the increased permeability for paracellular marker fluorescein. Further immunohistochemistry analysis revealed proinflammatory cytokine induced translocation of the NF-κB p65 subunit into Caco-2 cell nuclei, which was inhibited by α-MSH. As a result the IL-6 and IL-8 production of Caco-2 monolayers were also decreased with different patterns by the addition of α-MSH to the culture medium. In conclusion, Caco-2 cells showed a positive immunostaining for melanocortin-1 receptor and α-MSH protected Caco-2 cells against inflammatory barrier dysfunction and inflammatory activation induced by tumor necrosis factor-α and interleukin-1β cytokines. PMID:28103316

  3. Reducing renal uptake of 90Y- and 177Lu-labeled alpha-melanocyte stimulating hormone peptide analogues

    Energy Technology Data Exchange (ETDEWEB)

    Miao, Yubin; Fisher, Darrell R.; Quinn, Thomas P.

    2006-06-15

    The purpose of this study was to improve the tumor-to-kidney uptake ratios of 90Y- and 177Lu-[1,2,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-Re-Cys,D-Phe,Arg]alpha-melanocyte stimulating hormone (DOTA-RE(Arg)CCMSH), through coupling a negatively charged glutamic acid (Glu) to the peptide sequence. A new peptide of DOTA-Re(Glu,Arg)CCMSH was designed, synthesized and labeled with 90Y and 177Lu. Pharmacokinetics of 90Y- and 177Lu-DOTA-RE(Glu,Arg)CCNSH were determined in B16/F1 murine melanoma-bearing C57 mice. Both exhibited significantly less renal uptake than 90Y- and 177Lu-DOTA-Re(Arg)CCMSH at 30 min and at 2, 3, and 24 h after dose administration. The renal uptake values of 90Y- and 177Lu-DOTA-Re(Glu,Arg)CCMSH were 28.16% and 28.81% of those of 90Y- and 177Lu-DOTA-RE(Arg)CCMSH, respectively, at 4 hr post-injection. We also showed higher tumor-to-kidney uptake ratios 2.28 and 1.69 times that of 90Y- and 177Lu-DOTA-Re(Arg)CCMSH, respectively, at 4 h post-injection. The90Y- and 177Lu-DOTA-Re(Glu,Arg)CCMSH activity accumulation was low in normal organs except for kidneys. Coupling a negatively charged amino acid (Glu) to the CCMSH peptide sequence dramatically reduced the renal uptake values and increased the tumor-to-kidney uptake ratios of 90Y- and 177Lu-DOTA-Re(Glu,Arg)CCMSH, facilitating their potential applications as radiopharmaceuticals for targeted radionuclide therapy of melanoma.

  4. Reducing renal uptake of 9Y- and 177Lu-labeled alpha-melanocyte stimulating hormone peptide analogues

    International Nuclear Information System (INIS)

    Miao Yubin; Fisher, Darrell R.; Quinn, Thomas P.

    2006-01-01

    Objective: The purpose of this study was to improve the tumor-to-kidney uptake ratios of 9 Y- and 177 Lu-[1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-Re-Cys 3,4,1 , D-Phe 7 , Arg 11 ]α-melanocyte stimulating hormone 3-13 {DOTA-Re(Arg 11 )CCMSH} through coupling a negatively charged glutamic acid (Glu) to the peptide sequence. Methods: A new peptide of DOTA-Re(Glu 2 , Arg 11 )CCMSH was designed, synthesized and labeled with 9 Y and 177 Lu. Pharmacokinetics of 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH was determined in B16/F1 murine melanoma-bearing C57 mice. Results: 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH exhibited significantly (P 9 Y- and 177 Lu-DOTA-Re(Arg 11 )CCMSH at 30 min and at 2, 4 and 24 h after dose administration. The renal uptake values of 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH were 28.16% and 28.81% of those of 9 Y- and 177 Lu-DOTA-Re(Arg 11 )CCMSH, respectively, at 4 h postinjection. 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH displayed higher tumor-to-kidney uptake ratios than 9 Y- and 177 Lu-DOTA-Re(Arg 11 )CCMSH at 30 min and at 2, 4 and 24 h after dose administration. The tumor-to-kidney uptake ratio of 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH was 2.28 and 1.69 times of 9 Y- and 177 Lu-DOTA-Re(Arg 11 )CCMSH, respectively, at 4 h postinjection. The 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH activity accumulation was low in normal organs except for kidney. Conclusions: Coupling a negatively charged amino acid (Glu) to the CCMSH peptide sequence dramatically reduced the renal uptake values and increased the tumor-to-kidney uptake ratios of 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH, facilitating their potential applications as radiopharmaceuticals for targeted radionuclide therapy of melanoma

  5. Reducing renal uptake of {sup 9}Y- and {sup 177}Lu-labeled alpha-melanocyte stimulating hormone peptide analogues

    Energy Technology Data Exchange (ETDEWEB)

    Miao Yubin [Department of Internal Medicine, University of Missouri-Columbia, Columbia, MO 65211 (United States) and Department of Dermatology, University of Missouri-Columbia, Columbia, MO 65211 (United States) and Harry S. Truman Memorial Veteran Hospital, Columbia, MO 65201 (United States)]. E-mail: ymiao@salud.unm.edu; Fisher, Darrell R. [Pacific Northwest National Laboratory, Richland, WA 99352 (United States); Quinn, Thomas P. [Harry S. Truman Memorial Veteran Hospital, Columbia, MO 65201 (United States); Department of Biochemistry, University of Missouri-Columbia, Columbia, MO 65211 (United States); Department of Radiology, University of Missouri-Columbia, Columbia, MO 65211 (United States)

    2006-08-15

    Objective: The purpose of this study was to improve the tumor-to-kidney uptake ratios of {sup 9}Y- and {sup 177}Lu-[1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-Re-Cys{sup 3,4,1}, D-Phe{sup 7}, Arg{sup 11}]{alpha}-melanocyte stimulating hormone{sub 3-13} {l_brace}DOTA-Re(Arg{sup 11})CCMSH{r_brace} through coupling a negatively charged glutamic acid (Glu) to the peptide sequence. Methods: A new peptide of DOTA-Re(Glu{sup 2}, Arg{sup 11})CCMSH was designed, synthesized and labeled with {sup 9}Y and {sup 177}Lu. Pharmacokinetics of {sup 9}Y- and {sup 177}Lu-DOTA-Re(Glu{sup 2}, Arg{sup 11})CCMSH was determined in B16/F1 murine melanoma-bearing C57 mice. Results: {sup 9}Y- and {sup 177}Lu-DOTA-Re(Glu{sup 2}, Arg{sup 11})CCMSH exhibited significantly (P<.05) less renal uptake values than {sup 9}Y- and {sup 177}Lu-DOTA-Re(Arg{sup 11})CCMSH at 30 min and at 2, 4 and 24 h after dose administration. The renal uptake values of {sup 9}Y- and {sup 177}Lu-DOTA-Re(Glu{sup 2}, Arg{sup 11})CCMSH were 28.16% and 28.81% of those of {sup 9}Y- and {sup 177}Lu-DOTA-Re(Arg{sup 11})CCMSH, respectively, at 4 h postinjection. {sup 9}Y- and {sup 177}Lu-DOTA-Re(Glu{sup 2}, Arg{sup 11})CCMSH displayed higher tumor-to-kidney uptake ratios than {sup 9}Y- and {sup 177}Lu-DOTA-Re(Arg{sup 11})CCMSH at 30 min and at 2, 4 and 24 h after dose administration. The tumor-to-kidney uptake ratio of {sup 9}Y- and {sup 177}Lu-DOTA-Re(Glu{sup 2}, Arg{sup 11})CCMSH was 2.28 and 1.69 times of {sup 9}Y- and {sup 177}Lu-DOTA-Re(Arg{sup 11})CCMSH, respectively, at 4 h postinjection. The {sup 9}Y- and {sup 177}Lu-DOTA-Re(Glu{sup 2}, Arg{sup 11})CCMSH activity accumulation was low in normal organs except for kidney. Conclusions: Coupling a negatively charged amino acid (Glu) to the CCMSH peptide sequence dramatically reduced the renal uptake values and increased the tumor-to-kidney uptake ratios of {sup 9}Y- and {sup 177}Lu-DOTA-Re(Glu{sup 2}, Arg{sup 11})CCMSH, facilitating their potential applications

  6. 203Pb-Labeled Alpha-Melanocyte-Stimulating Hormone Peptide as an Imaging Probe for Melanoma Detection

    Energy Technology Data Exchange (ETDEWEB)

    Yubin, Miao; Figueroa, Said D.; Fisher, Darrell R.; Moore, Herbert A.; Testa, Richard F.; Hoffman, Timothy J.; Quinn, Thomas P.

    2008-05-01

    Abbreviations: a-MSH; alpha melanocyte stimulating hormone, DOTA; 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, Re(Arg11)CCMSH; DOTA-[Cys3,4,10, D-Phe7, Arg11]a-MSH3-13, NDP; [Nle4,d-Phe7] a-MSH3-13. Abstract Peptide-targeted alpha therapy with 200 mCi of 212Pb-DOTA-Re(Arg11)CCMSH cured 45% of B16/F1 murine melanoma-bearing C57 mice in a 120-day study, highlighting its melanoma treatment potential. However, there is a need to develop an imaging surrogate for patient specific dosimetry and to monitor the tumor response to 212Pb-DOTA-Re(Arg11)CCMSH therapy. The purpose of this study was to evaluate the potential of 203Pb-DOTA-Re(Arg11)CCMSH as a matched-pair SPECT imaging agent for 212Pb-DOTA-Re(Arg11)CCMSH. Method: DOTA-Re(Arg11)CCMSH was labeled with 203Pb in 0.5 M NH4OAc buffer at pH 5.4. The internalization and efflux of 203Pb-DOTA-Re(Arg11)CCMSH were determined in B16/F1 melanoma cells. The pharmacokinetics of 203Pb-DOTA-Re(Arg11)CCMSH were examined in B16/F1 melanoma-bearing C57 mice. A micro-SPECT/CT imaging study was performed with 203Pb-DOTA-Re(Arg11)CCMSH in a B16/F1 melanoma-bearing C57 mouse at 2 h post-injection. Results: 203Pb-DOTA-Re(Arg11)CCMSH was easily prepared in NH4OAc buffer and completely separated from the excess non-radiolabeled peptide by RP-HPLC. 203Pb-DOTA-Re(Arg11)CCMSH displayed fast internalization and extended retention in B16/F1 cells. Approximately 73% of 203Pb-DOTA-Re(Arg11)CCMSH activity internalized after a 20-min incubation at 25C. After incubating the cells in culture media for 20 min, 78% of internalized activity remained in the cells. 203Pb-DOTA-Re(Arg11)CCMSH exhibited similar biodistribution pattern with 212Pb-DOTA-Re(Arg11)CCMSH in B16/F1 melanoma-bearing mice. 203Pb-DOTA-Re(Arg11)CCMSH exhibited the peak tumor uptake of 12.00 +/- 3.20 %ID/g at 1 h post-injection. The tumor uptake gradually decreased to 3.43 +/- 1.12 %ID/g at 48 h post-injection. 203Pb-DOTA-Re(Arg11)CCMSH exhibited the peak tumor to kidney

  7. Receptor-Mediated Melanoma Targeting with Radiolabeled α-Melanocyte-Stimulating Hormone: Relevance of the Net Charge of the Ligand

    Directory of Open Access Journals (Sweden)

    Alex N. Eberle

    2017-04-01

    Full Text Available A majority of melanotic and amelanotic melanomas overexpress melanocortin type 1 receptors (MC1Rs for α-melanocyte-stimulating hormone. Radiolabeled linear or cyclic analogs of α-MSH have a great potential as diagnostic or therapeutic tools for the management of malignant melanoma. Compounds such as [111In]DOTA-NAP-amide exhibit high affinity for the MC1R in vitro, good tumor uptake in vivo, but they may suffer from relatively high kidney uptake and retention in vivo. We have shown previously that the introduction of negative charges into radiolabeled DOTA-NAP-amide peptide analogs may enhance their excretion and reduce kidney retention. To address the question of where to place negative charges within the ligand, we have extended these studies by designing two novel peptides, Ac-Nle-Asp-His-d-Phe-Arg-Trp-Gly-Lys(DOTA-d-Asp-d-Asp-OH (DOTA-NAP-d-Asp-d-Asp with three negative charges at the C-terminal end (overall net charge of the molecule −2 and DOTA-Gly-Tyr(P-Nle-Asp-His-d-Phe-Arg-Trp-NH2 (DOTA-Phospho-MSH2-9 with two negative charges in the N-terminal region (net charge −1. The former peptide showed markedly reduced receptor affinity and biological activity by >10-fold compared to DOTA-NAP-amide as reference compound, and the latter peptide displayed similar bioactivity and receptor affinity as the reference compound. The uptake by melanoma tumor tissue of [111In]DOTA-Phospho-MSH2-9 was 7.33 ± 0.47 %ID/g 4 h after injection, i.e., almost equally high as with [111In]DOTA-NAP-amide. The kidney retention was 2.68 ± 0.18 %ID/g 4 h after injection and hence 44% lower than that of [111In]DOTA-NAP-amide. Over an observation period from 4 to 48 h, the tumor-to-kidney ratio of [111In]DOTA-Phospho-MSH2-9 was 35% more favorable than that of the reference compound. In a comparison of DOTA-NAP-d-Asp-d-Asp, DOTA-Phospho-MSH2-9 and DOTA-NAP-amide with five previously published analogs of DOTA-NAP-amide that altogether cover a range

  8. Influence of ascorbic acid on in vivo amidation of alpha-melanocyte stimulating hormone in guinea pig pituitary

    DEFF Research Database (Denmark)

    Fenger, M; Hilsted, L

    1988-01-01

    The effect of ascorbic acid depletion on the amidation of alphamelanocyte stimulating hormone (alpha MSH) was studied in vivo in guinea pig pituitary. After four weeks, the concentration of ascorbic acid was 1.20 +/- 0.11 mumol/g tissue (mean +/- SD) in the pituitary and 0.34 +/- 0.07 mumol/g tis...

  9. Melaleuca quinquenervia essential oil inhibits α-melanocyte-stimulating hormone-induced melanin production and oxidative stress in B16 melanoma cells.

    Science.gov (United States)

    Chao, Wen-Wan; Su, Chia-Chi; Peng, Hsin-Yi; Chou, Su-Tze

    2017-10-15

    Essential oils are odorous, volatile products of plant secondary metabolism, which are found in many leaves and stems. They show important biological activities, which account for the development of aromatherapy used in complementary and alternative medicine. The essential oil extracted from Melaleuca quinquenervia (Cav.) S.T. Blake (paperbark) (MQ-EO) has various functional properties. The aim of this study is to investigate the chemical composition of MQ-EO by using gas chromatography-mass spectrometry (GC-MS) and evaluate its tyrosinase inhibitory activity. Gas chromatography-mass spectrometry (GC-MS)-based metabolomics was used to identify 18 components in MQ-EO. The main components identified were 1,8-cineole (21.60%), α-pinene (15.93%), viridiflorol (14.55%), and α-terpineol (13.73%). B16 melanoma cells were treated with α-melanocyte-stimulating hormone (α-MSH) in the presence of various concentrations of MQ-EO or its major compounds. Cell viability was accessed by MTT assay and cellular tyrosinase activity and melanin content were determined by using spectrophotographic methods. The antioxidant mechanism of MQ-EO in α-MSH stimulated B16 cells was also investigated. In α-melanocyte-stimulating hormone (α-MSH)-stimulated murine B16 melanoma cells, MQ-EO, 1,8-cineole, α-pinene, and α-terpineol significantly reduced melanin content and tyrosinase activity. Moreover, MQ-EO, 1,8-cineole, α-pinene, and α-terpineol decreased malondialdehyde (MDA) levels. In addition, restored glutathione (GSH) levels, glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase activities were increased in α-MSH-stimulated B16 cells. MQ-EO not only decreased apoptosis but also reduced DNA damage in α-MSH stimulated B16 cells. These results showed that MQ-EO and its main components, 1,8-cineole, α-pinene, and α-terpineol, possessed potent anti-tyrosinase and anti-melanogenic activities besides the antioxidant properties. The active functional components of MQ

  10. Influence of ascorbic acid on in vivo amidation of alpha-melanocyte stimulating hormone in guinea pig pituitary

    DEFF Research Database (Denmark)

    Fenger, M; Hilsted, L

    1988-01-01

    The effect of ascorbic acid depletion on the amidation of alphamelanocyte stimulating hormone (alpha MSH) was studied in vivo in guinea pig pituitary. After four weeks, the concentration of ascorbic acid was 1.20 +/- 0.11 mumol/g tissue (mean +/- SD) in the pituitary and 0.34 +/- 0.07 mumol......-39) immunoreactivity was observed in the depleted guinea pigs. Gel chromatography and reversed-phase high-performance luquid chromatography showed that the alpha MSH and ACTH (1-14) immunoreactivity was of low molecular weight and partly mono- or diacetylated. Depletion of ascorbic acid had no influence on the degree...... of acetylation of alpha MSH and ACTH (1-14). It is concluded that depletion of ascorbic acid reduces the in vivo amidation of ACTH (1-14) in the guinea pig pituitary....

  11. α-Melanocyte-stimulating hormone ameliorates ocular surface dysfunctions and lesions in a scopolamine-induced dry eye model via PKA-CREB and MEK-Erk pathways.

    Science.gov (United States)

    Ru, Yusha; Huang, Yue; Liu, Huijuan; Du, Juan; Meng, Zhu; Dou, Zexia; Liu, Xun; Wei, Rui Hua; Zhang, Yan; Zhao, Shaozhen

    2015-12-21

    Dry eye is a highly prevalent, chronic, and multifactorial disease that compromises quality of life and generates socioeconomic burdens. The pathogenic factors of dry eye disease (DED) include tear secretion abnormalities, tear film instability, and ocular surface inflammation. An effective intervention targeting the pathogenic factors is needed to control this disease. Here we applied α-Melanocyte-stimulating hormone (α-MSH) twice a day to the ocular surface of a scopolamine-induced dry eye rat model. The results showed that α-MSH at different doses ameliorated tear secretion, tear film stability, and corneal integrity, and corrected overexpression of proinflammatory factors, TNF-α, IL-1β, and IFN-γ, in ocular surface of the dry eye rats. Moreover, α-MSH, at 10(-4) μg/μl, maintained corneal morphology, inhibited apoptosis, and restored the number and size of conjunctival goblet cells in the dry eye rats. Mechanistically, α-MSH activated both PKA-CREB and MEK-Erk pathways in the dry eye corneas and conjunctivas; pharmacological blockade of either pathway abolished α-MSH's protective effects, suggesting that both pathways are necessary for α-MSH's protection under dry eye condition. The peliotropic protective functions and explicit signaling mechanism of α-MSH warrant translation of the α-MSH-containing eye drop into a novel and effective intervention to DED.

  12. In vivo evaluation of {sup 99m}Tc/{sup 188}Re-labeled linear alpha-melanocyte stimulating hormone analogs for specific melanoma targeting

    Energy Technology Data Exchange (ETDEWEB)

    Chen Jianqing; Giblin, Michael F.; Wang, Nannan; Jurisson, Silvia S.; Quinn, Thomas P. E-mail: quinnt@missouri.edu

    1999-08-01

    Radiolabeled alpha-melanocyte stimulating hormone ({alpha}-MSH) analogs were examined in melanoma-bearing mice to determine the effects of peptide length, structure, and radiometal chelation chemistry on tumor targeting and in vivo biodistribution. The linear {alpha}-MSH analogs [Nle{sup 4}, D-Phe{sup 7}]{alpha}-MSH (NDPMSH) and [D-Phe{sup 7}]{alpha}-MSH{sub 5-10} (DPMSH) were radiolabeled with {sup 99m}Tc and {sup 188}Re via the addition of tetrafluorophenyl mercapto-acetylglycylglycyl-gamma-aminobutyrate (MAG{sub 2}) or tetrapeptide Ac-Cys-Gly-Cys-Gly (CGCG) chelation moieties. {sup 125}I-Tyr{sup 2}-NDPMSH was obtained by direct iodination of the Tyr{sup 2} residue. Tumor uptake of {sup 99m}Tc-labeled CGCG- and MAG{sub 2}-NDPMSH analogs at 30 min postinjection were 6.52 {+-} 1.11 %ID/g and 4.17 {+-} 1.34 %ID/g, respectively, resulting in a significantly higher tumor-to-blood uptake ratio than that of {sup 125}I-NDPMSH or a shorter {alpha}-MSH analog, {sup 99m}Tc-CGCG-DPMSH. The combination of radiolabeling efficacy and in vivo tumor uptake highlights the potential of {sup 99m}Tc-CGCG-NDPMSH as a melanoma imaging agent.

  13. Chronic delivery of α-melanocyte-stimulating hormone in rat hypothalamus using albumin-alginate microparticles: effects on food intake and body weight.

    Science.gov (United States)

    Lucas, N; Legrand, R; Breton, J; Déchelotte, P; Edwards-Lévy, F; Fetissov, S O

    2015-04-02

    Chronic delivery of neuropeptides in the brain is a useful experimental approach to study their long-term effects on various biological parameters. In this work, we tested albumin-alginate microparticles, as a potential delivery system, to study if continuous release in the hypothalamus of α-melanocyte-stimulating hormone (α-MSH), an anorexigenic neuropeptide, may result in a long-term decrease in food intake and body weight. The 2-week release of α-MSH from peptide-loaded particles was confirmed by an in vitro assay. Then, daily food intake and body weight were studied for 18 days in rats injected bilaterally into the paraventricular hypothalamic nucleus with particles loaded or not with α-MSH. A decrease in body weight gain, persisting throughout the study, was found in rats injected with α-MSH-charged particles as compared with rats receiving non-charged particles and with rats injected with the same dose of α-MSH in solution. Food intake was significantly decreased for 3 days in rats receiving α-MSH-loaded particles and it was not followed by the feeding rebound effect which appears after food restriction. The presence of α-MSH-loaded particles in the hypothalamus was confirmed by immunohistochemistry. In conclusion, our study validates albumin-alginate microparticles as a new carrier system for long-term delivery of neuropeptides in the brain and demonstrates that chronic delivery of α-MSH in the hypothalamus results in a prolonged suppression of food intake and a decrease of body weight gain in rats. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  14. Systemic photoprotection in solar urticaria with α-melanocyte-stimulating hormone analogue [Nle4-D-Phe7]-α-MSH.

    Science.gov (United States)

    Haylett, A K; Nie, Z; Brownrigg, M; Taylor, R; Rhodes, L E

    2011-02-01

    Solar urticaria is a rare photosensitivity disorder demonstrating a range of action spectra, which can inflict a very large impact on life quality despite available treatments. Melanin broadly reduces skin penetration by ultraviolet-visible wavelengths, thus increased melanization may protect in solar urticaria. To examine quantitatively for impact of the potent α-melanocyte stimulating hormone analogue afamelanotide ([Nle(4)-D-Phe(7)]-α-MSH, Scenesse(®); Clinuvel Pharmaceuticals Ltd, Melbourne, Vic., Australia) on the solar urticaria response and skin melanization. Five patients with solar urticaria received a single dose of 16 mg subcutaneous afamelanotide implant in winter time. Melanin density was assessed spectrophotometrically from day 0 to day 60. Detailed monochromated light testing to geometric dose series (increment ) of wavelengths 300-600 nm was performed at 0, 30 and 60 days, with assessment of weal and flare area and minimum urticarial dose (MUD). Data were analysed by repeated-measures anova. Mean melanin density increased by day 7, peaked at day 15 and remained elevated at day 60 (P=0·03, 0·01, 0·02 vs. baseline, respectively). Baseline phototesting revealed action spectra of 320-400 (n=1), 320-500 (n=2), 300-600 (n=1) and 370-500 nm (n=1), and on afamelanotide mean rises in MUD of 1-12 and 1-3 dose increments were seen at the individual wavelengths tested, at 30 and 60 days, respectively. A significant fall in weal area occurred across responding wavelengths from 300 to 600 nm at 60 days postimplant (P=0·049 vs. baseline), accompanied by greater than twofold overall increase in MUD (P=0·058 vs. baseline). Melanization following afamelanotide is accompanied by reduction in solar urticaria response across a broad spectrum of wavelengths. Further study is warranted to assess clinical benefit under ambient conditions in summer. © 2011 The Authors. BJD © 2011 British Association of Dermatologists.

  15. Alpha-melanocyte stimulating hormone-induced anorexia in Japanese quail (Coturnix japonica) likely involves the ventromedial hypothalamus and paraventricular nucleus of the hypothalamus.

    Science.gov (United States)

    Lear, Taylor; Liu, Lingbin; O'Donnell, Madison; McConn, Betty R; Denbow, D Michael; Cline, Mark A; Gilbert, Elizabeth R

    2017-10-01

    Alpha-melanocyte stimulating hormone (α-MSH) reduces food intake in birds and mammals. The objective of this experiment was to determine effects of α-MSH on food and water intake, and hypothalamic c-Fos immunoreactivity and appetite-associated factor mRNA in Japanese quail (Coturnix japonica), a species that has not undergone the same artificial selection for growth-related traits as the chicken. At 7days post-hatch, 3-h-fasted quail were intracerebroventricularly (ICV) injected into the lateral ventricle with 0 (vehicle), 0.5, 5, or 50pmol of α-MSH and food and water intake were recorded at 30min intervals for 180min. In the second and third experiment, quail were injected with 50pmol α-MSH and hypothalami were collected at 1h to determine c-Fos immunoreactivity and mRNA abundance, respectively. At 30min, quail injected with 5 or 50pmol of α-MSH ate and drank less than vehicle-injected quail. Quail injected with 50pmol ate less for the entire duration of the experiment and drank less than vehicle-injected quail for 120min post-injection. Hypothalamic expression of agouti-related peptide and DOPA decarboxylase were greater in vehicle- than α-MSH-injected quail, whereas melanocortin receptor 4 (MC4R) mRNA was greater in α-MSH- than vehicle-injected birds. Alpha-MSH injection was associated with more c-Fos immunoreactive cells in the ventromedial hypothalamus (VMH) and paraventricular nucleus (PVN) of the hypothalamus. Results suggest that the anorexigenic effect of α-MSH is conserved among avians and that effects in quail are associated with the VMH and PVN and involve MC4R. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Fluorine-18-labeled [Nle{sup 4},D-Phe{sup 7}]-{alpha}-MSH, an {alpha}-melanocyte stimulating hormone analogue

    Energy Technology Data Exchange (ETDEWEB)

    Vaidyanathan, Ganesan; Zalutsky, Michael R

    1997-02-01

    The {alpha}-melanocyte stimulating hormone ({alpha}-MSH) analogue [N1e{sup 4},D-Phe{sup 7}]-{alpha}-MSH was labeled with {sup 18}F using N-succinimidyl 4-[{sup 18}F]fluorobenzoate ([{sup 18}F]SFB) in >80% radiochemical yield. The IC{sub 50} values of [N1e{sup 4},D-Phe{sup 7}]-{alpha}-MSH and para-fluorobenzoyl-[N1e{sup 4},D-Phe{sup 7}]-{alpha}-MSH ([N1e{sup 4},D-Phe{sup 7},Lys{sup 11}-({sup 18}F)PFB]-{alpha}-MSH) for inhibiting the binding of meta-[{sup 131}I]iodobenzoyl-[N1e{sup 4},D-Phe{sup 7}]-{alpha}-MSH ([N1e{sup 4},D-Phe{sup 7},Lys{sup 11}-({sup 131}I)MIB]-{alpha}-MSH) to B16-F1 murine melanoma cells were 89 {+-} 9 pM and 112 {+-} 22 pM, respectively, suggesting that addition of 4-fluorobenzoate did not compromise {alpha}-MSH receptor binding affinity. Binding of [N1e{sup 4},D-Phe{sup 7},Lys{sup 11}-({sup 18}F)PFB]-{alpha}-MSH was influenced by the specific activity of the preparation (400-1000 Ci/mmol). The normal tissue clearance of [N1e{sup 4},D-Phe{sup 7},Lys{sup 11}-({sup 18}F)PFB]-{alpha}-MSH in mice was quite rapid, with little evidence for defluorination.

  17. A {sup 99m}Tc(CO){sub 3}-labeled pyrazolyl-{alpha}-melanocyte-stimulating hormone analog conjugate for melanoma targeting

    Energy Technology Data Exchange (ETDEWEB)

    Raposinho, Paula D.; Correia, Joao D.G.; Alves, Susana [Departamento de Quimica, ITN, Estrada Nacional 10, 2686-953 Sacavem (Portugal); Botelho, Maria F.; Santos, Ana C. [Instituto de Biofisica/Biomatematica, IBILI-Faculdade de Medicina de Coimbra, 300-548 Coimbra (Portugal); Santos, Isabel [Departamento de Quimica, ITN, Estrada Nacional 10, 2686-953 Sacavem (Portugal)], E-mail: isantos@itn.pt

    2008-01-15

    Melanoma primary tumors can be, in most cases, removed surgically, whereas there is no satisfactory treatment for metastatic melanoma, being almost always lethal at this stage. Therefore, early detection of primary melanoma tumors is essential. The finding that melanocortin-1 receptor (MC1R) is overexpressed in isolated melanoma cells and melanoma tissues led to the radiolabeling of several {alpha}-melanocyte-stimulating hormone ({alpha}-MSH) analogs for early detection and treatment of melanoma. We have coupled the {alpha}-MSH analog Ac-Nle-Asp-His-D-Phe-Arg-Trp-Gly-Lys-NH{sub 2}, through the {epsilon}-amino group of Lys{sup 11}, to a pyrazolyl-containing chelator (pz). The resulting pz-{alpha}-MSH analog reacted with the fac-[{sup 99m}Tc(CO){sub 3}]{sup +} moiety, giving [Ac-Nle{sup 4},Asp{sup 5},D-Phe{sup 7},Lys{sup 11}(pz-{sup 99m}Tc(CO){sub 3})]{alpha}-MSH{sub 4-11} in high yield, high specific activity and high radiochemical purity. This radioconjugate, which presents remarkable stability in vitro, exhibited time- and temperature-dependent internalization (4 h at 37{sup o}C; 56.7% maximum internalization) and high cellular retention (only 38% was released from the cell after 5 h) in murine melanoma B16F1 cells. A significant tumor uptake [4.2{+-}0.9%ID/g, at 4 h postinjection (p.i.)] was also obtained in melanoma-bearing C57BL6 mice. The in vivo affinity and specificity of the radioconjugate to MC1R were demonstrated by receptor-blocking studies with the potent NDP-MSH agonist (63.5% reduction in tumor uptake at 4 h p.i.)

  18. Technetium-99m-labeled Arg-Gly-Asp-conjugated alpha-melanocyte stimulating hormone hybrid peptides for human melanoma imaging

    Energy Technology Data Exchange (ETDEWEB)

    Yang Jianquan; Guo Haixun [College of Pharmacy, University of New Mexico, Albuquerque, NM 87131 (United States); Miao Yubin, E-mail: ymiao@salud.unm.ed [College of Pharmacy, University of New Mexico, Albuquerque, NM 87131 (United States); Cancer Research and Treatment Center, University of New Mexico, Albuquerque, NM 87131 (United States); Department of Dermatology, University of New Mexico, Albuquerque, NM 87131 (United States)

    2010-11-15

    Introduction: The purpose of this study was to examine whether {sup 99m}Tc-labeled Arg-Gly-Asp (RGD)-conjugated alpha-melanocyte stimulating hormone ({alpha}-MSH) hybrid peptide targeting both melanocortin-1 (MC1) and {alpha}{sub v{beta}3} integrin receptors was superior in melanoma targeting to {sup 99m}Tc-labeled {alpha}-MSH or RGD peptide targeting only the MC1 or {alpha}{sub v{beta}3} integrin receptor. Methods: RGD-Lys-(Arg{sup 11})CCMSH, RAD-Lys-(Arg{sup 11})CCMSH and RGD-Lys-(Arg{sup 11})CCMSHscramble were designed to target both MC1 and {alpha}{sub v{beta}3} integrin receptors, MC1 receptor only and {alpha}{sub v{beta}3} integrin receptor only, respectively. The MC1 or {alpha}{sub v{beta}3} integrin receptor binding affinities of three peptides were determined in M21 human melanoma cells. The melanoma targeting properties of {sup 99m}Tc-labeled RGD-Lys-(Arg{sup 11})CCMSH, RAD-Lys-(Arg{sup 11})CCMSH and RGD-Lys-(Arg{sup 11})CCMSHscramble were determined in M21 human melanoma-xenografted nude mice. Meanwhile, the melanoma uptake of {sup 99m}Tc-RGD-Lys-(Arg{sup 11})CCMSH was blocked with various non-radiolabeled peptides in M21 melanoma xenografts. Results: RGD-Lys-(Arg{sup 11})CCMSH displayed 2.0 and 403 nM binding affinities to both MC1 and {alpha}{sub v{beta}3} integrin receptors, whereas RAD-Lys-(Arg{sup 11})CCMSH or RGD-Lys-(Arg{sup 11})CCMSHscramble lost their {alpha}{sub v{beta}3} integrin receptor binding affinity by greater than 248-fold or MC1 receptor binding affinity by more than 100-fold, respectively. The melanoma uptake of {sup 99m}Tc-RGD-Lys-(Arg{sup 11})CCMSH was 2.49 and 2.24 times (P < .05) the melanoma uptakes of {sup 99m}Tc-RAD-Lys-(Arg{sup 11})CCMSH and {sup 99m}Tc-RGD-Lys-(Arg{sup 11})CCMSHscramble at 2 h post-injection, respectively. Either RGD or (Arg{sup 11})CCMSH peptide co-injection could block 42% and 57% of the tumor uptake of {sup 99m}Tc-RGD-Lys-(Arg{sup 11})CCMSH, whereas the coinjection of RGD+(Arg{sup 11})CCMSH peptide mixture

  19. Growth hormone stimulation test

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003377.htm Growth hormone stimulation test To use the sharing features on this page, please enable JavaScript. The growth hormone (GH) stimulation test measures the ability of the ...

  20. The central effects of alpha-melanocyte stimulating hormone (α-MSH) in chicks involve changes in gene expression of neuropeptide Y and other factors in distinct hypothalamic nuclei.

    Science.gov (United States)

    Delp, Meghan S; Cline, Mark A; Gilbert, Elizabeth R

    2017-06-09

    Alpha-melanocyte stimulating hormone (α-MSH) is a satiety-inducing factor in birds and mammals although central mechanisms mediating its effects on appetite in birds are poorly understood. Thus, the objective of the present study was to determine effects of centrally-injected α-MSH on c-Fos and gene expression in chick appetite-associated hypothalamic nuclei. At 4days post-hatch, 3h-fasted chicks were intracerebroventricularly (ICV) injected with 0 (vehicle) or 0.12nmol α-MSH and 1h later, hypothalamus samples were collected for measuring c-Fos immunoreactivity and mRNA abundance of appetite-associated factors in hypothalamic nuclei. There were more c-Fos immunoreactive cells in the arcuate nucleus (ARC), dorsomedial nucleus (DMN), lateral hypothalamus (LH), and paraventricular nucleus (PVN) of α-MSH- than vehicle-injected chicks. Neuropeptide Y (NPY), oxytocin receptor (OXTR), and agouti-related peptide (AgRP) mRNAs were greater in α-MSH- than vehicle-injected chicks in the ARC. In the PVN, NPY receptor sub-type 1 (NPYR1) mRNA was reduced while c-Fos mRNA was increased in response to treatment with α-MSH. NPY, c-Fos, and DOPA decarboxylase (DDC) mRNAs were greater in treated than vehicle-injected chicks in the DMN. Results suggest that during the first hour post-injection, the appetite-inhibiting effects of α-MSH involve activation of the ARC, DMN, PVN, and LH, and corresponding changes in transcriptional regulation of factors involved with NPY, AgRP and mesotocin signaling, and monoamine synthesis. The effects of these changes may include an inhibition of NPY signaling in the PVN to induce satiety and stimulation of NPY/AgRP neurons in the ARC in an attempt to restore homeostatic levels of food intake. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. alpha-Melanocyte-stimulating hormone is contained in nerve terminals innervating thyrotropin-releasing hormone-synthesizing neurons in the hypothalamic paraventricular nucleus and prevents fasting-induced suppression of prothyrotropin-releasing hormone gene expression.

    Science.gov (United States)

    Fekete, C; Légrádi, G; Mihály, E; Huang, Q H; Tatro, J B; Rand, W M; Emerson, C H; Lechan, R M

    2000-02-15

    The hypothalamic arcuate nucleus has an essential role in mediating the homeostatic responses of the thyroid axis to fasting by altering the sensitivity of prothyrotropin-releasing hormone (pro-TRH) gene expression in the paraventricular nucleus (PVN) to feedback regulation by thyroid hormone. Because agouti-related protein (AGRP), a leptin-regulated, arcuate nucleus-derived peptide with alpha-MSH antagonist activity, is contained in axon terminals that terminate on TRH neurons in the PVN, we raised the possibility that alpha-MSH may also participate in the mechanism by which leptin influences pro-TRH gene expression. By double-labeling immunocytochemistry, alpha-MSH-IR axon varicosities were juxtaposed to approximately 70% of pro-TRH neurons in the anterior and periventricular parvocellular subdivisions of the PVN and to 34% of pro-TRH neurons in the medial parvocellular subdivision, establishing synaptic contacts both on the cell soma and dendrites. All pro-TRH neurons receiving contacts by alpha-MSH-containing fibers also were innervated by axons containing AGRP. The intracerebroventricular infusion of 300 ng of alpha-MSH every 6 hr for 3 d prevented fasting-induced suppression of pro-TRH in the PVN but had no effect on AGRP mRNA in the arcuate nucleus. alpha-MSH also increased circulating levels of free thyroxine (T4) 2.5-fold over the levels in fasted controls, but free T4 did not reach the levels in fed controls. These data suggest that alpha-MSH has an important role in the activation of pro-TRH gene expression in hypophysiotropic neurons via either a mono- and/or multisynaptic pathway to the PVN, but factors in addition to alpha-MSH also contribute to the mechanism by which leptin administration restores thyroid hormone levels to normal in fasted animals.

  2. α-Melanocyte stimulating hormone (MSH) and prostaglandin E2 (PGE2) drive melanosome transfer by promoting filopodia delivery and shedding spheroid granules: Evidences from atomic force microscopy observation.

    Science.gov (United States)

    Ma, Hui-Jun; Ma, Hui-Yong; Yang, Yang; Li, Peng-Cheng; Zi, Shao-Xia; Jia, Chi-Yu; Chen, Rong

    2014-12-01

    Skin pigmentation is accomplished by production of melanin in melanosome and by transfer of these organelles from melanocytes (MCs) to surrounding keratinocytes (KCs). However, the detailed mechanism is still unknown. We aimed to investigate the morphological structure changes on human epidermal MCs and KCs, which were either mono-cultured or co-cultured, with or without the treatment of both α-Melanocyte-stimulating hormone (α-MSH) and prostaglandin E2 (PGE2), by atomic force microscopy (AFM) and to provide more direct proofs for process of melanosome transfer. Human epidermal MCs and KCs were isolated and co-cultured with 1:10 ratio in a defined Keratinocyte-serum free medium (K-SFM). After exposure with 100 nM α-MSH or 20 μM PGE2 for 3 days, cells were fixed with 0.5% glutaraldehyde and AFM images of scanning observation were captured by contacting and tapping model under normal atmospheric pressure and temperature. It showed that human epidermal MCs in culture had secondary or tertiary branches. Except for globular granules structure on the surface of dendrites, some filopodia were protruded on the tips and lateral sides of the dendrites. The administration of α-MSH and PGE2 made not only the dendrites thinner and longer, but also the globular granules more intensive and denser. Many spheroid granules were shed from branches of dendrite and most of them adhered with dense filopodia. Compared with untreated group, the number of filopodia per cell, diameter of filopodia, and shedding spheroid granules per field all increased following α-MSH and PGE2 exposure (P<0.05, n=3). However, many crest-like protrusions, which were distributed homogenously on the surface of mono-cultured KCs, were less changed after α-MSH and PGE2 exposure. In co-culture model, α-MSH and PGE2 increased the number of transferred melanosomes in KCs under laser confocal microscopic examination. Filopodia were observed only on the adhesion area of KCs and MCs in a coiled style by AFM

  3. Ethyl acetate extract from Panax ginseng C.A. Meyer and its main constituents inhibit α-melanocyte-stimulating hormone-induced melanogenesis by suppressing oxidative stress in B16 mouse melanoma cells.

    Science.gov (United States)

    Jiang, Rui; Xu, Xiao-Hao; Wang, Ke; Yang, Xin-Zhao; Bi, Ying-Fei; Yan, Yao; Liu, Jian-Zeng; Chen, Xue-Nan; Wang, Zhen-Zhong; Guo, Xiao-Li; Zhao, Da-Qing; Sun, Li-Wei

    2017-08-17

    Hyperpigmentation disease involves darkening of the skin color due to melanin overproduction. Panax ginseng C.A. Meyer is a well-known traditional Chinese medicine and has a long history of use as a skin lightener to inhibit melanin formation in China, Korea and some other Asian countries. However, the constituents and the molecular mechanisms by which they affect melanogenesis are not fully clear. The purpose of this study was to identify the active ingredient in Panax ginseng C.A. Meyer extract that inhibits mushroom tyrosinase activity and to investigate the antioxidative capacity and molecular mechanisms of the effective extract on melanogenesis in B16 mouse melanoma cells. Aqueous extracts of Panax ginseng C.A. Meyer were successively fractionated with an equal volume of chloroform, ethyl acetate, and n-butyl alcohol to determine the effects by examining the activity of mushroom tyrosinase. The effective fraction was analyzed using HPLC and LC-MS. The antioxidative capacity and the inhibitory effects on melanin content, cell intracellular tyrosinase activity, and melanogenesis protein levels were determined in α-melanocyte-stimulating hormone (α-MSH)-treated B16 mouse melanoma cells. The ethyl acetate extract from Panax ginseng C.A. Meyer (PG-2) had the highest inhibiting effect on mushroom tyrosinase, mainly contained phenolic acids, including protocatechuic acid, vanillic acid, p-coumaric acid, salicylic acid, and caffeic acid, and exhibited apparent antioxidant activity in vitro. PG-2 and its main constituents significantly decreased melanin content, suppressed cellular tyrosinase activity, and reduced expression of tyrosinase protein to inhibit B16 cells melanogenesis induced by α-MSH, and no cytotoxic effects were observed. They also inhibited cellular reactive oxygen species (ROS) generation, increased superoxide dismutase (SOD) activity and glutathione (GSH) level in α-MSH-treated B16 cells effectively. And those activities of its main constituents

  4. Thyrotropin-releasing hormone selectively stimulates human hair follicle pigmentation.

    Science.gov (United States)

    Gáspár, Erzsébet; Nguyen-Thi, Kim T; Hardenbicker, Celine; Tiede, Stephan; Plate, Christian; Bodó, Eniko; Knuever, Jana; Funk, Wolfgang; Bíró, Tamás; Paus, Ralf

    2011-12-01

    In amphibians, thyrotropin-releasing hormone (TRH) stimulates skin melanophores by inducing secretion of α-melanocyte-stimulating hormone in the pituitary gland. However, it is unknown whether this tripeptide neurohormone exerts any direct effects on pigment cells, namely, on human melanocytes, under physiological conditions. Therefore, we have investigated whether TRH stimulates pigment production in organ-cultured human hair follicles (HFs), the epithelium of which expresses both TRH and its receptor, and/or in full-thickness human skin in situ. TRH stimulated melanin synthesis, tyrosinase transcription and activity, melanosome formation, melanocyte dendricity, gp100 immunoreactivity, and microphthalmia-associated transcription factor expression in human HFs in a pituitary gland-independent manner. TRH also stimulated proliferation, gp100 expression, tyrosinase activity, and dendricity of isolated human HF melanocytes. However, intraepidermal melanogenesis was unaffected. As TRH upregulated the intrafollicular production of "pituitary" neurohormones (proopiomelanocortin transcription and ACTH immunoreactivity) and as agouti-signaling protein counteracted TRH-induced HF pigmentation, these pigmentary TRH effects may be mediated in part by locally generated melanocortins and/or by MC-1 signaling. Our study introduces TRH as a novel, potent, selective, and evolutionarily highly conserved neuroendocrine factor controlling human pigmentation in situ. This physiologically relevant and melanocyte sub-population-specific neuroendocrine control of human pigmentation deserves clinical exploration, e.g., for preventing or reversing hair graying.

  5. Growth hormone stimulation test (image)

    Science.gov (United States)

    ... stimulation test is usually performed to identify if hGH (human growth hormone) is deficient. The test is ... amino acid arginine in a vein to raise hGH levels. The test measures the ability of the ...

  6. Follicle-stimulating hormone (FSH) blood test

    Science.gov (United States)

    ... ency/article/003710.htm Follicle-stimulating hormone (FSH) blood test To use the sharing features on this page, please enable JavaScript. The follicle stimulating hormone (FSH) blood test measures the level of FSH in blood. FSH ...

  7. Thyroid stimulating hormone and subclinical thyroid dysfunction

    International Nuclear Information System (INIS)

    Guo Yongtie

    2008-01-01

    Subclinical thyroid dysfunction has mild clinical symptoms. It is nonspecific and not so noticeable. It performs only for thyroid stimulating hormone rise and decline. The value of early diagnosis and treatment of thyroid stimulating hormone in subclinical thyroid dysfunction were reviewed. (authors)

  8. 21 CFR 862.1690 - Thyroid stimulating hormone test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Thyroid stimulating hormone test system. 862.1690... Systems § 862.1690 Thyroid stimulating hormone test system. (a) Identification. A thyroid stimulating hormone test system is a device intended to measure thyroid stimulating hormone, also known as...

  9. UVB-Stimulated TNFα Release from Human Melanocyte and Melanoma Cells Is Mediated by p38 MAPK

    Directory of Open Access Journals (Sweden)

    Visalini Muthusamy

    2013-08-01

    Full Text Available Ultraviolet (UV radiation activates cell signaling pathways in melanocytes. As a result of altered signaling pathways and UV-induced cellular damage, melanocytes can undergo oncogenesis and develop into melanomas. In this study, we investigated the effect of UV-radiation on p38 MAPK (mitogen-activated protein kinase, JNK and NFκB pathways to determine which plays a major role in stimulating TNFα secretion in human HEM (melanocytes and MM96L (melanoma cells. MM96L cells exhibited 3.5-fold higher p38 activity than HEM cells at 5 min following UVA + B radiation and 1.6-fold higher JNK activity at 15–30 min following UVB+A radiation, while NFκB was minimally activated in both cells. Irradiated HEM cells had the greatest fold of TNFα secretion (UVB: 109-fold, UVA + B: 103-fold & UVB+A: 130-fold when co-exposed to IL1α. The p38 inhibitor, SB202190, inhibited TNFα release by 93% from UVB-irradiated HEM cells. In the UVB-irradiated MM96L cells, both SB202190 and sulfasalazine (NFκB inhibitor inhibited TNFα release by 52%. Although, anisomycin was a p38 MAPK activator, it inhibited TNFα release in UV-irradiated cells. This suggests that UV-mediated TNFα release may occur via different p38 pathway intermediates compared to those stimulated by anisomycin. As such, further studies into the functional role p38 MAPK plays in regulating TNFα release in UV-irradiated melanocyte-derived cells are warranted.

  10. Stimulation of cyclic GMP efflux in human melanocytes by hypergravity generated by centrifugal acceleration

    NARCIS (Netherlands)

    Ivanova, Krassimira; Zadeh, Nahid Hamidi; Block, Ingrid; Das, Pranab K.; Gerzer, Rupert

    2004-01-01

    Gravity alteration (micro- and hypergravity) is known to influence cell functions. As guanosine 3',5'-cyclic monophosphate (cGMP) plays an important role in human melanocyte functions and different guanylyl cyclase isoforms are responsible for cGMP synthesis in human non-metastatic and metastatic

  11. A method for quantifying melanosome transfer efficacy from melanocytes to keratinocytes in vitro.

    Science.gov (United States)

    Lin, Hwang-Chi; Shieh, Bin-Han; Lu, Mei-Hua; Chen, Jang-Yi; Chang, Li-Tze; Chao, Chung-Faye

    2008-10-01

    Several different in vivo and in vitro bioassays are used to evaluate melanosome transfer efficacy from melanocytes to keratinocytes. However, these methods are complicated and time consuming. Here, we report on a simple, rapid, direct, and reliable in vitro method for observing the process of melanosome transfer from melanocytes to keratinocytes. First, we selected and tested a melanoma cell line RPMI-7951 that can normally synthesize melanin and transfer from mature melanosomes to keratinocytes in vitro. We cocultured these cells with a human ovarian teratoma transformed epidermal carcinoma cell line, which is also capable of accepting melanosomes transferred from melanocytes, as in normal keratinocytes. The cells were cocultured for 24-72 h and double labeled with FITC-conjugated antibody against the melanosome-associated protein TRP-1, and with Cy5-conjugated antibody against the keratinocyte-specific marker keratin 14. The cells were examined by fluorescence microscope and flow cytometry. Melanosome transfer from melanocytes to keratinocytes increased in a time-dependent manner. To verify the accessibility of this method, the melanosome transfer inhibitor, a serine protease inhibitor, 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride, and a melanosome transfer stimulator, alpha-melanocyte-stimulating hormone, were added. The serine protease inhibitor decreased melanosome transfer, and alpha-melanocyte-stimulating hormone increased melanosome transfer, in a dose-dependent manner. In conclusion, this is a simple, rapid, and effective model system to quantify the melanosome transfer efficacy from melanocytes to keratinocytes in vitro.

  12. 21 CFR 522.1002 - Follicle stimulating hormone.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Follicle stimulating hormone. 522.1002 Section 522...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1002 Follicle stimulating hormone. (a)(1) Specifications. Each package contains 2 vials. One vial...

  13. Ultraviolet stimulated melanogenesis by human melanocytes is augmented by di-acyl glycerol but not TPA

    International Nuclear Information System (INIS)

    Friedmann, P.S.; Wren, F.E.; Matthews, J.N.

    1990-01-01

    Epidermal melanocytes (MC) synthesize melanin in response to ultraviolet radiation (UVR). The mechanisms mediating the UV-induced activation of melanogenesis are unknown but since UVR induces turnover of membrane phospholipids generating prostaglandins (PGs) and other products, it is possible that one of these might provide the activating signal. We have examined the effects of prostaglandins (PGs) E1, E2, D2, F2 alpha, and di-acyl glycerol upon the UV-induced responses of cultured human MC and the Cloudman S91 melanoma cell line. The PGs had little effect on unirradiated cells and did not alter the response to UVR in either human MC or S91 melanoma cells. However, a synthetic analogue of di-acyl glycerol, 1-oleyl 2-acetyl glycerol (OAG), caused a significant (P less than 0.0001), dose-related augmentation of melanin content both in human MC (seven-fold) and S91 cells (three-fold). UVR caused a significant augmentation of the OAG-induced melanogenesis of both human MC and S91 cells. Since OAG is known to activate protein kinase C, it was possible that the observed modulation of the UVR signal could be via that pathway. Di-octanoyl glycerol, another di-acyl glycerol, which activates kinase C, caused a small (70%) increase in melanogenesis in MC which was not altered by UVR. However, 12-0 tetradecanoyl phorbol 13-acetate (TPA), a potent activator of protein kinase C, had no significant effect on either basal or UV-induced melanin synthesis in either cell type. These data suggest that the UV-induced signal activating melanogenesis could be mediated by di-acyl glycerol. Furthermore, they imply that the signal is transduced via an alternative, pathway that might be independent of protein kinase C

  14. Interference with follicle stimulating hormone regulation of human ovarian function

    NARCIS (Netherlands)

    B.C.J.M. Fauser (Bart)

    1996-01-01

    textabstractThis review summarizes observations on the background and potential clinical significance of interference with follicle stimulating hormone (FSH) regulation of human ovarian function. This interference may occur at the level of the pituitary by the secretion

  15. Effect of two follicle stimulating hormone (FSH) preparations and ...

    African Journals Online (AJOL)

    wool sheep to superovulation with two follicles stimulating hormone (FSH) preparations and simplified superovulatory treatments. In Experiment I, 22 adult Xinji fine-wool sheep were randomly allocated in equal number (n = 11) to two groups ...

  16. Growth hormone stimulation test - series (image)

    Science.gov (United States)

    ... infants and children to identify human growth hormone (hGH) deficiency as a cause of growth retardation. It ... test, as exercise or increased activity can alter hGH levels. Inform your health-care provider if you ...

  17. FSH (Follicle-Stimulating Hormone) Test

    Science.gov (United States)

    ... Culture Blood Gases Blood Ketones Blood Smear Blood Typing Blood Urea Nitrogen (BUN) BNP and NT-proBNP ... Luteinizing Hormone (LH) Lyme Disease Tests Magnesium Maternal Serum Screening, Second Trimester Measles and Mumps Tests Mercury ...

  18. 21 CFR 862.1300 - Follicle-stimulating hormone test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Follicle-stimulating hormone test system. 862.1300... Systems § 862.1300 Follicle-stimulating hormone test system. (a) Identification. A follicle-stimulating hormone test system is a device intended to measure follicle-stimulating hormone (FSH) in plasma, serum...

  19. Control of Pituitary Thyroid-stimulating Hormone Synthesis and Secretion by Thyroid Hormones during Xenopus Metamorphosis

    Science.gov (United States)

    Serum thyroid hormone (TH) concentrations in anuran larvae rise rapidly during metamorphosis. Such a rise in an adult anuran would inevitably trigger a negative feedback response resulting in decreased synthesis and secretion of thyroid-stimulating hormone (TSH) by the pituitary....

  20. Luteinizing hormone and follicle stimulating hormone synergy: A review of role in controlled ovarian hyper-stimulation

    Directory of Open Access Journals (Sweden)

    Gottumukkala Achyuta Rama Raju

    2013-01-01

    Full Text Available Luteinizing hormone (LH in synergy with follicle stimulating hormone (FSH stimulates normal follicular growth and ovulation. FSH is frequently used in assisted reproductive technology (ART. Recent studies have facilitated better understanding on the complementary role of the LH to FSH in regulation of the follicle; however, role of LH in stimulation of follicle, optimal dosage of LH in stimulation and its importance in advanced aged patients has been a topic of discussion among medical fraternity. Though the administration of exogenous LH with FSH is obligatory for controlled ovarian stimulation in patients with hypogonadotropic hypogonadism, there is still a paucity of information of its usage in other patient population. In this review we looked in to the multiple roles that LH plays complementary to FSH to better understand the LH requirement in patients undergoing ART.

  1. Abba Kastin: The melanocyte stimulating hormone story and the future of the proteophathies.

    Science.gov (United States)

    Miller, Lyle H

    2015-10-01

    From a personal viewpoint, Abba was always a congenial colleague and a good friend. I recall the hours of unraveling complex, confusing, and many times contradictory data sets with him and the excitement we both felt as what had been puzzling began to make sense. Most of all, I feel privileged to have Abba as a long and valued friend. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Tyrosol and Its Analogues Inhibit Alpha-Melanocyte-Stimulating Hormone Induced Melanogenesis

    Directory of Open Access Journals (Sweden)

    Kuo-Ching Wen

    2013-11-01

    Full Text Available Melanin is responsible for skin color and plays a major role in defending against harmful external factors such as ultraviolet (UV irradiation. Tyrosinase is responsible for the critical steps of melanogenesis, including the rate-limiting step of tyrosine hydroxylation. The mechanisms of action of skin hypopigmenting agents are thought to be based on the ability of a given agent to inhibit the activity of tyrosinase and, hence, down regulate melanin synthesis. Tyrosol and its glycoside, salidroside, are active components of Rhodiola rosea, and in our preliminary study we found that Rhodiola rosea extract inhibited melanogenesis. In this study, we examined the effects of tyrosol and its analogues on melanin synthesis. We found that treatment of B16F0 cells to tyrosol (1, 4-hydroxyphenylacetic acid (5, 3-hydroxyphenylacetic acid (6, 2-hydroxyphenylacetic acid (7, or salidroside (11 resulted in a reduction in melanin content and inhibition of tyrosinase activity as well as its expression. Tyrosol (1, 4-hydroxyphenylacetic acid (5 and 2-hydroxyphenylacetic acid (7 suppressed MC1R expression. Tyrosol (1, 4-hydroxyphenylacetic acid (5, 3-hydroxyphenylacetic acid (6, and 2-hydroxyphenylacetic acid (7 inhibited α-MSH induced TRP-1 expression, but salidroside (11 did not. All the compounds did not affect MITF and TRP-2 expression. Furthermore, we found that the cell viability of tyrosol (1, 4-hydroxyphenylacetic acid (5, 3-hydroxyphenylacetic acid (6, and 2-hydroxyphenylacetic acid (7 at concentrations below 4 mM and salidroside (11 at concentrations below 0.5 mM were higher than 90%. The compounds exhibited metal-coordinating interactions with copper ion in molecular docking with tyrosinase. Our results suggest that tyrosol, 4-hydroxyphenylacetic acid, 3-hydroxyphenylacetic acid, 2-hydroxyphenylacetic acid, and salidroside are potential hypopigmenting agents.

  3. An extract of Withania somnifera attenuates endothelin-1-stimulated pigmentation in human epidermal equivalents through the interruption of PKC activity within melanocytes.

    Science.gov (United States)

    Nakajima, Hiroaki; Wakabayashi, Yuki; Wakamatsu, Kazumasa; Imokawa, Genji

    2011-09-01

    Redox imbalances have been shown to be closely linked to a variety of altered cellular responses and profoundly affect intracellular signaling pathways, especially the PKC/MAPK pathway which is a major pathway involved in regulating melanogenesis within human melanocytes. To elucidate the effects of redox balance regulation on epidermal hyperpigmentary disorders, an antioxidant-rich herb extract of Withania somnifera was used to assess its effect on endothelin-1 (EDN1)-stimulated pigmentation in human epidermis equivalents and its biological mechanisms analysed. Addition of the Withania somnifera extract (10 µg/mL) elicited a marked depigmenting effect on EDN1 (10 nm)-stimulated pigmentation which was accompanied by a significant decrease in eumelanin content. Real-time RT-PCR and western blotting revealed that the stimulated expression of melanocyte-specific mRNAs and proteins, including microphthalmia associated transcription factor (MITF), was significantly suppressed at days 7-10 of culture by the Withania somnifera extract (10 µg/mL), suggesting an impairment in intracellular signaling upstream of gene expression. Signaling analysis revealed that in Withania somnifera extract (10 µg/mL)-treated human melanoma cells in culture, there was a marked deficiency in EDN1 (10 nm)-stimulated phosphorylation of Raf-1, MEK, ERK, MITF and Cyclic AMP responsive element binding protein (CREB) at 15 min after EDN1 treatment. Consistently, treatment with withaferin A, a major component of the Withania somnifera extract, at concentrations of 10-50 µm also significantly down-regulated the EDN1 stimulated phosphorylation of Raf-1, MEK, ERK, MITF and CREB at 15 min after EDN1 treatment. Since Raf-1 is phosphorylated by protein kinase C (PKC) activity, these findings indicate that the Withania somnifera extract attenuates EDN1-stimulated pigmentation by preferentially inhibiting EDN1-triggered PKC activity. Copyright © 2011 John Wiley & Sons, Ltd.

  4. Thyroid Stimulating Hormone values from cord blood in neonates ...

    African Journals Online (AJOL)

    Objectives: To determine thyroid stimulating hormone (TSH) levels from cord blood in neonates and to establish the practice for possible application of congenital hypothyroidism screening in Ethiopia. Methods: TSH was measured from cord blood of 1207 consecutive new-borns in the maternal wards of St. Paul, Ghandi ...

  5. Hormonal, functional and genetic biomarkers in controlled ovarian stimulation

    DEFF Research Database (Denmark)

    Alviggi, Carlo; Humaidan, Peter; Ezcurra, Diego

    2012-01-01

    single patient characteristics. These could potentially be used to match patients with the right treatment options to optimise efficacy, safety and tolerability during COS. Currently, age and follicle-stimulating hormone (FSH) level remain the most commonly used single patient characteristics in clinical...... to guide COS. The antral follicle count is a functional biomarker that could be useful in determining the dose of FSH necessary during stimulation and the success of treatment. Finally, in the future, genetic screening may allow an individual patient's response to stimulation during COS to be predicted...

  6. Ultraviolet radiation stimulates a biphasic pattern of 1,2-diacylglycerol formation in cultured human melanocytes and keratinocytes by activation of phospholipases C and D

    International Nuclear Information System (INIS)

    Carsberg, C.J.; Friedmann, P.S.; Ohanian, J.

    1995-01-01

    Ultraviolet radiation (UVR) induces melanin synthesis by human epidermal melanocytes, and phospholipid-derived 1,2-diacyl-glycerols (DAGs) have been implicated in mediating this response. In previous experiments, addition of the synthetic DAG l-oleoyl-2-acetylglycerol to cultured pigment cells stimulated melanogensis. The purpose of the present study was to analyse the effects of UVR on the endogenous generation of DAGs. It was found that in a number of cultured cell types, including human melanocytes and B16 mouse melanoma cells, but also human keratinocytes and Swiss 3T3 fibroblasts, exposure to a single dose of UVR stimulated a biphasic increase in endogenous DAG formation. An early transient rise, over seconds, was followed by a more sustained delayed rise over minutes. The early rise in DAG levels was accompanied by a transient rise in inositol trisphosphate formation, indicating activation of phosphatidylinositol-specific phospholipase C. The delayed rise was accompanied by activation of phospholipase D. The endogenous DAG formation by pigment cells is further evidence for the involvement of DAGs in UVR-induced epidermal melanin synthesis. Since DAG formation is also seen in other cells types, it is possible that DAGs may be involved in an array of UVR-induced responses. (author)

  7. Induction of retinal-dependent calcium influx in human melanocytes by UVA or UVB radiation contributes to the stimulation of melanosome transfer.

    Science.gov (United States)

    Hu, Qing-Mei; Yi, Wen-Juan; Su, Meng-Yun; Jiang, Shan; Xu, Shi-Zheng; Lei, Tie-Chi

    2017-12-01

    The transfer of melanosomes from melanocytes to neighbouring keratinocytes is critical to protect the skin from the deleterious effects of ultraviolet A (UVA) and ultraviolet B (UVB) irradiation; however, the initial factor(s) that stimulates melanosome transfer remains unclear. In this study, we investigated the induction of retinal-dependent calcium (Ca 2+ ) influx in melanocytes (MCs) by UVA or UVB irradiation and the effect of transient receptor potential cation channel subfamily M member 1 (TRPM1) (melastatin1)-related Ca 2+ influx on melanosome transfer. Primary human epidermal MCs were exposed to physiological doses of UVB or UVA light and loaded with a calcium indicator Fluo-4 dye. The change of intracellular calcium of MCs was monitored using a two-photon confocal fluorescence microscopy. MCs were co-cultured with human epidermal keratinocytes (KCs) in the absence or presence of voriconazole (a TRPM1 blocker) or calcium chelators. MCs were also transfected with TRPM1 siRNA for silencing the expression of TRPM1 gene. The melanosome transfer in the co-cultured cells was quantitatively analysed using flow cytometry and was further confirmed by immunofluorescent double-staining. The protein levels and distributions of TRPM1, OPN3 and OPN5 in MCs were measured by Western blotting or immunofluorescent staining. The retinal-dependent Ca 2+ influx of UVA-exposed melanocytes differed greatly from that of UVB-exposed melanocytes in the timing-phase. The protein expression of TRPM1 in mono- and co-cultured MCs was dose-dependently up-regulated by UVA and UVB. TRPM1 siRNA-mediated knockdown and the blockage of TRPM1 channel using a putative antagonist (voriconazole) significantly inhibited melanosome transfer in co-cultures following UVA or UVB exposure. The distinct time-phases of Ca 2+ influx in MCs induced by UVA or UVB contribute to the consecutive stimulation of melanosome transfer, thereby providing a potent photoprotection against harmful UV radiation. © 2017

  8. Increasing Goat Productivity Through the Improvement of Endogenous Secretion of Pregnant Hormones Using Follicle Stimulating Hormone

    Directory of Open Access Journals (Sweden)

    Andriyanto Andriyanto

    2011-05-01

    Full Text Available Abstract. Previous studies reported that the improvement of endogenous estrogen and progesterone secretions during gestation improved fetal prenatal growth, birth weight, mammary gland growth and development, milk production, litter size, pre- and post-weaning growths. An experiment was conducted to apply the improvement of endogenous secretion of pregnant hormones during pregnancy to increase goat productivity. Thirty-six female ettawah-cross does were divided into 2 groups. Group 1 (control: 18 does included does without improvement of endogenous secretion of pregnant hormones and Group 2 (treatment: 18 does included does with improvement of endogenous secretion of pregnant hormones using follicle stimulating hormones to stimulate super ovulation. The application of this technology increased total offspring born (control: 25 offspring; treatment: 42 offspring, average litter size (control: 1.88; treatment: 2.33, offspring birth weight (control: 2.85±0.50 kg; treatment: 3.82±0.40 kg, and does milk production (control: 1.36±0.34 L/does/day; treatment: 2.10±0.21 L/does/day. Offspring born to does with improved endogenous secretion of pregnant hormones had better weaning weight (control: 11.17±1.99 kg/offspring; treatment: 14.5±1.11 kg/offspring. At weaning period, does with improved endogenous secretion of pregnant hormones produced offspring with total weaning weight twice as heavy as control does (control: 189.9 kg; treatment: 403.6 kg. By a simple calculation of economic analysis, this technology application could increase gross revenue per does until weaning by Rp. 432.888,89. It was concluded that this technology is economically feasible to be applied in small-scale farm. Key Words: follicle stimulating hormone, pregnant hormones, endogenous secretion, super ovulation, ettawah-cross does

  9. Pigmentation, Melanocyte Colonization, and p53 Status in Basal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Lídia M. Frey

    2011-01-01

    Full Text Available Basal cell carcinoma (BCC is the most common neoplasm in the Caucasian population. Only a fraction of BCC exhibits pigmentation. Lack of melanocyte colonization has been suggested to be due to p53-inactivating mutations in the BCC cells interfering with the p53-proopiomelanocortin pathway and the production of alpha melanocyte-stimulating hormone in the tumor. To evaluate this, we determined tumor pigmentation as well as expression of melan-A and of p53 in 49 BCC tissues by means of immunohistochemistry. As expected, we observed a positive relation between tumor pigmentation and melan-A positive intra-tumoral melanocytes. Melanocyte colonization and, to a lesser extent, p53 overexpression showed intraindividual heterogeneity in larger tumors. p53 overexpression, which is indicative of p53 mutations, was not correlated to melanocyte colonization of BCC. Sequencing of exon 5–8 of the p53 gene in selected BCC cases revealed that colonization by melanocytes and BCC pigmentation is neither ablated by p53 mutations nor generally present in BCCs with wild-type p53.

  10. Substantial Effect of Melanin Influencing Factors on Melanogenesis in Muzzle Melanocytes of Differently Colored Hanwoo

    Directory of Open Access Journals (Sweden)

    Touseef Amna

    2012-07-01

    Full Text Available The present study was designed to investigate the effect of α-melanocyte-stimulating hormone (α-MSH, nitric oxide (NO and L-cysteine on melanin production and expression of related genes MC1R, Tyr, Tyrp-1 and Tyrp-2 in muzzle melanocytes of differently colored three native Hanwoo cattle. Muzzle samples were taken from black, brindle and brown Hanwoo and purified melanocytes were cultured with α-MSH, nitric oxide and L-cysteine at 100 nM, 50 µM and 0.07 mg/ml of media respectively. The amounts of total melanin, eumelanin and mRNA expression at Tyr, Tyrp-1, Tyrp-2 and MC1R levels were quantified. α-MSH and nitric oxide significantly increased (p<0.05 the amount of total melanin in black and brindle whereas eumelanin production in brown Hanwoo muzzle melanocytes. On the contrary, L-cysteine greatly (p<0.05 depressed the eumelanin production in black color but increased in brown. Simultaneously, up regulation of Tyr by nitric oxide and α-MSH and down regulation of Tyr, Tyrp-2 and MC1R genes by L-cysteine were observed in muzzle melanocytes of all three phenotypes. The results of this study revealed nitric oxide and α-MSH contribute hyper-pigmentation by enhancing eumelanogenesis whereas L-cysteine contributes to pheomelanin production in different colored Hanwoo muzzle melanocytes.

  11. Pigmentation, Melanocyte Colonization, and p53 Status in Basal Cell Carcinoma

    International Nuclear Information System (INIS)

    Frey, L. M.; Houben, R.; Brocker, E. B.

    2011-01-01

    Basal cell carcinoma (BCC) is the most common neoplasm in the Caucasian population. Only a fraction of BCC exhibits pigmentation. Lack of melanocyte colonization has been suggested to be due to p53-inactivating mutations in the BCC cells interfering with the p53-proopiomelanocortin pathway and the production of alpha melanocyte-stimulating hormone in the tumor. To evaluate this, we determined tumor pigmentation as well as expression of melan-A and of p53 in 49 BCC tissues by means of immunohistochemistry. As expected, we observed a positive relation between tumor pigmentation and melan-A positive intra-tumoral melanocytes. Melanocyte colonization and, to a lesser extent, p53 overexpression showed intraindividual heterogeneity in larger tumors. p53 overexpression, which is indicative of p53 mutations, was not correlated to melanocyte colonization of BCC. Sequencing of exon 5-8 of the p53 gene in selected BCC cases revealed that colonization by melanocytes and BCC pigmentation is neither ablated by p53 mutations nor generally present in BCCs with wild-type p53.

  12. Low temperature stimulates alpha-melanophore-stimulating hormone secretion and inhibits background adaptation in Xenopus laevis.

    NARCIS (Netherlands)

    Tonosaki, Y; Cruijsen, P.M.; Nishiyama, K; Yaginuma, H; Roubos, E.W.

    2004-01-01

    It is well-known that alpha-melanophore-stimulating hormone (alpha-MSH) release from the amphibian pars intermedia (PI) depends on the light condition of the animal's background, permitting the animal to adapt the colour of its skin to background light intensity. In the present study, we carried out

  13. A comprehensive curated resource for follicle stimulating hormone signaling

    Directory of Open Access Journals (Sweden)

    Sharma Jyoti

    2011-10-01

    Full Text Available Abstract Background Follicle stimulating hormone (FSH is an important hormone responsible for growth, maturation and function of the human reproductive system. FSH regulates the synthesis of steroid hormones such as estrogen and progesterone, proliferation and maturation of follicles in the ovary and spermatogenesis in the testes. FSH is a glycoprotein heterodimer that binds and acts through the FSH receptor, a G-protein coupled receptor. Although online pathway repositories provide information about G-protein coupled receptor mediated signal transduction, the signaling events initiated specifically by FSH are not cataloged in any public database in a detailed fashion. Findings We performed comprehensive curation of the published literature to identify the components of FSH signaling pathway and the molecular interactions that occur upon FSH receptor activation. Our effort yielded 64 reactions comprising 35 enzyme-substrate reactions, 11 molecular association events, 11 activation events and 7 protein translocation events that occur in response to FSH receptor activation. We also cataloged 265 genes, which were differentially expressed upon FSH stimulation in normal human reproductive tissues. Conclusions We anticipate that the information provided in this resource will provide better insights into the physiological role of FSH in reproductive biology, its signaling mediators and aid in further research in this area. The curated FSH pathway data is freely available through NetPath (http://www.netpath.org, a pathway resource developed previously by our group.

  14. Receptors for thyrotropin-releasing hormone, thyroid-stimulating hormone, and thyroid hormones in the macaque uterus: effects of long-term sex hormone treatment.

    Science.gov (United States)

    Hulchiy, Mariana; Zhang, Hua; Cline, J Mark; Hirschberg, Angelica Lindén; Sahlin, Lena

    2012-11-01

    Thyroid gland dysfunction is associated with menstrual cycle disturbances, infertility, and increased risk of miscarriage, but the mechanisms are poorly understood. However, little is known about the regulation of these receptors in the uterus. The aim of this study was to determine the effects of long-term treatment with steroid hormones on the expression, distribution, and regulation of the receptors for thyrotropin-releasing hormone (TRHR) and thyroid-stimulating hormone (TSHR), thyroid hormone receptor α1/α2 (THRα1/α2), and THRβ1 in the uterus of surgically menopausal monkeys. Eighty-eight cynomolgus macaques were ovariectomized and treated orally with conjugated equine estrogens (CEE; n = 20), a combination of CEE and medroxyprogesterone acetate (MPA; n = 20), or tibolone (n = 28) for 2 years. The control group (OvxC; n = 20) received no treatment. Immunohistochemistry was used to evaluate the protein expression and distribution of the receptors in luminal epithelium, glands, stroma, and myometrium of the uterus. Immunostaining of TRHR, TSHR, and THRs was detected in all uterine compartments. Epithelial immunostaining of TRHR was down-regulated in the CEE + MPA group, whereas in stroma, both TRHR and TSHR were increased by CEE + MPA treatment as compared with OvxC. TRHR immunoreactivity was up-regulated, but THRα and THRβ were down-regulated, in the myometrium of the CEE and CEE + MPA groups. The thyroid-stimulating hormone level was higher in the CEE and tibolone groups as compared with OvxC, but the level of free thyroxin did not differ between groups. All receptors involved in thyroid hormone function are expressed in monkey uterus, and they are all regulated by long-term steroid hormone treatment. These findings suggest that there is a possibility of direct actions of thyroid hormones, thyroid-stimulating hormone and thyrotropin-releasing hormone on uterine function.

  15. Follicle stimulating hormone receptor in mesenchymal stem cells integrates effects of glycoprotein reproductive hormones.

    Science.gov (United States)

    Tourkova, Irina L; Witt, Michelle R; Li, La; Larrouture, Quitterie; Liu, Li; Luo, Jianhua; Robinson, Lisa J; Blair, Harry C

    2015-01-01

    Previously we reported that follicle stimulating hormone (FSH) affects bone degradation in human cells and in follicle stimulating hormone receptor (FSH-R) null mice. Here we describe a FSH-R knockout bone-formation phenotype. We used mesenchymal stem cells (MSCs), osteoblast precursors that express FSH-R, to determine whether FSH regulates bone formation. FSH stimulates MSC cell adhesion 1-3 h and proliferation at 24 h after addition. On the basis of phylogenetic and clinical precedents, we also examined effects of pregnant levels of human chorionic gonadotropin (hCG) on MSCs. We found effects similar to those of FSH, and RNAi knockdown of FSH-R abrogated both FSH and hCG effects on MSCs. In contrast to effects on MSCs, neither FSH nor hCG had significant effects on osteoblast maturation. Also in MSCs, short-term treatment by FSH and hCG altered signaling pathways for proliferation, including Erk1/2 phosphorylation. Our results show augmentation of MSC proliferation by either FSH at menopausal levels or hCG at normal pregnant levels. We conclude that FSH-R participates in regulation of MSC precursor pools in response to either FSH or hCG, integrating the effects of these two glycoprotein hormones. © 2014 New York Academy of Sciences.

  16. Fetal intermediate lobe is stimulated by parturition.

    Science.gov (United States)

    Facchinetti, F; Lanzani, A; Genazzani, A R

    1989-11-01

    The fetal pituitary gland secretes beta-endorphin in blood in response to delivery. However, other forms of endorphin have recently been observed in the fetal pituitary, such as N-acetyl-beta-endorphin, which is devoid of opiate activity, and a desacetylated form of alpha-melanocyte-stimulating hormone. Both endorphins originate in the pituitary intermediate lobe. The sensitivity of this lobe to labor stress was assessed by the evaluation of beta-endorphin, N-acetyl-beta-endorphin, melanocyte-stimulating hormone, and desacetylated alpha-melanocyte-stimulating hormone in maternal plasma and cord blood in 11 cases of vaginal delivery and 10 cases of elective cesarean section without labor. Plasma peptide levels were determined by specific radioimmunoassays after extraction on Sep-Pak C-18 cartridges and high-performance liquid chromatography fractionation. Cord blood samples of infants delivered vaginally showed higher beta-endorphin (8.5 +/- 1.6 pmol/L, mean +/- SE) and desacetylated alpha-melanocyte-stimulating hormone (13.6 +/- 3.2 pmol/L) levels than those delivered by elective cesarean section (3.7 +/- 0.8 and 4.2 +/- 1.1 pmol/L, for beta-endorphin and desacetylated alpha-melanocyte-stimulating hormone, respectively). N-acetyl-beta-endorphin and alpha-melanocyte-stimulating hormone levels do not differ in relation to the mode of delivery. In maternal circulation beta-endorphin levels were higher in those delivered vaginally (5.2 pm 1) than in women who had cesarean sections (2.5 +/- 0.5 pmol/L), whereas no changes were found for the other peptides. In vaginal deliveries, the level of desacetylated alpha-melanocyte-stimulating hormone was higher in cord blood (13.6 +/- 3.2 pmol/L) than in maternal plasma (6.5 +/- 3 pmol/L); there were no significant differences with regard to the other peptides. Fetal and maternal levels of all the peptides were similar in cases of cesarean section. We conclude that parturition activates proopiomelanocortin peptide release from

  17. Ghrelin stimulation of growth hormone-releasing hormone neurons is direct in the arcuate nucleus.

    Directory of Open Access Journals (Sweden)

    Guillaume Osterstock

    2010-02-01

    Full Text Available Ghrelin targets the arcuate nucleus, from where growth hormone releasing hormone (GHRH neurones trigger GH secretion. This hypothalamic nucleus also contains neuropeptide Y (NPY neurons which play a master role in the effect of ghrelin on feeding. Interestingly, connections between NPY and GHRH neurons have been reported, leading to the hypothesis that the GH axis and the feeding circuits might be co-regulated by ghrelin.Here, we show that ghrelin stimulates the firing rate of identified GHRH neurons, in transgenic GHRH-GFP mice. This stimulation is prevented by growth hormone secretagogue receptor-1 antagonism as well as by U-73122, a phospholipase C inhibitor and by calcium channels blockers. The effect of ghrelin does not require synaptic transmission, as it is not antagonized by gamma-aminobutyric acid, glutamate and NPY receptor antagonists. In addition, this hypothalamic effect of ghrelin is independent of somatostatin, the inhibitor of the GH axis, since it is also found in somatostatin knockout mice. Indeed, ghrelin does not modify synaptic currents of GHRH neurons. However, ghrelin exerts a strong and direct depolarizing effect on GHRH neurons, which supports their increased firing rate.Thus, GHRH neurons are a specific target for ghrelin within the brain, and not activated secondary to altered activity in feeding circuits. These results support the view that ghrelin related therapeutic approaches could be directed separately towards GH deficiency or feeding disorders.

  18. Paracrine Interactions of Thyroid Hormones and Thyroid Stimulation Hormone in the Female Reproductive Tract have an Impact on Female Fertility

    OpenAIRE

    Stavreus Evers, Anneli

    2012-01-01

    Thyroid disease often causes menstrual disturbances and infertility problems. Thyroid hormone (TH) acts through its receptors, transcription factors present in most cell types in the body. Thyroid stimulating hormone (TSH) stimulates TH synthesis in the thyroid gland, but seems to have other functions as well in the female reproductive tract. The receptors of both TH and TSH increase in the receptive endometrium, suggesting that they are important for implantation, possible by influencing inf...

  19. Thyroid-Stimulating Hormone Receptor Antibodies in Pregnancy: Clinical Relevance

    Science.gov (United States)

    Bucci, Ines; Giuliani, Cesidio; Napolitano, Giorgio

    2017-01-01

    Graves’ disease is the most common cause of thyrotoxicosis in women of childbearing age. Approximately 1% of pregnant women been treated before, or are being treated during pregnancy for Graves’ hyperthyroidism. In pregnancy, as in not pregnant state, thyroid-stimulating hormone (TSH) receptor (TSHR) antibodies (TRAbs) are the pathogenetic hallmark of Graves’ disease. TRAbs are heterogeneous for molecular and functional properties and are subdivided into activating (TSAbs), blocking (TBAbs), or neutral (N-TRAbs) depending on their effect on TSHR. The typical clinical features of Graves’ disease (goiter, hyperthyroidism, ophthalmopathy, dermopathy) occur when TSAbs predominate. Graves’ disease shows some peculiarities in pregnancy. The TRAbs disturb the maternal as well as the fetal thyroid function given their ability to cross the placental barrier. The pregnancy-related immunosuppression reduces the levels of TRAbs in most cases although they persist in women with active disease as well as in women who received definitive therapy (radioiodine or surgery) before pregnancy. Changes of functional properties from stimulating to blocking the TSHR could occur during gestation. Drug therapy is the treatment of choice for hyperthyroidism during gestation. Antithyroid drugs also cross the placenta and therefore decrease both the maternal and the fetal thyroid hormone production. The management of Graves’ disease in pregnancy should be aimed at maintaining euthyroidism in the mother as well as in the fetus. Maternal and fetal thyroid dysfunction (hyperthyroidism as well as hypothyroidism) are in fact associated with several morbidities. Monitoring of the maternal thyroid function, TRAbs measurement, and fetal surveillance are the mainstay for the management of Graves’ disease in pregnancy. This review summarizes the biochemical, immunological, and therapeutic aspects of Graves’ disease in pregnancy focusing on the role of the TRAbs in maternal and fetal

  20. Mapping the follicle-stimulating hormone-induced signalling networks

    Directory of Open Access Journals (Sweden)

    Pauline eGloaguen

    2011-10-01

    Full Text Available Follicle-stimulating hormone (FSH is a central regulator of male and female reproductive function. Over the last decade, there has been a growing perception of the complexity associated with FSH-induced cellular signalling. It is now clear that the canonical Gs/cAMP/PKA pathway is not the sole mechanism that must be considered in FSH biological actions. In parallel, consistent with the emerging concept of biased agonism, several examples of ligand-mediated selective signalling pathway activation by gonadotropin receptors have been reported. In this context, it is important to gain an integrative view of the signalling pathways induced by FSH and how they interconnect to form a network. In this review, we propose a first attempt at building topological maps of various pathways known to be involved in the FSH-induced signalling network. We discuss the multiple facets of FSH-induced signalling and how they converge to the hormone integrated biological response. Despite of their incompleteness, these maps of the FSH-induced signalling network represent a first step towards gaining a system-level comprehension of this hormone’s actions, which may ultimately facilitate the discovery of novel regulatory processes and therapeutic strategies for infertilities and non-steroidal contraception.

  1. Significance of the Melanocortin 1 and Endothelin B Receptors in Melanocyte Homeostasis and Prevention of Sun-Induced Genotoxicity

    Directory of Open Access Journals (Sweden)

    Zalfa A. Abdel-Malek

    2016-08-01

    Full Text Available The membrane bound melanocortin 1 receptor (MC1R, and the endothelin B receptor (ENDBR are two G-protein coupled receptors that play important roles in constitutive regulation of melanocytes and their response to ultraviolet radiation (UVR, the main etiological factor for melanoma. The human MC1R is a Gs protein-coupled receptor, which is activated by its agonists α-melanocyte stimulating hormone (α-melanocortin; α-MSH and adrenocorticotropic hormone (ACTH. The ENDBR is a Gq coupled-receptor, which is activated by Endothelin (ET-3 during embryonic development, and ET-1 postnatally. Pigmentation and the DNA repair capacity are two major factors that determine the risk for melanoma. Activation of the MC1R by its agonists stimulates the synthesis of eumelanin, the dark brown photoprotective pigment. In vitro studies showed that α-MSH and ET-1 interact synergistically in the presence of basic fibroblast growth factor (bFGF to stimulate human melanocyte proliferation and melanogenesis, and to inhibit UVR-induced apoptosis. An important function of the MC1R is reduction of oxidative stress and activation of DNA repair pathways. The human MC1R is highly polymorphic, and MC1R variants, particularly those that cause loss of function of the expressed receptor, are associated with increased melanoma risk independently of pigmentation. These variants compromise the DNA repair and antioxidant capacities of human melanocytes. Recently, activation of ENDBR by ET-1 was reported to reduce the induction and enhance the repair of UVR-induced DNA photoproducts. We conclude that α-MSH and ET-1 and their cognate receptors MC1R and ENDBR reduce the risk for melanoma by maintaining genomic stability of melanocytes via modulating the DNA damage response to solar UVR. Elucidating the response of melanocytes to UVR should improve our understanding of the process of melanomagenesis, and lead to effective melanoma chemoprevention, as well as therapeutic strategies.

  2. Discrepancies between Antimullerian Hormone and Follicle Stimulating Hormone in Assisted Reproduction

    Directory of Open Access Journals (Sweden)

    Munawar Hussain

    2013-01-01

    Full Text Available Data from 107 women undergoing their first IVF/ICSI were analyzed. Relationships between antimullerian hormone (AMH and follicle stimulating hormone (FSH were analyzed after dividing patients into four groups according to AMH/FSH levels. Concordance was noted in 57% of women (both AMH/FSH either normal or abnormal while 43%of women had discordant values (AMH/FSH one hormone normal and the other abnormal. Group 1 (AMH and FSH in normal range and group 2 (normal AMH and high FSH were younger compared to group 3 (low AMH and normal FSH and group 4 (both AMH/FSH abnormal. Group 1 showing the best oocyte yield was compared to the remaining three groups. Groups 3 and 4 required higher dose of gonadotrophins for controlled ovarian hyperstimulation showing their low ovarian reserve. There was no difference in cycle cancellation, clinical pregnancy, and live birth/ongoing pregnancy rate in all groups. These tests are useful to predict ovarian response but whether AMH is a substantially better predictor is not yet established.

  3. Overnight Levels of Luteinizing Hormone, Follicle-Stimulating Hormone and Growth Hormone before and during Gonadotropin-Releasing Hormone Analogue Treatment in Short Boys Born Small for Gestational Age

    NARCIS (Netherlands)

    van der Kaay, Danielle C. M.; de Jong, Frank H.; Rose, Susan R.; Odink, Roelof J. H.; Bakker-van Waarde, Willie M.; Sulkers, Eric J.; Hokken-Koelega, Anita C. S.

    2009-01-01

    Aims: To evaluate if 3 months of gonadotropin-releasing hormone analogue (GnRHa) treatment results in sufficient suppression of pubertal luteinizing hormone (LH) and follicle-stimulating hormone (FSH) profile patterns in short pubertal small for gestational age (SGA) boys. To compare growth hormone

  4. Effects of long-term nadolol treatment on serum thyroidal hormones and thyroid stimulating hormone in patients with hypertensive disease

    International Nuclear Information System (INIS)

    Gumbatov, N.B.; Mustafaev, I.I.; Kasumova, F.Z.; Mamedova, R.N.; Akhmedova, Z.G.; Samojlenko, T.I.

    1990-01-01

    In 20 males with Stage 2 hypertensive disease, effects of 2-week-, 2-, and 6-month monotherapy with nadolol given in doses 40 to 160 mg daily were examined on the levels of thyroidal hormones (T 3 and T 4 ) and thyroid-stimulating hormone by means of radioimmunoassay. At the all stages of the therapy, the mean values of the examined parameters were significantly unchanged. Nadolol was found to cause a decrease in T 3 concentrations at its high baseline values (r=-0.57; p 3 levels in most cases. An inverse relationship was established between the altered serum T 3 levels and the thyroid-stimulating hormone concentration

  5. Stimulation of human trophoblast invasion by placental growth hormone.

    Science.gov (United States)

    Lacroix, Marie-Christine; Guibourdenche, Jean; Fournier, Thierry; Laurendeau, Ingrid; Igout, Ahmed; Goffin, Vincent; Pantel, Jacques; Tsatsaris, Vassilis; Evain-Brion, Daniele

    2005-05-01

    A critical step in establishment of human pregnancy is the invasion of the uterus wall by the extravillous cytotrophoblast (EVCT), a process regulated by multiple autocrine and paracrine factors. Hormones belonging to the GH/prolactin family are expressed at the maternofetal interface. Because they are involved in cell motility in various models, we examined the possible regulatory role of human placental GH (hPGH) in EVCT invasiveness. By using an in vitro invasion model, we found that EVCT isolated from first-trimester chorionic villi and cultured on Matrigel secreted hPGH and expressed human GH receptor (hGHR). These data were confirmed by in situ immunohistochemistry. EVCT expressed the full-length and truncated forms of hGHR, and the Janus kinase-2/signal transducer and activator of transcription factor-5 signaling pathway was activated in EVCT by hPGH treatment. Strong hPGH and hGHR expression was observed when EVCT invaded Matrigel and moved through the pores of the filter on which they were cultured. hPGH stimulated EVCT invasiveness, and this effect was inhibited by a Janus kinase-2 inhibitor. Interestingly, hPGH was more efficient than pituitary GH in stimulating EVCT invasiveness. These results offer the first evidence for a placental role of hPGH and suggest an autocrine/paracrine role of hPGH in the regulation of trophoblast invasion.

  6. Thyroid stimulating hormone increases hepatic gluconeogenesis via CRTC2.

    Science.gov (United States)

    Li, Yujie; Wang, Laicheng; Zhou, Lingyan; Song, Yongfeng; Ma, Shizhan; Yu, Chunxiao; Zhao, Jiajun; Xu, Chao; Gao, Ling

    2017-05-05

    Epidemiological evidence indicates that thyroid stimulating hormone (TSH) is positively correlated with abnormal glucose levels. We previously reported that TSH has direct effects on gluconeogenesis. However, the underlying molecular mechanism remains unclear. In this study, we observed increased fasting blood glucose and glucose production in a mouse model of subclinical hypothyroidism (only elevated TSH levels). TSH acts via the classical cAMP/PKA pathway and CRTC2 regulates glucose homeostasis. Thus, we explore whether CRTC2 is involved in the process of TSH-induced gluconeogenesis. We show that TSH increases CRTC2 expression via the TSHR/cAMP/PKA pathway, which in turn upregulates hepatic gluconeogenic genes. Furthermore, TSH stimulates CRTC2 dephosphorylation and upregulates p-CREB (Ser133) in HepG2 cells. Silencing CRTC2 and CREB decreases the effect of TSH on PEPCK-luciferase, the rate-limiting enzyme of gluconeogenesis. Finally, the deletion of TSHR reduces the levels of the CRTC2:CREB complex in mouse livers. This study demonstrates that TSH activates CRTC2 via the TSHR/cAMP/PKA pathway, leading to the formation of a CRTC2:CREB complex and increases hepatic gluconeogenesis. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. 76 FR 2807 - New Animal Drugs; Change of Sponsor; Follicle Stimulating Hormone

    Science.gov (United States)

    2011-01-18

    ... sponsor for a new animal drug application (NADA) for follicle stimulating hormone from Ausa International... HUMAN SERVICES Food and Drug Administration 21 CFR Parts 510 and 522 New Animal Drugs; Change of Sponsor; Follicle Stimulating Hormone AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The...

  8. Levothyroxine dosage is associated with stability of thyroid-stimulating hormone values.

    Science.gov (United States)

    Pecina, Jennifer; Garrison, Gregory M; Bernard, Matthew E

    2014-03-01

    In patients treated for hypothyroidism, the usual practice is to monitor thyroid-stimulating hormone values yearly once a therapeutic dosage of levothyroxine is determined. This study investigates whether there are any clinical predictors that could identify a subset of patients who might be monitored safely on a less frequent basis. With the use of a retrospective study design, 715 patients treated for hypothyroidism who had a normal (ie, therapeutic) thyroid-stimulating hormone value in 2006 while taking levothyroxine were identified. All thyroid-stimulating hormone values were then obtained through December 31, 2012. By using a Cox proportional hazard model, gender, age, body mass index, history of chronic autoimmune thyroiditis, initial thyroid-stimulating hormone level, and levothyroxine dose were analyzed for time to first abnormal thyroid-stimulating hormone value. Age, gender, history of chronic autoimmune thyroiditis, and body mass index at the time of initial normal thyroid-stimulating hormone were not associated significantly with time to abnormal thyroid-stimulating hormone value. Levothyroxine dose >125 μg/day had an increased hazard ratio of 2.4 (95% confidence interval, 1.7-3.4; P 125 μg/day did. Transformed thyroid-stimulating hormone value (which represents a measure of how far the initial thyroid-stimulating hormone was from the midpoint of the normal range) also had an increased hazard ratio of 1.14 (95% confidence interval, 1.1-1.2; P levothyroxine, we propose that a testing interval up to 2 years may be acceptable if their thyroid-stimulating hormone is well within the normal range. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Human growth hormone binding and stimulation of insulin biosynthesis in cloned rat insulinoma cells

    DEFF Research Database (Denmark)

    Billestrup, Nils

    1985-01-01

    Binding of 125I labelled human growth hormone to cloned insulin producing RIN-5AH cells is described. Binding was specific for somatotropic hormones since both human and rat growth hormone could compete for binding sites, whereas much higher concentrations of lactogenic hormones were needed to in...... to inhibit binding. Culture of RIN-5AH cells in the presence of hGH stimulated insulin biosynthesis by 85%....

  10. Increased follicle-stimulating hormone is associated with higher assisted reproduction use after vasectomy reversal.

    Science.gov (United States)

    Hsiao, Wayland; Sultan, Raymond; Lee, Richard; Goldstein, Marc

    2011-06-01

    Of men with vasectomy 6% elect to have more children. When considering vasectomy reversal vs in vitro fertilization/intracytoplasmic sperm injection, an elucidation of preoperative factors that predict surgical success would help determine appropriate management. We tested the hypothesis that preoperative follicle-stimulating hormone 10 U/l or greater predict a lower paternity rate after vasectomy reversal. Using preoperative follicle-stimulating hormone levels we retrospectively reviewed the records of patients who underwent vasectomy reversal. Follicle-stimulating hormone was measured in cases suspicious for impaired spermatogenesis. The final analysis included 206 men, who were divided by follicle-stimulating hormone less than 10 U/l (normal in 155) and 10 U/l or greater (high in 51). Nominal logistic regression was performed to evaluate assisted reproduction predictors. Mean ± SD follicle-stimulating hormone in the normal and high groups was 5.1 ± 2.2 and 16.2 ± 6.2 U/l, respectively. Postoperative semen parameters were similar. However, in the high hormone group there was greater use of any type of assisted reproduction (78.4% vs 54.8%, p = 0.0028). On multivariate analysis follicle-stimulating hormone 10 U/l or greater (OR 3.02, 95% CI 1.34-6.83) and vasoepididymostomy that was bilateral or to a solitary testis (OR 3.26, 95% CI 1.09-9.69) was associated with greater assisted reproduction use. We evaluated preoperative follicle-stimulating hormone as a predictor of reproductive outcome in men with suspected subfertility who underwent vasectomy reversal. Increased follicle-stimulating hormone was associated with a higher rate of assisted reproduction even after controlling for confounding covariates. Thus, men with increased follicle-stimulating hormone should be counseled on the increased likelihood of needing assisted reproduction to achieve pregnancy after vasectomy reversal. Copyright © 2011 American Urological Association Education and Research, Inc

  11. Immunodetection of Luteinizing Hormone (LH, Follicle-Stimulating Hormone (FSH, Thyroid Stimulating Hormone (TSH and Prolactin (PRL in Brachionus calyciflorus (Rotifera: Monogononta

    Directory of Open Access Journals (Sweden)

    Jesús Alvarado-Flores

    2009-12-01

    Full Text Available The endocrine system controls and coordinates behavioral, biochemical, and physiological processes through signal mechanisms using neuropeptides or products of neurosecretory cells. Among invertebrates, this system is poorly studied in rotifers, in which estrogens and androgens significantly affect sexual reproduction. This is the first report of the presence of the Luteinizing Hormone (LH, Follicle-Stimulating Hormone (FSH, Thyroid Stimulating Hormone (TSH and Prolactin (PRL in rotifers. Analyses included the avidin-biotin-peroxidase complex method with primary antibodies LH (Anti-Rat LH serum for RIA, PRL (Anti-Rat PRL serum for RIA, FSH (Anti-Rat FSH serum for RIA and TSH (Anti-Rat TSH serum for RIA. These hormones were found in females, males and parthenogenetic and sexual eggs of the freshwater Brachionus calyciflorus. The immunoreactivity of FSH, LH, TSH and PRL in females was observed in: ovaries, cerebrum, mastax, stomach, lorica, and the stomach gland. However, in males LH was observed only at the trochal disk and cerebrum. The hormones FSH, TSH and PRL, were observed in testicles, contractil vesicles, and cementary gland of males. Regarding amictic or parthenogenetic eggs, the hormones LH, FSH, TSH, and PRL were located mainly in the micromeres, and the staining in the macromeres was weak. On the other hand, in the mictic or sexual eggs the inner shell is stained for the hormones PRL and LH, opposite to the staining of FSH and TSH, located mainly in the embryo. In general, immuno-reactivity was observed in areas important for the reproductive, excretory, digestive and developmental processes. Rev. Biol. Trop. 57 (4: 1049-1058. Epub 2009 December 01.Se logró detectar la presencia de las hormonas: Hormona Luteinizante (LH, Hormona Folículo Estimulante (FSH, Hormona Estimulante de la Tiroides (TSH y Prolactina (PRL en Brachionus calyciflorus siendo el primer reporte de la presencia de dichas hormonas en rotíferos. Estas hormonas fueron

  12. Fluoride Exposure, Follicle Stimulating Hormone Receptor Gene Polymorphism and Hypothalamus-pituitary-ovarian Axis Hormones in Chinese Women.

    Science.gov (United States)

    Zhao, Ming Xu; Zhou, Guo Yu; Zhu, Jing Yuan; Gong, Biao; Hou, Jia Xiang; Zhou, Tong; Duan, Li Ju; Ding, Zhong; Cui, Liu Xin; Ba, Yue

    2015-09-01

    The effects of fluoride exposure on the functions of reproductive and endocrine systems have attracted widespread attention in academic circle nowadays. However, it is unclear whether the gene-environment interaction may modify the secretion and activity of hypothalamus-pituitary- ovarian (HPO) axis hormones. Thus, the aim of this study was to explore the influence of fluoride exposure and follicle stimulating hormone receptor (FSHR) gene polymorphism on reproductive hormones in Chinese women. A cross sectional study was conducted in seven villages of Henan Province, China during 2010-2011. A total of 679 women aged 18-48 years were recruited through cluster sampling and divided into three groups, i.e. endemic fluorosis group (EFG), defluoridation project group (DFPG), and control group (CG) based on the local fluoride concentration in drinking water. The serum levels of gonadotropin releasing hormone (GnRH), follicle stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) were determined respectively and the FSHR polymorphism was detected by real time PCR assay. The results provided the preliminary evidence indicating the gene-environment interaction on HPO axis hormones in women. Copyright © 2015 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  13. Neural correlates of erotic stimulation under different levels of female sexual hormones.

    Directory of Open Access Journals (Sweden)

    Birgit Abler

    Full Text Available Previous studies have demonstrated variable influences of sexual hormonal states on female brain activation and the necessity to control for these in neuroimaging studies. However, systematic investigations of these influences, particularly those of hormonal contraceptives as compared to the physiological menstrual cycle are scarce. In the present study, we investigated the hormonal modulation of neural correlates of erotic processing in a group of females under hormonal contraceptives (C group; N = 12, and a different group of females (nC group; N = 12 not taking contraceptives during their mid-follicular and mid-luteal phases of the cycle. We used functional magnetic resonance imaging to measure hemodynamic responses as an estimate of brain activation during three different experimental conditions of visual erotic stimulation: dynamic videos, static erotic pictures, and expectation of erotic pictures. Plasma estrogen and progesterone levels were assessed in all subjects. No strong hormonally modulating effect was detected upon more direct and explicit stimulation (viewing of videos or pictures with significant activations in cortical and subcortical brain regions previously linked to erotic stimulation consistent across hormonal levels and stimulation type. Upon less direct and less explicit stimulation (expectation, activation patterns varied between the different hormonal conditions with various, predominantly frontal brain regions showing significant within- or between-group differences. Activation in the precentral gyrus during the follicular phase in the nC group was found elevated compared to the C group and positively correlated with estrogen levels. From the results we conclude that effects of hormonal influences on brain activation during erotic stimulation are weak if stimulation is direct and explicit but that female sexual hormones may modulate more subtle aspects of sexual arousal and behaviour as involved in sexual

  14. Overnight levels of luteinizing hormone, follicle-stimulating hormone and growth hormone before and during gonadotropin-releasing hormone analogue treatment in short boys born small for gestational age

    NARCIS (Netherlands)

    D.C.M. van der Kaay (Danielle); F.H. de Jong (Frank); S.R. Rose (Susan); R.J.H. Odink (Roelof); W.M. Bakker-Van Waarde (Willie); E.J. Sulkers (Eric); A.C.S. Hokken-Koelega (Anita)

    2009-01-01

    textabstractAims: To evaluate if 3 months of gonadotropin-releasing hormone analogue (GnRHa) treatment results in sufficient suppression of pubertal luteinizing hormone (LH) and follicle-stimulating hormone (FSH) profile patterns in short pubertal small for gestational age (SGA) boys. To compare

  15. Low temperature stimulates alpha-melanophore-stimulating hormone secretion and inhibits background adaptation in Xenopus laevis.

    Science.gov (United States)

    Tonosaki, Y; Cruijsen, P M J M; Nishiyama, K; Yaginuma, H; Roubos, E W

    2004-11-01

    It is well-known that alpha-melanophore-stimulating hormone (alpha-MSH) release from the amphibian pars intermedia (PI) depends on the light condition of the animal's background, permitting the animal to adapt the colour of its skin to background light intensity. In the present study, we carried out nine experiments on the effect of low temperature on this skin adaptation process in the toad Xenopus laevis, using the skin melanophore index (MI) bioassay and a radioimmunoassay to measure skin colour adaptation and alpha-MSH secretion, respectively. We show that temperatures below 8 degrees C stimulate alpha-MSH secretion and skin darkening, with a maximum at 5 degrees C, independent of the illumination state of the background. No significant stimulatory effect of low temperature on the MI and alpha-MSH plasma contents was noted when the experiment was repeated with toads from which the neurointermediate lobe (NIL) had been surgically extirpated. This indicates that low temperature stimulates alpha-MSH release from melanotrope cells located in the PI. An in vitro superfusion study with the NIL demonstrated that low temperature does not act directly on the PI. A possible role of the central nervous system in cold-induced alpha-MSH release from the PI was tested by studying the hypothalamic expression of c-Fos (as an indicator for neuronal activity) and the coexistence of c-Fos with the regulators of melanotrope cell activity, neuropeptide Y (NPY) and thyrotrophin-releasing hormone (TRH), using double fluorescence immunocytochemistry. Upon lowering temperature from 22 degrees C to 5 degrees C, in white-adapted animals c-Fos expression decreased in NPY-producing suprachiasmatic-melanotrope-inhibiting neurones (SMIN) in the ventrolateral area of the suprachiasmatic nucleus (SC) but increased in TRH-containing neurones of the magnocellular nucleus. TRH is known to stimulate melanotrope alpha-MSH release. We conclude that temperatures around 5 degrees C inactivate the SMIN

  16. Dissociation of human follicle-stimulating hormone. Comparison with luteinizing hormone.

    Science.gov (United States)

    Reichert, L E; Ramsey, R B

    1975-04-25

    Rat testis tissue receptor assays were utilized to study the kinetics of dissociation of human follicle-stimulating hormone (hFSH) and luteinizing hormone (hLH) under varying conditions of urea concentration and pH. In these competitive protein binding assays, 125I-hFSH and 125I-hLH were the radioligands and hormone dissociation was followed by a decrease in the ability of the dissociating hormone to inhibit uptake of the radioligand by tissue receptors. Rate data for dissociation of the gonadotropins were analyzed for quality of fit to first or second order integrated rate equations by nonlinear regression analysis. Treatment of hFSH with 4 M urea at pH 8 and 25 degrees for 22 hours did not result in significant dissociation, whereas in 8 M urea, over 90% dissociation was observed. The rate of dissociation of hFSH in 8 M urea was increased approximately 4-fold by raising the temperature from 25 to 37 degrees. Similar results were obtained when dissociation of hFSH was followed through use of an accepted whole animal bioassay for FSH, thus confirming the reliability of the tissue receptor assay for such dissociation studies. Kinetic studies showed that hFSH was undissociated by incubation in 6 M urea of pH 8 after 4 hours at 25 degrees. In contrast, hLH was 90% dissociated under similar conditions. This differential rate of inactivation of hLH allowed preparation of hFSH having significant reduced levels of contaminating LH activity, as determined by tissue receptor assays and by whole animal bioassays. Marked differences were noted in the rate of dissociation of hFSH and hLH under acid conditions. hFSH completely dissociated after approximately 2 min of incubation of pH 2 (25 degrees), and over 90% dissociated after 15 min of incubation at pH 3. In contrast, hLH was dissociated 60% after 20 min of incubation at pH 2 (25 degrees) and 40% dissociated after 60 min at pH 3. Neither hormone was significantly dissociated at pH 4.4 after 60 min, but hFSH showed a

  17. Epidermal growth factor (EGF) inhibits stimulated thyroid hormone secretion in the mouse

    International Nuclear Information System (INIS)

    Ahren, B.

    1987-01-01

    It is known that epidermal growth factor (EGF) inhibits iodide uptake in the thyroid follicular cells and lowers plasma levels of thyroid hormones upon infusion into sheep and ewes. In this study, the effects of EGF on basal and stimulated thyroid hormone secretion were investigated in the mouse. Mice were pretreated with 125 I and thyroxine; the subsequent release of 125 I is an estimation of thyroid hormone secretion. It was found that basal radioiodine secretion was not altered by intravenous injection of EGF (5 micrograms/animal). However, the radioiodine secretion stimulated by both TSH (120 microU/animal) and vasoactive intestinal peptide (VIP; 5 micrograms/animal) were inhibited by EGF (5 micrograms/animal). At a lower dose level (0.5 microgram/animal), EGF had no influence on stimulated radioiodine secretion. In conclusion, EGF inhibits stimulated thyroid hormone secretion in the mouse

  18. Prenatal and Neonatal Thyroid Stimulating Hormone Levels and Autism Spectrum Disorders

    Science.gov (United States)

    Yau, Vincent M.; Lutsky, Marta; Yoshida, Cathleen K.; Lasley, Bill; Kharrazi, Martin; Windham, Gayle; Gee, Nancy; Croen, Lisa A.

    2015-01-01

    Thyroid hormones are critical for normal brain development. This study examined autism spectrum disorders (ASD) and thyroid stimulating hormone (TSH) levels measured in mid-pregnancy maternal serum and infant blood after birth. Three groups of children born in Orange County, CA in 2000-2001 were identified: ASD (n = 78), developmental delay…

  19. Do anabolic nutritional supplements stimulate human growth hormone secretion in elderly women with heart failure?

    NARCIS (Netherlands)

    Smeets, Ellen T.H.C.; Schutzler, Scott E.; Wei, Jeanne Y.; Azhar, Gohar; Wolfe, Robert R.

    2017-01-01

    Growth hormone treatment has gained attention over the past decade as a treatment for heart failure. Human growth hormone (HGH) must be administered by injections (usually daily), so there is considerable advantage to stimulation of endogenous secretion by amino acid-based nutritional

  20. Secretion of biologically active glycoforms of bovine follicle stimulating hormone in plants

    NARCIS (Netherlands)

    Dirnberger, D.; Steinkellner, H.; Abdennebi, L.; Remy, J.J.; Wiel, van de D.

    2001-01-01

    We chose the follicle stimulating hormone (FSH), a pituitary heterodimeric glycoprotein hormone, as a model to assess the ability of the plant cell to express a recombinant protein that requires extensive N-glycosylation for subunit folding and assembly, intracellular trafficking, signal

  1. Gallium-68-labeled DOTA-rhenium-cyclized {alpha}-melanocyte-stimulating hormone analog for imaging of malignant melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Wei Lihui [Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110 (United States); Miao Yubin; Gallazzi, Fabio; Quinn, Thomas P. [Department of Biochemistry, University of Missouri-Columbia, Columbia, MO 65212 (United States); Welch, Michael J. [Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110 (United States); Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110 (United States); Vavere, Amy L. [Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110 (United States); Lewis, Jason S. [Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110 (United States); Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110 (United States)], E-mail: j.s.lewis@wustl.edu

    2007-11-15

    Introduction: Diagnosis of malignant melanoma is critical, since a patient's prognosis is poor. Previous studies have shown that {sup 64}Cu- and {sup 86}Y-DOTA-ReCCMSH(Arg{sup 11}) have the potential for early detection of malignant melanoma by exploiting the sensitivity and high resolution of positron emission tomography (PET). This encouraged us to investigate DOTA-ReCCMSH(Arg{sup 11}) labeled with another {beta}{sup +}-emitting radionuclide, {sup 68}Ga. Methods: DOTA-ReCCMSH(Arg{sup 11}) was successfully labeled with {sup 68}Ga at pH 3.8-4 at 85{sup o}C. Acute biodistribution and small-animal PET imaging studies were performed in mice bearing B16/F1 melanoma tumor. Results: Biodistribution studies showed moderate receptor-mediated tumor uptake, fast nontarget organ clearance and high tumor to nontarget tissue ratios. Preadministration of D-lysine significantly reduced kidney uptake without affecting the uptake of the agent in the tumor. Small-animal PET images showed that the tumor could be clearly visualized at all time points examined (0.5-2 h) with the standardized uptake value analysis following a similar trend as the biodistribution data. Conclusions: The preliminary data obtained suggest that {sup 68}Ga-DOTA-ReCCMSH(Arg{sup 11}) is a promising PET imaging agent for early detection of malignant melanoma.

  2. Metastatic melanoma imaging with an {sup 111}In-labeled lactam bridge-cyclized {alpha}-melanocyte-stimulating hormone peptide

    Energy Technology Data Exchange (ETDEWEB)

    Guo Haixun; Shenoy, Nalini; Gershman, Benjamin M.; Yang, Jianquan [College of Pharmacy, University of New Mexico, Albuquerque, NM 87131 (United States); Sklar, Larry A. [College of Pharmacy, University of New Mexico, Albuquerque, NM 87131 (United States); Cancer Research and Treatment Center, University of New Mexico, Albuquerque, NM 87131 (United States); Department of Pathology, University of New Mexico, Albuquerque, NM 87131 (United States); Miao Yubin [College of Pharmacy, University of New Mexico, Albuquerque, NM 87131 (United States); Cancer Research and Treatment Center, University of New Mexico, Albuquerque, NM 87131 (United States); Department of Dermatology, University of New Mexico, Albuquerque, NM 87131 (United States)], E-mail: ymiao@salud.unm.edu

    2009-04-15

    Introduction: The purpose of this study was to examine whether a novel lactam bridge-cyclized {sup 111}In-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-Gly-Glu-c[Lys-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Arg-Pro-Val-Asp] {l_brace}DOTA-GlyGlu-CycMSH{r_brace} could be an effective imaging probe for metastatic melanoma detection. Methods: {sup 111}In-DOTA-GlyGlu-CycMSH was prepared and purified by reverse-phase high-performance liquid chromatography (RP-HPLC). The internalization and efflux of {sup 111}In-DOTA-GlyGlu-CycMSH were examined in B16/F10 melanoma cells. The biodistribution of {sup 111}In-DOTA-GlyGlu-CycMSH was determined in B16/F10 pulmonary metastatic melanoma-bearing and normal C57 mice. Pulmonary metastatic melanoma imaging was performed by small-animal single-photon emission computed tomography (SPECT)/CT (Nano-SPECT/CT) using {sup 111}In-DOTA-GlyGlu-CycMSH as an imaging probe and compared with 2-[{sup 18}F]fluoro-2-deoxy-D-glucose ([{sup 18}F]FDG) positron emission tomography (PET) imaging. Results: {sup 111}In-DOTA-GlyGlu-CycMSH was readily prepared with greater than 95% radiolabeling yield. {sup 111}In-DOTA-GlyGlu-CycMSH displayed rapid internalization and extended efflux in B16/F10 cells. {sup 111}In-DOTA-GlyGlu-CycMSH exhibited significantly (P<.05) higher uptakes (2.00{+-}0.74%ID/g at 2 h post-injection and 1.83{+-}0.12%ID/g at 4 h post-injection) in metastatic melanoma-bearing lung than that in normal lung (0.08{+-}0.08%ID/g and 0.05{+-}0.05%ID/g at 2 and 4 h post-injection, respectively). The activity accumulation in normal organs was low (<0.5%ID/g) except for the kidneys 2 and 4 h post-injection. B16/F10 pulmonary melanoma metastases were clearly visualized with {sup 111}In-DOTA-GlyGlu-CycMSH 2 h post-injection rather than with [{sup 18}F]FDG 1 h post-injection. Conclusions: {sup 111}In-DOTA-GlyGlu-CycMSH exhibited favorable metastatic melanoma-targeting and -imaging properties, highlighting its potential as an effective imaging probe for metastatic melanoma detection.

  3. Recent advances in the understanding of how neuropeptide Y and ?-melanocyte stimulating hormone function in adipose physiology

    OpenAIRE

    Shipp, Steven L.; Cline, Mark A.; Gilbert, Elizabeth R.

    2016-01-01

    Communication between the brain and the adipose tissue has been the focus of many studies in recent years, with the ?brain-fat axis? identified as a system that orchestrates the assimilation and usage of energy to maintain body mass and adequate fat stores. It is now well-known that appetite-regulating peptides that were studied as neurotransmitters in the central nervous system can act both on the hypothalamus to regulate feeding behavior and also on the adipose tissue to modulate the storag...

  4. Molecular cloning, genomic organization, and developmental regulation of a novel receptor from Drosophila melanogaster structurally related to members of the thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone/choriogonadotropin receptor family from mammals

    DEFF Research Database (Denmark)

    Hauser, F; Nothacker, H P; Grimmelikhuijzen, C J

    1997-01-01

    ); follicle-stimulating hormone (FSH); luteinizing hormone/choriogonadotropin (LH/CG)) receptor family from mammals. This homology includes a very large, extracellular N terminus (20% sequence identity with rat TSH, 19% with rat FSH, and 20% with the rat LH/CG receptor) and a seven-transmembrane region (53...... receptor family member from insects....

  5. Follicle-Stimulating Hormone Increases the Risk of Postmenopausal Osteoporosis by Stimulating Osteoclast Differentiation.

    Science.gov (United States)

    Wang, Jie; Zhang, Wenwen; Yu, Chunxiao; Zhang, Xu; Zhang, Haiqing; Guan, Qingbo; Zhao, Jiajun; Xu, Jin

    2015-01-01

    The objectives of this study were to observe the changes in follicle-stimulating hormone (FSH) and bone mineral density (BMD) in postmenopausal women, to research the relationship between FSH and postmenopausal osteoporosis, and to observe the effects of FSH on osteoclast differentiation in RAW264.7 cells. We analyzed 248 postmenopausal women with normal bone metabolism. A radioimmunoassay (RIA) was used to detect serum FSH, luteinizing hormone (LH), and estradiol (E2). Dual-energy X-ray absorptiometry was used to measure forearm BMD. Then, we analyzed the age-related changes in serum FSH, LH and E2. Additionally, FSH serum concentrations were compared between a group of postmenopausal women with osteoporosis and a control group. Osteoclasts were induced from RAW264.7 cells in vitro by receptor activator of nuclear factor kappa B ligand (RANKL), and these cells were treated with 0, 5, 10, and 20 ng/ml FSH. After the osteoclasts matured, tartrate-resistant acid phosphatase (TRAP) staining was used to identify osteoclasts, and the mRNA expression levels of genes involved in osteoclastic phenotypes and function, such as receptor activator of NF-κB (Rank), Trap, matrix metalloproteinase-9 (Mmp-9) and Cathepsin K, were detected in different groups using real-time PCR (polymerase chain reaction). 1. FSH serum concentrations in postmenopausal women with osteoporosis increased notably compared with the control group. 2. RANKL induced RAW264.7 cell differentiation into mature osteoclasts in vitro. 3. FSH increased mRNA expression of genes involved in osteoclastic phenotypes and function, such as Rank, Trap, Mmp-9 and Cathepsin K, in a dose-dependent manner. The circulating concentration of FSH may play an important role in the acceleration of bone loss in postmenopausal women. FSH increases osteoclastogenesis in vitro.

  6. Follicle-Stimulating Hormone Increases the Risk of Postmenopausal Osteoporosis by Stimulating Osteoclast Differentiation.

    Directory of Open Access Journals (Sweden)

    Jie Wang

    Full Text Available The objectives of this study were to observe the changes in follicle-stimulating hormone (FSH and bone mineral density (BMD in postmenopausal women, to research the relationship between FSH and postmenopausal osteoporosis, and to observe the effects of FSH on osteoclast differentiation in RAW264.7 cells.We analyzed 248 postmenopausal women with normal bone metabolism. A radioimmunoassay (RIA was used to detect serum FSH, luteinizing hormone (LH, and estradiol (E2. Dual-energy X-ray absorptiometry was used to measure forearm BMD. Then, we analyzed the age-related changes in serum FSH, LH and E2. Additionally, FSH serum concentrations were compared between a group of postmenopausal women with osteoporosis and a control group. Osteoclasts were induced from RAW264.7 cells in vitro by receptor activator of nuclear factor kappa B ligand (RANKL, and these cells were treated with 0, 5, 10, and 20 ng/ml FSH. After the osteoclasts matured, tartrate-resistant acid phosphatase (TRAP staining was used to identify osteoclasts, and the mRNA expression levels of genes involved in osteoclastic phenotypes and function, such as receptor activator of NF-κB (Rank, Trap, matrix metalloproteinase-9 (Mmp-9 and Cathepsin K, were detected in different groups using real-time PCR (polymerase chain reaction.1. FSH serum concentrations in postmenopausal women with osteoporosis increased notably compared with the control group. 2. RANKL induced RAW264.7 cell differentiation into mature osteoclasts in vitro. 3. FSH increased mRNA expression of genes involved in osteoclastic phenotypes and function, such as Rank, Trap, Mmp-9 and Cathepsin K, in a dose-dependent manner.The circulating concentration of FSH may play an important role in the acceleration of bone loss in postmenopausal women. FSH increases osteoclastogenesis in vitro.

  7. Predicting the Probability of Abnormal Stimulated Growth Hormone Response in Children After Radiotherapy for Brain Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Hua Chiaho, E-mail: Chia-Ho.Hua@stjude.org [Department of Radiological Sciences, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Wu Shengjie [Department of Biostatistics, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Chemaitilly, Wassim [Division of Endocrinology, Department of Pediatric Medicine, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Lukose, Renin C.; Merchant, Thomas E. [Department of Radiological Sciences, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States)

    2012-11-15

    Purpose: To develop a mathematical model utilizing more readily available measures than stimulation tests that identifies brain tumor survivors with high likelihood of abnormal growth hormone secretion after radiotherapy (RT), to avoid late recognition and a consequent delay in growth hormone replacement therapy. Methods and Materials: We analyzed 191 prospectively collected post-RT evaluations of peak growth hormone level (arginine tolerance/levodopa stimulation test), serum insulin-like growth factor 1 (IGF-1), IGF-binding protein 3, height, weight, growth velocity, and body mass index in 106 children and adolescents treated for ependymoma (n = 72), low-grade glioma (n = 28) or craniopharyngioma (n = 6), who had normal growth hormone levels before RT. Normal level in this study was defined as the peak growth hormone response to the stimulation test {>=}7 ng/mL. Results: Independent predictor variables identified by multivariate logistic regression with high statistical significance (p < 0.0001) included IGF-1 z score, weight z score, and hypothalamic dose. The developed predictive model demonstrated a strong discriminatory power with an area under the receiver operating characteristic curve of 0.883. At a potential cutoff point of probability of 0.3 the sensitivity was 80% and specificity 78%. Conclusions: Without unpleasant and expensive frequent stimulation tests, our model provides a quantitative approach to closely follow the growth hormone secretory capacity of brain tumor survivors. It allows identification of high-risk children for subsequent confirmatory tests and in-depth workup for diagnosis of growth hormone deficiency.

  8. Predicting the Probability of Abnormal Stimulated Growth Hormone Response in Children After Radiotherapy for Brain Tumors

    International Nuclear Information System (INIS)

    Hua Chiaho; Wu Shengjie; Chemaitilly, Wassim; Lukose, Renin C.; Merchant, Thomas E.

    2012-01-01

    Purpose: To develop a mathematical model utilizing more readily available measures than stimulation tests that identifies brain tumor survivors with high likelihood of abnormal growth hormone secretion after radiotherapy (RT), to avoid late recognition and a consequent delay in growth hormone replacement therapy. Methods and Materials: We analyzed 191 prospectively collected post-RT evaluations of peak growth hormone level (arginine tolerance/levodopa stimulation test), serum insulin-like growth factor 1 (IGF-1), IGF-binding protein 3, height, weight, growth velocity, and body mass index in 106 children and adolescents treated for ependymoma (n = 72), low-grade glioma (n = 28) or craniopharyngioma (n = 6), who had normal growth hormone levels before RT. Normal level in this study was defined as the peak growth hormone response to the stimulation test ≥7 ng/mL. Results: Independent predictor variables identified by multivariate logistic regression with high statistical significance (p < 0.0001) included IGF-1 z score, weight z score, and hypothalamic dose. The developed predictive model demonstrated a strong discriminatory power with an area under the receiver operating characteristic curve of 0.883. At a potential cutoff point of probability of 0.3 the sensitivity was 80% and specificity 78%. Conclusions: Without unpleasant and expensive frequent stimulation tests, our model provides a quantitative approach to closely follow the growth hormone secretory capacity of brain tumor survivors. It allows identification of high-risk children for subsequent confirmatory tests and in-depth workup for diagnosis of growth hormone deficiency.

  9. Association of the thyroid stimulating hormone receptor gene (TSHR) with Graves' disease

    DEFF Research Database (Denmark)

    Brand, Oliver J; Barrett, Jeffrey C; Simmonds, Matthew J

    2009-01-01

    Graves' disease (GD) is a common autoimmune disease (AID) that shares many of its susceptibility loci with other AIDs. The thyroid stimulating hormone receptor (TSHR) represents the primary autoantigen in GD, in which autoantibodies bind to the receptor and mimic its ligand, thyroid stimulating h...

  10. Growth of melanocytes in human epidermal cell cultures

    International Nuclear Information System (INIS)

    Staiano-Coico, L.; Hefton, J.M.; Amadeo, C.; Pagan-Charry, I.; Madden, M.R.; Cardon-Cardo, C.

    1990-01-01

    Epidermal cell cultures were grown in keratinocyte-conditioned medium for use as burn wound grafts; the melanocyte composition of the grafts was studied under a variety of conditions. Melanocytes were identified by immunohistochemistry based on a monoclonal antibody (MEL-5) that has previously been shown to react specifically with melanocytes. During the first 7 days of growth in primary culture, the total number of melanocytes in the epidermal cultures decreased to 10% of the number present in normal skin. Beginning on day 2 of culture, bipolar melanocytes were present at a mean cell density of 116 +/- 2/mm2; the keratinocyte to melanocyte ratio was preserved during further primary culture and through three subpassages. Moreover, exposure of cultures to mild UVB irradiation stimulated the melanocytes to proliferate, suggesting that the melanocytes growing in culture maintained their responsiveness to external stimuli. When the sheets of cultured cells were enzymatically detached from the plastic culture flasks before grafting, melanocytes remained in the basal layer of cells as part of the graft applied to the patient

  11. Response to thyrotropin-releasing hormone stimulation tests in preterm infants with transient hypothyroxinemia of prematurity.

    Science.gov (United States)

    Yamamoto, A; Kawai, M; Iwanaga, K; Matsukura, T; Niwa, F; Hasegawa, T; Heike, T

    2015-09-01

    Whether hormone supplementation is necessary for infants with transient hypothyroxinemia of prematurity (THOP) remains controversial, and further analysis of the hypothalamus-pituitary-thyroid axis of infants with THOP is necessary. Thyrotropin-releasing hormone (TRH) stimulation tests were performed at 2 weeks of age in 50 infants with a gestational age of 30 weeks or less, and the data were analyzed retrospectively. Subjects were divided into three groups; group A consisted of euthyroid infants, group B consisted of infants with THOP and group C consisted of hypothyroid infants. The basal and peak thyroid-stimulating hormone level of group C in response to TRH stimulation tests was significantly higher than the others, but no differences were observed between groups A and B. The response of infants with THOP to the TRH stimulation test was not different from that of euthyroid infants, which suggested that their hypothalamic-pituitary-thyroid axis was appropriately regulated in infants with THOP.

  12. Ovarian response to recombinant human follicle-stimulating hormone

    DEFF Research Database (Denmark)

    Arce, Joan-Carles; Andersen, Anders Nyboe; Fernández-Sánchez, Manuel

    2014-01-01

    OBJECTIVE: To evaluate the dose-response relationship of a novel recombinant human FSH (rhFSH; FE 999049) with respect to ovarian response in patients undergoing IVF/intracytoplasmic sperm injection treatment; and prospectively study the influence of initial antimüllerian hormone (AMH) concentrat......OBJECTIVE: To evaluate the dose-response relationship of a novel recombinant human FSH (rhFSH; FE 999049) with respect to ovarian response in patients undergoing IVF/intracytoplasmic sperm injection treatment; and prospectively study the influence of initial antimüllerian hormone (AMH...

  13. Kisspeptin stimulates growth hormone release by utilizing Neuropeptide Y pathways and is dependent on the presence of ghrelin

    Science.gov (United States)

    Although kisspeptin is the primary stimulator of gonadotropin releasing hormone secretion and therefore the hypothalamic-pituitary gonadal axis, new findings suggest kisspeptin can also regulate additional neuroendocrine processes including release of growth hormone (GH). Central delivery of kisspep...

  14. Recent advancements in the hormonal stimulation of ovulation in swine

    Directory of Open Access Journals (Sweden)

    Knox RV

    2015-10-01

    Full Text Available Robert V Knox Department of Animal Sciences, 360 Animal Sciences Laboratory, University of Illinois, Champaign Urbana, IL, USA Abstract: Induction of ovulation for controlled breeding is available for use around the world, and conditions for practical application appear promising. Many of the hormones available, such as human chorionic gonadotropin (hCG, gonadotropin-releasing hormone (GnRH and its analogs, as well as porcine luteinizing hormone (pLH, have been shown to be effective for advancing or synchronizing ovulation in gilts and weaned sows. Each of the hormones has unique attributes with respect to the physiology of its actions, how it is administered, its efficacy, and approval for use. The timing for induction of ovulation during the follicle phase is critical as follicle maturity changes over time, and the success of the response is determined by the stage of follicle development. Female fertility is also a primary factor affecting the success of ovulation induction and fixed time insemination protocols. Approximately 80%–90% of female pigs will develop mature follicles following weaning in sows and synchronization of estrus in gilts. However, those gilts and sows with follicles that are less developed and mature, or those that develop with abnormalities, will not respond to an ovulatory surge of LH. To address this problem, some protocols induce follicle development in all females, which can improve the overall reliability of the ovulation response. Control of ovulation is practical for use with fixed time artificial insemination and should prove highly advantageous for low-dose and single-service artificial insemination and for use with frozen-thawed and sex-sorted sperm. Keywords: artificial insemination, follicle, hormone, ovulation, swine

  15. Paracrine interactions of thyroid hormones and thyroid stimulation hormone in the female reproductive tract have an impact on female fertility

    Directory of Open Access Journals (Sweden)

    Anneli eStavreus-Evers

    2012-03-01

    Full Text Available Thyroid disease often causes menstrual disturbances and infertility problems. Thyroid hormone (TH acts through its receptors, transcription factors present in most cell types in the body. Thyroid stimulating hormone (TSH stimulates TH synthesis in the thyroid gland, but seems to have other functions as well in the female reproductive tract. The receptors of both TH and TSH increase in the receptive endometrium, suggesting that they are important for implantation, possible by influencing inflammatory mediators such as LIF. The roles of these receptors in the ovary need further studies. However, it is likely that the thyroid system is important for both follicular and embryo development. The association between thyroid disease and infertility indicate that TH and TSH affect the endometrium and ovary on the paracrine level.

  16. Histamine effect on melanocyte proliferation and vitiliginous keratinocyte survival.

    Science.gov (United States)

    Kim, Nan-Hyung; Lee, Ai-Young

    2010-12-01

    Repigmention of vitiligo requires melanocyte proliferation and migration. Keratinocytes have been shown to play a role in this process. Data from this laboratory showed that bee venom (BV) stimulated melanocyte proliferation and migration as well as melanogenesis. As histamine release is associated with BV, its effect on melanocyte proliferation and migration was examined. Cultured normal human melanocytes treated with histamine were studied with and without receptor-specific antagonists or agonists. The effect of histamine on vitiliginous keratinocytes, in cultured cells treated with a PI3K inhibitor in the presence of TNF-α, was also examined. Histamine exerted a more significant effect on melanocyte proliferation than on melanogenesis. This occurred through the H2 receptor with complex signalling to ERK, CREB, and Akt activation, which stimulated melanocyte migration. Histamine and the H2 receptor agonist also increased survival of vitiliginous, but not normal, keratinocytes, with NF-κB activation. Because expression levels of the H2 receptor was significantly decreased in depigmented compared to normally pigmented epidermis, in patients with vitiligo, histamine may increase the survival of vitiliginous keratinocytes. Overall, histamine stimulated the proliferation and migration of melanocytes and the vitiliginous keratinocyte survival, providing the basis for novel therapeutic approaches to vitiligo repigmentation. © 2010 John Wiley & Sons A/S.

  17. Molecular cloning, genomic organization, and developmental regulation of a novel receptor from Drosophila melanogaster structurally related to members of the thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone/choriogonadotropin receptor family from mammals

    DEFF Research Database (Denmark)

    Hauser, F; Nothacker, H P; Grimmelikhuijzen, C J

    1997-01-01

    Using oligonucleotide probes derived from consensus sequences for glycoprotein hormone receptors, we have cloned an 831-amino acid residue-long receptor from Drosophila melanogaster that shows a striking structural homology with members of the glycoprotein hormone (thyroid-stimulating hormone (TSH...... phasing. This indicates that the Drosophila receptor is evolutionarily related to the mammalian receptors. The Drosophila receptor gene is located at position 90C on the right arm of the third chromosome. The receptor is strongly expressed starting 8-16 h after oviposition, and the expression stays high...

  18. Fibronectin-Containing Extracellular Vesicles Protect Melanocytes against Ultraviolet Radiation-Induced Cytotoxicity.

    Science.gov (United States)

    Bin, Bum-Ho; Kim, Dae-Kyum; Kim, Nan-Hyung; Choi, Eun-Jeong; Bhin, Jinhyuk; Kim, Sung Tae; Gho, Yong Song; Lee, Ai-Young; Lee, Tae Ryong; Cho, Eun-Gyung

    2016-05-01

    Skin melanocytes are activated by exposure to UV radiation to secrete melanin-containing melanosomes to protect the skin from UV-induced damage. Despite the continuous renewal of the epidermis, the turnover rate of melanocytes is very slow, and they survive for long periods. However, the mechanisms underlying the survival of melanocytes exposed to UV radiation are not known. Here, we investigated the role of melanocyte-derived extracellular vesicles in melanocyte survival. Network analysis of the melanocyte extracellular vesicle proteome identified the extracellular matrix component fibronectin at a central node, and the release of fibronectin-containing extracellular vesicles was increased after exposure of melanocytes to UVB radiation. Using an anti-fibronectin neutralizing antibody and specific inhibitors of extracellular vesicle secretion, we demonstrated that extracellular vesicles enriched in fibronectin were involved in melanocyte survival after UVB radiation. Furthermore, we observed that in the hyperpigmented lesions of patients with melasma, the extracellular space around melanocytes contained more fibronectin compared with normal skin, suggesting that fibronectin is involved in maintaining melanocytes in pathological conditions. Collectively, our findings suggest that melanocytes secrete fibronectin-containing extracellular vesicles to increase their survival after UVB radiation. These data provide important insight into how constantly stimulated melanocytes can be maintained in pathological conditions such as melasma. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Regulation of eumelanin/pheomelanin synthesis and visible pigmentation in melanocytes by ligands of the melanocortin 1 receptor.

    Science.gov (United States)

    Le Pape, Elodie; Wakamatsu, Kazumasa; Ito, Shosuke; Wolber, Rainer; Hearing, Vincent J

    2008-08-01

    The production of melanin in the hair and skin is tightly regulated by the melanocortin 1 receptor (MC1R) whose activation is controlled by two secreted ligands, alpha-melanocyte stimulating hormone (alphaMSH) and agouti signal protein (ASP). As melanin is extremely stable, lasting years in biological tissues, the mechanism underlying the relatively rapid decrease in visible pigmentation elicited by ASP is of obvious interest. In this study, the effects of ASP and alphaMSH on the regulation of melanin synthesis and on visible pigmentation were assessed in normal murine melanocytes and were compared with the quick depigmenting effect of the tyrosinase inhibitor, phenylthiourea (PTU). alphaMSH increased pheomelanin levels prior to increasing eumelanin content over 4 days of treatment. Conversely, ASP switched off the pigment synthesis pathway, reducing eu- and pheo-melanin synthesis within 1 day of treatment that was proportional to the decrease in tyrosinase protein level and activity. These results demonstrate that the visible depigmentation of melanocytes induced by ASP does not require the degradation of existing melanin but rather is due to the dilution of existing melanin by melanocyte turnover, which emphasizes the importance of pigment distribution to visible color.

  20. Intra-pituitary relationship of follicle stimulating hormone and luteinizing hormone during pubertal development in Atlantic bluefin tuna (Thunnus thynnus).

    Science.gov (United States)

    Berkovich, Nadia; Corriero, Aldo; Santamaria, Nicoletta; Mylonas, Constantinos C; Vassallo-Aguis, Robert; de la Gándara, Fernando; Meiri-Ashkenazi, Iris; Zlatnikov, Vered; Gordin, Hillel; Bridges, Christopher R; Rosenfeld, Hanna

    2013-12-01

    As part of the endeavor aiming at the domestication of Atlantic bluefin tuna (BFT; Thunnus thynnus), first sexual maturity in captivity was studied by documenting its occurrence and by characterizing the key hormones of the reproductive axis: follicle stimulating hormone (FSH) and luteinizing hormone (LH). The full length sequence encoding for the related hormone β-subunits, bftFSHβ and bftLHβ, were determined, revealing two bftFSHβ mRNA variants, differing in their 5' untranslated region. A quantitative immuno-dot-blot assay to measure pituitary FSH content in BFT was developed and validated enabling, for the first time in this species, data sets for both LH and FSH to be compared. The expression and accumulation patterns of LH in the pituitary showed a steady increase of this hormone, concomitant with fish age, reaching higher levels in adult females compared to males of the same age class. Conversely, the pituitary FSH levels were elevated only in 2Y and adult fish. The pituitary FSH to LH ratio was consistently higher (>1) in immature than in maturing or pubertal fish, resembling the situation in mammals. Nevertheless, the results suggest that a rise in the LH storage level above a minimum threshold may be an indicator of the onset of puberty in BFT females. The higher pituitary LH levels in adult females over males may further support this notion. In contrast three year-old (3Y) males were pubertal while cognate females were still immature. However, it is not yet clear whether the advanced puberty in the 3Y males was a general feature typifying wild BFT populations or was induced by the culture conditions. Future studies testing the effects of captivity and hormonal treatments on precocious maturity may allow for improved handling of this species in a controlled environment which would lead to more cost-efficient farming. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Effect of the human follicle-stimulating hormone-binding inhibitor ...

    Indian Academy of Sciences (India)

    The follicle-stimulating hormone (FSH)-binding inhibitor (FSHBI), purified by our laboratory from human ovarian follicular fluid, has been shown to suppress ovulation and induce follicular atresia/apoptosis in mice as well as impair fertility in marmosets, the new world monkeys. The octapeptide, a peptide corresponding to ...

  2. Establishment of a serum thyroid stimulating hormone (TSH) reference interval in healthy adults

    DEFF Research Database (Denmark)

    Jensen, Esther; Hyltoft Petersen, Per; Blaabjerg, Ole

    2004-01-01

    It has previously been shown that thyroid antibodies affect thyroid stimulating hormone (TSH) concentrations in men and women and that TSH levels are predictive of future thyroid disease. We investigated the validity of the National Academy of Clinical Biochemistry (NACB) guidelines regarding...

  3. Taste matters-effects of bypassing oral stimulation on hormone and appetite responses

    NARCIS (Netherlands)

    Spetter, M.S.; Mars, M.; Viergever, M.A.; Graaf, de C.; Smeets, P.A.M.

    2014-01-01

    The interaction between oral and gastric signals is an important part of food intake regulation. Previous studies suggest that bypassing oral stimulation diminishes the suppression of hunger and increases gastric emptying rate. However, the role of appetite hormones, like cholecystokinin-8 and

  4. Follicle Stimulating Hormone is an accurate predictor of azoospermia in childhood cancer survivors.

    Directory of Open Access Journals (Sweden)

    Thomas W Kelsey

    Full Text Available The accuracy of Follicle Stimulating Hormone as a predictor of azoospermia in adult survivors of childhood cancer is unclear, with conflicting results in the published literature. A systematic review and post hoc analysis of combined data (n = 367 were performed on all published studies containing extractable data on both serum Follicle Stimulating Hormone concentration and semen concentration in survivors of childhood cancer. PubMed and Medline databases were searched up to March 2017 by two blind investigators. Articles were included if they contained both serum FSH concentration and semen concentration, used World Health Organisation certified methods for semen analysis, and the study participants were all childhood cancer survivors. There was no evidence for either publication bias or heterogeneity for the five studies. For the combined data (n = 367 the optimal Follicle Stimulating Hormone threshold was 10.4 IU/L with specificity 81% (95% CI 76%-86% and sensitivity 83% (95% CI 76%-89%. The AUC was 0.89 (95%CI 0.86-0.93. A range of threshold FSH values for the diagnosis of azoospermia with their associated sensitivities and specificities were calculated. This study provides strong supporting evidence for the use of serum Follicle Stimulating Hormone as a surrogate biomarker for azoospermia in adult males who have been treated for childhood cancer.

  5. Characterization of follicle stimulating hormone profiles in normal ovulating women.

    Science.gov (United States)

    Ecochard, René; Guillerm, Agnes; Leiva, René; Bouchard, Thomas; Direito, Ana; Boehringer, Hans

    2014-07-01

    To describe FSH profile variants. Observational study. Multicenter collaborative study. A total of 107 women. Women collected daily first morning urine and underwent serial ovarian ultrasound. The individual FSH cyclic profiles demonstrated a significant departure from the currently accepted model. A decline in FSH levels at the end of the follicular phase was observed in only 42% of cycles. The absence of this decline was significantly associated with a shorter luteal phase and higher pregnanediol-3α-glucuronide, FSH, and LH levels at the time of ovulation. In 34% of the cycles, significant FSH variability was observed throughout the follicular phase; this variability was associated with higher body mass index and lower overall FSH and LH levels throughout the cycle. The FSH peak occurs on average 2 hours before ovulation. The FSH peak duration was shorter than the LH peak. These results suggest that average FSH profiles may not reflect the more complex dynamics of daily hormonal variations in the menstrual cycle. It is possible that discrepancies between the average normal FSH profile and the individual day-to-day variants can be used to detect abnormalities. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  6. Impact of light exposure on thyroid-stimulating hormone results using the Siemens Advia Centaur TSH-3Ultra assay.

    Science.gov (United States)

    Armer, Jane; Giles, Diane; Lancaster, Ian; Brownbill, Kathryn

    2017-09-01

    Background Thyroid-stimulating hormone (TSH) is used as the first-line test of thyroid function. Siemens Healthcare Diagnostics recommend that Siemens Centaur reagents must be protected from light in the assay information and on reagent packaging. We have compared the effect of light exposure on results using Siemens TSH-3Ultra and follicle-stimulating hormone reagents. The thyroid-stimulating hormone reagent includes fluoroscein thiocyanate whereas the follicle-stimulating hormone reagent does not. Methods Three levels of quality controls were analysed using SiemensTSH-3Ultra and follicle-stimulating hormone reagent packs that had been kept protected from light or exposed to light at 6-h intervals for 48 h and then at 96 h. Results Thyroid-stimulating hormone results were significantly lower after exposure of TSH-3Ultra reagent packs to light. Results were >15% lower at all three levels of quality control following 18 h of light exposure and continued to decrease until 96 h. There was no significant difference in follicle-stimulating hormone results whether reagents had been exposed to or protected from light. Conclusions Thyroid-stimulating hormone results but not follicle-stimulating hormone results are lowered after exposure of reagent packs to light. Laboratories must ensure that TSH-3Ultra reagents are not exposed to light and analyse quality control samples on every reagent pack to check that there has not been light exposure prior to delivery. The labelling on TSH-3Ultra reagent packs should reflect the significant effect of light exposure compared with the follicle-stimulating hormone reagent. We propose that the effect of light exposure on binding of fluoroscein thiocyanate to the solid phase antibody causes the falsely low results.

  7. MC1R and the response of melanocytes to ultraviolet radiation

    Energy Technology Data Exchange (ETDEWEB)

    Rouzaud, Francois [Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Building 37, Room 2132, Bethesda, MD 20892 (United States); Kadekaro, Ana Luisa [Department of Dermatology, University of Cincinnati, College of Medicine, Cincinnati, OH 45267 (United States); Abdel-Malek, Zalfa A. [Department of Dermatology, University of Cincinnati, College of Medicine, Cincinnati, OH 45267 (United States); Hearing, Vincent J. [Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Building 37, Room 2132, Bethesda, MD 20892 (United States)]. E-mail: hearingv@nih.gov

    2005-04-01

    The constitutive color of our skin plays a dramatic role in our photoprotection from solar ultraviolet radiation (UVR) that reaches the Earth and in minimizing DNA damage that gives rise to skin cancer. More than 120 genes have been identified and shown to regulate pigmentation, one of the key genes being melanocortin 1 receptor (MC1R) that encodes the melanocortin 1 receptor (MC1R), a seven-transmembrane G protein-coupled receptor expressed on the surface of melanocytes. Modulation of MC1R function regulates melanin synthesis by melanocytes qualitatively and quantitatively. The MC1R is regulated by the physiological agonists {alpha}-melanocyte-stimulating hormone ({alpha}MSH) and adrenocorticotropic hormone (ACTH), and antagonist agouti signaling protein (ASP). Activation of the MC1R by binding of an agonist stimulates the synthesis of eumelanin primarily via activation of adenylate cyclase. The significance of cutaneous pigmentation lies in the photoprotective effect of melanin, particularly eumelanin, against sun-induced carcinogenesis. Epidermal melanocytes and keratinocytes respond to UVR by increasing their expression of {alpha}MSH and ACTH, which up-regulate the expression of MC1R, and consequently enhance the response of melanocytes to melanocortins. Constitutive skin pigmentation dramatically affects the incidence of skin cancer. The pigmentary phenotype characterized by red hair, fair complexion, inability to tan and tendency to freckle is an independent risk factor for all skin cancers, including melanoma. The MC1R gene is highly polymorphic in human populations, and allelic variation at this locus accounts, to a large extent, for the variation in pigmentary phenotypes and skin phototypes (SPT) in humans. Several allelic variants of the MC1R gene are associated with the red hair and fair skin (RHC) phenotype, and carrying one of these variants is thought to diminish the ability of the epidermis to respond to DNA damage elicited by UVR. The MC1R gene is

  8. MC1R and the response of melanocytes to ultraviolet radiation

    International Nuclear Information System (INIS)

    Rouzaud, Francois; Kadekaro, Ana Luisa; Abdel-Malek, Zalfa A.; Hearing, Vincent J.

    2005-01-01

    The constitutive color of our skin plays a dramatic role in our photoprotection from solar ultraviolet radiation (UVR) that reaches the Earth and in minimizing DNA damage that gives rise to skin cancer. More than 120 genes have been identified and shown to regulate pigmentation, one of the key genes being melanocortin 1 receptor (MC1R) that encodes the melanocortin 1 receptor (MC1R), a seven-transmembrane G protein-coupled receptor expressed on the surface of melanocytes. Modulation of MC1R function regulates melanin synthesis by melanocytes qualitatively and quantitatively. The MC1R is regulated by the physiological agonists α-melanocyte-stimulating hormone (αMSH) and adrenocorticotropic hormone (ACTH), and antagonist agouti signaling protein (ASP). Activation of the MC1R by binding of an agonist stimulates the synthesis of eumelanin primarily via activation of adenylate cyclase. The significance of cutaneous pigmentation lies in the photoprotective effect of melanin, particularly eumelanin, against sun-induced carcinogenesis. Epidermal melanocytes and keratinocytes respond to UVR by increasing their expression of αMSH and ACTH, which up-regulate the expression of MC1R, and consequently enhance the response of melanocytes to melanocortins. Constitutive skin pigmentation dramatically affects the incidence of skin cancer. The pigmentary phenotype characterized by red hair, fair complexion, inability to tan and tendency to freckle is an independent risk factor for all skin cancers, including melanoma. The MC1R gene is highly polymorphic in human populations, and allelic variation at this locus accounts, to a large extent, for the variation in pigmentary phenotypes and skin phototypes (SPT) in humans. Several allelic variants of the MC1R gene are associated with the red hair and fair skin (RHC) phenotype, and carrying one of these variants is thought to diminish the ability of the epidermis to respond to DNA damage elicited by UVR. The MC1R gene is considered a

  9. Some biological properties of human chorionic follicle stimulating hormone

    International Nuclear Information System (INIS)

    Tojo, Shimpei; Ashitaka, Yoshihiko; Maruo, Takeshi; Nishimoto, Hiroyuki

    1975-01-01

    The biological properties of human chorionic FSH (hCFSH) for rat ovaries were investigated. Highly purified hCFSH had similar response to the ovarian augmentation test as bovine FSH and significantly enhanced 3 H-thymidine uptake by granulosa cells and theca cells in the ovary of hypophysectomized rat. In contrast, highly purified hCG little responded to the ovarian augmentation test and had no effect on 3 H-thymidine uptake by the ovary. These results indicate that hCFSH may promote the follicular growth of ovary resulting from granulosa cell proliferation and its enlargement. In addition, freshly harvested porcine granulosa cells were employed in an in vitro system to investigate specific binding of hCFSH to ovarian receptor. Radioiodinated hCFSH ( 125 I-hCFSH) and hCG ( 125 I-hCG) were respectively incubated with cell suspensions. Binding of these hormone preparations was proportional to the cell number and increased with the time of incubation through 120 minutes. The binding ability of 125 I-hCFSH to the cells was greater than that of 125 I-hCG. Increasing concentrations of unlabeled hCFSH in the incubation mixture progressively inhibited the uptake of 125 I-hCFSH by granulosa cells. Unlabeled hCG was not able to compete with 125 I-hCFSH binding. The similar phenomenon to inhibit the binding of 125 I-hCG to the cells was also recognized in the presence of unlabeled hCG. These findings suggest that granulosa cell has at least two different types of receptor sites: one for hCFSH and the other for hCG. (auth.)

  10. Secondary Amenorrhea with Low Serum Luteinizing Hormone and Follicle-stimulating Hormone Caused by an Inhibin A- and Inhibin B-producing Granulosa Cell Tumor

    Directory of Open Access Journals (Sweden)

    Marzieh Agha-Hosseini

    2009-03-01

    Conclusion: A granulosa cell tumor secretes inhibin A and B, which suppress follicle-stimulating hormone and luteinizing hormone release through a central mechanism. This leads to amenorrhea, which can be misdiag-nosed as hypothalamic amenorrhea. Inhibin-producing ovarian tumors must be considered in the assessment of patients with apparent hypothalamic amenorrhea.

  11. Profile of follitropin alpha/lutropin alpha combination for the stimulation of follicular development in women with severe luteinizing hormone and follicle-stimulating hormone deficiency

    Directory of Open Access Journals (Sweden)

    Rinaldi L

    2016-05-01

    Full Text Available Leonardo Rinaldi, Helmy Selman One Day Medical Center, IVF Unit, Rome, Italy Abstract: A severe gonadotropin deficiency together with chronic estradiol deficiency leading to amenorrhea characterizes patients suffering from hypogonadotropic hypogonadism. Administration of both follicle-stimulating hormone (FSH and luteinizing hormone (LH to these patients has been shown to be essential in achieving successful stimulation of follicular development, ovulation, and rescue of fertility. In recent years, the availability of both recombinant FSH (rFSH and recombinant LH (rLH has provided a new therapeutic option for the stimulation of follicular growth in hypopituitary–hypogonadotropic women (World Health Organization Group I. In this article, we review the data reported in the literature to highlight the role and the efficacy of using recombinant gonadotropins, rFSH and rLH, in the treatment of women with severe LH/FSH deficiency. Although the studies on this issue are limited and the experiences available in the literature are few due to the small number of such patients, it is clearly evident that the recombinant gonadotropins rFSH and rLH are efficient in treating patients affected by hypogonadotropic hypogonadism. The results observed in the studies reported in this review suggest that recombinant gonadotropins are able to induce proper follicular growth, oocyte maturation, and eventually pregnancy in this group of women. Moreover, the clinical use of recombinant gonadotropins in this type of patients has given more insight into some endocrinological aspects of ovarian function that have not yet been fully understood. Keywords: follicular growth, gonadotropins, implantation, ovarian stimulation, pregnancy

  12. Impact of growth hormone (GH) and follicle stimulating hormone (FSH) on in vitro canine preantral follicle development and estradiol production.

    Science.gov (United States)

    Serafim, M K B; Duarte, A B G; Silva, G M; Souza, C E A; Magalhães-Padilha, D M; Moura, A A A; Silva, L D M; Campello, C C; Figueiredo, J R

    2015-04-01

    Evaluate the effect of different concentrations of growth hormone (GH) on the in vitro development of domestic dog (Canis lupus familiaris) preantral follicles in the presence or absence of follicle stimulating hormone (FSH). Secondary preantral follicles, isolated by microdissection, were cultured in a medium composed of αMEM with bovine serum albumin (BSA), glutamine, hypoxanthine, insulin, transferrin, selenium and ascorbic acid (αMEM(+)-control) added at different concentrations of GH (GH10 ng/ml or GH50 ng/ml) and FSH (GH10+FSH, GH50+FSH). Follicle development was evaluated based on the percentage of intact follicles, antrum formation, follicular diameter, follicular viability using fluorescent markers and estradiol production. GH50 was the only treatment that maintained the same percentage of normal morphologically follicles from day 0 to day 18 of culture (PGH50 supplemented with FSH (GH50+FSH) resulted in the highest average follicular diameter (PGH50+FSH treatment groups actively and increasingly secreted estradiol from day 6 to 18 of culture (PGH benefits the maintenance of follicular morphology in a dose-dependent manner and, in association with FSH, stimulates in vitro follicular growth and estradiol production. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Preparation of quality control samples in radioimmunoassay for thyroid stimulating hormone (TSH)

    International Nuclear Information System (INIS)

    Ali, O.M.

    2006-03-01

    To days, the radioimmunoassay is becomes the best technique to analysis different concentrations of substance, especially in medical and research laboratories. Although the specificity of RIA techniques, the quality controls must takes place to give good results as possible. In this dissertation i prepared quality control samples of thyroid stimulating hormone (TSH), to use it in RIA techniques and to control the reliability results of those laboratories which used these methods. We used China production kits of RIA method to determine the level of hormone (low-normal-high) concentration. Statistical parameters were used to drown the control chart of the mean to these data.(Author)

  14. Lactogenic hormones stimulate expression of lipogenic genes but not glucose transporters in bovine mammary gland.

    Science.gov (United States)

    Shao, Y; Wall, E H; McFadden, T B; Misra, Y; Qian, X; Blauwiekel, R; Kerr, D; Zhao, F-Q

    2013-02-01

    During the onset of lactation, there is a dramatic increase in the expression of glucose transporters (GLUT) and a group of enzymes involved in milk fat synthesis in the bovine mammary gland. The objective of this study was to investigate whether the lactogenic hormones mediate both of these increases. Bovine mammary explants were cultured for 48, 72, or 96 h with the following hormone treatments: no hormone (control), IGF-I, insulin (Ins), Ins + hydrocortisone + ovine prolactin (InsHPrl), or Ins + hydrocortisone + prolactin + 17β-estradiol (InsHPrlE). The relative expression of β-casein, α-lactalbumin, sterol regulatory element binding factor 1 (SREBF1), fatty acid synthase (FASN), acetyl-CoA carboxylase α (ACACA), stearyol-CoA desaturase (SCD), GLUT1, GLUT8, and GLUT12 were measured by real-time PCR. Exposure to the lactogenic hormone combinations InsHPrl and InsHPrlE for 96 h stimulated expression of β-casein and α-lactalbumin mRNA by several hundred-fold and also increased the expression of SREBF1, FASN, ACACA, and SCD genes in mammary explants (P hormone combinations had no effect on GLUT1 or GLUT8 expression and inhibited GLUT12 expression by 50% after 72 h of treatment (P hormone treatments. Moreover, treatment of dairy cows with bovine prolactin had no effect on GLUT expression in the mammary gland. In conclusion, lactogenic hormones clearly stimulate expression of milk protein and lipogenic genes, but they do not appear to mediate the marked up-regulation of GLUT expression in the mammary gland during the onset of lactation. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Single vagus nerve stimulation reduces early postprandial C-peptide levels but not other hormones or postprandial metabolism.

    Science.gov (United States)

    Tang, M W; van Nierop, F S; Koopman, F A; Eggink, H M; Gerlag, D M; Chan, M W; Zitnik, R; Vaz, F M; Romijn, J A; Tak, P P; Soeters, M R

    2018-02-01

    A recent study in rheumatoid arthritis (RA) patients using electrical vagus nerve stimulation (VNS) to activate the inflammatory reflex has shown promising effects on disease activity. Innervation by the autonomic nerve system might be involved in the regulation of many endocrine and metabolic processes and could therefore theoretically lead to unwanted side effects. Possible effects of VNS on secretion of hormones are currently unknown. Therefore, we evaluated the effects of a single VNS on plasma levels of pituitary hormones and parameters of postprandial metabolism. Six female patients with RA were studied twice in balanced assignment (crossover design) to either VNS or no stimulation. The patients selected for this substudy had been on VNS therapy daily for at least 3 months and at maximum of 24 months. We compared 10-, 20-, and 30-min poststimulus levels to baseline levels, and a 4-h mixed meal test was performed 30 min after VNS. We also determined energy expenditure (EE) by indirect calorimetry before and after VNS. VNS did not affect pituitary hormones (growth hormone, thyroid stimulating hormone, adrenocorticotropic hormone, prolactin, follicle-stimulating hormone, and luteinizing hormone), postprandial metabolism, or EE. Of note, VNS reduced early postprandial insulin secretion, but not AUC of postprandial plasma insulin levels. Cortisol and catecholamine levels in serum did not change significantly. Short stimulation of vagal activity by VNS reduces early postprandial insulin secretion, but not other hormone levels and postprandial response. This suggests VNS as a safe treatment for RA patients.

  16. Labelling of human follicle stimulant hormone with 125I, for radioimmunoassay

    International Nuclear Information System (INIS)

    Pinto, H.; Werner, R.S.; Lerario, A.C.; Toledo e Souza, I.T. de; Wajchenberg, B.L.; Pieroni, R.R.

    1976-01-01

    An efficient labeling of human Follicle Stimulant Harmone is essential to development of sensitive radioimmunoassays. Iodination by Chloramine T method frequently is subject to severe iodination damage and some preparations are unaccetable for radioimmunoassays. Modifications to the Hunter method, changing incubation time, reaction temperature and reducing Chloramine T amount used in the reaction, were performed in obtaining a more effective labeling. FSH-125 I fraction obtained from Sephadex G-75 column purification presented excellent immunoreactivity and quality control of the steps of the reaction demonstrated a high percentage (90%) of intact Follicle Stimulant Hormone [pt

  17. Basal and Adrenocorticotropic Hormone Stimulated Plasma Cortisol Levels Among Egyptian Autistic Children: Relation to Disease Severity

    Directory of Open Access Journals (Sweden)

    Hewedi Doaa H

    2010-10-01

    Full Text Available Abstract Background Autism is a disorder of early childhood characterized by social impairment, communication abnormalities and stereotyped behaviors. The hypothalamic-pituitary-adrenocortical (HPA axis deserves special attention, since it is the basis for emotions and social interactions that are affected in autism. Aim To assess basal and stimulated plasma cortisol, and adrenocorticotropic hormone (ACTH levels in autistic children and their relationship to disease characteristics. Methods Fifty autistic children were studied in comparison to 50 healthy age-, sex- and pubertal stage- matched children. All subjects were subjected to clinical evaluation and measurement of plasma cortisol (basal and stimulated and ACTH. In addition, electroencephalography (EEG and intelligence quotient (IQ assessment were done for all autistic children. Results Sixteen% of autistic patients had high ACTH, 10% had low basal cortisol and 10% did not show adequate cortisol response to ACTH stimulation. Autistic patients had lower basal (p = 0.032 and stimulated cortisol (p = 0.04 and higher ACTH (p = 0.01 than controls. Childhood Autism Rating Scale (CARS score correlated positively with ACTH (r = 0.71, p = 0.02 and negatively with each of basal (r = -0.64, p = 0.04 and stimulated cortisol (r = -0.88, p Conclusions The observed hormonal changes may be due to a dysfunction in the HPA axis in autistic individuals. Further studies are warranted regarding the role of HPA axis dysfunction in the pathogenesis of autism.

  18. Recombinant luteinizing hormone priming in multiple follicular stimulation for in-vitro fertilization in downregulated patients.

    Science.gov (United States)

    Lisi, F; Caserta, D; Montanino, M; Berlinghieri, V; Bielli, W; Carfagna, P; Carra, M C; Costantino, A; Lisi, R; Poverini, R; Ciardo, F; Rago, R; Marci, R; Moscarini, M

    2012-09-01

    Follicle development is controlled amongst other factors by pituitary gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) that act in synergy in completing follicle maturation. Exogenous gonadotropins, combined with gonadotropin-releasing hormone agonists, have been successfully used in patients with ovulatory disorders undergoing assisted reproduction. There is some evidence of a beneficial role of androgens or LH administration before FSH stimulation. This study was designed to verify whether the addition of LH in the early follicular phase, in downregulated patients undergoing follicular stimulation for assisted reproduction, would add benefits in terms of general outcomes and pregnancy rates. We compared two groups of patients one of which was treated with recombinant FSH (rFSH) alone and the other with rFSH plus recombinant LH (rLH), in the early follicular phase only. The number of eggs recovered was higher in the group treated with FSH only; however, the number of embryos available at transfer was similar in the two groups and, more importantly, the number of Grades I and II embryos was higher in the group pretreated with LH. Similarly, although biochemical pregnancy rate and clinical pregnancy rates were similar in both groups, a beneficial role of LH priming was demonstrated by the higher implantation rate achieved in these patients.

  19. Rapid and transitory stimulation of 3-O-methylglucose transport by growth hormone

    International Nuclear Information System (INIS)

    Carter-Su, C.; Rozsa, F.W.; Wang, Xueyan; Stubbart, J.R.

    1988-01-01

    The regulation of hexose transport by growth hormone (GH) was investigated using isolated rat adipocytes. GH caused a rapid (<3 min) rise in rates of 3-O-methylglucose transport that reached a maximum of two to six times the basal rates in 10-30 min. The stimulation of transport was transitory, and rates of transport started to decline 15-30 min after GH was added. Transport stimulation required a period of preincubation; no stimulation was observed in freshly isolated cells. GH stimulated hexose transport between 100 and 5,000 ng/ml, with a 50% effective dose between 200 and 300 ng/ml. Depletion of cellular ATP by 2,4-dinitrophenol blocked the ability of GH to stimulate transport but not the decline of transport rates following stimulation by GH. In contrast, an inhibitor of RNA synthesis, actinomycin D, had no effect on either the initial stimulation by GH or the initial subsequent decline of transport when added simultaneously or 15 min prior to GH. Actinomycin D did, however, cause a second rise in hexose transport at ∼120 min that was blocked by 2,4-dinitrophenol. These results suggest that changes in glucose transport contribute to the effects of GH on carbohydrate and lipid metabolism in adipose tissue. These changes are rapid, of substantial magnitude, and of a complex nature, suggesting that regulation of glucose transport by GH most likely involves multiple mechanisms

  20. alpha-difluoromethylornithine modifies gonadotropin-releasing hormone release and follicle-stimulating hormone secretion in the immature female rat.

    Science.gov (United States)

    Thyssen, S M; Becú-Villalobos, D; Lacau-Mengido, I M; Libertun, C

    1997-06-01

    Polyamines play an essential role in tissue growth and differentiation, in body weight increment, in brain organization, and in the molecular mechanisms of hormonal action, intracellular signaling, and cell-to-cell communication. In a previous study, inhibition of their synthesis by alpha-difluoromethylornithine (DFMO), a specific and irreversible inhibitor of ornithine decarboxylase, during development in female rats, was followed by prolonged high follicle-stimulating hormone (FSH) serum level and a delayed puberty onset. Those changes were relatively independent of body mass and did not impair posterior fertility. The present work studies the mechanisms and site of action of polyamine participation in FSH secretion during development. DFMO was injected in female rats between Days 1 and 9 on alternate days. At 10 days of age, hypothalami from control and DFMO rats were perifused in vitro, and basal and potassium-induced gonadotropin-releasing hormone (GnRH) release were measured. The response to membrane depolarization was altered in DFMO hypothalami. Increased GnRH release in response to a low K+ concentration was evidenced. Adenohypophyses of the same treated prepubertal rats were perifused in vitro and the response to GnRH pulses was checked. In DFMO-treated rats, higher FSH release was observed, with no changes in LH or PRL secretion. Finally, pituitary GnRH receptor number in adenohypophyseal membranes from treated and control groups was quantified. A significant reduction in specific binding was evident in hypophyses from DFMO-treated rats when compared with binding in the control group. In summary, DFMO treatment in a critical developmental period in the female rat impacts the immature GnRH neuronal network and immature gonadotropes. A delay in maturation is evidenced by a higher sensitivity to secretagogs in both pituitary glands and hypothalamic explants. These events could explain the prolonged high FSH serum levels and delayed puberty onset seen in

  1. Influence of ionizing radiation on the rate of substance axon transport and its hormone-stimulated increase in rat nerves

    International Nuclear Information System (INIS)

    Frol'kyis, V.V.; Tanin, S.A.; Martsinko, V.Yi.; Gorban', Je.M.

    1997-01-01

    The influence of x-ray on the rate of substance axon transport (AT) and its hormone-stimulated increase was studied. The study involved 80 Wistar male rats aged 8 - 10 months. Post-irradiation reduction of AT rate is one of the factors, forming trophic disturbances, while anabolic hormones can prevent them

  2. Screening the Tox21 10K library for thyroid stimulating hormone receptor agonist and antagonist activity (SOT annual meeting)

    Science.gov (United States)

    Thyroid-stimulating hormone (TSH) regulates thyroid hormone (TH) production via binding to its receptor (TSHR). The roles of TSHR in human pathologies including hyper/hypothyroidism, Grave’s disease, and thyroid cancer are known, but it is currently unknown whether TSHR is an imp...

  3. Occurrence of postmenopausal-like acidic follicle-stimulating hormone (FSH) isoforms precedes the rise of FSH before menopause.

    NARCIS (Netherlands)

    Thomas, C.M.G.; Span, P.N.; Smeenk, J.M.J.; Hanssen, R.G.; Braat, D.D.M.; Sweep, F.C.

    2009-01-01

    OBJECTIVE: To assess the glycoform distribution patterns of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) during the menstrual cycle at different ages and FSH levels, after menopause, and with premature ovarian failure (POF). DESIGN: Controlled clinical study. SETTING: Healthy

  4. Extended hormone binding site of the human thyroid stimulating hormone receptor: distinctive acidic residues in the hinge region are involved in bovine thyroid stimulating hormone binding and receptor activation.

    Science.gov (United States)

    Mueller, Sandra; Kleinau, Gunnar; Jaeschke, Holger; Paschke, Ralf; Krause, Gerd

    2008-06-27

    The human thyroid stimulating hormone receptor (hTSHR) belongs to the glycoprotein hormone receptors that bind the hormones at their large extracellular domain. The extracellular hinge region of the TSHR connects the N-terminal leucine-rich repeat domain with the membrane-spanning serpentine domain. From previous studies we reasoned that apart from hormone binding at the leucine-rich repeat domain, additional multiple hormone contacts might exist at the hinge region of the TSHR by complementary charge-charge recognition. Here we investigated highly conserved charged residues in the hinge region of the TSHR by site-directed mutagenesis to identify amino acids interacting with bovine TSH (bTSH). Indeed, the residues Glu-297, Glu-303, and Asp-382 in the TSHR hinge region are essential for bTSH binding and partially for signal transduction. Side chain substitutions showed that the negative charge of Glu-297 and Asp-382 is necessary for recognition of bTSH by the hTSHR. Multiple combinations of alanine mutants of the identified positions revealed an increased negative effect on hormone binding. An assembled model suggests that the deciphered acidic residues form negatively charged patches at the hinge region resulting in an extended binding mode for bTSH on the hTSHR. Our data indicate that certain positively charged residues of bTSH might be involved in interaction with the identified negatively charged amino acids of the hTSHR hinge region. We demonstrate that the hinge region represents an extracellular intermediate connector for both hormone binding and signal transduction of the hTSHR.

  5. Pesticide Exposure Alters Follicle-Stimulating Hormone Levels in Mexican Agricultural Workers

    Science.gov (United States)

    Recio, Rogelio; Ocampo-Gómez, Guadalupe; Morán-Martínez, Javier; Borja-Aburto, Victor; López-Cervantes, Malaquías; Uribe, Marisela; Torres-Sánchez, Luisa; Cebrián, Mariano E.

    2005-01-01

    Organophosphorous pesticides (OPs) are suspected of altering reproductive function by reducing brain acetylcholinesterase activity and monoamine levels, thus impairing hypothalamic and/or pituitary endocrine functions and gonadal processes. Our objective was to evaluate in a longitudinal study the association between OP exposure and serum levels of pituitary and sex hormones. Urinary OP metabolite levels were measured by gas–liquid chromatography, and serum pituitary and sex hormone levels by enzymatic immunoassay and radioimmunoassay in 64 men. A total of 147 urine and blood samples were analyzed for each parameter. More than 80% of the participants had at least one OP metabolite in their urine samples. The most frequent metabolite found was diethylthiophosphate (DETP; 55%), followed by diethylphosphate (DEP; 46%), dimethylthiophosphate (DMTP; 32%), and dimethyldithiophosphate (DMDTP; 31%). However, the metabolites detected at higher concentrations were DMTP, DEP, DMDTP, and dimethylphosphate. There was a high proportion of individuals with follicle-stimulating hormone (FSH) concentrations outside the range of normality (48%). The average FSH serum levels were higher during the heavy pesticide spraying season. However, a multivariate analysis of data collected in all periods showed that serum FSH levels were negatively associated with urinary concentrations of both DMTP and DMDTP, whereas luteinizing hormone (LH) was negatively associated with DMTP. We observed no significant associations between estradiol or testosterone serum levels with OP metabolites. The hormonal disruption in agricultural workers presented here, together with results from experimental animal studies, suggests that OP exposure disrupts the hypothalamic–pituitary endocrine function and also indicates that FSH and LH are the hormones most affected. PMID:16140621

  6. Molecular cloning, characterization and expression of thyroid-stimulating hormone receptor in channel catfish.

    Science.gov (United States)

    Goto-Kazeto, Rie; Kazeto, Yukinori; Trant, John M

    2009-05-01

    Thyroid-stimulating hormone receptors (TSHRs) are primarily expressed in the thyroid of vertebrates, however recently, transcripts encoding TSHR have been found abundantly in the gonads in a variety of fish species. The purpose of this study is to characterize the channel catfish TSHR and to examine whether the transcript are translated into protein in the gonad or store the transcript as maternal RNA for later use. The cDNA encoding the TSHR was isolated from the channel catfish thyroid but the transcript was determined to be expressed in a number of tissues, including the gonads. In fact, the ovarian expression of TSHR changed significantly during the reproductive season and peaked after the vitellogenic growth phase. Furthermore, the TSHR transcript was also detected in unfertilized eggs but not in fertilized egg of catfish. LM-PAT analysis demonstrated that catfish TSHR transcripts were fully polyadenylated in thyroidal follicles, gonads and unfertilized eggs suggesting that they were translated into protein opposed to being "stored mRNA". Western blot analysis using polyclonal antibodies against the catfish TSHR verified this assumption by visualizing immunoreactive protein in the thyroid, testis, and the post-vitellogenic ovary in abundance. A functional assay clearly showed that the recombinant catfish TSHR was specifically activated by bovine TSH but not by recombinant catfish follicle-stimulating hormone (FSH) and luteinizing hormone (LH). As in other species, the heterologous gonadotropin, hCG, partially activated the receptor. These results suggested that TSHR plays important roles for gametogenesis rather than embryogenesis.

  7. Hormonal stimulation of the recovery of spermatogenesis following chemo- or radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Meistrich, M.L. [Univ. of Texas, M.D. Anderson Cancer Center, Dept. of Experimental Radiation Oncology, Houston, Texas (United States)

    1998-01-01

    Radiation and chemotherapeutic drugs produce prolonged depression of sperm counts in rodents and humans. Previously, three approaches have been developed in experimental animals that have had some success in preventing or reversing this toxicity. These approaches included pretreatment with hormones that suppress spermatogenesis, stimulation of stem cell number, and supplementation with testosterone. A different rationale for the ability of particular hormonal treatments to reverse prolonged azoospermia is presented in this review. In many cases prolonged azoospermia occurs even though the stem spermatogonia survive the toxic insult, but the differentiation of these spermatogonia to produce sperm fails. In the rat, the block appears to be at the differentiation of the A spermatogonia. Hormone treatments with testosterone or with GnRH agonists, which suppress intratesticular testosterone levels, relieve this block and result in the production of differentiating cells. When the hormone treatment is stopped the production of differentiating cells continues, mature sperm are produced, and fertility is restored. If a similar mechanism can be demonstrated to hold in humans, the fertility of men who have been rendered infertile by treatments for testicular and other cancers could be improved. (au). 100 refs.

  8. Hormonal stimulation of the recovery of spermatogenesis following chemo- or radiotherapy

    International Nuclear Information System (INIS)

    Meistrich, M.L.

    1998-01-01

    Radiation and chemotherapeutic drugs produce prolonged depression of sperm counts in rodents and humans. Previously, three approaches have been developed in experimental animals that have had some success in preventing or reversing this toxicity. These approaches included pretreatment with hormones that suppress spermatogenesis, stimulation of stem cell number, and supplementation with testosterone. A different rationale for the ability of particular hormonal treatments to reverse prolonged azoospermia is presented in this review. In many cases prolonged azoospermia occurs even though the stem spermatogonia survive the toxic insult, but the differentiation of these spermatogonia to produce sperm fails. In the rat, the block appears to be at the differentiation of the A spermatogonia. Hormone treatments with testosterone or with GnRH agonists, which suppress intratesticular testosterone levels, relieve this block and result in the production of differentiating cells. When the hormone treatment is stopped the production of differentiating cells continues, mature sperm are produced, and fertility is restored. If a similar mechanism can be demonstrated to hold in humans, the fertility of men who have been rendered infertile by treatments for testicular and other cancers could be improved. (au)

  9. Giant Congenital Melanocytic Nevus

    DEFF Research Database (Denmark)

    Rasmussen, Bo Sonnich; Henriksen, Trine Foged; Kølle, Stig-Frederik Trojahn

    2015-01-01

    Giant congenital melanocytic nevi (GCMN) occur in 1:20,000 livebirths and are associated with increased risk of malignant transformation. The treatment of GCMN from 1981 to 2010 in a tertiary referral center was reviewed evaluating the modalities used, cosmetic results, associated complications......% versus 44% required unplanned additional surgery, respectively. Complications were noted in 25% and 67% of the patients, respectively. Cosmetic result was satisfying in 76% of patients without difference between the groups. No malignant transformation was found during a mean follow-up of 11 years....... Curettage is a gentle alternative to excision with a lower complication rate and good cosmetic outcome....

  10. Gonadotropin-Releasing Hormone Stimulate Aldosterone Production in a Subset of Aldosterone-Producing Adenoma

    Science.gov (United States)

    Kishimoto, Rui; Oki, Kenji; Yoneda, Masayasu; Gomez-Sanchez, Celso E.; Ohno, Haruya; Kobuke, Kazuhiro; Itcho, Kiyotaka; Kohno, Nobuoki

    2016-01-01

    Abstract We aimed to detect novel genes associated with G protein-coupled receptors (GPCRs) in aldosterone-producing adenoma (APA) and elucidate the mechanisms underlying aldosterone production. Microarray analysis targeting GPCR-associated genes was conducted using APA without known mutations (APA-WT) samples (n = 3) and APA with the KCNJ5 mutation (APA-KCNJ5; n = 3). Since gonadotropin-releasing hormone receptor (GNRHR) was the highest expression in APA-WT by microarray analysis, we investigated the effect of gonadotropin-releasing hormone (GnRH) stimulation on aldosterone production. The quantitative polymerase chain reaction assay results revealed higher GNRHR expression levels in APA-WT samples those in APA-KCNJ5 samples (P APA-WT samples, and there was a significant and positive correlation between GNRHR and LHCGR expression in all APA samples (r = 0.476, P APA-WT (n = 9), which showed higher GNRHR and LHCGR levels, had significantly higher GnRH-stimulated aldosterone response than those with APA-KCNJ5 (n = 13) (P APA-WT, and the molecular analysis including the receptor expression associated with clinical findings of GnRH stimulation. PMID:27196470

  11. Secretion of Growth Hormone in Response to Muscle Sensory Nerve Stimulation

    Science.gov (United States)

    Grindeland, Richard E.; Roy, R. R.; Edgerton, V. R.; Gosselink, K. L.; Grossman, E. J.; Sawchenko, P. E.; Wade, Charles E. (Technical Monitor)

    1994-01-01

    Growth hormone (GH) secretion is stimulated by aerobic and resistive exercise and inhibited by exposure to actual or simulated (bedrest, hindlimb suspension) microgravity. Moreover, hypothalamic growth hormone-releasing factor (GRF) and preproGRF mRNA are markedly decreased in spaceflight rats. These observations suggest that reduced sensory input from inactive muscles may contribute to the reduced secretion of GH seen in "0 G". Thus, the aim of this study was to determine the effect of muscle sensory nerve stimulation on secretion of GH. Fed male Wistar rats (304 +/- 23 g) were anesthetized (pentobarbital) and the right peroneal (Pe), tibial (T), and sural (S) nerves were cut. Electrical stimulation of the distal (D) or proximal (P) ends of the nerves was implemented for 15 min. to mimic the EMG activity patterns of ankle extensor muscles of a rat walking 1.5 mph. The rats were bled by cardiac puncture and their anterior pituitaries collected. Pituitary and plasma bioactive (BGH) and immunoactive (IGH) GH were measured by bioassay and RIA.

  12. Do hormonal contraceptives stimulate growth of neurofibromas? A survey on 59 NF1 patients

    Directory of Open Access Journals (Sweden)

    Mautner Victor-Felix

    2005-02-01

    Full Text Available Abstract Background Neurofibromas are benign tumors of the peripheral nerves and hallmark of neurofibromatosis type 1 (NF1, a tumor suppressor gene syndrome. Neurofibromas mostly start developing at puberty and can increase in size and number during pregnancy. Expression of progesterone receptors has been found in 75% of the tumors. Many female NF1 patients are thus concerned about the possibility that hormonal contraceptives may stimulate the growth of their neurofibromas. Methods A survey was carried out on 59 female NF1 patients who are practicing or have practiced hormonal contraception to examine the effect of the various contraceptives on the growth of neurofibromas. Results Majority (53 out of 58 of patients who received oral estrogen-progestogen or pure progestogen preparations reported no associated tumor growth. In contrast, significant tumor growth was reported by two patients who received depot contraceptive containing high dose of synthetic progesterone. Conclusions Oral contraceptives do not seem to stimulate the growth of neurofibromas in NF1 patients. High doses of progesterone might stimulate the growth of neurofibromas and deserve more caution.

  13. Anti-Müllerian hormone, follicle stimulating hormone, antral follicle count, and risk of menopause within 5 years.

    Science.gov (United States)

    Kim, Catherine; Slaughter, James C; Wang, Erica T; Appiah, Duke; Schreiner, Pamela; Leader, Benjamin; Calderon-Margalit, Ronit; Sternfeld, Barbara; Siscovick, David; Wellons, Melissa

    2017-08-01

    To evaluate the ability of concentration of anti-Müllerian hormone (AMH), antral follicle count (AFC), and concentration of follicle stimulating hormone (FSH) to predict the onset of menopause. The Coronary Artery Risk Development in Young Adults Study (CARDIA) Women's Study was an ancillary study to CARDIA, a population-based study of adults aged 18-30 years followed for 3 decades. For this report, participants were women (n=426) who had attended the CARDIA year 15-16 (2000-2001) examination, had at least one ovary, were not pregnant, and underwent serum AMH and FSH measurement and transvaginal ultrasonography in 2002-2003. The probability of menopause in 5 years based upon AMH, FSH, and AFC. The mean age of the women at the time of AMH, FSH, and AFC assessment was 43 years. The cumulative incidence of menopause at 25 years (or follow-up) was 27% (n=426), and the incidence within 5 years was 13% (n=55). Among women aged 45-49 years, undetectable AMH concentrations were associated with a greater than 60% probability of menopause within 5 years, whereas approximately 1/3 of women with no or just one antral follicle experienced menopause within 5 years. Both low and high concentrations of FSH were associated with greater odds of menopause than intermediate concentrations. Models with multiple markers did not improve the prediction of menopause over that afforded by models with single markers. The ability to predict onset of menopause was improved with any of the three menopausal markers in addition to age. AMH concentrations were more closely associated with menopause than AFC or FSH. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. A rapid solid-phase radioimmunoassay for human plasma follicle-stimulating hormone

    International Nuclear Information System (INIS)

    Lovesey, A.C.

    1980-01-01

    The measurement of plasma levels of human follicle-stimulating hormone (FSH) has proved to be of value for the study of the hypothalamic-hypophyseal-gonadal axis, greatly facilitating the diagnosis and management of problems relating to the menopause and infertility. A solid-phase radioimmunoassay for human FSH has been developed. This system is characterised by high precision, is economical, and is considerably faster to operate than conventional double antibody systems used in the hospital assay service. Reference values for plasma FSH in various endocrine states are recorded and discussed. (author)

  15. Relationship between thyroid stimulating hormone and thyroid stimulating immunoglobulin in Graves' hyperthyroidism.

    Science.gov (United States)

    Woeber, K A

    2011-03-01

    In Graves' hyperthyroidism, suppression of serum TSH after restoration of normal serum T4 and T3 with treatment has been attributed to binding of TSH-receptor antibodies to TSH receptors in the pituitary. Accordingly, the relationship between TSH and serum thyroid stimulating immunoglobulin (TSI) was examined during follow-up of patients with Graves' hyperthyroidism. 23 patients with Graves' hyperthyroidism were identified who met the inclusion criteria of at least 24 months follow-up after initiation of methimazole and availability of concurrent measurements of serum TSH and TSI. TSI disappeared in 12 patients (Group A) and persisted in 11 patients (Group B). Initial T4 was not significantly different between the 2 groups. However, TSI was significantly lower in Group A than Group B [median (interquartile range) 179 (152-212)% vs 255 (208-369)%, p=0.0009]. In Group A, TSH normalized during treatment, and this anteceded disappearance of TSI by a significant time interval [median (interquartile range) 6 (3-8) months vs 15 (11-20) months, p=0.005]. In Group B, TSI persisted in all patients during follow-up ranging from 24 to 73 months. No correlation was found to exist between serum TSH and TSI, and for Group B TSI at final follow-up was not significantly different from the initial value [median (interquartile range) 255 (208-369)% vs 236 (160-310)%, p=0.4]. These findings do not support the suggestion that TSI has a direct suppressive effect on TSH secretion.

  16. Effect of 4 weeks of octreotide treatment on prolactin, thyroid stimulating hormone and thyroid hormones in acromegalic patients. A double blind placebo-controlled cross-over study

    DEFF Research Database (Denmark)

    Andersen, M; Hansen, T B; Bollerslev, J

    1995-01-01

    We aimed to test the hypothesis, that octreotide has a suppressive effect on unstimulated and TRH-stimulated PRL levels in both normo- and hyperprolactinaemic acromegalic patients, and besides to evaluate the effect of octreotide on unstimulated TSH and thyroid hormones. The present study is a do...

  17. Eccrine-Centric Melanocytic Nevus.

    Science.gov (United States)

    Fertig, Raymond M; Berghoff, Adar; Cervantes, Jessica; Darwin, Evan; Jukic, Drazen

    2017-10-27

    Benign melanocytic neoplasms present with a diverse array of well-known histopathologic patterns. It is imperative to recognize the benign patterns to render accurate diagnoses. We describe here an interesting and hitherto not described low-power architectural pattern of a benign melanocytic lesion: eccrine-centric melanocytic nevus. The patient was a 50-year-old African American woman who noticed a new mole on her foot that began as a dark speck but quickly grew larger. The lesion was excised to exclude the possibility of melanoma. Upon review of the specimen, the lesion was noted to demonstrate a distinctive pattern consistent with a melanocytic nevus of possible congenital onset. Remarkably, the ducts of eccrine glands were increased in density and the nests of melanocytes were found solely in a peri-eccrine distribution without melanocytes in any other locations (ie, interstitial, perifollicular). Additionally, all melanocytes in the nevus were rather heavily pigmented. Although this pattern demonstrated no atypical features that would cause one to consider it malignant to the trained eye, this presentation could implicate a metastatic disease (well-delineated nests in the dermis without concomitant interstitial component) and it is important to recognize.

  18. COMPARATIVE STUDY ON THE HORMONAL STIMULATION STERLET (ACIPENSER RUTHENUS, LINNAEUS, 1758 USING CARP HYPOPHYSIS AND ARTIFICIAL HORMONE TYPE NERESTIN 5-5A

    Directory of Open Access Journals (Sweden)

    R. C. DIMA

    2009-10-01

    Full Text Available Starting from the particular sturgeon reproductive biology, propagation of technology through artificial comprises a number of phases required including: selection, parking broodstocks cell maturation and sexual stimulation in order fertilized their conditions provided. To stimulate the process of sexual maturation of the sexual elements for sterlet could be hypophysis and also analogue gonadothropic hormone type Nerestin 5. Literature attesting to the use of sterlet dry hypophysis treated with acetone (Maria Caloianu-Iordăchel, 1973 and employing successful hormone analogue found as LHRHa (N.Patrichi and collaborators, 1989- unpublished data. Advantages and disadvantages of using hypophysis or gonadotropic hormone analogue fdhgghNerestin 5 are very important and decisive for modern aquaculture the century XXI century.

  19. Molecular analysis of the koala reproductive hormones and their receptors: gonadotrophin-releasing hormone (GnRH), follicle-stimulating hormone β and luteinising hormone β with localisation of GnRH.

    Science.gov (United States)

    Busby, E R; Soeta, S; Sherwood, N M; Johnston, S D

    2014-12-01

    During evolution, reproductive hormones and their receptors in the brain-pituitary-gonadal axis have been altered by genetic mechanisms. To understand how the neuroendocrine control of reproduction evolved in mammals, it is important to examine marsupials, the closest group to placental mammals. We hypothesised that at least some of the hormones and receptors found in placental mammals would be present in koala, a marsupial. We examined the expression of koala mRNA for the reproductive molecules. Koala cDNAs were cloned from brain for gonadotrophin-releasing hormones (GnRH1 and GnRH2) or from pituitary for GnRH receptors, types I and II, follicle-stimulating hormone (FSH)β and luteinising hormone (LH)β, and from gonads for FSH and LH receptors. Deduced proteins were compared by sequence alignment and phylogenetic analysis with those of other vertebrates. In conclusion, the koala expressed mRNA for these eight putative reproductive molecules, whereas at least one of these molecules is missing in some species in the amniote lineage, including humans. In addition, GnRH1 and 2 are shown by immunohistochemistry to be expressed as proteins in the brain. © 2014 British Society for Neuroendocrinology.

  20. Hormones

    Science.gov (United States)

    Hormones are your body's chemical messengers. They travel in your bloodstream to tissues or organs. They work ... glands, which are special groups of cells, make hormones. The major endocrine glands are the pituitary, pineal, ...

  1. Proteomic and functional profiles of a follicle-stimulating hormone positive human nonfunctional pituitary adenoma.

    Science.gov (United States)

    Wang, Xiaowei; Guo, Tianyao; Peng, Fang; Long, Ying; Mu, Yun; Yang, Haiyan; Ye, Ningrong; Li, Xuejun; Zhan, Xianquan

    2015-06-01

    Nonfunctional pituitary adenoma (NFPA) is highly heterogeneous with different hormone-expressed subtypes in NFPA tissues including follicle-stimulating hormone (FSH) positive, luteinizing hormone-positive, FSH/luteinizing hormone-positive, and negative types. To analyze in-depth the variations in the proteomes among different NFPA subtypes for our long-term goal to clarify molecular mechanisms of NFPA and to detect tumor biomarker for personalized medicine practice, a reference map of proteome of a human FSH-expressed NFPA tissue was described here. 2DE and PDQuest image analysis were used to array each protein. MALDI-TOF PMF and human Swiss-Prot databases with MASCOT search were used to identify each protein. A good 2DE pattern with high level of between-gel reproducibility was attained with an average positional deviation 1.98 ± 0.75 mm in the IEF direction and 1.62 ± 0.68 mm in the SDS-PAGE direction. Approximately 1200 protein spots were 2DE-detected and 192 redundant proteins that were contained in 141 protein spots were PMF-identified, representing 107 nonredundant proteins. Those proteins were located in cytoplasm, nucleus, plasma membrane, extracellular space, and so on, and those functioned in transmembrane receptor, ion channel, transcription/translation regulator, transporter, enzyme, phosphatase, kinase, and so on. Several important pathway networks were characterized from those identified proteins with DAVID and Ingenuity Pathway Analysis systems, including gluconeogenesis and glycolysis, mitochondrial dysfunction, oxidative stress, cell-cycle alteration, MAPKsignaling system, immune response, TP53-signaling, VEGF-signaling, and inflammation signaling pathways. Those resulting data contribute to a functional profile of the proteome of a human FSH-positive NFPA tissue, and will serve as a reference for the heterogeneity analysis of NFPA proteomes. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Associations between brominated flame retardants in human milk and thyroid-stimulating hormone (TSH) in neonates.

    Science.gov (United States)

    Eggesbø, Merete; Thomsen, Cathrine; Jørgensen, Jens V; Becher, Georg; Odland, Jon Øyvind; Longnecker, Matthew P

    2011-08-01

    Brominated flame retardants (BFRs) have been in widespread use in a vast array of consumer products since the 1970s. The metabolites of some BFRs show a structural similarity to thyroid hormones and experimental animal studies have confirmed that they may interfere with thyroid hormone homeostasis. A major concern has been whether intrauterine exposure to BFRs may disturb thyroid homeostasis since the fetal brain is particularly susceptible to alterations in thyroid hormones. However, few reports on newborns have been published to date. To evaluate the association between BFRs and neonatal thyroid-stimulating hormone (TSH). We studied six polybrominated diphenyl ethers (PBDEs) measured in milk samples from 239 women who were part of the "Norwegian Human Milk Study" (HUMIS), 2003-2006. Hexabromocyclododecane (HBCD) and BDE-209 were measured in a subset of the women (193 and 46 milk samples, respectively). The milk was sampled at a median of 33 days after delivery. TSH was measured in babies three days after delivery as part of the routine national screening program for early detection of congenital hypothyroidism. Additional information was obtained through the Medical Birth Registry and questionnaires to the mothers. The PBDE concentrations in human milk in Norway were comparable to concentrations reported from other European countries and Asia, but not the US and Canada where levels are approximately one order of higher magnitude. We observed no statistically significant associations between BDE-47, 99, 153, 154, 209 and HBCD in human milk and TSH in models adjusted for possible confounders and other environmental toxicants including polychlorinated biphenyls (PCBs). We did not observe an association between TSH and exposure to HBCD and PBDEs within the exposure levels observed. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Microarray analysis sheds light on the dedifferentiating role of agouti signal protein in murine melanocytes via the Mc1r

    Science.gov (United States)

    Le Pape, Elodie; Passeron, Thierry; Giubellino, Alessio; Valencia, Julio C.; Wolber, Rainer; Hearing, Vincent J.

    2009-01-01

    The melanocortin-1 receptor (MC1R) is a key regulator of pigmentation in mammals and is tightly linked to an increased risk of skin cancers, including melanoma, in humans. Physiologically activated by α-melanocyte stimulating hormone (αMSH), MC1R function can be antagonized by a secreted factor, agouti signal protein (ASP), which is responsible for the lighter phenotypes in mammals (including humans), and is also associated with increased risk of skin cancer. It is therefore of great interest to characterize the molecular effects elicited by those MC1R ligands. In this study, we determined the gene expression profiles of murine melan-a melanocytes treated with ASP or αMSH over a 4-day time course using genome-wide oligonucleotide microarrays. As expected, there were significant reductions in expression of numerous melanogenic proteins elicited by ASP, which correlates with its inhibition of pigmentation. ASP also unexpectedly modulated the expression of genes involved in various other cellular pathways, including glutathione synthesis and redox metabolism. Many genes up-regulated by ASP are involved in morphogenesis (especially in nervous system development), cell adhesion, and extracellular matrix-receptor interactions. Concomitantly, ASP enhanced the migratory potential and the invasiveness of melanocytic cells in vitro. These results demonstrate the role of ASP in the dedifferentiation of melanocytes, identify pigment-related genes targeted by ASP and by αMSH, and provide insights into the pleiotropic molecular effects of MC1R signaling that may function during development and may affect skin cancer risk. PMID:19174519

  4. Modulation of cultured porcine granulosa cell responsiveness to follicle stimulating hormone and epidermal growth factor

    International Nuclear Information System (INIS)

    Buck, P.A.

    1986-01-01

    Ovarian follicular development is dependent upon the coordinated growth and differentiation of the granulosa cells which line the follicle. Follicle stimulating hormone (FSH) induces granulosa cell differentiation both in vivo and in vitro. Epidermal growth factor (EGF) stimulates granulosa cell proliferation in vitro. The interaction of these two effectors upon selected parameters of growth and differentiation was examined in monolayer cultures of porcine granulose cells. Analysis of the EGF receptor by 125 I-EGF binding revealed that the receptor was of high affinity with an apparent dissociation constant of 4-6 x 10 -10 M. The average number of receptors per cell varied with the state of differentiation both in vivo and in vitro; highly differentiated cells bound two-fold less 125 I-EGF and this effect was at least partially induced by FSH in vitro. EGF receptor function was examined by assessing EGF effects on cell number and 3 H-thymidine incorporation. EGF stimulated thymidine incorporation in both serum-free and serum-supplemented culture, but only in serum-supplemented conditions was cell number increased. EGF receptor function was inversely related to the state of differentiation and was attenuated by FSH. The FSH receptor was examined by 125 I-FSH binding. EGF increased FSH receptor number, and lowered the affinity of the receptor. The function of these receptors was assessed by 125 I-hCG binding and progesterone radioimmunoassay. If EGF was present continuously in the cultures. FSH receptor function was attenuated regardless of FSH receptor number. A preliminary effort to examine the mechanism of this interaction was performed by analyzing hormonally controlled protein synthesis with 35 S-methionine labeling, SDS polyacrylamide gel electrophoresis and fluorography. FSH promoted the expression of a 27,000 dalton protein. This effect was attenuated by EGF

  5. Localization and quantification of binding sites for follicle-stimulating hormone, luteinizing hormone, growth hormone, and insulin-like growth factor I in sheep ovarian follicles.

    Science.gov (United States)

    Eckery, D C; Moeller, C L; Nett, T M; Sawyer, H R

    1997-09-01

    In sheep, growth and development of ovarian follicles beyond 2 mm in diameter is acutely dependent on gonadotropin support. As a consequence, following hypophysectomy (HPX) or hypothalamic-pituitary stalk disconnection (HPD), growth of follicles beyond 2 mm is arrested and all follicles > 2 mm undergo atresia. Although administration of exogenous gonadotropins stimulates follicular growth and ovulation in HPD ewes, follicles in HPX ewes remain unresponsive unless growth hormone (GH) is also given. To determine whether the difference in follicular sensitivity to gonadotropins after HPD (gonadotropin sensitive) or HPX (gonadotropin insensitive) is related to the distribution and quantity of binding sites for FSH, LH, and/or insulin-like growth factor I (IGF-I), binding sites for these hormones were localized and quantified using topical autoradiography in healthy follicles from control (pituitary-intact), HPD, and HPX ewes. In addition, in situ hybridization was performed to localize mRNA for GH and FSH receptors. Irrespective of treatment, binding of FSH and mRNA for FSH receptor were greatest (p membrana granulosa; LH binding was greatest (p receptor was most abundant (p membrana granulosa and oocytes of small antral and preantral follicles. Compared to levels in controls and HPD ewes, the level of GH receptor mRNA was lower (p receptors for FSH, LH, or IGF-I. The observed reduction of mRNA for GH receptor in the membrana granulosa of follicles from HPX ewes provides evidence that GH may play an important role in early stages of folliculogenesis and that it is involved in the maintenance of sensitivity to gonadotropins.

  6. Data on the characterization of follicle-stimulating hormone monoclonal antibodies and localization in Japanese eel pituitary

    Directory of Open Access Journals (Sweden)

    Dae-Jung Kim

    2016-09-01

    Full Text Available Monoclonal antibodies were generated against recombinant follicle-stimulating hormone (rec-FSH from Japanese eel Anguilla japonica; rec-FSH was produced in Escherichia coli and purified using Ni-NTA Sepharose column chromatography.In support of our recent publication, ''Production and characterization of monoclonal antibodies against recombinant tethered follicle-stimulating hormone from Japanese eel Anguilla japonica'' [1], it was important to characterize the specificity of eel follicle-stimulating hormone antibodies. Here, the production and ELISA system of these monoclonal antibodies are presented. The affinity-purified monoclonal antibodies specifically detected eel rec-FSH in ELISA and on western blots of rec-FSH produced from CHO cells. Immunohistochemical analysis revealed that FSH staining was specifically localized in the eel pituitary. Keywords: Japanese eel, FSH, Monoclonal Antibody

  7. Efficacy of quantifying melanosome transfer with flow cytometry in a human melanocyte-HaCaT keratinocyte co-culture system in vitro.

    Science.gov (United States)

    Ma, Hui-Jun; Zhao, Guang; Zi, Shao-Xia; Li, Dong-Guang; Liu, Wen; Yang, Qing-Qi

    2010-08-01

    In this study, we describe a simple, specific, reproducible and quantitative assay system to assess melanosome transfer. We first established a co-culture model of normal human epidermal melanocytes and HaCaT keratinocytes. The cells were co-cultured for 72 h in a serum-free keratinocyte growth media and double labelled with Fluorescein isothiocyanate (FITC)-conjugated antibody against the melanosome-specific protein gp100, and with Phycoerythrin (PE)-conjugated antibody against the keratinocyte-specific marker cytokeratin. Then, the cells were examined using co-focal microscope and flow cytometry. The increased melanosome transfer from melanocytes to HaCaT keratinocytes was observed in a time-dependent manner. To verify the accessibility of this method, two known melanosome transfer inhibitors and two known melanosome transfer stimulators were applied. Consistent with previous investigation, soybean trypsin inhibitor (STI), niacinamide inhibited melanosome transfer, alpha-melanocyte stimulating hormone (alpha-MSH) and keratinocyte growth factor (KGF) increased melanosome transfer, respectively, in a dose-dependent manner. The model used in this study could thus represent a rapid and reliable tool to identify modulators of human melanosome transfer.

  8. Impairing follicle-stimulating hormone (FSH) signaling in vivo: targeted disruption of the FSH receptor leads to aberrant gametogenesis and hormonal imbalance.

    Science.gov (United States)

    Dierich, A; Sairam, M R; Monaco, L; Fimia, G M; Gansmuller, A; LeMeur, M; Sassone-Corsi, P

    1998-11-10

    Pituitary gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone stimulate the gonads by regulating germ cell proliferation and differentiation. FSH receptors (FSH-Rs) are localized to testicular Sertoli cells and ovarian granulosa cells and are coupled to activation of the adenylyl cyclase and other signaling pathways. Activation of FSH-Rs is considered essential for folliculogenesis in the female and spermatogenesis in the male. We have generated mice lacking FSH-R by homologous recombination. FSH-R-deficient males are fertile but display small testes and partial spermatogenic failure. Thus, although FSH signaling is not essential for initiating spermatogenesis, it appears to be required for adequate viability and motility of the sperms. FSH-R-deficient females display thin uteri and small ovaries and are sterile because of a block in folliculogenesis before antral follicle formation. Although the expression of marker genes is only moderately altered in FSH-R -/- mice, drastic sex-specific changes are observed in the levels of various hormones. The anterior lobe of the pituitary gland in females is enlarged and reveals a larger number of FSH- and thyroid-stimulating hormone (TSH)-positive cells. The phenotype of FSH-R -/- mice is reminiscent of human hypergonadotropic ovarian dysgenesis and infertility.

  9. Pegvisomant-primed growth hormone (GH) stimulation test is useful in identifying true GH deficient children.

    Science.gov (United States)

    Radetti, Giorgio; Elsedfy, Heba H; Khalaf, Randa; Meazza, Cristina; Pagani, Sara; El Kholy, Mohamed; Albertini, Riccardo; De Stefano, Anna Maria; Navarra, Antonella; De Silvestri, Annalisa; Bozzola, Mauro

    2017-07-01

    Provocative stimulation tests for growth hormone (GH) assessment have poor reproducibility and can often elicit false positive results in normal children. The aim of our study was to confirm the capability of pegvisomant as an enhancer of GH secretion in unmasking false-positive results in short children (height GH testing. A prospective study was conducted between March and August 2016. Twenty short children (10 males and 10 females), aged 4.6-13.4 years, previously diagnosed as GH deficient (GHD) were included in the study. All subjects received 1 mg/kg of pegvisomant subcutaneously; three days later an insulin tolerance test (ITT) was performed. Insulin-like growth factor-I (IGF-I) was evaluated before and three days after pegvisomant administration. After pegvisomant priming and the ITT stimulation test, 12 out of the 20 children initially classified as GHD showed a GH peak of more than 10 ng/ml and were thus reclassified as short normal. Furthermore, a significant reduction of IGF-I was observed in the GHD group (pre IGF-I: median (IQR) 144.0 (109-248) ng/ml, post IGF-I: 98 (49-165) ng/ml; pGH stimulation tests can be used to improve the reliability of the diagnostic work-up in GH deficiency.

  10. Thyroid-stimulating hormone elevation misdiagnosed as subclinical hypothyroidism following non-convulsive status epilepticus: a case report

    Directory of Open Access Journals (Sweden)

    Kunii Yasuto

    2011-09-01

    Full Text Available Abstract Introduction Non-convulsive status epilepticus is a form of epileptic seizure that occurs without convulsions. Recent reviews suggest that the diagnosis of non-convulsive status epilepticus remains difficult. Here, we report the case of a patient with thyroid-stimulating hormone elevation misdiagnosed as subclinical hypothyroidism following non-convulsive status epilepticus. Case presentation Our patient was a 68-year-old Japanese woman. The results of endocrine testing after her first episode of non-convulsive status epilepticus suggested latent subclinical hypothyroidism: she had elevated thyroid-stimulating hormone with normal levels of free tri-iodothyronine and free thyroxine. On examination, a diagnosis of thyroid disorder was not supported by other test results and our patient remained untreated. A follow-up examination revealed that her thyroid-stimulating hormone levels had spontaneously normalized. When she consulted another doctor for confusion, the transient increase in thyroid-stimulating hormone levels following non-convulsive status epilepticus was mistaken for subclinical hypothyroidism, and unfortunately treated with levothyroxine. Our patient then experienced levothyroxine-induced non-convulsive status epilepticus. Conclusions In this report, we suggested possible mechanisms for latent hypothyroid-like hormone abnormality following epileptic seizures and the possibility of provoking epileptic seizures by administering levothyroxine for misdiagnosed subclinical hypothyroidism.

  11. Clonal relationships between thyroid-stimulating hormone receptor-stimulating antibodies illustrate the effect of hypermutation on antibody function

    DEFF Research Database (Denmark)

    Padoa, Carolyn J; Larsen, Sanne L; Hampe, Christiane S

    2009-01-01

    Summary Graves' disease is characterized by production of agonist antibodies to the thyroid-stimulating hormone receptor (TSHR), but knowledge of the genetic and somatic events leading to their aberrant production is limited. We describe the genetic analysis of two monoclonal antibodies (mAbs) wi......, in experimentally immunized mice, multiple pathogenic antibodies to TSHR can arise from a single clone by a series of somatic mutations in the V-region genes and may give an insight into how such antibodies develop spontaneously in autoimmune Graves' disease....... relationship and derivation from a single precursor B-cell clone. The IGHV-region genes of the two mAbs underwent high degrees of somatic hypermutation by sharing numerous mutations before diverging, while the IGLV genes evolved separately. Interestingly, the mutations were present in both the complementarity...... that the chimeras retained TSAb activities, confirming the close functional relatedness of the V-region genes. Importantly, the IGLV genes in chimeric rFabs had a dominant stimulatory effect at low concentrations, while the IGHV genes had a dominant effect at higher concentrations. Our findings demonstrate that...

  12. Growth hormone-releasing hormone stimulates GH release while inhibiting ghrelin- and sGnRH-induced LH release from goldfish pituitary cells.

    Science.gov (United States)

    Grey, Caleb L; Chang, John P

    2013-06-01

    Goldfish GH-releasing hormone (gGHRH) has been recently identified and shown to stimulate GH release in goldfish. In goldfish, neuroendocrine regulation of GH release is multifactorial and known stimulators include goldfish ghrelin (gGRLN19) and salmon gonadotropin-releasing hormone (sGnRH), factors that also enhance LH secretion. To further understand the complex regulation of pituitary hormone release in goldfish, we examined the interactions between gGHRH, gGRLN19, and sGnRH on GH and LH release from primary cultures of goldfish pituitary cells in perifusion. Treatment with 100nM gGHRH for 55min stimulated GH release. A 5-min pulse of either 1nM gGRLN19 or 100nM sGnRH induced GH release in naïve cells, and these were just as effective in cells receiving gGHRH. Interestingly, gGHRH abolished both gGRLN19- and sGnRH-induced LH release and reduced basal LH secretion levels. These results suggest that gGHRH does not interfere with sGnRH or gGRLN19 actions in the goldfish somatotropes and further reveal, for the first time, that GHRH may act as an inhibitor of stimulated and basal LH release by actions at the level of pituitary cells. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Melanocyte pigmentation inversely correlates with MCP-1 production and angiogenesis-inducing potential.

    Science.gov (United States)

    Adini, Irit; Adini, Avner; Bazinet, Lauren; Watnick, Randolph S; Bielenberg, Diane R; D'Amato, Robert J

    2015-02-01

    The incidence of certain angiogenesis-dependent diseases is higher in Caucasians than in African Americans. Angiogenesis is amplified in wound healing and cornea models in albino C57 mice compared with black C57 mice. Moreover, mouse and human melanocytes with low pigmentation stimulate endothelial cell (EC) proliferation and migration in vitro more than melanocytes with high pigmentation. This effect is due, in part, to the secretion of an angiogenic protein called fibromodulin (FMOD) from lowly pigmented melanocytes. Herein, we expand upon the mechanism contributing to increased angiogenesis in lighter skin and report that monocyte chemotactic protein-1 (MCP-1) is secreted by nonpigmented mouse melanocytes by 5- to 10-fold more than pigmented melanocytes. MCP-1 protein stimulates EC proliferation and migration in vitro and angiogenesis in vivo. Mechanistic studies determine that FMOD is upstream of MCP-1 and promotes its secretion from both melanocytes and activated ECs via stimulation of NF-κB activity. Mice injected with FMOD-neutralizing antibodies show 2.3-fold decreased levels of circulating MCP-1. Human studies confirmed that, on average, Caucasians have 2-fold higher serum levels of MCP-1 than African Americans. Taken together, this study implicates the FMOD/MCP-1 pathway in the regulation of angiogenesis by local melanocytes and suggests that melanogenic activity may protect against aberrant angiogenic diseases. © FASEB.

  14. Similar clinical features among patients with severe adult growth hormone deficiency diagnosed with insulin tolerance test or arginine or glucagon stimulation tests

    DEFF Research Database (Denmark)

    Toogood, Andrew; Brabant, Georg; Maiter, Dominique

    2012-01-01

    To determine whether insulin tolerance tests (ITTs), arginine stimulation tests (ASTs), and glucagon stimulation tests (GST) identify patients who have similar clinical features of growth hormone (GH) deficiency when a diagnostic GH threshold of 3 μg/L is used.......To determine whether insulin tolerance tests (ITTs), arginine stimulation tests (ASTs), and glucagon stimulation tests (GST) identify patients who have similar clinical features of growth hormone (GH) deficiency when a diagnostic GH threshold of 3 μg/L is used....

  15. Cycling Exercise with Electrical Stimulation of Antagonist Muscles Increases Plasma Growth Hormone and IL-6.

    Science.gov (United States)

    Omoto, Masayuki; Matsuse, Hiroo; Hashida, Ryuki; Takano, Yoshio; Yamada, Shin; Ohshima, Hiroshi; Tagawa, Yoshihiko; Shiba, Naoto

    2015-11-01

    Performing aerobics and resistance exercise at exactly the same time has not been available although combining both types of exercise in one training program has been attempted. The hybrid training system (HTS) is a resistance exercise that combines voluntary concentric muscle contractions with electrically stimulated eccentric muscle contractions. We devised an exercise technique using HTS on a cycle ergometer (HCE). Growth hormone (GH) and lactate are indicators of adequate training intensity. Interleukin-6 (IL-6) reflects enhancing lipid metabolism. The purpose of this study was to show that HCE provides sufficient exercise to stimulate the secretion of GH, lactate and IL-6. We compared an HCE test with cycle ergometer alone (CE). Ten healthy male subjects performed HCE and CE tests for 30 minutes each. The workload of both tests was set the same at 40% of each subject's peak oxygen uptake. For HCE, 2-minute HTS and 1-minute rest intervals were repeated. GH, lactate, and IL-6 were evaluated before and immediately after exercise, and at 15, 30 and 60 minutes. GH and lactate increased immediately after HCE. Moreover, the degree of the increases in GH after HCE (0 and 15 minutes) was higher than that after CE. IL-6 increased after HCE at 30 min, and the rate of change was higher than for CE. These results showed that HCE was more efficient in stimulating acute increases in GH, lactate and IL-6 than CE at the same workload. We may be able to combine electrically stimulated resistance exercise with aerobic exercise using HCE.

  16. Impact of preoperative hormonal stimulation on postoperative complication rates after hypospadias repair: a meta-analysis.

    Science.gov (United States)

    Chao, Min; Zhang, Yin; Liang, Chaozhao

    2017-06-01

    To improve the surgical outcome of hypospadias repair surgery, preoperative hormonal stimulation (PHS) has been proposed. We conducted a meta-analysis to evaluate the impact of preoperative hormonal stimulation (PHS) treatment on complication rates following hypospadias repair surgery. A comprehensive literature search up to June 1st, 2015 was carried out for relevant studies. After literature identification and data extraction, relative ratio (RR) was calculated to compare postoperative complication rates. Heterogeneity among individual studies was tested using the Cochran χ2 Q test and quantified by calculating the I2 index. Meta-regression was applied to find potential affective factors. Overall, 428 patients from 6 studies had undergone primary hypospadias repair, of which 171 (39.95%) received some form of PHS with human chorionic gonadotropin (HCG), dihydrotestosterone (DHT) or testosterone (T). They underwent three different types of surgical techniques, including onlay island flap (N.=277), tubularized incised plate (N.=99) and Koyanagi urethroplasty (N.=52). These 6 studies classified the complication rates based on PHS. The relative ratio (RR) for a complication occurring following PHS use was 1.18 (95% CI: 0.70-2.00, Z=0.91, P=0.539). Significant heterogeneity (I2=47.1%, P=0.092) among various research literature was found and meta-regression was undertaken for the heterogeneity, but surgical technique, mean age of patients at time of surgery, types of PHS and the quality of studies were not the cause of heterogeneity. Use of T, DHT and HCG prior to hypospadias repair does not appear to increase the incidence of postoperative complications, but further investigation is needed.

  17. Relationship between thyroid stimulating hormone and various components of metabolic syndrome

    International Nuclear Information System (INIS)

    Majeed, S.; Hashim, R.

    2015-01-01

    To determine the relation between thyroid stimulating hormone and various components of metabolic syndrome. Study Design: Descriptive cross-sectional study. Place and Duration of Study: Pathology department, Army Medical College of National University of Sciences and Technology (NUST) Islamabad and Military Hospital (MH), Rawalpindi, Pakistan; from January to March 2013. Material and Methods: Hundred adult inhabitants (30-60 years) of Rawalpindi participated in this study. Subjects who fulfilled the WHO criteria for metabolic syndrome (MetS) were included and those who had any thyroid illness, or were using any thyroid medications were excluded from this study. For thyroid function tests (TFT's), serum thyroid stimulating hormone (TSH), total tri-iodothyronine (TT3), free throxine (FT4) were estimated. Insulin resistance (IR) was measured by Homeostasis Model Assessment for IR (HOMA-IR). Data was analyzed by SPSS-18. Results: Out of 50 subjects of control group, 26 (52%) were male and 24 (48%) were female. Basal metabolic rate (BMI), serum triglyceride (TG), HOMA-IR were higher and serum high density lipoprotein cholesterol (HDL-c) was lower in MetS patients. There was no significant difference in serum TT3 and FT4 between MetS patients and control group, however, mean serum TSH levels were higher in MetS (2.622 + 0.924 vs 5.002 + 1.074 mIU/l, p<0.001). In correlation analysis, serum TSH was positively and significantly correlated with BMI (r=0.344, p=0.014) and HOMA-IR (r=0.419, p<0.002). Conclusion: These results suggest that serum TSH correlates with various components of metabolic syndrome patients. Analysis of serum TSH levels in metabolic syndrome patients may prove beneficial in preventing the various cardiometabolic complications in such patients. (author)

  18. Effects of Exercise on B-Endorphin and Follicle Stimulating Hormone Levels among Female Army Officer

    Directory of Open Access Journals (Sweden)

    Ruqaiyah Ruqaiyah

    2014-06-01

    Material and Methods: Fourty six healthy female army officer volunteered for the study. All of them gave written consent regarding their participation. The subjects were categorized in two groups: high-intensity exercise (HE, 23 subjects and non exercise (NE, 23 subjects. The inclusion criteria were amenorrhea, no consumption of reproductive hormonal, age between 21-40 years, and not involved in diet programme, while the exclusion criteria were any factors that could interfere with normality. High intensity-exercise was performed chronically by running for between 1953-3200 meter, three times per day, 6 days per weeks, for 7 months. Serum beta-endorphin was measured immunoenzymatically using an ELISA method. FSH serum was measured by chemiluminescence method. Results: Age, body weight, height and onset of menarchee were not significantly different between group (P > 0.05. High-intensity exercise significantly increase the B -endorphin level compared to the control (P 0.01. The level of FSH significantly decrease in the HE group than that the NE group (P 0.01. Conclusion: In conclusion, the high-intensitiy exercise on among female army officer can increase B-endorphin and decrease follicle stimulating hormone level. [Cukurova Med J 2014; 39(3.000: 496-500

  19. Do Thyroxine and Thyroid-Stimulating Hormone Levels Reflect Urinary Iodine Concentrations?

    Science.gov (United States)

    Soldin, Offie P.; Tractenberg, Rochelle E.; Pezzullo, John C.

    2013-01-01

    The toxicity of environmental chemicals such as nitrates, thiocynates, and perchlorates, some therapeutics, and dietary goitrogens can lower thyroidal iodine uptake and result in hypothyroidism and goiter. Iodine sufficiency, essential for normal thyroid hormone synthesis, is critical during gestation to assure that sufficient thyroxine (T4) and iodine reach the developing fetus. Spot urinary iodide (UI) measurements are used globally to indicate and monitor iodine sufficiency of populations. In individuals, however, UI are not routinely measured; instead, normal serum thyroid-stimulating hormone (TSH) and T4 concentrations serve as surrogate indicators of iodine sufficiency as well as thyroidal health. Our objective was to examine the relationship between UI concentrations and serum T4 and TSH concentrations in individuals in an ‘‘iodine-sufficient population.’’ Using a cross-sectional sample of the US population (n = 7628) from the National Health and Nutrition Examination Survey (NHANES III; 1988–1994) database, we examined the relationship among UI, T4, and TSH in pregnant and nonpregnant women and in men (15–44 years). There was a lack of relationship between UI (or UI/Cr) concentrations and serum T4 or TSH concentrations. Therefore, TSH and T4 are not appropriate markers of UI concentrations in this population. Monitoring the status of iodine nutrition of individuals in the United States may be important because serum TSH and T4 concentrations do not indicate low iodine status. PMID:15795649

  20. Population Pharmacokinetic Modelling of FE 999049, a Recombinant Human Follicle-Stimulating Hormone, in Healthy Women After Single Ascending Doses

    OpenAIRE

    Rose, Trine H?yer; R?shammar, Daniel; Erichsen, Lars; Grundemar, Lars; Ottesen, Johnny T.

    2016-01-01

    Objective The purpose of this analysis was to develop a population pharmacokinetic model for a novel recombinant human follicle-stimulating hormone (FSH) (FE 999049) expressed from a human cell line of foetal retinal origin (PER.C6?) developed for controlled ovarian stimulation prior to assisted reproductive technologies. Methods Serum FSH levels were measured following a single subcutaneous FE 999049 injection of 37.5, 75, 150, 225 or 450?IU in 27 pituitary-suppressed healthy female subjects...

  1. Ovarian stimulation with follicle-stimulating hormone under increasing or minimal concentration of progesterone in dairy cows.

    Science.gov (United States)

    El-Sherry, T M; Matsui, M; Kida, K; Miyamoto, A; Megahed, G A; Shehata, S H; Miyake, Y-I

    2010-03-01

    The objective of this study was to investigate the effect of the presence or absence of Corpus luteum (CL) on the follicular population during superstimulation in dairy cows (Holstein-Friesian cattle). Animals were divided into two groups as follows: (1) Growing CL group (G1): Cows (n=7) received a total dose of 28 Armour units (AU) follicle-stimulating hormone (FSH) through the first 4 d (twice daily) after spontaneous ovulation (Day 0). (2) CL Absence group (G2): Cows (n=10) received prostaglandin F(2alpha) (PGF(2alpha)) at 9 or 10 d after ovulation. After 36h, all the follicles (larger than 5mm) were aspirated (Day 0). The FSH treatment started 24h after aspiration and continued for 4 d. The number of small (3 to or = 8mm) follicles was examined on Days 1, 3, and 5 in all groups. Blood samples were collected daily for 5 d, and progesterone (P(4)), estradiol (E(2)), insulin-like growth factor-1 (IGF-1), and growth hormone (GH) in plasma were measured by enzyme immunoassays. The results showed that in G1, the P(4) level increased gradually from 0.5 ng/mL at Day 1 to 2 ng/mL at Day 5, whereas in G2, the P(4) level was completely below 0.5 ng/mL. All cows of the G2 group showed an increase of E(2) at Day 3 or Day 4 followed by an increase of IGF-1 within 24h, while GH increased concomitantly with the E(2) increase in 8 of 10 trials. On the other hand, cows of the G1 group showed neither E(2) nor IGF-1 increase. Moreover, at the end of the treatment, the number of follicles in the G2 group was significantly increased compared with that of the G1 group (22.8+/-2.0 vs. 11.6+/-2.0). In conclusion, low P(4) level during FSH treatment enhanced multiple follicular growth and E(2) secretion, which was followed by increase of IGF-1 and GH. Therefore, the absence of the CL may play a critical role in the superovulation response by controlling the number of growing follicles. Copyright 2010 Elsevier Inc. All rights reserved.

  2. Selective use of corifollitropin for controlled ovarian stimulation for IVF in patients with low anti-Müllerian hormone

    DEFF Research Database (Denmark)

    Nielsen, Anna Pors; Korsholm, Anne-Sofie; Lemmen, Josephine G.

    2016-01-01

    Corifollitropin, a long-acting follicle-stimulating hormone (FSH) analogue used for in vitro fertilization (IVF), does not allow individualization of dosage, and the ovarian response is similar to around 300 IU of daily recombinant FSH. This has raised concerns about the risk of ovarian hyperstim...

  3. First-trimester maternal serum human thyroid-stimulating hormone in chromosomally normal and Down syndrome pregnancies

    NARCIS (Netherlands)

    Pratt, JJ; de Wolf, BTHM; Mantingh, A

    Maternal serum human thyroid-stimulating hormone (TSH) levels were investigated in chromosomally normal and Down syndrome pregnancies to determine whether TSH can be used as a marker for Down syndrome in the first trimester. Measurements were conducted on stored serum samples collected from 23 Down

  4. INTERVENSI FOLICLE STIMULATING HORMONE (FSH DALAM PROSES REMATURASI INDUK IKAN GABUS HARUAN Channa Striata Blkr DIDALAM WADAH BUDIDAYA

    Directory of Open Access Journals (Sweden)

    Akhmad Ridha Fani

    2016-06-01

    Full Text Available Snakehead and other fish species in waters of the swamp doing spawning at the beginning or in the middle of the rainy season. Gonadal maturation process so as to return time is limited. Aquaculture development is highly dependent on the availability of seeds that meet the timeliness, quality and quantity. The seeds can be produced continuously if supported by the availability of mature broodstock with good quality eggs. Some research about the role of hormones and or the use of stimulants to the success in support of gonad development and spawning, such as; Siam Jambal fish, Pangasius hypophthalmus (Ernawati 1999, Catfish, Clarias batrachus (Zairin et al. 2001, and catfish, Hemibagrus nemurus (Supriyadi 2005. By because they were with potential memamfaatkan folicle Stimulating Hormone (FSH that serves as the control at the start of the reproductive cycle up to ovulation and spermiasi in fish. The aim of this study was to determine the effect of the injection folicle Stimulating Hormone (FSH in the parent rematurisasi catfish. Results from the start 17007-52327 item, 0,63-1,07mm egg diameter, IGS range of 4, 13 to 8.50%, and ranged from 0.86 2.4% IHS. Based on the results of the study injection folicle Stimulating Hormone (FSH capable mepersingkat rematurasi processing time.

  5. Increased nuclear tri-iodothyronine binding and thyroid hormone-stimulated glucose consumption in mononuclear blood cells from patients with liver cirrhosis

    DEFF Research Database (Denmark)

    Kvetny, J; Matzen, L

    1991-01-01

    between the groups, but thyroid hormone-stimulated oxygen consumption was depressed in cells from patients with AC (P less than 0.05) compared with patients with LC and with controls. We conclude that both thyroid hormone-stimulated glucose consumption and T3 nuclear receptor binding in cells from...

  6. Effect of Intravenous or Perivascular Injection of Synthetic Adrenocorticotropic Hormone on Stimulation Test Results in Dogs.

    Science.gov (United States)

    Johnson, C M; Kass, P H; Cohen, T A; Feldman, E C

    2017-05-01

    Standard protocols for adrenocorticotropic hormone (ACTH) stimulation testing (ACTHst) often involve intravenous (IV) injection of corticotropin. ACTH might be unintentionally injected into the perivascular (PV) space. To compare stimulation test results after IV and PV injections of ACTH. Twenty privately owned dogs were studied: 10 healthy and 10 with trilostane-treated naturally occurring hyperadrenocorticism (HAC). Prospective study. Each of 20 dogs underwent 2 ACTHst not dogs had an IV ACTHst first and PV second; 5 healthy and 5 HAC dogs had a PV ACTHst first and IV second. Blood samples for measurement of serum cortisol concentration were collected before and 1 hour after ACTH administration. No significant difference in results was demonstrated when comparing serum cortisol concentrations after IV and PV ACTH administration in all 20 dogs (median μg/dL; interval μg/dL: 8.2; 1.4-17.4 versus 7.8; 0.9-16.9; P = .23). No significant difference in results was demonstrated when comparing serum cortisol concentrations after IV and PV ACTH administration in the 10 healthy dogs (median μg/dL; interval μg/dL: 10.9; 7.3-17.4 versus 10.6; 7.1-16.9; P = .54) or in the 10 HAC dogs (median μg/dL; interval μg/dL: 6.3; 1.4-8.6 versus 5.2; 0.9-8.7; P = .061). Perivascular administration of ACTH does not significantly alter stimulation test results in healthy dogs or in dogs with HAC undergoing therapy with trilostane. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  7. Human growth hormone binding and stimulation of insulin biosynthesis in cloned rat insulinoma cells

    DEFF Research Database (Denmark)

    Billestrup, Nils

    1985-01-01

    Binding of 125I labelled human growth hormone to cloned insulin producing RIN-5AH cells is described. Binding was specific for somatotropic hormones since both human and rat growth hormone could compete for binding sites, whereas much higher concentrations of lactogenic hormones were needed...

  8. Therapeutic Efficacy of a {sup 188}Re-Labeled {alpha}-Melanocyte-Stimulating Hormone Peptide Analog in Murine and Human Melanoma-Bearing Mouse Models

    Energy Technology Data Exchange (ETDEWEB)

    Miao, Yubin; Owen, Nellie K.; Fisher, Darrell R.; Hoffman, Timothy J.; Quinn, Thomas P.

    2005-01-01

    The purpose of this study was to examine the therapeutic efficacy of {sup 188}Re-(Arg{sup 11})CCMSH in the B16/F1 murine melanoma and TXM13 human melanoma bearing mouse models. Method: (Arg11)CCMSH was synthesized and labeled with {sup 188}Re to form {sup 188}Re-(Agr{sup 11})CCMSH. B16/F1 melanoma tumor bearing mice were administrated with 200 Ci, 600 Ci and 2x400 Ci of {sup 188}Re-(Arg{sup 11})CCMSH via the tail vein, respectively. TXM13 melanoma tumor hearing mice were separately injected with 600 Ci, 2x400 Ci and 1000 Ci of 100Re-(Arg{sup 11})CCMSH through the tail vein. Two groups of 10 mice bearing either B16/F1 or TXM13 tumors were injected with saline as untreated controls. Results: In contrast to the untreated control group, {sup 188}Re(Arg11)CCMSH yielded rapid and lasting therapeutic effects in the treatment groups with either B16/F1 or TXM13 tumors. The tumor growth rate was reduced and the survival rate was prolonged in the treatment groups. Treatment with 2x400 Ci of {sup 188}Re-Arg{sup 11}CCMSH significantly extended the mean life of B16/F1 tumor mice (p<0.05), while the mean life of TXm13 tumor mice was significantly prolonged after treatment with 600 Ci and 1000 Ci doses of {sup 188}Re-(Arg{sup 11})CCMSH (p<0.05 High-dose {sup 188}Re-(Arg{sup 11}))CCMSH produced no observed normal-tissue toxicity. Conclusions: The therapy study results revealed that {sup 188}Re-Arg11 CCMSH yielded significant therapeutic effects in both B16/F1 murine melanoma and TXM13 human melanoma bearing mouse models. {sup 188}Re-(Arg{sup 11})CCMSH appears to be a promising radiolabeled peptide for targeted radionuclide therapy of melanoma.

  9. Tumor-targeting properties of {sup 90}Y- and {sup 177}Lu-labeled {alpha}-melanocyte stimulating hormone peptide analogues in a murine melanoma model

    Energy Technology Data Exchange (ETDEWEB)

    Miao Yubin [Department of Internal Medicine, University of Missouri-Columbia, Columbia, MO 65211 (United States) and Department of Biochemistry, University of Missouri-Columbia, Columbia, MO 65211 (United States); Harry S. Truman Memorial Veteran Hospital, Columbia, MO 65201 (United States)]. E-mail: miaoy@missouri.edu; Hoffman, Timothy J. [Department of Internal Medicine, University of Missouri-Columbia, Columbia, MO 65211 (United States); Harry S. Truman Memorial Veteran Hospital, Columbia, MO 65201 (United States); Quinn, Thomas P. [Department of Biochemistry, University of Missouri-Columbia, Columbia, MO 65211 (United States); Harry S. Truman Memorial Veteran Hospital, Columbia, MO 65201 (United States); Department of Radiology, University of Missouri-Columbia, Columbia, MO 65211 (United States)

    2005-07-01

    The purpose of this study was to compare the tumor-targeting properties of {sup 90}Y-DOTA-Re(Arg{sup 11})CCMSH and {sup 177}Lu-DOTA-Re(Arg{sup 11})CCMSH in a murine melanoma mouse model. Methods: The in vitro properties of cellular internalization and retention of {sup 90}Y-DOTA-Re(Arg{sup 11})CCMSH and {sup 177}Lu-DOTA-Re(Arg{sup 11})CCMSH were studied in B16/F1 murine melanoma cells. The pharmacokinetics of {sup 90}Y-DOTA-Re(Arg{sup 11})CCMSH and {sup 177}Lu-DOTA-Re(Arg{sup 11})CCMSH were determined in B16/F1 melanoma-bearing C57 mice. Results: {sup 90}Y-DOTA-Re(Arg{sup 11})CCMSH and {sup 177}Lu-DOTA-Re(Arg{sup 11})CCMSH exhibited fast cellular internalization and extended cellular retention in B16/F1 cells. High receptor-mediated tumor uptake and retention coupled with fast whole-body clearance of {sup 90}Y-DOTA-Re(Arg{sup 11})CCMSH and {sup 177}Lu-DOTA-Re(Arg{sup 11})CCMSH were demonstrated in B16/F1 tumor-bearing C57 mice. The tumor uptakes of {sup 90}Y-DOTA-Re(Arg{sup 11})CCMSH and {sup 177}Lu-DOTA-Re(Arg{sup 11})CCMSH were 25.70{+-}4.64 and 14.48{+-}0.85 %ID/g at 2 h, and 14.09{+-}2.73 and 17.68{+-}3.32 %ID/g at 4 h postinjection. There was little activity accumulated in normal organs except for kidney. Conclusions: High tumor-targeting properties of {sup 90}Y-DOTA-Re(Arg{sup 11})CCMSH and {sup 177}Lu-DOTA-Re(Arg{sup 11})CCMSH highlighted their potential as radiopharmaceuticals for targeted radionuclide therapy of melanoma in further investigations.

  10. Chick subcutaneous and abdominal adipose tissue depots respond differently in lipolytic and adipogenic activity to α-melanocyte stimulating hormone (α-MSH).

    Science.gov (United States)

    Shipp, Steven L; Wang, Guoqing; Cline, Mark A; Gilbert, Elizabeth R

    2017-07-01

    In birds, α-MSH is anorexigenic, but effects on adipose tissue are unknown. Four day-old chicks were intraperitoneally injected with 0 (vehicle), 5, 10, or 50μg of α-MSH and subcutaneous and abdominal adipose tissue collected at 60min for RNA isolation (n=10). Plasma was collected post-euthanasia at 60 and 180min for measuring non-esterified fatty acids (NEFA) and α-MSH (n=10). Relative to the vehicle, food intake was reduced in the 50μg-treated group. Plasma NEFAs were greater in 10μg than vehicle-treated chicks at 3h. Plasma α-MSH was 3.06±0.57ng/ml. In subcutaneous tissue, melanocortin receptor 5 (MC5R) mRNA was increased in 10μg, MC2R and CCAAT-enhancer-binding protein β (C/EBPβ) mRNAs increased in 50μg, peroxisome proliferator-activated receptor γ and C/EBPα decreased in 5, 10 and 50μg, and Ki67 mRNA decreased in 50μg α-MSH-injected chicks, compared to vehicle-injected chicks. In abdominal tissue, adipose triglyceride lipase mRNA was greater in 10μg α-MSH- than vehicle-treated chicks. Cells isolated from abdominal fat that were treated with 10 and 100nM α-MSH for 4h expressed more MC5R and perilipin-1 than control cells (n=6). Cells that received 100nM α-MSH expressed more fatty acid binding protein 4 and comparative gene identification-58 mRNA than control cells. Glycerol-3-phosphate dehydrogenase (G3PDH) activity was greater in cells at 9days post-differentiation that were treated with 1 and 100nM α-MSH for 4h than in control cells (n=3). Results suggest that α-MSH increases lipolysis and reduces adipogenesis in adipose tissue. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Tumor-targeting properties of 90Y- and 177Lu-labeled α-melanocyte stimulating hormone peptide analogues in a murine melanoma model

    International Nuclear Information System (INIS)

    Miao Yubin; Hoffman, Timothy J.; Quinn, Thomas P.

    2005-01-01

    The purpose of this study was to compare the tumor-targeting properties of 90 Y-DOTA-Re(Arg 11 )CCMSH and 177 Lu-DOTA-Re(Arg 11 )CCMSH in a murine melanoma mouse model. Methods: The in vitro properties of cellular internalization and retention of 90 Y-DOTA-Re(Arg 11 )CCMSH and 177 Lu-DOTA-Re(Arg 11 )CCMSH were studied in B16/F1 murine melanoma cells. The pharmacokinetics of 90 Y-DOTA-Re(Arg 11 )CCMSH and 177 Lu-DOTA-Re(Arg 11 )CCMSH were determined in B16/F1 melanoma-bearing C57 mice. Results: 90 Y-DOTA-Re(Arg 11 )CCMSH and 177 Lu-DOTA-Re(Arg 11 )CCMSH exhibited fast cellular internalization and extended cellular retention in B16/F1 cells. High receptor-mediated tumor uptake and retention coupled with fast whole-body clearance of 90 Y-DOTA-Re(Arg 11 )CCMSH and 177 Lu-DOTA-Re(Arg 11 )CCMSH were demonstrated in B16/F1 tumor-bearing C57 mice. The tumor uptakes of 90 Y-DOTA-Re(Arg 11 )CCMSH and 177 Lu-DOTA-Re(Arg 11 )CCMSH were 25.70±4.64 and 14.48±0.85 %ID/g at 2 h, and 14.09±2.73 and 17.68±3.32 %ID/g at 4 h postinjection. There was little activity accumulated in normal organs except for kidney. Conclusions: High tumor-targeting properties of 90 Y-DOTA-Re(Arg 11 )CCMSH and 177 Lu-DOTA-Re(Arg 11 )CCMSH highlighted their potential as radiopharmaceuticals for targeted radionuclide therapy of melanoma in further investigations

  12. Endocannabinoids Stimulate Human Melanogenesis via Type-1 Cannabinoid Receptor*

    Science.gov (United States)

    Pucci, Mariangela; Pasquariello, Nicoletta; Battista, Natalia; Di Tommaso, Monia; Rapino, Cinzia; Fezza, Filomena; Zuccolo, Michela; Jourdain, Roland; Finazzi Agrò, Alessandro; Breton, Lionel; Maccarrone, Mauro

    2012-01-01

    We show that a fully functional endocannabinoid system is present in primary human melanocytes (normal human epidermal melanocyte cells), including anandamide (AEA), 2-arachidonoylglycerol, the respective target receptors (CB1, CB2, and TRPV1), and their metabolic enzymes. We also show that at higher concentrations AEA induces normal human epidermal melanocyte apoptosis (∼3-fold over controls at 5 μm) through a TRPV1-mediated pathway that increases DNA fragmentation and p53 expression. However, at lower concentrations, AEA and other CB1-binding endocannabinoids dose-dependently stimulate melanin synthesis and enhance tyrosinase gene expression and activity (∼3- and ∼2-fold over controls at 1 μm). This CB1-dependent activity was fully abolished by the selective CB1 antagonist SR141716 or by RNA interference of the receptor. CB1 signaling engaged p38 and p42/44 mitogen-activated protein kinases, which in turn activated the cyclic AMP response element-binding protein and the microphthalmia-associated transcription factor. Silencing of tyrosinase or microphthalmia-associated transcription factor further demonstrated the involvement of these proteins in AEA-induced melanogenesis. In addition, CB1 activation did not engage the key regulator of skin pigmentation, cyclic AMP, showing a major difference compared with the regulation of melanogenesis by α-melanocyte-stimulating hormone through melanocortin 1 receptor. PMID:22431736

  13. Substance P stimulates Growth Hormone (GH) and GH-Releasing Hormone (GHRH) secretions through tachykinin NK2 receptors in sheep.

    Science.gov (United States)

    Lemamy, Guy-Joseph; Guillaume, Viviane; Ndéboko, Bénédicte; Mouecoucou, Justine; Oliver, Charles

    2012-05-01

    Substance P is ubiquitous undecapeptide belonging to the tachykinins family. It has been found in the hypothalamus and is involved in the hypothalamo-hypophysial axis in several mammals, including human. Previous studies have shown that substance P increases GH secretions in rats and human. In this study, we have shown that intravenously infused substance P in sheep caused an increased level of Growth Hormone (GH) and GH-Releasing Hormone (GHRH), and decreased Somatotropin Release Inhibiting Hormone (SRIH) secretions. GH was obtained from peripheral blood. GHRH and SRIH were directly collected from hypophysial portal blood, using a trans-nasal surgery technique in a vigil sheep that allowed accessing to hypothalamo-hypophysial portal vessels. Hormones assays were performed by radioimmunoassay (RIA). Moreover, we showed that substance P-induced GH and GHRH secretion appears to be mediated by NK2 tachykinin receptors, since it is specifically blocked by a non peptidic tachykinin NK2 receptor antagonist (SR48968, Sanofi, Montpellier, France) whereas a non peptidic tachykinin NK1 antagonist (SR140333, Sanofi, Montpellier, France) failed to modify GH and GHRH hormones secretions. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Neonatal thyroid-stimulating hormone concentration and psychomotor development at preschool age.

    Science.gov (United States)

    Trumpff, Caroline; De Schepper, Jean; Vanderfaeillie, Johan; Vercruysse, Nathalie; Van Oyen, Herman; Moreno-Reyes, Rodrigo; Tafforeau, Jean; Vandevijvere, Stefanie

    2016-12-01

    Thyroid hormones are essential for normal brain development. The aim of this study is to assess if high concentration of thyroid stimulating hormone (TSH) that is below the clinical threshold (5-15 mIU/L) at neonatal screening is linked to psychomotor development impairments in the offspring at preschool age. A total of 284 Belgian preschool children 4-6 years old and their mothers were included in the study. The children were randomly selected from the total list of neonates screened in 2008, 2009 and 2010 by the Brussels newborn screening centre. The sampling was stratified by gender and TSH range (0.45-15 mIU/L). Infants with congenital hypothyroidism (>15 mIU/L), low birth weight and/or prematurity were excluded. Psychomotor development was assessed using the Charlop-Atwell scale of motor coordination. The iodine status of children was determined using median urinary iodine concentration. Socioeconomic, parental and child potential confounding factors were measured through a self-administered questionnaire. TSH level was not significantly associated with total motor score (average change in z-score per unit increase in TSH is 0.02 (-0.03, 0.07), p=0.351), objective motor score (p=0.794) and subjective motor score (p=0.124). No significant associations were found using multivariate regression model to control confounding factors. Mild thyroid dysfunction in the newborn-reflected by an elevation of TSH that is below the clinical threshold (5-15 mIU/L)-was not associated with impaired psychomotor development at preschool age. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  15. Penggunaan Follicle Stimulating Hormone dan Pregnant Mare Serum Gonadotrophin untuk Superovulasi pada Sapi Persilangan Brahman

    Directory of Open Access Journals (Sweden)

    Adrian

    2009-12-01

    Full Text Available Twenty cattle were used in this experiment to determine the effect of administration follicle stimulating hormone (FSH and pregnant mare serum gonadotrophin (PMSG hormones on superovulation of Brahman cross cattle. The experiment was designed into completely randomized design with 5 treatments as follows. Treatments 1 (T1: 4 mg of FSH was injected twice a day intra-ovary, T2: 8 mg of FSH was injected twice a day intra-ovary, T3: 300 IU of PMSG was injected single dose intra-ovary, T4: 600 IU of PMSG was injected single dose intra-ovary, T5: 40 mg of FSH was injected intramuscular. All experimental cattle were oestrus synchronized using 15 mg of PGF2α twice at 11-days intervals. Number of corpus luteum (CL was detected by rectal palpation at day-7 after artificial insemination. Results showed that 19 cattle (95% indicated oestrus sign. Eleven cattle (57.9% showed oestrus sign 2 days after PGF2α injection and the rest 8 cattle (42.1% oestrus sign was detected at 3 days after PGF2α injection. FSH and PMSG treatments increased significantly (P<0.05 number of CL. The highest CL number was found in T5, meanwhile number of CL in T2 and T4 were higher compared to T1 and T3. The average treatment effect could produce 6.8±5.42 CL with range 2–26 CL. On the other hand single dose treatment of 600 IU PMSG (T4 showed high significant number of non ovulatory (persistent follicle compared to other treatments (T1, T2, T3 and T5 on average number of persistent follicle 2.0±1.97 from 19 cattles. It is concluded that the best superovulation treatment was produced by injection 40 mg of FSH intra-musculary.

  16. Leptin Is Produced by Parathyroid Glands and Stimulates Parathyroid Hormone Secretion.

    Science.gov (United States)

    Hoang, Don; Broer, Niclas; Sosa, Julie A; Abitbol, Nathalie; Yao, Xiaopan; Li, Fangyong; Rivera-Molina, Felix; Toomre, Derek K; Roman, Sanziana A; Sue, Gloria; Kim, Samuel; Li, Alexander Y; Callender, Glenda G; Simpson, Christine; Narayan, Deepak

    2017-12-01

    We asked if leptin and its cognate receptor were present in normal and diseased parathyroid glands, and if so, whether they had any functional effects on parathyroid hormone (PTH) secretion in parathyroid neoplasms. The parathyroid glands acting through PTH play a critical role in the regulation of serum calcium. Based on leptin's recently discovered role in bone metabolism, we hypothesized these glands were the sites of a functional interaction between these 2 hormones. From July 2010 to July 2011, 96 patients were enrolled in a prospective study of leptin and hyperparathyroidism, all of whom were enrolled based on their diagnosis of hyperparathyroidism, and their candidacy for surgical intervention provided informed consent. Immediately after parathyroidectomy, 100 to 300 mg of adenomatous or hyperplastic diseased parathyroid tissue was prepared and processed according to requirements of the following: in situ hybridization, immunohistochemistry, immunofluorescence by conventional and spinning disc confocal microscopy, electron microscopy, parathyroid culture, whole organ explant, and animal model assays. Leptin, leptin receptor (long isoform), and PTH mRNA transcripts and protein were detected in an overlapping fashion in parathyroid chief cells in adenoma and hyperplastic glands, and also in normal parathyroid by in situ hybridization, qRT-PCR, and immunohistochemistry. Confocal microscopy confirmed active exogenous leptin uptake in cultured parathyroid cells. PTH secretion in explants increased in response to leptin and decreased with leptin receptor signaling inhibition by AG490, a JAK2/STAT3 inhibitor. Ob/ob mice injected with mouse leptin exhibited increased PTH levels from baseline. Taken together, these data suggest that leptin is a functionally active product of the parathyroid glands and stimulates PTH release.

  17. Congenital melanocytic nevi management: question

    Directory of Open Access Journals (Sweden)

    Stefania Guida

    2016-03-01

    Full Text Available A 12-year-old girl presented to our attention for a pigmented lesion having greatest diameter of 2.5 cm, located on her left forehead, involving the ipsilateral eyebrow. This lesion had appeared as a flat brown macule at birth. With passing years, the lesion showed an increased diameter and thickness and it became progressively darker.1. What reasons can justify the excision of congenital melanocytic nevi?2. Which treatment do you think would be more appropriate?3. Is there a right age to remove a congenital melanocytic nevus?

  18. Bilateral diffuse uveal melanocytic proliferation

    DEFF Research Database (Denmark)

    Klemp, Kristian; Kiilgaard, Jens Folke; Heegaard, Steffen

    2017-01-01

    Bilateral diffuse uveal melanocytic proliferation (BDUMP) is a rare paraneoplastic intraocular disease that causes progressive visual loss in patients driven by an IgG factor associated with an underlying malignancy. Characteristic ocular findings include exudative retinal detachment, rapid...... cataract formation and uveal melanocytic tumours. The awareness and documentation of BDUMP has increased during the past decade, and the increasing amount of data collected demonstrates the effect of treatment with plasmapheresis and the value of diagnostic tools in BDUMP such as genetic and immunologic...

  19. Thyroid-stimulating hormone, anti-thyroid antibodies, and pregnancy outcomes.

    Science.gov (United States)

    Plowden, Torie C; Schisterman, Enrique F; Sjaarda, Lindsey A; Perkins, Neil J; Silver, Robert; Radin, Rose; Kim, Keewan; Galai, Noya; DeCherney, Alan H; Mumford, Sunni L

    2017-12-01

    Overt thyroid dysfunction has been associated with adverse obstetric outcomes. However, less is known regarding subclinical hypothyroidism or thyroid autoimmunity and their relationship to pregnancy complications. The purpose of this study was to examine the association between prepregnancy anti-thyroid antibodies and subclinical hypothyroidism and preterm delivery, gestational diabetes mellitus, and preeclampsia. We conducted a secondary analysis of a prospective cohort of 18- to 40-year-old women with 1-2 previous pregnancy losses (n=1193) who participated in a multicenter randomized, placebo-controlled trial of low-dose aspirin. Prepregnancy levels of thyroid-stimulating hormone, free thyroxine, thyroglobulin antibody, and thyroid peroxidase antibody were measured. Relative risks and 95% confidence intervals were estimated with the use of generalized linear models with adjustment for age and body mass index. Among women with an ongoing pregnancy of >20 weeks estimated gestational age, there was no association between prepregnancy thyroid-stimulating hormone level (>2.5 vs ≤2.5 mIU/L) and preterm delivery (adjusted relative risk, 0.77; 95% confidence interval, 0.40-1.47), gestational diabetes mellitus (adjusted relative risk, 1.28; 95% confidence interval, 0.54-3.04), or preeclampsia (adjusted relative risk, 1.20; 95% confidence interval, 0.71-2.04). Similarly, among women with thyroid antibodies, there was no increase in the likelihood of preterm delivery (relative risk, 1.26; 95% confidence interval, 0.65-2.45), gestational diabetes mellitus (relative risk, 1.33; 95% confidence interval, 0.51-3.49), or preeclampsia (relative risk, 1.02; 95% confidence interval, 0.54-1.92), compared with women without these antibodies. Among women with 1-2 previous pregnancy losses, subclinical hypothyroidism and thyroid autoimmunity were not associated with an increased risk of preterm delivery, gestational diabetes mellitus, or preeclampsia. These data support current

  20. Metastatic Follicular Thyroid Carcinoma Secreting Thyroid Hormone and Radioiodine Avid without Stimulation: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Syed A. Abid

    2014-01-01

    Full Text Available Introduction. This is an extremely rare case of a patient with metastatic follicular thyroid cancer who continued to produce thyroid hormone and was iodine scan positive without stimulation after thyroidectomy and radioiodine (I-131 therapy. Patient Findings. A 76-year-old Caucasian male was diagnosed with metastatic follicular thyroid carcinoma on lung nodule biopsy. Total thyroidectomy was performed and he was ablated with 160 mCi of I-131 after recombinant human thyrotropin (rhTSH stimulation. Whole body scan (WBS after treatment showed uptake in bilateral lungs, right sacrum, and pelvis. The thyroglobulin decreased from 2,063 to 965 four months after treatment but rapidly increased to 2,506 eleven months after I-131. Thyroid stimulating hormone (TSH remained suppressed and free T4 remained elevated after I-131 therapy without thyroid hormone supplementation. He was treated with an additional 209 mCi with WBS findings positive in lung and pelvis. Despite I-131, new metastatic lesions were noted in the left thyroid bed and large destructive lesion to the first cervical vertebrae four months after the second I-131 dose. Conclusions. This case is exceptional because of its rarity and also due to the dissociation between tumor differentiation and aggressiveness. The metastatic lesions continued to secrete thyroid hormone and remained radioiodine avid with rapid progression after I-131 therapy.

  1. Clomiphene citrate and letrozole to reduce follicle-stimulating hormone consumption during ovarian stimulation: systematic review and meta-analysis.

    Science.gov (United States)

    Bechtejew, T N; Nadai, M N; Nastri, C O; Martins, W P

    2017-09-01

    To assess the available evidence comparing effectiveness of ovarian stimulation (OS) using clomiphene citrate (CC) and/or letrozole (LTZ) to reduce follicle-stimulating hormone (FSH) consumption compared with standard OS. We performed a systematic review and meta-analysis of randomized controlled trials that compared reproductive outcomes following in-vitro fertilization. We searched 11 electronic databases and hand-searched the reference lists of included studies and related reviews. We stratified the results, separating studies according to the oral agent used (CC or LTZ) and the characteristics of the included women (expected poor ovarian response or other women). When combining the results of the included studies, we assessed the relative risk (RR) for live birth, clinical pregnancy, miscarriage and cycle cancelation, the Peto odds ratio (OR) for ovarian hyperstimulation syndrome (OHSS) and mean difference (MD) for the number of oocytes retrieved and FSH consumption. A total of 22 studies were included in the review. Considering women with expected poor ovarian response, the available evidence suggested that using CC to reduce FSH consumption during OS provided similar rates of live birth (RR, 0.9 (95% CI, 0.6-1.2), moderate-quality evidence) and clinical pregnancy (RR, 1.0 (95% CI, 0.8-1.4), moderate-quality evidence); the use of LTZ did not cause a relevant change in the number of oocytes retrieved (MD, -0.4 (95% CI, -0.9 to 0.1), high-quality evidence). Considering the studies evaluating other women, the available evidence suggested that using CC to reduce FSH consumption during OS reduced the number of oocytes retrieved (MD, -4.6 (95% CI, -6.1 to -3.0), high-quality evidence) and risk of OHSS (Peto OR, 0.2 (95% CI, 0.1-0.3), moderate-quality evidence), while results were similar for rates of live birth (RR, 0.9 (95% CI, 0.7-1.1), moderate-quality evidence) and clinical pregnancy (RR, 1.0 (95% CI, 0.8-1.1), high-quality evidence). The quality of the evidence

  2. Progesterone and Follicle Stimulating Hormone interact and promote goat preantral follicles survival and development in vitro

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    Isabel B. Lima-Verde

    2012-04-01

    Full Text Available We investigated the effects of progesterone and follicle stimulating hormone (FSH on survival and growth of caprine preantral follicles. Pieces of ovarian tissue were cultured for 1 or 7 days in minimum essential medium (MEM alone or containing progesterone (1, 2.5, 5, 10 or 20ng/mL, FSH (50ng/mL or the interaction between progesterone and FSH. Fresh (non-cultured control and cultured ovarian tissues were processed for histological and ultrastructural studies. After 7 days the addition of FSH to all progesterone concentrations maintained the percentage of normal follicles similar to fresh control. At day 7 of culture, a higher percentage of developing follicles was observed only in 2.5ng/ml of progesterone associated with FSH or 10ng/ml of progesterone alone when compared with control. From day 1 to day 7 of culture, a significant increase in the percentage of developing follicles was observed in MEM and 2.5ng/ml of progesterone + FSH. In addition, after 7 days, in all treatments, there was a significant increase in follicular diameter when compared with control, except for MEM alone and in 5ng/ml of progesterone + FSH or 10ng/ml of progesterone alone. Ultrastructural studies confirmed follicular integrity after 7 days of culture in 2.5ng/ml of progesterone with FSH. In conclusion, this study demonstrated that the interaction between progesterone and FSH maintains ultrastructural integrity, stimulates primordial follicles activation and further growth of cultured caprine preantral follicles.

  3. Association of High Vitamin D Status with Low Circulating Thyroid-Stimulating Hormone Independent of Thyroid Hormone Levels in Middle-Aged and Elderly Males

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    Qingqing Zhang

    2014-01-01

    Full Text Available Background. A recent study has reported that high circulating 25-hydroxyvitamin D [25(OHD] is associated with low circulating thyroid-stimulating hormone (TSH levels, but only in younger individuals. The goal of the present study was to explore the relationship between vitamin D status and circulating TSH levels with thyroid autoimmunity and thyroid hormone levels taken into consideration in a population-based health survey of middle-aged and elderly individuals. Methods. A total of 1,424 Chinese adults, aged 41–78 years, were enrolled in this cross-sectional study. Serum levels of 25(OHD, TSH, thyroid hormones, and thyroid autoantibodies were measured. Results. The prevalence of vitamin D insufficiency was 94.29% in males and 97.22% in females, and the prevalence of vitamin D deficiency was 55.61% in males and 69.64% in females. Vitamin D status was not associated with positive thyroid autoantibodies after controlling for age, gender, body mass index, and smoking status. Higher 25(OHD levels were associated with lower TSH levels after controlling for age, FT4 and FT3 levels, thyroid volume, the presence of thyroid nodule(s, and smoking status in males. Conclusion. High vitamin D status in middle-aged and elderly males was associated with low circulating TSH levels independent of thyroid hormone levels.

  4. Bilateral vanished testes diagnosed with a single blood sample showing very high gonadotropins (follicle-stimulating hormone and luteinizing hormone) and very low inhibin B

    DEFF Research Database (Denmark)

    Thorup, Jørgen Mogens; Petersen, Bodil Laub; Kvist, Kolja

    2011-01-01

    Objective. In boys with cryptorchidism median serum values of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are higher and median serum values of inhibin B lower than in normal controls. Serum values of inhibin B reflect the state of germinative epithelium in cryptorchid testes...... with bilateral cryptorchidism younger than 7 years of age at surgery for bilateral cryptorchidism (median age 1 year and 9 months). Results. The serum levels of hormones for the patients with vanished testes were: inhibin B 5-18 pg/ml, FSH 41-191 IU/l and LH 3.9-56 IU/l. The patients all had karyotype 46,xy....... The serum levels of hormones from group II were: inhibin B median 122 (range 20-404) pg/ml, FSH median 0.8 (range 0.2-3.5) IU/l and LH median 0.2 (range 0.1-3.2) IU/l. The serum levels of inhibin B, FSH and LH from the boys with vanished testes were significantly different from the serum levels of the boys...

  5. Effect of Oil Paint Fumes Inhalation on the Level of Serum Thyroid Hormones and Thyroid Stimulating Hormone in Rats

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    M. Siavashi

    2016-09-01

    Full Text Available Aims: The exposure to chemical materials and colors affects thyroid gland functions. The aim of this study was to investigate the effects of fume inhalation of oil-based paints on the serum level of thyroid hormones in female and male rats. Materials & Methods: In the experimental study, 15 male and 15 female Wistar rats were studied. The rats were divided into six 5-rat groups including a control group and groups with either 1- or 8-hour a day exposure to the paint fumes by gender division. The serum levels of T3, T4, and TSH thyroid hormones were measured after 10 weeks. Data was analyzed by SPSS 20 software using two-way ANOVA and Tukey’s post-hoc. Findings: Mean values of T3 and T4 hormones were significantly reduced in both 1- and 8-hour male and female groups than control group (p<0.001. In addition, the more the inhalation time, the more the reduction was. Any reduction in T3 in females in 1-hour (p<0.001 and 8–hour (p<0.05 groups was significantly more than the males. Nevertheless, a significant reduction in T4 was only in 1-hour group (p<0.001. Mean TSH hormone was significantly increased due to the inhalation of paint fume than control group (p<0.001. In addition, such an increase was significant in the female rats in 8-hour group than the male group (p<0.01. Conclusion: The inhalation of oil-based paint fume leads to a reduction in the serum levels of T3 and T4 thyroid hormones, while increases TSH serum level. Such an effect is stronger in the females.

  6. Follicle-stimulating hormone (FSH), current suicidal ideation and attempt in female patients with major depressive disorder.

    Science.gov (United States)

    Kim, Bora; Kang, Eun-Suk; Fava, Maurizio; Mischoulon, David; Soskin, David; Yu, Bum-Hee; Lee, Dongsoo; Lee, Dong-Yun; Park, Hyung-Doo; Jeon, Hong Jin

    2013-12-30

    Current suicidal ideation and attempts are more commonly found in female patients with major depressive disorder (MDD) than in males. However, little is known about the relationship between activity of female reproductive hormones and suicide. The study population consisted of 490 female MDD patients of age ≥18. They were assessed by the Mini-International Neuropsychiatric Interview. At the same visit, we measured blood Follicle-Stimulating Hormone (FSH), Luteinizing Hormone (LH), estradiol, progesterone, Adrenocorticotropic Hormone (ACTH), cortisol, thyroid hormones, and prolactin. Blood FSH showed a significant difference among female MDD patients with suicide attempt, those with ideation, and those without within the previous month. Post-hoc analysis also showed that FSH was significantly lower in MDD patients with suicide attempt and ideation than those without, whereas other hormones showed no differences between those with and without attempt. FSH was negatively associated with current suicidality scores after adjustment for age and education years in all age groups. FSH was significantly lower in those with current suicide ideation or attempt than those without in age 45 years or under, but not in other age groups. In conclusion, blood FSH is significantly lower in female MDD patients with current suicide attempt or ideation than those without, especially in age 45 years or under. © 2013 Elsevier Ireland Ltd. All rights reserved.

  7. Thyroid stimulating hormone and leptin levels and severe growth retardation among beta- thalassaemic patients

    International Nuclear Information System (INIS)

    Dayer, D.; Salahcheh, M.; Jazayeri, S.M.H.; Kaydani, G.A.; Kadkhodaei Elyaderani, M.K.; Shaneh, S.

    2012-01-01

    Objective: It has been proposed that thyroid stimulating hormone (TSH) influences leptin secretion from adipocytes. We evaluated the association between TSH and leptin levels in thalassaemic patients with growth retardation. Methodology: Blood samples were collected from 30 major thalassaemic patients and 24 normal subjects (range: 12 - 20 y). Both Leptin and TSH were measured by Enzyme-Linked Immunosorbent Assay (ELISA) method. The anthropomorphic data were collected based on standard methods. Independent sample t-test and Pearson's correlation were used to analyze data. Results: Patients had severe growth retardation. Mean concentration of leptin in thalassaemic mean value of serum TSH concentration of lepton in thalassaemic patients was significantly lower than normal subjects (2.26 +- 2,61 vs 13.14 +- 15.95 ng/ml). The mean value os serum TSH concentration in beta- thalassaemic patients was higher than normal subjects. But the difference was not statistically significant (P = 0.146). There was no marked relationship between TSH and leptin concentration in thalassaemic patients (r= -0.022, P =0.909) and in control group (r =0.289, P=0.214). Conclusion: In beta - thalassaemic patients and normal group leptin secretion is a not affected by TSH concentration. (author)

  8. Targeting the thyroid gland with thyroid-stimulating hormone (TSH)-nanoliposomes.

    Science.gov (United States)

    Paolino, Donatella; Cosco, Donato; Gaspari, Marco; Celano, Marilena; Wolfram, Joy; Voce, Pasquale; Puxeddu, Efisio; Filetti, Sebastiano; Celia, Christian; Ferrari, Mauro; Russo, Diego; Fresta, Massimo

    2014-08-01

    Various tissue-specific antibodies have been attached to nanoparticles to obtain targeted delivery. In particular, nanodelivery systems with selectivity for breast, prostate and cancer tissue have been developed. Here, we have developed a nanodelivery system that targets the thyroid gland. Nanoliposomes have been conjugated to the thyroid-stimulating hormone (TSH), which binds to the TSH receptor (TSHr) on the surface of thyrocytes. The results indicate that the intracellular uptake of TSH-nanoliposomes is increased in cells expressing the TSHr. The accumulation of targeted nanoliposomes in the thyroid gland following intravenous injection was 3.5-fold higher in comparison to untargeted nanoliposomes. Furthermore, TSH-nanoliposomes encapsulated with gemcitabine showed improved anticancer efficacy in vitro and in a tumor model of follicular thyroid carcinoma. This drug delivery system could be used for the treatment of a broad spectrum of thyroid diseases to reduce side effects and improve therapeutic efficacy. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Clinical manifestations of low bone mass in amenorrhea patients with elevated follicular stimulating hormone.

    Science.gov (United States)

    Yu, Qi; Lin, Shouqing; He, Fangfang; Li, Baoluo; Lin, Yuan; Zhang, Tao; Zhang, Ying

    2002-09-01

    To study the characteristics of low bone mass in amenorrhea patients with elevated follicular stimulating hormone (FSH). Amenorrhea patients with elevated FSH: Primary amenorrhea 18 cases, secondary amenorrhea 171 cases and age matched controls with normal menstruation, 180 cases. The descriptive parameters were: estrogen, alkaline phosphatase, urinary excretion of calcium to creatine ratio, cortical bone mineral density at the right radius measured by single photon absorptiometry and trabecular bone mineral density at the lumbar vertebra body measured by quantitative computerized tomography. Average E(2) levels in amenorrhea patients is under 150 pmol/L with significantly higher alkaline phosphatase and urine calcium to creatine ratio values than the normal menstruation group. Cortical bone mineral density in the secondary amenorrhea group (655 +/- 69 mg/cm(2)) was significantly lower than that of the normal menstruation group (677 +/- 56 mg/cm(2), P < 0.01). Trabecular bone mineral density in the secondary amenorrhea group (145 +/- 26 mg/cm(3)) was significantly lower than that of the NOR group (192 +/- 28 mg/cm(3), P < 0.001). The disparity with the normal menstruation group is even greater in the primary amenorrhea group. Bone mineral density of the amenorrhea patients was negatively correlated with duration of the menopause. Serum estrodiol levels in amenorrhea patients was so low that bone turnover was accelerated. This led to insufficient bone accumulation and a dramatically drop in trabecular bone mineral density. The extent was closely related to age of onset of amenorrhea and the duration of ovarian failure.

  10. Human growth hormone stimulates proliferation of human retinal microvascular endothelial cells in vitro

    International Nuclear Information System (INIS)

    Rymaszewski, Z.; Cohen, R.M.; Chomczynski, P.

    1991-01-01

    Growth hormone (GH) has been implicated in the pathogenesis of proliferative diabetic retinopathy. The authors sought to determine whether this could be mediated by an effect of GH on proliferation of endothelial cells, and, for this purpose, established long-term cultures of human retinal microvascular endothelial cells (hREC) from normal postmortem human eyes. High-purity hREC preparations were selected for experiments, based on immunogluorescence with acetylated low density lipoprotein (LDL) and anti-factor VIII-related antigen. Growth requirements for these cells were complex, including serum for maintenance at slow growth rates and additional mitogens for more rapid proliferation. Exposure of hREC to physiologic doses of human GH (hGH) resulted in 100% greater cell number vs. control but could be elicited only in the presence of serum. When differing serum conditions were compared, hGH stimulated [ 3 H]thymidine incorporation up to 1.6- to 2.2-fold under each condition and increased DNA content significantly in the presence of human, horse, and fetal calf serum. In summary, hREC respond to physiologic concentrations of hGH in vitro with enhanced proliferation. This specific effect of GH on retinal microvascular endothelial cells supports the hypothesis of role for GH in endothelial cell biology

  11. Detecting congenital hypothyroidism with newborn screening: the relevance of thyroid-stimulating hormone cutoff values.

    Science.gov (United States)

    Silvestrin, Stela Maris; Leone, Claudio; Leone, Cléa Rodrigues

    To assess the prevalence of congenital hypothyroidism and the ability of various neonatal thyroid-stimulating hormone (TSHneo) cutoff values to detect this disease. This cohort study was based on the retrospective collection of information available from the Reference Service for Newborn Screening database for all live births from January 1, 2010, to December 31, 2012, assessed using the Newborn Screening Program of a Brazilian state, Brazil. The infants were divided into two groups: I - Control: infants with normal newborn screening tests and II - Study: infants with congenital hypothyroidism. Analysis included comparing the TSHneo levels from both groups. A receiver operating characteristic (ROC) curve was constructed to assess the TSHneo cutoff values. Using a TSHneo cutoff value of 5.0μIU/mL, 50 out of 111,705 screened infants had diagnosis of congenital hypothyroidism (prevalence 1:2234 live births). The ROC curve showed that TSHneo value of 5.03μIU/mL had 100% sensitivity and the greatest associated specificity (93.7%). The area under the curve was 0.9898 (pvalue of 5.0μIU/mL adopted by the Newborn Screening Program of a Brazilian state was the most appropriate for detecting congenital hypothyroidism and most likely explains the high prevalence that was found. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  12. Methylation of the thyroid stimulating hormone receptor: diagnostic marker of malignity in thyroid cancer

    International Nuclear Information System (INIS)

    Marrero Rodriguez, Maria Teresa

    2007-01-01

    The methylation state of the gene promoter for the receptor of the thyroid stimulating hormone (TSH) in the diagnosis of thyroid tumors of epithelial origin was analyzed. The study was conducted in thyroid tissue obtained from paraffin blocks of different thyroid pathologies (papillary, follicular and undifferentiated carcinoma and follicular adenomas). The work was done by using the DNA modification technique with sodium bisulfite, and polymerase chain reaction was applied to analyze the gene methylation state. Methylation of the promoter for the gene of the TSH receptor was found in the papillary carcinomas (33 of 40; 82.5 %), in 10 undifferentiated carcinomas (100 %), and in 10 of the 15 follicular carcinomas analyzed (66.6 %). No methylation was observed in the 8 follicular adenomas under study. The methylation of the gene for the TSH receptor was proposed as a new diagnostic marker of malignity and as a basis for using demethylating agents together with radioiodine therapy in patients with thyroid cancer of epithelial origin that do not respond to therapy. (Author)

  13. The effect of the NMDA receptor-dependent signaling pathway on cell morphology and melanosome transfer in melanocytes.

    Science.gov (United States)

    Ni, Jing; Wang, Nan; Gao, Lili; Li, Lili; Zheng, Siwen; Liu, Yuejian; Ozukum, Molu; Nikiforova, Anna; Zhao, Guangming; Song, Zhiqi

    2016-12-01

    The pigmentation of skin and hair in mammals is driven by the intercellular transfer of melanosome from the melanocyte to surrounding keratinocytes However, the detailed molecular mechanism is still a subject of investigation. To investigate the effects of N-methyl-d-aspartate (NMDA) receptor-dependent signaling pathway on melanocyte morphologic change and melanosome transfer between melanocytes and keratinocytes. The expression and the intracellular distribution of NMDA receptor in human melanocyte were analyzed by Western blot and immunofluorescence staining. Melanocytes were treated with 100μM NMDA receptor antagonist MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine maleate] and 100μM NMDA receptor agonist NMDA, after which the morphological change of melanocyte dendrites and filopodias were observed by scanning electron microscope. The β-tubulin distribution and intracellular calcium concentration ([Ca 2+ ] i ) were observed by immunofluorescence staining and flow cytometry under the same treatment respectively. In addition, melanocytes and keratinocytes were co-cultured with or without treatment of MK-801, and the melanosome transfer efficacy were analyzed by flow cytometry. We show that human epidermal melanocytes expresses NMDA receptor 1, one subtype of the ionotropic glutamate receptors (iGluRs). Stimulation with agonist of NMDA receptor increased the number of melanocyte filopodia. In contrast, blockage of NMDA receptor with antagonist decreased the number of melanocyte filopodia and this morphological change was accompanied by the disorganization of β-tubulin microfilaments in the intracellular cytoskeleton. In melanocyte-keratinocyte co-cultures, numerous melanocyte filopodia connect to keratinocyte plasma membranes; agonist of NMDA receptor exhibited an increased number of melanocyte filopodia attachments to keratinocyte, while antagonist of NMDA receptor led to a decreased. Moreover, antagonist of NMDA receptor decreased

  14. Increased Progesterone/Estradiol Ratio on the Day of hCG Administration Adversely Affects Success of In Vitro Fertilization–Embryo Transfer in Patients Stimulated with Gonadotropin-releasing Hormone Agonist and Recombinant Follicle-stimulating Hormone

    Directory of Open Access Journals (Sweden)

    Yu-Che Ou

    2008-06-01

    Conclusion: Premature luteinization, defined as late follicular P/E2 ratio of > 1 in long GnRHa cycles with rFSH stimulation, adversely affected ovarian responses and clinical outcomes. It seems unrelated to preovulatory luteinizing hormone (LH elevation and LH/hCG content of gonadotropins and could be associated with poor ovarian response and the presence of dysmature follicles. [Taiwan J Obstet Cynecol 2008;47(2:1 68-1 74

  15. Thyroid stimulating hormone stimulates the expression of glucose transporter 2 via its receptor in pancreatic β cell line, INS-1 cells.

    Science.gov (United States)

    Lyu, Jingya; Imachi, Hitomi; Yoshimoto, Takuo; Fukunaga, Kensaku; Sato, Seisuke; Ibata, Tomohiro; Kobayashi, Toshihiro; Dong, Tao; Yonezaki, Kazuko; Yamaji, Nao; Kikuchi, Fumi; Iwama, Hisakazu; Ishikawa, Ryou; Haba, Reiji; Sugiyama, Yasunori; Zhang, Huanxiang; Murao, Koji

    2018-01-31

    Thyroid stimulating hormone (TSH) stimulates the secretion of thyroid hormones by binding the TSH receptor (TSHR). TSHR is well-known to be expressed in thyroid tissue, excepting it, TSHR has also been expressed in many other tissues. In this study, we have examined the expression of TSHR in rat pancreatic islets and evaluated the role of TSH in regulating pancreas-specific gene expression. TSHR was confirmed to be expressed in rodent pancreatic islets and its cell line, INS-1 cells. TSH directly affected the glucose uptake in INS cells by up-regulating the expression of GLUT2, and furthermore this process was blocked by SB203580, the specific inhibitor of the p38 MAPK signaling pathway. Similarly, TSH stimulated GLUT2 promoter activity, while both a dominant-negative p38MAPK α isoform (p38MAPK α-DN) and the specific inhibitor for p38MAPK α abolished the stimulatory effect of TSH on GLUT2 promoter activity. Finally, INS-1 cells treated with TSH showed increased protein level of glucokinase and enhanced glucose-stimulated insulin secretion. Together, these results confirm that TSHR is expressed in INS-1 cells and rat pancreatic islets, and suggest that activation of the p38MAPK α might be required for TSH-induced GLUT2 gene transcription in pancreatic β cells.

  16. Ultraviolet radiation directly induces pigment production by cultured human melanocytes

    International Nuclear Information System (INIS)

    Friedmann, P.S.; Gilchrest, B.A.

    1987-01-01

    In humans the major stimulus for cutaneous pigmentation is ultraviolet radiation (UVR). Little is known about the mechanism underlying this response, in part because of the complexity of interactions in whole epidermis. Using a recently developed culture system, human melanocytes were exposed daily to a physiologic range of UVR doses from a solar simulator. Responses were determined 24 hours after the last exposure. There was a dose-related increase in melanin content per cell and uptake of 14 C-DOPA, accompanied by growth inhibition. Cells from donors of different racial origin gave proportionately similar increases in melanin, although there were approximately tenfold differences in basal values. Light and electron microscopy revealed UVR-stimulated increases in dendricity as well as melanosome number and degree of melanization, analogous to the well-recognized melanocyte changes following sun exposure of intact skin. Similar responses were seen with Cloudman S91 melanoma cells, although this murine cell line required lower UVR dosages and fewer exposures for maximal stimulation. These data establish that UVR is capable of directly stimulating melanogenesis. Because cyclic AMP elevation has been associated in some settings with increased pigment production by cultured melanocytes, preliminary experiments were conducted to see if the effects of UVR were mediated by cAMP. Both alpha-MSH and isobutylmethylxanthine (IBMX), as positive controls, caused a fourfold increase in cAMP level in human melanocytes and/or S91 cells, but following a dose of UVR sufficient to stimulate pigment production there was no change in cAMP level up to 4 hours after exposure. Thus, it appears that the UVR-induced melanogenesis is mediated by cAMP-independent mechanisms

  17. Eclosion hormone stimulates cyclic GMP levels in Manduca sexta nervous tissue via arachidonic acid metabolism with little or no contribution from the production of nitric oxide.

    Science.gov (United States)

    Morton, D B; Giunta, M A

    1992-10-01

    The neuropeptide eclosion hormone acts directly on the nervous system of the tobacco hornworm, Manduca sexta, to trigger ecdysis behavior at the end of each molt. Previous studies have shown that the action of eclosion hormone is mediated via the intracellular messenger cyclic GMP. In the present study we have investigated the mechanisms involved in the eclosion hormone-stimulated increases in cyclic GMP. No stimulation of guanylate cyclase was seen in homogenized nervous tissue, suggesting that eclosion hormone does not directly stimulate a membrane-bound form of guanylate cyclase. Nitric oxide synthase inhibitors, N-methylarginine and nitroarginine, had no effect on eclosion hormone-stimulated cyclic GMP levels. By contrast, 4-bromophenacyl bromide, an inhibitor of arachidonic acid release, and nordihydroguaiaretic acid, an inhibitor of arachidonic acid metabolism, almost completely abolished the eclosion hormone-stimulated cyclic GMP increase. We hypothesize that eclosion hormone receptors are coupled to a lipase, activation of which causes the release of arachidonic acid. Either the arachidonic acid directly stimulates the soluble guanylate cyclase or further metabolism of arachidonic acid yields compounds that activate guanylate cyclase.

  18. Factors that predict a positive response on gonadotropin-releasing hormone stimulation test for diagnosing central precocious puberty in girls

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    Junghwan Suh

    2013-12-01

    Full Text Available PurposeThe rapid increase in the incidence of precocious puberty in Korea has clinical and social significance. Gonadotropin-releasing hormone (GnRH stimulation test is required to diagnose central precocious puberty (CPP, however this test is expensive and time-consuming. This study aimed to identify factors that can predict a positive response to the GnRH stimulation test.MethodsClinical and laboratory parameters, including basal serum luteinizing hormone (LH, follicle-stimulating hormone (FSH, and estradiol (E2, were measured in 540 girls with clinical signs of CPP.ResultsTwo hundred twenty-nine of 540 girls with suspected CPP had a peak serum LH level higher than 5 IU/L (the CPP group. The CPP group had advanced bone age (P<0.001, accelerated yearly growth rate (P<0.001, increased basal levels of LH (P=0.02, FSH (P<0.001, E2 (P=0.001, and insulin-like growth factor-I levels (P<0.001 compared to the non-CPP group. In contrast, body weight (P<0.001 and body mass index (P<0.001 were lower in the CPP group. Although basal LH was significantly elevated in the CPP group compared to the non-CPP group, there was considerable overlap between the 2 groups. Cutoff values of basal LH (0.22 IU/L detected CPP with 87.8% sensitivity and 20.9% specificity.ConclusionNo single parameter can predict a positive response on the GnRH stimulation test with both high sensitivity and specificity. Therefore, multiple factors should be considered in evaluation of sexual precocity when deciding the timing of the GnRH stimulation test.

  19. Effect of maternal and neonatal factors on cord blood thyroid stimulating hormone

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    Sheetal G Lakshminarayana

    2016-01-01

    Full Text Available Background: Congenital hypothyroidism (CH is most common preventable cause of mental retardation in children. Cord blood Thyroid Stimulating Hormone (CBTSH level is an accepted screening tool for CH. Objectives: To study CBTSH profile in neonates born at tertiary care referral center and to analyze the influence of maternal and neonatal factors on their levels. Design: Cross retrospective sectional study. Methods: Study population included 979 neonates (males = 506 to females = 473. The CBTSH levels were estimated using electrochemiluminescence immunoassay on Cobas analyzer. Kit based cut-offs of TSH level were used for analysis. All neonates with abnormal CBSTH levels, were started on levothyroxine supplementation 10 μg/Kg/day and TSH levels were reassessed as per departmental protocol. Results: The mean CBTSH was 7.82 μIU/mL (Range 0.112 to 81.4, SD = 5.48. The mean CBTSH level was significantly higher in first order neonates, neonates delivered by assisted vaginal delivery and normal delivery, delivered at term or preterm, neonates with APGAR score 16.10 and 16.1 μIU/mL was significantly higher in neonates delivered by assisted vaginal delivery and normal delivery, term and preterm neonates, APAGR score of 16.10 and <1.0 led to a recall of 5.41% of neonates which is practicable given the scenario in our Country. The mode of delivery and perinatal stress factors have a significant impact on CBTSH levels and any rise to be seen in the light of these factors. The prevalence rate of CH after recall was ~3 in 1000 live births.

  20. Isolated low follicle stimulating hormone (FSH in infertile males – a preliminary report

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    Nader Salama

    2013-09-01

    Full Text Available Objectives: High levels of follicle stimulating hormone (FSH in infertile males received a significant attention and exploration. Studies investigating the isolated deficiency of FSH in males are few, and its real prevalence is still unknown. Therefore, the objectives of the current study was to report the prevalence of isolated low FSH in infertile males and highlight their demographics and standard sperm parameters. Methods: Records of 3335 infertile men were retrospectively checked. Patients with isolated low FSH were retrieved. FSH levels were categorized into 3 groups based on the number of affected sperm parameter (s. Study variables were also arranged into 2 groups in relation to smoking history. A control group was included to document the changes in sperm morphology. Results: Isolated low FSH (1.146 ± 0.219 mIU/mL was found in 29 (0.87% patients. All patients showed at least one abnormal sperm parameter. The abnormal parameters were present in different combinations within the same patient but with no significant correlations with the FSH levels. The FSH levels got lower as the number of the affected sperm parameters increased although the decline was insignificant. The most frequent abnormal parameter presented was sperm morphology (86.2%. Anomalous sperm morphology was highly and significantly demonstrated in the head; specifically in acrosome. Abnormal sperm parameters were present in both smoking and nonsmoking groups but with no significant differences in between. Conclusions: Isolated low FSH among infertile males has a low prevalence. This may be associated with abnormality in semen parameters; particularly sperm morphology. These patients are suggested to be found as a primary entity. However, an additional work-up is highly recommended to validate this hypothesis.

  1. The effect of recombinant follicle-stimulating hormone on semen parameters after varicocelectomy in infertile men

    Directory of Open Access Journals (Sweden)

    Atoosa Bagheri Behzad

    2015-12-01

    Full Text Available Background: Infertility is defined as failure to achieve pregnancy after one year of unprotected sexual intercourse. Infertility can be related to male or female factors. Varicocele is the most common cause of infertility in men that is correctable with surgery. The purpose of this study was to determine the effects of recombinant follicle-stimulating hormone (rFSH on semen parameters in infertile men. Methods: This randomized clinical trial was done on 96 infertile men admitted to the Women's General Hospital Mohebe-Yas from September 2014 to September 2015. Inclusion criteria were to include varicocelectomy for unilateral idiopathic varicoceles and consent to participate in the study. Allergy to the drug combination and patient dissatisfaction were exclusion criteria. Patients participating in the study were divided into two groups randomly, one group received recombinant FSH three times a week and the other group received a placebo (normal saline in the same way. After three months, the improvement of semen parameters, including motility, morphology and sperm count as well as the complications were determined in both groups. The data were analyzed with statistical software SPSS version 13 (Chicago, IL, USA. Results: A total of 96 patients were enrolled in two groups of 48 men and women; both groups were matched in terms of underlying factors. The rate of improvement in the morphology and motility of sperm in the treated group was significantly more than the placebo group (P= 0.0001; but the changes in sperm count were not significantly different between the groups (P= 0.495. Conclusion: In summary, based on the results obtained in this study, it can be concluded that recombinant FSH is effective on improving semen parameters in infertile men after varicocelectomy compared with a placebo group and its major impact is on the morphology and motility of sperm.

  2. Abnormal Thyroid-Stimulating Hormone and Chronic Kidney Disease in Elderly Adults in Taipei City.

    Science.gov (United States)

    Chuang, Mei-Hsing; Liao, Kuo-Meng; Hung, Yao-Min; Wang, Paul Yung-Pou; Chou, Yi-Chang; Chou, Pesus

    2016-06-01

    To examine whether older people with abnormal thyroid function are more likely to develop chronic kidney disease (CKD) over a 5-year follow-up period. Retrospective cohort study. Health examination data from the Taipei Databank for Public Health Analysis. Individuals aged 65 and older (N = 41,454). Thyroid-stimulating hormone (TSH) levels were repeatedly measured, and subjects were categorized into four thyroid function groups (hyperthyroid, euthyroid, subclinical hypothyroid, overt hypothyroid). The risk of incident CKD was evaluated using a stepwise Cox proportional hazards regression model adjusted for sex, baseline age, hypertension, diabetes mellitus (DM), dyslipidemia, hyperuricemia, anemia, obesity, liver function, smoking, and alcohol. Higher TSH levels were associated with greater risk of subsequent CKD. Individuals with subclinical hypothyroidism (hazard ratio (HR) = 1.15, 95% confidence interval (CI) = 1.05-1.26) and those with overt hypothyroidism (HR = 1.27, 95% CI = 1.04-1.55) were more likely than those who were euthyroid to have CKD. Women were more likely to have CKD than men (HR = 1.11, 95% CI = 1.06-1.16). When stratified by gender, subclinical hypothyroidism in women was associated with an increased risk of developing CKD (HR = 1.22; 95% CI = 1.08-1.39). When stratified by DM, subclinical hypothyroidism and overt hypothyroidism were associated with an increased risk of developing CKD in nondiabetics (HR = 1.19; 95% CI = 1.07-1.31; and HR = 1.34; 95% CI = 1.08-1.65, respectively). This cohort study of elderly persons in Taipei City found a significant association between hypothyroidism and development of CKD in women and individuals without DM. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

  3. Studies on the structure of the follicle-stimulating hormone receptor using photoaffinity labeling procedures

    International Nuclear Information System (INIS)

    Smith, R.A.

    1985-01-01

    The general objective of this project was to study the structure of the follicle stimulating hormone (FSH) receptor using affinity labeling methods. A low density fraction derived from homogenates of bovine testis was found to contain high affinity and low capacity receptors specific for FSH. Electron microscopic examination of the fraction revealed structure resembling multilamellar membranous vesicles (MV). For photoaffinity labeling of the FSH receptors in MV, an azidobenzoyl- 125 I-analog of human FSH was prepared ( 125 I-AB-hFSH) and binding of specific FSH receptors was studied. 125 I-AB-hFSH binding of receptors was inhibited in a dose dependent manner by unlabeled hFSH, and binding was not prevented by structurally-related human chorionic gonadotropin (hCG). The formation of photocrosslinked protein of relative molecular mass (M/sub r/) 54,000, 64,000, 76,000, 84,000, 97,000 and 116,000 was found to be inhibited by unlabeled hFSH in a dose related manner, and to be dependent on photoactivation of the FSH derivative. The interpretation of the photoaffinity labeling experiments was that three proteins associated with the FSH receptor were photoaffinity labeled. Analysis by indirect means suggested that the three proteins were assembled to form oligomeric complexes, and based on the intensities and composition of the oligomeric species, spatial relationships of the polypeptides with respect to each other on the membrane surface were deduced. The results of photoaffinity labeling suggest the FSH receptor is composed of three subunits of M/sub r/ 38,000, 48,000, and 81,000 and exists in the membrane in part as a M/sub r/ 330,000 dimer

  4. Neonatal thyroid-stimulating hormone concentrations in Belgium: a useful indicator for detecting mild iodine deficiency?

    Directory of Open Access Journals (Sweden)

    Stefanie Vandevijvere

    Full Text Available It has been proposed that neonatal thyroid-stimulating hormone (TSH concentrations are a good indicator of iodine deficiency in the population. A frequency of neonatal TSH concentrations above 5 mU/L below 3% has been proposed as the threshold indicating iodine sufficiency. The objective of the present study was to evaluate feasibility and usefulness of nation-wide neonatal TSH concentration screening results to assess iodine status in Belgium. All newborns born in Belgium during the period 2009-2011 (n = 377713 were included in the study, except those suffering from congenital hypothyroidism and premature neonates. The frequency of neonatal TSH concentrations above 5 mU/L from 2009 to 2011 in Belgium fluctuated between 2.6 and 3.3% in the centres using the same TSH assay. There was a significant inverse association between neonatal TSH level and birth weight. The longer the duration between birth and screening, the lower the TSH level. Neonatal TSH levels were significantly lower in winter than in spring or autumn and significantly lower in spring and summer than in autumn while significantly higher in spring compared to summer. In conclusion, despite that pregnant women in Belgium are mildly iodine deficient, the frequency of neonatal TSH concentrations above 5 mU/L was very low, suggesting that the neonatal TSH threshold proposed for detecting iodine deficiency needs to be re-evaluated. Although neonatal TSH is useful to detect severe iodine deficiency, it should not be recommended presently for the evaluation of iodine status in mildly iodine deficient regions.

  5. Thyroid stimulating hormone levels in cord blood are not influenced by non-thyroidal mothers' diseases

    Directory of Open Access Journals (Sweden)

    Laura Sterian Ward

    2000-09-01

    Full Text Available CONTEXT: Screening programs not only offer the opportunity to trace and treat almost all cases of congenital hypothyroidism but also mean large savings to the health system. However, carefully planned strategies are necessary to extend their benefits and reduce costs. OBJECTIVE: To determine the possible influence of maternal diseases that affect maternal-fetal placenta dynamics on primary thyroid stimulating hormone (TSH screening for congenital hypothyroidism. DESIGN: Prospective non-randomized clinical trial with at least 3 months of follow-up. SETTING: A public university referral center [CAISM/Hospital das Clínicas, Faculty of Medicine, University of Campinas, Campinas, SP]. PARTICIPANTS: 415 neonates divided into 5 groups: eighty-three infants born from cardiac mothers; 98 from mothers that had toxemia; 54 of the mothers had diabetes mellitus; 40 were HIV positive and 140 had no diseases. INTERVENTION: All newborns had cord blood samples collected on filter paper at birth. MAIN MEASUREMENTS: TSH was measured from dried blood spots using a homemade immunofluorescence assay (sensitivity in dried blood spots = 0.1 mU/L. RESULTS: There was no significant difference in the mean TSH levels among the 5 groups. Moreover, TSH levels were around 5 mU/L in 48% of the newborns, indicating that our region is severely deficient in iodine. CONCLUSIONS: Our results indicate that primary TSH screening programs using cord blood are not affected by maternal diseases. We suggest that, besides its technical advantages over heel punctures with T4 primary approaches, neonatal screening using primary cord blood TSH may also be used as a monitoring tool for evaluation and control of iodine deficiency disorders (IDD.

  6. Relationship of thyroid-stimulating hormone with metabolic syndrome in a sample of euthyroid Pakistani population

    International Nuclear Information System (INIS)

    Saleem, M.S.; Khan, K.A.

    2011-01-01

    Metabolic Syndrome is a group of factors that predispose to cardiovascular diseases. The prevalence of metabolic syndrome is rising rapidly. Recently, a few studies have suggested that lower thyroid function in the reference range may be associated with metabolic syndrome, but the issue remains unsettled. We aimed to elucidate the relationship between thyroid function and components of metabolic syndrome in a sample of euthyroid Pakistani population. Methods: This analytical, cross-sectional study was conducted at the Department of Physiology, University of Health Sciences, Lahore, Pakistan, and extended over a period of 12 months. It included 100 subjects with metabolic syndrome in the study group and thirty subjects without metabolic syndrome in the control group with age ranging 45-55 years. Both groups had normal thyroid function. After a detailed history and clinical examination, fasting blood was analysed for glucose, triglycerides, high density lipoprotein-cholesterol along with thyroid-stimulating hormone (TSH) and free thyroxine. Results: Serum TSH was significantly higher in study group than in control group (p=0.040). Serum free thyroxine values of study group were slightly but not significantly lower than those of control group. Serum TSH correlated significantly and positively with serum triglycerides in all subjects and with waist circumference and diastolic blood pressure in men. Serum TSH showed a positive and linear relationship with the number of components of metabolic syndrome (p=0.016) in all subjects. Conclusion: High-normal TSH is associated with metabolic syndrome and its components. There may be increased risk of cardiovascular diseases with high-normal TSH levels. (author)

  7. Inhibin A, inhibin B, follicle-stimulating hormone, luteinizing hormone, estradiol, and sex hormone-binding globulin levels in 473 healthy infant girls

    DEFF Research Database (Denmark)

    Chellakooty, M; Schmidt, I M; Haavisto, A M

    2003-01-01

    The early postnatal regulation of reproductive hormones seems to be more complex in girls than in boys. The aim of this study was to describe inhibins A and B, FSH, LH, estradiol, and SHBG in a large prospective cohort of 473 unselected, healthy, 3-month-old girls. In full term, appropriate-for- ...

  8. Paediatric atypical spitzoid melanocytic neoplasm

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    Aileen F. Egan

    2017-12-01

    Full Text Available Cutaneous malignant melanoma is a rare occurrence in children, with an incidence of less than one case per million per year in children under ten years of age. However this statistic is reportedly increasing. Mortality rates in paediatric melanoma are not well described, however reports suggest that 5-year survival rates are improving beyond those of adults. This may be partly attributable to more intensive classification and staging of melanocytic lesions. Atypical spitzoid neoplasms (ASN are a subcategorisation of the diagnostic spectrum which extends from Spitz naevi to spitzoid melanoma, and are relatively more common than the latter. The clinical and histopathological features of such lesions are imprecise, leading to difficulties in making diagnoses and subsequent management. This report documents one such case arising within an atypical spitzoid melanocytic neoplasm and the clinical process undertaken. In particular we wished to highlight the molecular diagnostics utilised and their impact on the decision-making pathway.

  9. Ovine thyroid stimulating hormone (TSH) heterologously stimulates production of thyroid hormones from Chinese soft-shell turtle (Pelodiscus sinensis) and bullfrog (Rana catesbeiana and Rana rugulosa) thyroids in vitro.

    Science.gov (United States)

    Huang, Wei-Tung; Chien, Jung-Tsun; Weng, Ching-Feng; Jeng, Yung-Yue; Lu, Li-Chia; Yu, John Yuh-Lin

    2009-06-01

    Thyroid hormones are important for regulating a variety of developmental processes in vertebrates, including growth, differentiation, metamorphosis, and oxidative metabolism. In particular, this study focused on the in vitro production of thyroxine (T(4)) and triiodothyronine (T(3)) from thyroids in American bullfrogs (Rana catesbeiana), Chinese bullfrogs (Rana rugulosa Wiegmann), and Chinese soft-shell turtles (Pelodiscus sinensis) treated with ovine thyroid stimulating hormone (TSH) at different culture intervals (2, 4, 8, and 12 h) and dosages (1, 10, 50 or 100 ng). The levels of T(4) and T(3) in the tested animals were elevated upon stimulation in a time- and dose-dependent manner, indicating de novo synthesis of T(4) and T(3). Significantly higher hormone levels were observed in the Chinese bullfrog compared to the other two species, for both the time-course and dose-response experiments. Although the bullfrog secreted significantly higher levels of T(4) and T(3), a higher T(4)-conversion capacity was found in the Chinese soft-shell turtle. The highest ratios of T(3) to T(4) were observed in the American bullfrog and Chinese soft-shell turtle for the time-course and dose-response experiments, respectively. These findings suggest that the Chinese soft-shell turtle and bullfrog thyroids can accept ovine TSH for T(4)- and T(3)-formation in a time- and dose-dependent manner, supporting the hypothesis that the binding interactions between TSHs and thyroidal receptors are conserved in vertebrates.

  10. Evaluation of the influence of prenatal transportation stress on GnRH-stimulated luteinizing hormone and testosterone secretion in sexually mature Brahman bulls

    Science.gov (United States)

    This study examined the relationships of prenatal transportation stress (PNS) with cortisol, luteinizing hormone (LH), and testosterone secretion before and after gonadotrophin releashing hormone (GnRH) stimulation of sexually mature Brahman bulls derived from the calf crop of 96 Brahman cows (48 co...

  11. The Common Follicle-Stimulating Hormone Receptor (FSHR) Promoter Polymorphism FSHR -29G > A Affects Androgen Production in Normal Human Small Antral Follicles

    DEFF Research Database (Denmark)

    Borgbo, Tanni; Klučková, Hana; Macek, Milan

    2017-01-01

    Follicle-stimulating hormone receptors (FSHRs) are almost exclusively expressed on granulosa cells, and FSH action is probably most clearly reflected in intrafollicular hormone milieu of antral follicles. Little is known about the possible effects of the common single nucleotide polymorphism (SNP...

  12. Pulsatile luteinizing hormone and follicle-stimulating hormone secretion and gonadotropin subunit mRNA levels in the ovariectomized GPR-4 transgenic rat.

    Science.gov (United States)

    El Majdoubi, Mohammed; Paruthiyil, Sreenivasan; Weiner, Richard I

    2003-12-01

    Genetic targeting of the cAMP-specific phosphodiesterase 4D1 (PDE4D1) to gonadotropin-releasing hormone (GnRH) neurons in the GPR-4 transgenic rat resulted in decreased luteinizing hormone (LH) pulse frequency in castrated female and male rats. A similar decrease in the intrinsic GnRH pulse frequency was observed in GT1 GnRH cells expressing the PDE4D1 phosphodiesterase. We have extended these findings in ovariectomized (OVX) GPR-4 rats by asking what effect transgene expression had on pulsatile LH and follicle-stimulating hormone (FSH) secretion, plasma and pituitary levels of LH and FSH, and levels of the alpha-glycoprotein hormone subunit (alpha-GSU), LH-beta and FSH-beta subunit mRNAs. In OVX GPR-4 rats the LH pulse frequency but not pulse amplitude was decreased by 50% compared to wild-type littermate controls. Assaying the same samples for FSH, the FSH pulse frequency and amplitude were unchanged. The plasma and anterior pituitary levels of LH in the GPR-4 rats were significantly decreased by approximately 45%, while the plasma but not anterior pituitary level of FSH was significantly decreased by 25%. As measured by real-time RT-PCR, the mRNA levels for the alpha-GSU in the GPR-4 rats were significantly decreased by 41%, the LH-beta subunit by 38% and the FSH-beta subunit by 28%. We conclude that in the castrated female GPR-4 rats the decreased GnRH pulse frequency results in decreased levels of LH and FSH and in the alpha- and beta-subunit mRNA levels. Copyright 2003 S. Karger AG, Basel

  13. Estradiol and corticosterone stimulate the proliferation of a GH cell line, MtT/S: Proliferation of growth hormone cells.

    Science.gov (United States)

    Nogami, Haruo; Hiraoka, Yoshiki; Aiso, Sadakazu

    2016-08-01

    Estrogens are known as a potent growth-stimulator of the anterior pituitary cells such as prolactin cells and somatomammotroph cell lines, while glucocorticoids often inhibit cellular proliferation in the pituitary gland as well as in the extra-pituitary tissues. In this study, the involvement of these steroid hormones in the regulation of proliferation was examined in the MtT/S cells, secreting growth hormone (GH). Effects of estrogens and glucocorticoids were examined in MtT/S cells grown in the medium containing dextran-coated charcoal treated serum. The relative cell density after culture was estimated by the Cell Titer-Glo Luminescent Cell Viability Assay System, and the proliferation rate was determined by the BrdU incorporation method. The mRNA levels were determined by real-time PCR. Estradiol and the specific agonist for both estrogen receptor (ER) α and ERβ stimulated MtT/S growth at a dose dependent manner. The membrane impermeable estrogen, 17β-estradiol-bovine serum albumin conjugate also stimulated the MtT/S proliferation. The effects of all estrogens were inhibited by an estrogen receptor antagonist, ICI182780. Corticosterone stimulated the proliferation of MtT/S cells at doses lower than 10nM without stimulating GH gene transcription, whereas it did not change the proliferation rate at 1μM. The effects of corticosterone were inhibited by glucocorticoid receptor inhibitor, RU486, but not by the mineralocorticoid receptor antagonist, spironolactone. Both estrogens and glucocorticoids were found to stimulate the proliferation of MtT/S, increasing the mRNA expression of cyclins D1, D3, and E. The results suggest that estrogens and glucocorticoids may be involved in the mechanisms responsible for the proliferation of GH cells in the course of pituitary development, to maintain the population of GH cells in the adult pituitary gland, and also in the promotion of GH cell tumors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Melatonin in the thyroid gland: regulation by thyroid-stimulating hormone and role in thyroglobulin gene expression.

    Science.gov (United States)

    Garcia-Marin, R; Fernandez-Santos, J M; Morillo-Bernal, J; Gordillo-Martinez, F; Vazquez-Roman, V; Utrilla, J C; Carrillo-Vico, A; Guerrero, J M; Martin-Lacave, I

    2015-10-01

    Melatonin is an indoleamine with multiple functions in both plant and animal species. In addition to data in literature describing many other important roles for melatonin, such as antioxidant, circadian rhythm controlling, anti-aging, antiproliferative or immunomodulatory activities, our group recently reported that thyroid C-cells synthesize melatonin and suggested a paracrine role for this molecule in the regulation of thyroid activity. To discern the role played by melatonin at thyroid level and its involvement in the hypothalamic-pituitary-thyroid axis, in the present study we have analyzed the effect of thyrotropin in the regulation of the enzymatic machinery for melatonin biosynthesis in C cells as well as the effect of melatonin in the regulation of thyroid hormone biosynthesis in thyrocytes. Our results show that the key enzymes for melatonin biosynthesis (AANAT and ASMT) are regulated by thyroid-stimulating hormone. Furthermore, exogenous melatonin increases thyroglobulin expression at mRNA and protein levels on cultured thyrocytes and this effect is not strictly mediated by the upregulation of TTF1 or, noteworthy, PAX8 transcription factors. The present data show that thyroid C-cells synthesize melatonin under thyroid-stimulating hormone control and, consistently with previous data, support the hypothesis of a paracrine role for C-cell-synthesised melatonin within the thyroid gland. Additionally, in the present study we show evidence for the involvement of melatonin in thyroid function by directly-regulating thyroglobulin gene expression in follicular cells.

  15. The plant hormone abscisic acid increases in human plasma after hyperglycemia and stimulates glucose consumption by adipocytes and myoblasts.

    Science.gov (United States)

    Bruzzone, Santina; Ameri, Pietro; Briatore, Lucia; Mannino, Elena; Basile, Giovanna; Andraghetti, Gabriella; Grozio, Alessia; Magnone, Mirko; Guida, Lucrezia; Scarfì, Sonia; Salis, Annalisa; Damonte, Gianluca; Sturla, Laura; Nencioni, Alessio; Fenoglio, Daniela; Fiory, Francesca; Miele, Claudia; Beguinot, Francesco; Ruvolo, Vittorio; Bormioli, Mariano; Colombo, Giuseppe; Maggi, Davide; Murialdo, Giovanni; Cordera, Renzo; De Flora, Antonio; Zocchi, Elena

    2012-03-01

    The plant hormone abscisic acid (ABA) is released from glucose-challenged human pancreatic β cells and stimulates insulin secretion. We investigated whether plasma ABA increased during oral and intravenous glucose tolerance tests (OGTTs and IVGTTs) in healthy human subjects. In all subjects undergoing OGTTs (n=8), plasma ABA increased over basal values (in a range from 2- to 9-fold). A positive correlation was found between the ABA area under the curve (AUC) and the glucose AUC. In 4 out of 6 IVGTTs, little or no increase of ABA levels was observed. In the remaining subjects, the ABA increase was similar to that recorded during OGTTs. GLP-1 stimulated ABA release from an insulinoma cell line and from human islets, by ∼10- and 2-fold in low and high glucose, respectively. Human adipose tissue also released ABA in response to high glucose. Nanomolar ABA stimulated glucose uptake, similarly to insulin, in rat L6 myoblasts and in murine 3T3-L1 cells differentiated to adipocytes, by increasing GLUT-4 translocation to the plasma membrane. Demonstration that a glucose load in humans is followed by a physiological rise of plasma ABA, which can enhance glucose uptake by adipose tissues and muscle cells, identifies ABA as a new mammalian hormone involved in glucose metabolism.

  16. A genome-wide association study of thyroid stimulating hormone and free thyroxine in Danish children and adolescents

    DEFF Research Database (Denmark)

    Nielsen, Tenna Ruest Haarmark; Appel, Emil Vincent Rosenbaum; Svendstrup, Mathilde

    2017-01-01

    BackgroundHypothyroidism is associated with obesity, and thyroid hormones are involved in the regulation of body composition, including fat mass. Genome-wide association studies (GWAS) in adults have identified 19 and 6 loci associated with plasma concentrations of thyroid stimulating hormone (TSH......) and free thyroxine (fT4), respectively.ObjectiveThis study aimed to identify and characterize genetic variants associated with circulating TSH and fT4 in Danish children and adolescents and to examine whether these variants associate with obesity.MethodsGenome-wide association analyses of imputed genotype...... data with fasting plasma concentrations of TSH and fT4 from a population-based sample of Danish children, adolescents, and young adults, and a group of children, adolescents, and young adults with overweight and obesity were performed (N = 1,764, mean age = 12.0 years [range 2.5-24.7]). Replication...

  17. Effect of rabbit doe-litter separation on 24-hour changes of luteinizing hormone, follicle stimulating hormone and prolactin release in female and male suckling pups

    Directory of Open Access Journals (Sweden)

    Cardinali Daniel P

    2005-09-01

    Full Text Available Abstract Background The daily pattern of nursing of the rabbit pup by the doe is the most important event in the day for the newborn and is neatly anticipated by them. Such anticipation presumably needs a close correlation with changes in hormones that will allow the pups to develop an appropriate behavior. Although a number of circadian functions have been examined in newborn rabbits, there is no information on 24-h pattern of gonadotropin release or on possible sex-related differences in gonadotropin or prolactin (PRL release of pups. This study examined the 24-h changes of plasma luteinizing hormone (LH, follicle stimulating hormone (FSH and prolactin (PRL in 11 days old suckling female and male rabbits left with the mother or after short-term (i.e., 48 h doe-litter separation. Methods Animals were kept under controlled light-dark cycles (16 h – 8 h; lights on at 08:00 h. On day 9 post partum, groups of 6–7 female or male rabbit pups were separated from their mothers starting at 6 different time intervals in the 24 h cycle. Pups were killed 48 h after separation. At each time interval groups of male or female pups that stayed with the mother were killed as controls. Plasma, LH, FSH and PRL levels were measured by specific radioimmunoassays. Results In pups kept with their mother plasma FSH and LH maxima occurred at the first and second part of the light phase (at 13:00 and 17:00 – 21:00 h, respectively (females or as two peaks for each of the hormones (at 13:00 and 01:00 h (males. PRL release was similar in female and male rabbit pups kept with their mother, showing a 24-h pattern with two peaks, at 13:00 and 01:00 h, respectively. Mean 24-h values of gonadotropins and PRL did not differ between sexes. Isolation of pups for 48 h augmented circulating gonadotropin and PRL levels and distorted hormone 24-h pattern to a similar extent in both sexes. Conclusion Significant sex differences in 24-h changes in LH and FSH, but not in PRL

  18. Amides from Piper nigrum L. with dissimilar effects on melanocyte proliferation in-vitro.

    Science.gov (United States)

    Lin, Zhixiu; Liao, Yonghong; Venkatasamy, Radhakrishnan; Hider, Robert C; Soumyanath, Amala

    2007-04-01

    Melanocyte proliferation stimulants are of interest as potential treatments for the depigmentary skin disorder, vitiligo. Piper nigrum L. (Piperaceae) fruit (black pepper) water extract and its main alkaloid, piperine (1), promote melanocyte proliferation in-vitro. A crude chloroform extract of P. nigrum containing piperine was more stimulatory than an equivalent concentration of the pure compound, suggesting the presence of other active components. Piperine (1), guineensine (2), pipericide (3), N-feruloyltyramine (4) and N-isobutyl-2E, 4E-dodecadienamide (5) were isolated from the chloroform extract. Their activity was compared with piperine and with commercial piperlongumine (6) and safrole (7), and synthetically prepared piperettine (8), piperlonguminine (9) and 1-(3, 4-methylenedioxyphenyl)-decane (10). Compounds 6-10 either occur in P. nigrum or are structurally related. Compounds 1, 2, 3, 8 and 9 stimulated melanocyte proliferation, whereas 4, 5, 6, 7 and 10 did not. Comparison of structures suggests that the methylenedioxyphenyl function is essential for melanocyte stimulatory activity. Only those compounds also possessing an amide group were active, although the amino component of the amide group and chain linking it to the methylenedioxyphenyl group can vary. P. nigrum, therefore, contains several amides with the ability to stimulate melanocyte proliferation. This finding supports the traditional use of P. nigrum extracts in vitiligo and provides new lead compounds for drug development for this disease.

  19. The effect of follicular fluid hormones on oocyte recovery after ovarian stimulation: FSH level predicts oocyte recovery

    Directory of Open Access Journals (Sweden)

    Rinaudo Paolo F

    2009-04-01

    Full Text Available Abstract Background Ovarian stimulation for assisted reproductive technology (ART overcomes the physiologic process to develop a single dominant follicle. However, following stimulation, egg recovery rates are not 100%. The objective of this study is to determine if the follicular fluid hormonal environment is associated with oocyte recovery. Methods This is a prospective study involving patients undergoing ART by standard ovarian stimulation protocols at an urban academic medical center. A total of 143 follicular fluid aspirates were collected from 80 patients. Concentrations of FSH, hCG, estradiol, progesterone, testosterone and prolactin were determined. A multivariable regression analysis was used to investigate the relationship between the follicular fluid hormones and oocyte recovery. Results Intrafollicular FSH was significantly associated with oocyte recovery after adjustment for hCG (Adjusted odds ratio (AOR = 1.21, 95%CI 1.03–1.42. The hCG concentration alone, in the range tested, did not impact the odds of oocyte recovery (AOR = 0.99, 95%CI 0.93–1.07. Estradiol was significantly associated with oocyte recovery (AOR = 0.98, 95% CI 0.96–0.99. After adjustment for progesterone, the strength of association between FSH and oocyte recovery increased (AOR = 1.84, 95%CI 1.45–2.34. Conclusion The relationship between FSH and oocyte recovery is significant and appears to work through mechanisms independent of the sex hormones. FSH may be important for the physiologic event of separation of the cumulus-oocyte complex from the follicle wall, thereby influencing oocyte recovery. Current methods for inducing the final stages of oocyte maturation, with hCG administration alone, may not be optimal. Modifications of treatment protocols utilizing additional FSH may enhance oocyte recovery.

  20. Growth hormone responsiveness: peak stimulated growth hormone levels and other variables in idiopathic short stature (ISS): data from the National Cooperative Growth Study.

    Science.gov (United States)

    Moore, Wayne V; Dana, Ken; Frane, James; Lippe, Barbara

    2008-09-01

    In children with idiopathic short stature (ISS), growth hormone (GH) response to a provocative test will be inversely related to the first year response to hGH and be a variable accounting for a degree of responsiveness. Because high levels of GH are a characteristic of GH insensitivity, such as in Laron syndrome, it is possible that a high stimulated GH is associated with a lower first year height velocity among children diagnosed as having ISS. We examined the relationship between the peak stimulated GH levels in 3 ISS groups; GH >10 -40 ng/mL and the first year growth response to rhGH therapy. We also looked at 8 other predictor variables (age, sex, height SDS, height age, body mass index (BMI), bone age, dose, and SDS deficit from target parental height. Multiple regression analysis with the first year height as the dependent variable and peak stimulated GH was the primary endpoint. The predictive value of adding each of the other variables was then assessed. Mean change in height velocity was similar among the three groups, with a maximum difference among the groups of 0.6 cm/yr. There was a small but statistically significant correlation (r=-0.12) between the stimulated GH and first year height velocity. The small correlation between first year growth response and peak GH is not clinically relevant in defining GH resistance. No cut off level by peak GH could be determined to enhance the usefulness of this measure to predict response. Baseline age was the only clinically significant predictor, R-squared, 6.4%. All other variables contributed less than an additional 2% to the R-squared.

  1. The effect of long-term thyroid-stimulating hormone suppressive therapy on the gonadal steroid hormones of patients with thyroid carcinoma after surgery.

    Science.gov (United States)

    Liu, Xiaoli; Zhou, Ying; Liang, Nan; Hong, Yang; Dionigi, Gianlorenzo; Sun, Hui

    2017-10-01

    To analyze the effect of long-term thyroid-stimulating hormone (TSH) suppressive therapy on the gonadal hormones and related symptoms in patients after surgery. From 2008 to 2011, totally 238 patients were recruited, who underwent thyroid surgery and subsequent TSH suppression treatment in Department of thyroid Surgery, China-Japan Union hospital, Jilin University. Then their postoperative follow-up data (3-8 years) were collected, including operational method, pathological diagnosis, whether processed radioiodine therapy and the period/dose of TSH suppression treatment. In addition, the menstrual cycle, menstruation quantity, whether accompanied with dysmenorrheal and menstrual disorder or not, date of last menstrual period, ages of menopause and so on were also collected. (I) Neither the level nor the duration of TSH treatment had any function on estradiol (E2) and testosterone (T) in male patients; (II) in the subgroup of patients with TSH treatment for 3-5 years, patients who took high dose of TSH (TSH ≥0.5 U/L) obtained the lower T level compared with the group of medium dose (1.08±0.34 vs. 1.36±0.46 nmol/L, P=0.001); (III) in the medium dose (0.1 IU/L ≤ TSH hormone (FSH) did not show any change in terms of the dose and the duration of TSH treatment; (V) the menstrual volume, dysmenorrhea condition, menstrual cycle and menopause related indicators did not show any difference in terms of doses and duration of TSH treatment (P=0.701, 0.412 and 0.507 respectively). The long term of TSH repressive therapy after surgery did not affect T and E2 level in male patients. As for female patients, the impact was mainly reflected in the T and E2 levels especially in female sexual maturity but not FSH level. In addition, TSH treatment did not play any role on menstruation or menopause.

  2. Serum levels of thyroid hormones and thyroid stimulating hormone in patients with biliogenic and hyperlipidaemic acute pancreatitis: Difference and value in predicting disease severity.

    Science.gov (United States)

    Yang, Ning; Zhang, Dong-Lei; Hao, Jian-Yu; Wang, Guang

    2016-04-01

    To compare retrospectively serum levels of thyroid hormones (THs) and thyroid stimulating hormone (TSH) between patients with biliogenic acute pancreatitis (BAP) and those with hyperlipidaemic acute pancreatitis (HLAP), in order to assess their value for predicting the severity of acute pancreatitis (AP). Patients with AP were divided into BAP and HLAP groups, then further divided into either a mild AP (MAP) group or a moderately severe AP (MSAP) group. Routine blood parameters were measured. Free tri-iodothyronine (FT3), free thyroxine (FT4) and TSH levels were measured. Seventy-six patients with AP were enrolled in the study. FT3 and TSH levels were significantly higher in patients with MAP than in patients with MSAP. FT4 and TSH levels were significantly lower in the HLAP group than in the BAP group. TSH levels in both MAP and MSAP patients were significantly lower in the HLAP group than in the BAP group. TSH was inversely correlated with triglyceride levels in patients with HLAP. FT3 was a risk factor for MSAP in patients with AP and also demonstrated moderate accuracy in predicting AP severity. THs and TSH decrease with the severity of AP, especially in patients with HLAP. FT3 may be a useful biomarker for the early assessment of the severity of AP. © The Author(s) 2016.

  3. Melanocyte stem cell maintenance and hair graying.

    Science.gov (United States)

    Steingrímsson, Eiríkur; Copeland, Neal G; Jenkins, Nancy A

    2005-04-08

    Hair graying is an obvious sign of human aging, yet little was known about its causes. Two recent papers provide compelling evidence that hair graying is due to incomplete melanocyte stem cell maintenance and identify Pax3 and Mitf as key molecules that help regulate the balance between melanocyte stem cell maintenance and differentiation.

  4. Melanocyte colonization and pigmentation of breast carcinoma

    DEFF Research Database (Denmark)

    Mele, Marco; Laurberg, Tinne; Engberg Damsgaard, Tine

    2012-01-01

    Introduction. Melanocyte colonization of breast carcinoma by nonneoplastic melanocytes of epidermal origin is a rare and serious condition first described in 1977. We report on the exceptional clinical and pathological features of this migration phenomenon in a 74-year-old patient. Discussion...

  5. Genetics Home Reference: giant congenital melanocytic nevus

    Science.gov (United States)

    ... Additional NIH Resources (1 link) National Cancer Institute: What is Melanoma Educational Resources (10 links) Children's Hospital of Philadelphia: ... Large congenital melanocytic nevus Seattle Children's Hospital: Birthmarks What is a Large/Giant Congenital Melanocytic ... Organization for Rare Disorders (NORD) Nevus Outreach ...

  6. Population Pharmacokinetic Modelling of FE 999049, a Recombinant Human Follicle-Stimulating Hormone, in Healthy Women After Single Ascending Doses

    DEFF Research Database (Denmark)

    Rose, Trine Høyer; Röshammar, Daniel; Erichsen, Lars

    2016-01-01

    Objective: The purpose of this analysis was to develop a population pharmacokinetic model for a novel recombinant human follicle-stimulating hormone (FSH) (FE 999049) expressed from a human cell line of foetal retinal origin (PER.C6) developed for controlled ovarian stimulation prior to assisted...... effects population pharmacokinetic modelling in NONMEM 7.2.0. Results: A one-compartment model with first-order absorption and elimination rates was found to best describe the data. A transit model was introduced to describe a delay in the absorption process. The apparent clearance (CL/F) and apparent...... volume of distribution (V/F) estimates were found to increase with body weight. Body weight was included as an allometrically scaled covariate with a power exponent of 0.75 for CL/F and 1 for V/F. Conclusions: The single-dose pharmacokinetics of FE 999049 were adequately described by a population...

  7. Repetitive Stimulation of the Pituitary with Growth-Hormone-Releasing Hormone Alters the Proportion of 22 and 20 Kilodalton Human-Growth Hormone Released

    Directory of Open Access Journals (Sweden)

    Peter C. Hindmarsh

    2010-01-01

    Full Text Available Background/Aims. 20 Kilodalton-hGH (20 K-hGH is the second most abundant pituitary GH variant after 22 K-hGH. In the steady state the proportion of 20 : 22 K-hGH appears constant; does this proportion change with repetitive somatotroph stimulation? Methods. Forty adult males were randomised to receive a GHRH(1–29NH2 bolus (0.5 μg/kg (n=20 or 1.0 μg/kg (n=20, preceded or followed by a saline bolus, 1 week apart. Four to six weeks later, 10 subjects received 0.5 μg/kg GHRH(1–29NH2 at 0, 60, 120, and 180 minutes. Clearance rate of 22 and 20 K-hGH was measured in 10 subjects. Results. Total amount/proportion of 22 K-hGH/20 K-hGH secreted was similar for both GHRH(1–29NH2 doses. Repetitive stimulation reduced the amount of 22 K-hGH released whereas the amount of 20 K-hGH did not change significantly leading to an increase in the proportion of 20 K-hGH (P=.05. Half-life of 20 and 22 K-hGH were not significantly different (P=.55. Conclusions. Repetitive stimulation of the somatotroph may alter the proportion of GH variant released.

  8. Repetitive Stimulation of the Pituitary with Growth-Hormone-Releasing Hormone Alters the Proportion of 22 and 20 Kilodalton Human-Growth Hormone Released

    Directory of Open Access Journals (Sweden)

    Robinson IainCAF

    2010-05-01

    Full Text Available Background/Aims. 20 Kilodalton-hGH (20 K-hGH is the second most abundant pituitary GH variant after 22 K-hGH. In the steady state the proportion of 20 : 22 K-hGH appears constant; does this proportion change with repetitive somatotroph stimulation? Methods. Forty adult males were randomised to receive a GHRH(1–29 bolus   ( or   (, preceded or followed by a saline bolus, 1 week apart. Four to six weeks later, 10 subjects received   GHRH(1–29 at 0, 60, 120, and 180 minutes. Clearance rate of 22 and 20 K-hGH was measured in 10 subjects. Results. Total amount/proportion of 22 K-hGH/20 K-hGH secreted was similar for both GHRH(1–29 doses. Repetitive stimulation reduced the amount of 22 K-hGH released whereas the amount of 20 K-hGH did not change significantly leading to an increase in the proportion of 20 K-hGH . Half-life of 20 and 22 K-hGH were not significantly different . Conclusions. Repetitive stimulation of the somatotroph may alter the proportion of GH variant released.

  9. Hormonal control of luminescence from lantern shark (Etmopterus spinax) photophores.

    Science.gov (United States)

    Claes, Julien M; Mallefet, Jérôme

    2009-11-01

    The velvet belly lantern shark (Etmopterus spinax) emits a blue luminescence from thousands of tiny photophores. In this work, we performed a pharmacological study to determine the physiological control of luminescence from these luminous organs. Isolated photophore-filled skin patches produced light under melatonin (MT) and prolactin (PRL) stimulation in a dose-dependent manner but did not react to classical neurotransmitters. The alpha-melanocyte-stimulating hormone (alpha-MSH) had an inhibitory effect on hormonal-induced luminescence. Because luzindole and 4P-PDOT inhibited MT-induced luminescence, the action of this hormone is likely to be mediated through binding to the MT2 receptor subtype, which probably decreases the intracellular concentration of cyclic AMP (cAMP) because forskolin (a cAMP donor) strongly inhibits the light response to MT. However, PRL seems to achieve its effects via janus kinase 2 (JAK2) after binding to its receptor because a specific JAK2 inhibitor inhibits PRL-induced luminescence. The two stimulating hormones showed different kinetics as well as a seasonal variation of light intensity, which was higher in summer (April) than in winter (December and February). All of these results strongly suggest that, contrary to self-luminescent bony fishes, which harbour a nervous control mechanism of their photophore luminescence, the light emission is under hormonal control in the cartilaginous E. spinax. This clearly highlights the diversity of fish luminescence and confirms its multiple independent apparitions during the course of evolution.

  10. Effect of race, gender and age on thyroid and thyroid stimulating hormone levels in north west frontier province, Pakistan

    International Nuclear Information System (INIS)

    Ahmed, Z.; Khan, M.A.; Haq, A.U.

    2009-01-01

    Thyroid is one of the ductless endocrine gland, which is located immediately below the larynx on either side of and anterior to the trachea. The principal hormones of thyroid gland are thyroxine (T4) and triiodothyronine (T3). The current study was carried out to investigate the impact of race, gender and area on the levels of Thyroxine (T4), Triiodothyronine (T3) and Thyroid Stimulating Hormone (TSH) in normal healthy individuals. Methods: Serum levels of T4, T3 and TSH in 498 normal healthy individuals belonging to different districts of North West Frontier Province, Pakistan, were examined. Serum T4 and T3 were analysed by Radio Immuno Assay (RIA) method whereas TSH was estimated by Immunoradiometric assay (IRMA) method. Results: Levels of T4, T3 and TSH ranged from 53 to 167 m mu mol/L and 0.3-4.8 mu mol/L respectively. The levels of these hormones show significant change from the reference values that are used in clinical laboratories as well as in Institute of Rauclear Medicine (IRNUM), Peshawar, Pakistan. Conclusion: It is concluded that the age, gender, race and area, all have an appreciable effect on the levels T4, T3 and TSH. (author)

  11. Amenorrhea secondary to a vismodegib-induced blockade of follicle-stimulating hormone-receptor activation.

    Science.gov (United States)

    Strasswimmer, John; Latimer, Benjamin; Ory, Steven

    2014-08-01

    To report a novel mechanism suggestive of early ovarian failure secondary to the anti-tumor hedgehog-pathway inhibitor vismodegib. Case report and literature review. Academic and private dermatology and fertility practices. A 34-year-old nulliparous woman with locally advanced basal cell carcinomas who became amenorrheic while receiving oral therapy with vismodegib. Physical examination and endocrine evaluation. Elevated follicle-stimulating hormone (FSH) and low estrogen in the setting of a normal anti-Müllerian hormone. FSH was elevated; estrogen was low. Preantral follicles were detected and anti-Müllerian hormone activity was normal. Menses resumed 5 weeks after cessation of therapy. Vismodegib, a first-in-class inhibitor of the hedgehog signaling pathway is indicated for advanced basal cell carcinoma and is associated with amenorrhea. The mechanism is unknown; it has some features of ovarian failure but preserves ovarian potential through blockading of FSH-receptor-dependent signal transduction. This effect appears to be rapidly reversible upon cessation of therapy. Vismodegib and related compounds may have potential for a role in intervention for gynecologic and endocrine disorders and in therapy for other issues involving FSH-dependent function. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  12. Negative energy balance in a male songbird, the Abert's towhee, constrains the testicular endocrine response to luteinizing hormone stimulation

    Science.gov (United States)

    Davies, Scott; Gao, Sisi; Valle, Shelley; Bittner, Stephanie; Hutton, Pierce; Meddle, Simone L.; Deviche, Pierre

    2015-01-01

    ABSTRACT Energy deficiency can suppress reproductive function in vertebrates. As the orchestrator of reproductive function, endocrine activity of the hypothalamo-pituitary–gonadal (HPG) axis is potentially an important mechanism mediating such effects. Previous experiments in wild-caught birds found inconsistent relationships between energy deficiency and seasonal reproductive function, but these experiments focused on baseline HPG axis activity and none have investigated the responsiveness of this axis to endocrine stimulation. Here, we present data from an experiment in Abert's towhees, Melozone aberti, using gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) challenges to investigate whether energy deficiency modulates the plasma testosterone responsiveness of the HPG axis. Wild-caught birds were either ad libitum fed or energetically constrained via chronic food restriction during photoinduced reproductive development. Energy deficiency did not significantly affect the development of reproductive morphology, the baseline endocrine activity of the HPG axis, or the plasma testosterone response to GnRH challenge. Energy deficiency did, however, decrease the plasma testosterone responsiveness to LH challenge. Collectively, these observations suggest that energy deficiency has direct gonadal effects consisting of a decreased responsiveness to LH stimulation. Our study, therefore, reveals a mechanism by which energy deficiency modulates reproductive function in wild birds in the absence of detectable effects on baseline HPG axis activity. PMID:26333925

  13. The plant hormone abscisic acid stimulates the proliferation of human hemopoietic progenitors through the second messenger cyclic ADP-ribose.

    Science.gov (United States)

    Scarfì, Sonia; Fresia, Chiara; Ferraris, Chiara; Bruzzone, Santina; Fruscione, Floriana; Usai, Cesare; Benvenuto, Federica; Magnone, Mirko; Podestà, Marina; Sturla, Laura; Guida, Lucrezia; Albanesi, Ennio; Damonte, Gianluca; Salis, Annalisa; De Flora, Antonio; Zocchi, Elena

    2009-10-01

    Abscisic acid (ABA) is a hormone involved in pivotal physiological functions in higher plants, such as response to abiotic stress and control of seed dormancy and germination. Recently, ABA was demonstrated to be autocrinally produced by human granulocytes, beta pancreatic cells, and mesenchymal stem cells (MSC) and to stimulate cell-specific functions through a signaling pathway involving the second messenger cyclic ADP-ribose (cADPR). Here we show that ABA expands human uncommitted hemopoietic progenitors (HP) in vitro, through a cADPR-mediated increase of the intracellular calcium concentration ([Ca(2+)](i)). Incubation of CD34(+) cells with micromolar ABA also induces transcriptional effects, which include NF-kappaB nuclear translocation and transcription of genes encoding for several cytokines. Human MSC stimulated with a lymphocyte-conditioned medium produce and release ABA at concentrations sufficient to exert growth-stimulatory effects on co-cultured CD34(+) cells, as demonstrated by the inhibition of colony growth in the presence of an anti-ABA monoclonal antibody. These results provide a remarkable example of conservation of a stress hormone and of its second messenger from plants to humans and identify ABA as a new hemopoietic growth factor involved in the cross-talk between HP and MSC.

  14. Local administration of growth hormone stimulates tendon collagen synthesis in elderly men

    DEFF Research Database (Denmark)

    Vestergaard, P; Jørgensen, J.O.L.; Olesen, J.L.

    2012-01-01

    Tendon collagen content and circulating growth hormone (GH) are reduced in elderly. In a placebo-controlled, double-blinded study, we examined if local injections of rhGH enhance collagen synthesis in healthy elderly men (61 ± 1 yr). Two injections of rhGH or saline (control) were injected into e...

  15. Lipid mobilization and locomotor stimulation in Gryllus bimaculatus by topically applied adipokinetic hormone

    Czech Academy of Sciences Publication Activity Database

    Lorenz, M. W.; Zemek, Rostislav; Kodrík, Dalibor; Socha, Radomír

    2004-01-01

    Roč. 29, - (2004), s. 146-151 ISSN 0307-6962 R&D Projects: GA AV ČR IAA6007202 Institutional research plan: CEZ:AV0Z5007907 Keywords : Adipokinetic hormone * cricket * Grybi-AKH Subject RIV: ED - Physiology Impact factor: 1.352, year: 2004

  16. Effect of chronic exposure to gamma radiation and of hormonal stimulation with serum gonadotropin on catecholamine levels in hypothalamus, epiphysis and adrenals of ewes

    International Nuclear Information System (INIS)

    Pastorova, B.; Arendarcik, J.

    1989-01-01

    The effects were studied of exposure to whole body continuous irradiation and of the administration of serum gonadotropin (SG) on the concentration of catecholamines (epinephrine and norepinephrine) in the hypothalamus, epiphysis and adrenal glands of ewes during the anestric period with synchronized estrus. The first group (young barren ewes) and second group (older ewes) were exposed to continuous radiation of 60 Co for five days. The radiation was applied at a rate of 0.020 Gy per hour. After the termination of irradiation the ewes were subjected to hormonal stimulation by fractionated administration of 1500 I.U. SG. The third and fourth experimental groups of ewes were stimulated with 1500 I.U. SG without irradiation. Catecholamines were separated from the tissue supernatants by adsorption chromatography and the catecholamine contents in the eluates were determined spectrofluorometrically. Chronic exposure to gamma radiation and hormonal stimulation with SG reduced the concentration of norepinephrine in the whole hypothalamus of the sheep. A statistically significant decrease (P<0.001) was recorded in the medial and caudal hypothalamus of the adult ewes and in the rostral and caudal hypothalamus regions of the young ewes. A decrease in norepinephrine concentration, statistically significant in the caudal (P<0.01) and medial hypothalamus was recorded in the group of adult ewes after hormonal stimulation with SG without irradiation. The experimental group of young ewes responded to hormonal stimulation by a greater reduction of norepinephrine contents as compared with combined exposure to radiation and hormonal stimulation. It is assumed that the decrease in catecholamine concentration after hormonal stimulation with SG is associated with the increase in the contents of estrogens which act on the adrenergic receptors of the hypothalamus. (author). 4 figs., 21 refs

  17. Does the time interval between antimüllerian hormone serum sampling and initiation of ovarian stimulation affect its predictive ability in in vitro fertilization-intracytoplasmic sperm injection cycles with a gonadotropin-releasing hormone antagonist?

    DEFF Research Database (Denmark)

    Polyzos, Nikolaos P; Nelson, Scott M; Stoop, Dominic

    2013-01-01

    To investigate whether the time interval between serum antimüllerian hormone (AMH) sampling and initiation of ovarian stimulation for in vitro fertilization-intracytoplasmic sperm injection (IVF-ICSI) may affect the predictive ability of the marker for low and excessive ovarian response.......To investigate whether the time interval between serum antimüllerian hormone (AMH) sampling and initiation of ovarian stimulation for in vitro fertilization-intracytoplasmic sperm injection (IVF-ICSI) may affect the predictive ability of the marker for low and excessive ovarian response....

  18. Thyroid hormone stimulated glucose uptake in human mononuclear blood cells from normal persons and from patients with non-insulin-dependent diabetes mellitus

    DEFF Research Database (Denmark)

    Kvetny, J; Matzen, L

    1989-01-01

    of stimulation of cells from control subjects and patients with NIDDM revealed an identical oxygen consumption, whereas the thyroid hormone-induced glucose uptake was significantly increased in cells from patients with NIDDM. T4 (5 mumol/l) stimulation in controls: 1.34 +/- 0.23 mmol.l-1 (mg DNA)-1.h-1, in NIDDM...... an increased thyroid hormone induced glucose uptake, indicating increased thyroid hormone sensitivity. This observation contrasts the well known insulin insensitivity, suggesting separate mechanisms for glucose uptake elicited by insulin and thyroid hormones....... by physiological and supraphysiological concentrations of T3 and T4 in a dose-dependent manner (50-5000 nmol/l), whereas rT3 and T2 had no stimulatory effect. The effect of T3 and T4 was independent of new protein synthesis in that it was not blocked by tunicamycin (1 mg/l) and tiothepa (75 mg/l). Examination...

  19. Sick leave for follow-up control in thyroid cancer patients: comparison between stimulation with Thyrogen and thyroid hormone withdrawal.

    Science.gov (United States)

    Borget, I; Corone, C; Nocaudie, M; Allyn, M; Iacobelli, S; Schlumberger, M; De Pouvourville, G

    2007-05-01

    The clinical benefits of recombinant human thyroid-stimulating hormone (rhTSH; Thyrogen) are well established as an alternative stimulation procedure to thyroid hormone withdrawal in the diagnostic follow-up of thyroid cancer patients. By avoiding periods of hypothyroidism, patients do not suffer from a decreased quality of life and keep their ability to work. This study compared the frequency, the duration and the cost of sick leave for follow-up control between rhTSH and withdrawal. The study population consisted of patients with thyroid carcinoma first treated by thyroidectomy and radioiodine ablation. Patients were recruited at their control visit between October 2004 and May 2006 in three hospitals, both prospectively and retrospectively. Collection data consisted of patient information, job characteristics and duration of sick leave during the month before and the month after control. The valuation of sick leave used the friction cost method. Among the 306 patients included, 292 (95%) completed the entire questionnaire. The mean age was 46.7 years. Among the 194 active patients, patients treated with rhTSH, when compared with patients treated by withdrawal, were less likely to require sick leave (11 vs 33%; P=0.001). The mean duration of sick leave was shorter (3.1 vs 11.2 days; P=0.002) and indirect costs due to absenteeism accounted for 454 Euro +/- 1673 vs 1537 Euro +/- 2899 for withdrawal stimulation. For active patients, rhTSH treatment reduced the length and the cost of sick leave by 8.1 days and 1083 Euro per control respectively, when compared with withdrawal treatment.

  20. UVB-irradiated keratinocytes induce melanoma-associated ganglioside GD3 synthase gene in melanocytes via secretion of tumor necrosis factor α and interleukin 6

    Energy Technology Data Exchange (ETDEWEB)

    Miyata, Maiko [Department of Life and Medical Sciences, Chubu University Faculty of Life and Health Sciences, Matsumoto, Kasugai 487-8501 (Japan); Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Ichihara, Masatoshi; Tajima, Orie; Sobue, Sayaka; Kambe, Mariko [Department of Life and Medical Sciences, Chubu University Faculty of Life and Health Sciences, Matsumoto, Kasugai 487-8501 (Japan); Sugiura, Kazumitsu [Department of Dermatology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Furukawa, Koichi, E-mail: koichi@med.nagoya-u.ac.jp [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Furukawa, Keiko [Department of Life and Medical Sciences, Chubu University Faculty of Life and Health Sciences, Matsumoto, Kasugai 487-8501 (Japan); Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan)

    2014-03-07

    Highlights: • Melanocytes showed low ST8SIA1 and high B3GALT4 levels in contrast with melanomas. • Direct UVB irradiation of melanocytes did not induce ganglioside synthase genes. • Culture supernatants of UVB-irradiated keratinocytes induced ST8SIA1 in melanocytes. • TNFα and IL-6 secreted from keratinocytes enhanced ST8SIA1 expression in melanocytes. • Inflammatory cytokines induced melanoma-related ST8SIA1 in melanocytes. - Abstract: Although expression of gangliosides and their synthetic enzyme genes in malignant melanomas has been well studied, that in normal melanocytes has been scarcely analyzed. In particular, changes in expression levels of glycosyltransferase genes responsible for ganglioside synthesis during evolution of melanomas from melanocytes are very important to understand roles of gangliosides in melanomas. Here, expression of glycosyltransferase genes related to the ganglioside synthesis was analyzed using RNAs from cultured melanocytes and melanoma cell lines. Quantitative RT-PCR revealed that melanomas expressed high levels of mRNA of GD3 synthase and GM2/GD2 synthase genes and low levels of GM1/GD1b synthase genes compared with melanocytes. As a representative exogenous stimulation, effects of ultraviolet B (UVB) on the expression levels of 3 major ganglioside synthase genes in melanocytes were analyzed. Although direct UVB irradiation of melanocytes caused no marked changes, culture supernatants of UVB-irradiated keratinocytes (HaCaT cells) induced definite up-regulation of GD3 synthase and GM2/GD2 synthase genes. Detailed examination of the supernatants revealed that inflammatory cytokines such as TNFα and IL-6 enhanced GD3 synthase gene expression. These results suggest that inflammatory cytokines secreted from UVB-irradiated keratinocytes induced melanoma-associated ganglioside synthase genes, proposing roles of skin microenvironment in the promotion of melanoma-like ganglioside profiles in melanocytes.

  1. TRH [thyrotropin-releasing hormone] and BAY K 8644 synergistically stimulate prolactin release but not 45Ca2+ uptake

    International Nuclear Information System (INIS)

    Pachter, J.A.; Law, G.J.; Dannies, P.S.

    1988-01-01

    Thyrotropin-releasing hormone (TRH) and the Ca 2+ -channel agonist BAY K 8644 each induced transient increases in prolactin secretion from primary cultures of rat anterior pituitary cells in perfusion. When BAY K 8644 was added after a TRH-induced secretory peak, the additional effect of BAY K 8644 on prolactin release was approximately twofold greater over a 30-min period than the effect of BAY K 8644 on previously untreated cells. TRH and BAY K 8644 were also synergistic when added in the opposite order or simultaneously. Substitution of other agents for BAY K 8644 revealed that only high K + was at least additive with TRH in stimulating prolactin secretion; treatment with TRH inhibited, rather than facilitated, subsequent stimulation of prolactin secretion by angiotensin II or the ionophore A23187. The cooperative effect was not specific for TRH because BAY K 8644 also acted synergistically with angiotensin II or 40 mM K + . In GH 4 C 1 cells, in which TRH and BAY K 8644 were also synergistic in releasing prolactin, measurements with the fluorescent indicator indo-1 showed that TRH and BAY K 8644 could each elevate cytosolic Ca 2+ above the level stimulated by the other. Unexpectedly, TRH was found to inhibit BAY K 8644-stimulated 45 Ca 2+ uptake in both GH 4 C 1 and primary cultured cells. These results indicate that BAY K 8644 and TRH synergistically stimulate prolactin secretion by a mechanism other than a cooperative effect on the activity of dihydropyridine-sensitive Ca 2+ channels

  2. Melanocytes and melanin represent a first line of innate immunity against Candida albicans.

    Science.gov (United States)

    Tapia, Cecilia V; Falconer, Maryanne; Tempio, Fabián; Falcón, Felipe; López, Mercedes; Fuentes, Marisol; Alburquenque, Claudio; Amaro, José; Bucarey, Sergio A; Di Nardo, Anna

    2014-07-01

    Melanocytes are dendritic cells located in the skin and mucosae that synthesize melanin. Some infections induce hypo- or hyperpigmentation, which is associated with the activation of Toll-like receptors (TLRs), especially TLR4. Candida albicans is an opportunist pathogen that can switch between blastoconidia and hyphae forms; the latter is associated with invasion. Our objectives in this study were to ascertain whether C. albicans induces pigmentation in melanocytes and whether this process is dependent on TLR activation, as well as relating this with the antifungal activity of melanin as a first line of innate immunity against fungal infections. Normal human melanocytes were stimulated with C. albicans supernatants or with crude extracts of the blastoconidia or hyphae forms, and pigmentation and TLR2/TLR4 expression were measured. Expression of the melanosomal antigens Melan-A and gp100 was examined for any correlation with increased melanin levels or antifungal activity in melanocyte lysates. Melanosomal antigens were induced earlier than cell pigmentation, and hyphae induced stronger melanization than blastoconidia. Notably, when melanocytes were stimulated with crude extracts of C. albicans, the cell surface expression of TLR2/TLR4 began at 48 h post-stimulation and peaked at 72 h. At this time, blastoconidia induced both TLR2 and TLR4 expression, whereas hyphae only induced TLR4 expression. Taken together, these results suggest that melanocytes play a key role in innate immune responses against C. albicans infections by recognizing pathogenic forms of C. albicans via TLR4, resulting in increased melanin content and inhibition of infection. © The Author 2014. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Effects on steroid hormones secretion resulting from the acute stimulation of sectioning the superior ovarian nerve to pre-pubertal rats

    Directory of Open Access Journals (Sweden)

    Morales-Ledesma Leticia

    2012-10-01

    Full Text Available Abstract In the adult rat, neural signals arriving to the ovary via the superior ovarian nerve (SON modulate progesterone (P4, testosterone (T and estradiol (E2 secretion. The aims of the present study were to analyze if the SON in the pre-pubertal rat also modulates ovarian hormone secretion and the release of follicle stimulating hormone (FSH and luteinizing (LH hormone. P4, T, E2, FSH and LH serum levels were measured 30 or 60 minutes after sectioning the SON of pre-pubertal female rats. Our results indicate that the effects on hormone levels resulting from unilaterally or bilaterally sectioning the SON depends on the analyzed hormone, and the time lapse between surgery and autopsy, and that the treatment yielded asymmetric results. The results also suggest that in the pre-pubertal rat the neural signals arriving to the ovaries via the SON regulate the enzymes participating in P4, T and E2 synthesis in a non-parallel way, indicating that the mechanisms regulating the synthesis of each hormone are not regulated by the same signals. Also, that the changes in the steroids hormones are not explained exclusively by the modifications in gonadotropins secretion. The observed differences in hormone levels between rats sacrificed 30 and 60 min after surgery reflect the onset of the compensatory systems regulating hormones secretion.

  4. PAX3 expression in normal skin melanocytes and melanocytic lesions (naevi and melanomas.

    Directory of Open Access Journals (Sweden)

    Sandra Medic

    2010-04-01

    Full Text Available Cutaneous Malignant Melanoma is an aggressive form of skin cancer, arising in cutaneous melanocytes. The transcription factor PAX3 regulates melanocyte specification from neural crest cells during development but expression in differentiated melanocytes is uncertain. By contrast it is frequently found in melanomas and naevi and is a marker for melanoma staging and detection. In this study we analysed the expression of PAX3 across the spectrum of melanocytic cells, from normal melanocytes to cells of benign and malignant lesions to better assess its function in these various tissues. Pax3 and PAX3 (italicized refer to the mouse and human gene, respectively; whereas Pax3 and PAX3 (non-italicized refer to the corresponding mouse and human protein.PAX3 expression was analysed by immunohistochemistry and qRT-PCR. Immunofluorescence was used for co-expression with differentiation, migration and survival markers. As expected PAX3 expression was observed in naevi and melanoma cells. It was also found in melanocytes of normal skin where it co-expressed with melanocyte markers, MITF and MLANA. Co-expression with its downstream target, antiapoptotic factor BCL2L1 confirms PAX3 as a cell survival regulator. PAX3 was also co-expressed with melanoma cell migration marker MCAM in dermal naevi and melanoma cell nests, but this downstream target of PAX3 was not present in normal epidermal melanocytes, suggesting differential roles for PAX3 in normal epidermal melanocytes and melanoma cells. Most interestingly, a proportion of PAX3-positive epidermal melanocytes in normal skin show HES1 and Ki67 co-expression, indicating their less differentiated proliferative phenotype.Our results suggest that a previously identified role for PAX3, that of regulator of an undifferentiated plastic state, may operate in melanocytes of normal skin. This role, possibly required for cellular response to environmental stimuli, may contribute to formation and development of melanocytic

  5. Nanogold-polyaniline-nanogold microspheres-functionalized molecular tags for sensitive electrochemical immunoassay of thyroid-stimulating hormone

    Energy Technology Data Exchange (ETDEWEB)

    Cui Yuling; Chen Huafeng; Hou Li; Zhang Bing; Liu Bingqian; Chen Guonan [Ministry of Education Key Laboratory of Analysis and Detection for Food Safety, Fujian Province Key Laboratory of Analysis and Detection for Food Safety, Department of Chemistry and Chemical Engineering, Fuzhou University, Fuzhou 350108 (China); Tang Dianping, E-mail: dianping.tang@fzu.edu.cn [Ministry of Education Key Laboratory of Analysis and Detection for Food Safety, Fujian Province Key Laboratory of Analysis and Detection for Food Safety, Department of Chemistry and Chemical Engineering, Fuzhou University, Fuzhou 350108 (China)

    2012-08-13

    Highlights: Black-Right-Pointing-Pointer A novel immunosensing strategy was designed for detection of thyroid-stimulating hormone. Black-Right-Pointing-Pointer Using nanogold-polyaniline-nanogold microspheres as molecular tags. Black-Right-Pointing-Pointer Improvement of electrochemical activity of nanolabels. Black-Right-Pointing-Pointer Combination enzyme labels with nanolabels for signal amplification. - Abstract: Methods based on nanomaterial labels have been developed for electrochemical immunosensors and immunoassays, but most involved low sensitivity. Herein a novel class of molecular tags, nanogold-polyaniline-nanogold microspheres (GPGs), was first synthesized and functionalized with horseradish peroxidase-conjugated thyroid-stimulating hormone antibody (HRP-Ab{sub 2}) for sensitive electrochemical immunoassay of thyroid-stimulating hormone (TSH). X-ray diffraction, confocal Raman spectroscopy, scanning electron microscope and transmission electron microscope were employed to characterize the prepared GPGs. Based on a sandwich-type immunoassay format, the assay was performed in pH 5.0 acetate buffer containing 6.0 mmol L{sup -1} H{sub 2}O{sub 2} by using GPG-labeled HRP-Ab{sub 2} as molecular tags. Compared with pure polyaniline nanospheres and gold nanoparticles alone, the GPG hybrid nanostructures increased the surface area of the nanomaterials, and enhanced the immobilized amount of HRP-Ab{sub 2}. Several labeling protocols comprising HRP-Ab{sub 2}, nanogold particle-labeled HRP-Ab{sub 2}, and polyaniline nanospheres-labeled HRP-Ab{sub 2}, were also investigated for determination of TSH and improved analytical features were obtained by using the GPG-labeled HRP-Ab{sub 2}. With the GPG labeling method, the effects of incubation time and pH of acetate buffer on the current responses of the immunosensors were also studied. The strong attachment of HRP-Ab{sub 2} to the GPGs resulted in a good repeatability and intermediate precision down to 7%. The dynamic

  6. Induction of Chemokine Secretion and Monocyte Migration by Human Choroidal Melanocytes in Response to Proinflammatory Cytokines

    DEFF Research Database (Denmark)

    Jehs, Tina; Faber, Carsten; Udsen, Maja S.

    2016-01-01

    Purpose: To determine to which extent inflammatory cytokines affect chemokine secretion by primary human choroidal melanocytes (HCMs), their capacity to attract monocytes, and whether HCMs are able to influence the proliferation of activated T cells. Methods: Primary cultures of HCMs were...... established from eyes of 13 donors. Human choroidal melanocytes were stimulated with IFN-γ and TNF-α or with supernatant from activated T cells (T-cell–conditioned media [TCM]). Gene expression analysis was performed by using microarrays. Protein levels were quantified with ELISA or cytometric bead array...

  7. Human longevity is characterised by high thyroid stimulating hormone secretion without altered energy metabolism

    DEFF Research Database (Denmark)

    Jansen, S W; Akintola, A A; Roelfsema, F

    2015-01-01

    of nonagenarians with at least one nonagenarian sibling have increased TSH secretion but similar bioactivity of TSH and similar TH levels compared to controls. Healthy offspring and spousal controls had similar resting metabolic rate and core body temperature. We propose that pleiotropic effects of the HPT axis...... hormone (TH) in an inverse relationship. Greater longevity has been associated with higher TSH and lower TH levels, but mechanisms underlying TSH/TH differences and longevity remain unknown. The HPT axis plays a pivotal role in growth, development and energy metabolism. We report that offspring...... may favour longevity without altering energy metabolism....

  8. Corticotrophin-releasing hormone stimulation tests for the infants with relative adrenal insufficiency.

    Science.gov (United States)

    Iwanaga, Kougoro; Yamamoto, Akane; Matsukura, Takashi; Niwa, Fusako; Kawai, Masahiko

    2017-12-01

    Very low birthweight (VLBW) infants are considered to be vulnerable to relative adrenal insufficiency (RAI); however, diagnosis is difficult in some clinical settings. Considering this background, it is necessary to establish a diagnosis of RAI in preterm infants. In this study, we attempted to clarify the difference in response to CRH stimulation tests for preterm infants with or without RAI. Between June 2009 and December 2015, we performed CRH stimulation tests for preterm infants born at a gestational age of <30 weeks at around 2 weeks of age. Retrospectively, subjects were classified into two groups: infants with RAI (n = 9) or without RAI (n = 17) based on the clinical symptoms and responsiveness to hydrocortisone. We found no difference in base or peak serum cortisol levels related to CRH stimulation tests between the two groups; however, delta cortisol levels and responsive ratio (peak-to-base ratio) were significantly reduced in infants with RAI. 140 nmol/L for delta cortisol or 1.5 times for peak-to-base ratio may be cut-off levels in preterm infants. This study provides evidence that base cortisol levels of preterm infants with RAI were not different from those without RAI; however, CRH stimulation tests may be a useful tool for the diagnosis of RAI in preterm infants. © 2017 John Wiley & Sons Ltd.

  9. Is suppressed thyroid-stimulating hormone (TSH) associated with subclinical depression in the Danish General Suburban Population Study?

    DEFF Research Database (Denmark)

    Kvetny, Jan; Ellervik, Christina; Bech, Per

    2015-01-01

    BACKGROUND: The first phase of the Danish General Suburban Population Study (GESUS) including 8214 individuals was an attempt to evaluate the association between subclinical hypothyroidism without or with elevated peroxidase antibodies and depression. No such association was found. In the second...... phase, including 14,787 individuals, we have focused on suppressed TSH (thyroid-stimulating hormone) and depression. AIMS: To evaluate to what extent suppressed TSH is associated with subclinical depression. METHODS: The total scores of the Major Depression Inventory (MDI) were used to evaluate...... subclinical depression, both by its total score and by an algorithm of the subthreshold depressed by presence of at least three of the 10 ICD-10 depression symptoms. Serum levels of TSH were used to classify the individuals into suppressed (TSH

  10. Serum Thyroid-Stimulating Hormone Levels and Body Mass Index Percentiles in Children with Primary Hypothyroidism on Levothyroxine Replacement.

    Science.gov (United States)

    Shaoba, Asma; Basu, Sanjib; Mantis, Stelios; Minutti, Carla

    2017-12-15

    To determine the association, if any, between thyroid-stimulating hormone (TSH) levels and body mass index (BMI) percentiles in children with primary hypothyroidism who are chemically euthyroid and on treatment with levothyroxine. This retrospective cross-sectional study consisted of a review of medical records from RUSH Medical Center and Stroger Hospital, Chicago, USA of children with primary hypothyroidism who were seen in the clinic from 2008 to 2014 and who were chemically euthyroid and on treatment with levothyroxine for at least 6 months. The patients were divided into two groups based on their TSH levels (0.34-hypothyroidism who are chemically euthyroid on treatment with levothyroxine, there is a positive association between higher TSH levels and higher BMI percentiles. However, it is difficult to establish if the higher TSH levels are a direct cause or a consequence of the obesity. Further studies are needed to establish causation beyond significant association.

  11. Nitric Oxide-Mediated Regulation of GLUT by T3 and Follicle-Stimulating Hormone in Rat Granulosa Cells.

    Science.gov (United States)

    Tian, Ye; Ding, Yu; Liu, Juan; Heng, Dai; Xu, Kaili; Liu, Wenbo; Zhang, Cheng

    2017-06-01

    Thyroid hormones are important for normal reproductive function. Although 3,5,3'-triiodothyronine (T3) enhances follicle-stimulating hormone (FSH)-induced preantral follicle growth and granulosa cells development in vitro, little is known about the molecular mechanisms regulating ovarian development via glucose. In this study, we investigated whether and how T3 combines with FSH to regulate glucose transporter protein (GLUT) expression and glucose uptake in granulosa cells. In this study, we present evidence that T3 and FSH cotreatment significantly increased GLUT-1/GLUT-4 expression, and translocation in cells, as well as glucose uptake. These changes were accompanied by upregulation of nitric oxide (NO) synthase (NOS)3 expression, total NOS and NOS3 activity, and NO content in granulosa cells. Furthermore, we found that activation of the mammalian target of rapamycin (mTOR) and phosphoinositide 3-kinase (PI3K)/Akt pathway is required for the regulation of GLUT expression, translocation, and glucose uptake by hormones. We also found that l-arginine upregulated GLUT-1/GLUT-4 expression and translocation, which were related to increased glucose uptake; however, these responses were significantly blocked by N(G)-nitro-l-arginine methylester. In addition, inhibiting NO production attenuated T3- and FSH-induced GLUT expression, translocation, and glucose uptake in granulosa cells. Our data demonstrate that T3 and FSH cotreatment potentiates cellular glucose uptake via GLUT upregulation and translocation, which are mediated through the activation of the mTOR/PI3K/Akt pathway. Meanwhile, NOS3/NO are also involved in this regulatory system. These findings suggest that GLUT is a mediator of T3- and FSH-induced follicular development. Copyright © 2017 Endocrine Society.

  12. Corticotropin-releasing hormone stimulates expression of leptin, 11beta-HSD2 and syncytin-1 in primary human trophoblasts

    Directory of Open Access Journals (Sweden)

    Fahlbusch Fabian B

    2012-09-01

    Full Text Available Abstract Background The placental syncytiotrophoblast is the major source of maternal plasma corticotropin-releasing hormone (CRH in the second half of pregnancy. Placental CRH exerts multiple functions in the maternal organism: It induces the adrenal secretion of cortisol via the stimulation of adrenocorticotropic hormone, regulates the timing of birth via its actions in the myometrium and inhibits the invasion of extravillous trophoblast cells in vitro. However, the auto- and paracrine actions of CRH on the syncytiotrophoblast itself are unknown. Intrauterine growth restriction (IUGR is accompanied by an increase in placental CRH, which could be of pathophysiological relevance for the dysregulation in syncytialisation seen in IUGR placentas. Methods We aimed to determine the effect of CRH on isolated primary trophoblastic cells in vitro. After CRH stimulation the trophoblast syncytialisation rate was monitored via syncytin-1 gene expression and beta-hCG (beta-human chorionic gonadotropine ELISA in culture supernatant. The expression of the IUGR marker genes leptin and 11beta-hydroxysteroid dehydrogenase 2 (11beta-HSD2 was measured continuously over a period of 72 h. We hypothesized that CRH might attenuate syncytialisation, induce leptin, and reduce 11beta-HSD2 expression in primary villous trophoblasts, which are known features of IUGR. Results CRH did not influence the differentiation of isolated trophoblasts into functional syncytium as determined by beta-hCG secretion, albeit inducing syncytin-1 expression. Following syncytialisation, CRH treatment significantly increased leptin and 11beta-HSD2 expression, as well as leptin secretion into culture supernatant after 48 h. Conclusion The relevance of CRH for placental physiology is underlined by the present in vitro study. The induction of leptin and 11beta-HSD2 in the syncytiotrophoblast by CRH might promote fetal nutrient supply and placental corticosteroid metabolism in the phase

  13. Ovarian hyperstimulation syndrome due to follicle-stimulating hormone-secreting pituitary adenomas.

    Science.gov (United States)

    Caretto, Amelia; Lanzi, Roberto; Piani, Cecilia; Molgora, Michela; Mortini, Pietro; Losa, Marco

    2017-10-01

    Gonadotroph adenomas are pituitary adenomas with inefficient and variable secretory characteristics, that is why they are usually considered as a subgroup of nonfunctioning pituitary adenomas (NFPA) and are recognized only at immunohistochemistry. When gonadotroph adenomas secrete active hormones, they may cause spontaneous ovarian hyperstimulation syndrome (OHSS) in premenopausal women. Aim of our study is to describe three women with OHSS diagnosed before the removal of the adenoma and to calculate the prevalence of OHSS in premenopausal women with a clinical diagnosis of NFPA. We reviewed clinical records of premenopausal women that underwent neurosurgery for NFPA at our centre between 1993 and 2014. OHSS was diagnosed in patients with high levels of FSH, suppressed LH, hyperestrogenism, abdominal symptoms, polymenorrhea, enlarged ovaries with cysts or previous surgery for ovarian cysts. 171 women were included into the study; 62 (36.6%) had a gonadotroph adenoma diagnosed at immunohistochemistry. Two patients were retrospectively diagnosed as having OHSS due to gonadotroph adenoma and three had OHSS diagnosed before neurosurgery. The prevalence of OHSS was 2.9% in the overall group of patients with NFPA and 8.1% among patients with a gonadotroph adenoma detected at immunohistochemistry. Frequency of OHSS due to a gonadotroph adenoma is not negligible. Increased awareness of the characteristic clinical and hormonal picture should permit an early detection of this condition in premenopausal women with a pituitary adenoma.

  14. Low subjective socioeconomic status stimulates orexigenic hormone ghrelin - A randomised trial.

    Science.gov (United States)

    Sim, A Y; Lim, E X; Leow, M K; Cheon, B K

    2018-03-01

    Recent evidence suggests that lower perceived socioeconomic status is linked to increased appetite and intake of greater calories. Yet, whether insecurity of socioeconomic resources directly influences regulatory systems of appetite and energy intake is not known. Considering psychological states, mindsets and beliefs have shown to meaningfully affect physiological responses to food, the present study tested the hypothesis that low subjective socioeconomic status (SSS) will have a direct influence on physiological responses, such as appetite-related hormones (ghrelin, pancreatic polypeptide and insulin). Forty-eight healthy males were randomly (crossover, counterbalanced) assigned, to two experimental conditions where participants were either experimentally induced to feel low SSS or not (control; CON). Feelings of low SSS resulted in an increase in active ghrelin (an orexigenic hormone) following the SSS manipulation compared with baseline, while no change in active ghrelin was observed in CON. Furthermore, participants reported lower fullness and satiety following low SSS compared with CON. Our findings demonstrate that SSS may influence hunger regulation and appetite, and suggest that physiological systems regulating energy balance (i.e. caloric resources) may also be sensitive to perceived deprivation or imbalances in critical non-food resources (socioeconomic resources). Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. The Correlations of Anti-Mullerian Hormone, Follicle-Stimulating Hormone and Antral Follicle Count in Different Age Groups of Infertile Women

    Directory of Open Access Journals (Sweden)

    Ludmila Barbakadze

    2015-02-01

    Full Text Available Background: The objective of our study was to identify the correlations between the tests currently used in ovarian reserve assessment: anti-Mullerian hormone (AMH, follicle stimulating hormone (FSH and antral follicle count (AFC and to distinguish the most reliable markers for ovarian reserve in order to select an adequate strategy for the initial stages of infertility treatment. Materials and Methods: In this prospective study, 112 infertile women were assessed. Subjects were divided into three age groups: group I <35 years (n=39, group II 35-40 years (n=31, and group III 41-46 years (n=42. AMH, FSH and AFC were determined on days 2-3 of the patients’ menstrual cycles. Results: There was a significantly elevated negative correlation between age and AMH level (rs =-0.67, p<0.0001 and AFC (rs =-0.55, p<0.0001. We observed a significantly positive correlation between age and FSH (rs =0.38, p<0.0001. AMH negatively correlated with FSH (rs =-0.48, p<0.0001 and positively with AFC (r=- 0.71, p=0.0001. There was a moderate negative relation between FSH and AFC (r=-0.41, p=0.0001 and moderate positive relation between age and FSH (rs =0.38, p<0.0001. The correlation analysis performed in separate groups showed that AMH and AFC showed a statistically significant positive correlation for group I (r=0.57, p<0.0001, group II (r=0.69, p<0.0001 and group III (r=0.47, p<0.002. A statistically significant correlation between FSH and AMH was detected only in groups I (r=-0.41, p<0.02 and II (r=-0.55, p<0.0001. A statistically significant correlation existed between FSH and AFC only in group III (r=-0.42, p<0.006, as well as between age and AFC only in group I (r=-0.35, p<0.03. Conclusion: Currently, AMH should be considered as the more reliable of the ovarian reserve assessments tests compared to FSH. There is a strong positive correlation between serum AMH level and AFC. The use of AMH combined with AFC may improve ovarian reserve evaluation.

  16. A brief review of the use and utility of growth hormone stimulation testing in the NCGS: do we need to do provocative GH testing?

    Science.gov (United States)

    Wilson, Darrell M; Frane, James

    2005-07-01

    True growth hormone deficiency (GHD) in childhood, while rare, has major clinical consequences. GHD is often associated with other pituitary hormone deficiencies, so these children may require multiple hormonal replacement and close clinical follow-up to optimize their outcome. Growth hormone stimulation testing (GHST), as currently conducted, is not a reliable diagnostic tool. Both changes in growth hormone assay methodologies and increases in the diagnostic threshold contribute to the incorrect labeling of a substantial proportion of normal children as having idiopathic GHD. Fortunately, newer imaging technologies and laboratory tests form a more rational basis to diagnose true GHD. The use of GHST among GH-naive subjects (<20 years of age) enrolled in the National Cooperative Growth Study has declined over the past two decades, from a high of 89% between 1987 and 1989 to only 52% in 2002. Given that GH stimulation testing does not meaningfully aid in distinguishing those few children with true growth hormone deficiency from the much more common short normal child and that alternatives are now available, it is time to discontinue the routine use of GHST in children.

  17. The stimulatory effect of albumin on luteinizing hormone-stimulated Leydig cell steroid production depends on its fatty acid content and correlates with conformational changes

    NARCIS (Netherlands)

    R. Melsert (R.); O.J.M. Bos (O. J M); R.F. van der Linden (R.); M.J.E. Fischer (M. J E); S.M. Wilting (Saskia); L.H.M. Janssen (Lambert); J.W. Hoogerbrugge (Jos); F.F.G. Rommerts (Focko)

    1991-01-01

    markdownabstract__Abstract__ The effects of purified albumin species and albumin fragments (0.2–1% w/v) on short-term (4 h) steroid secretion by immature rat Leydig cells, in the presence of a maximally stimulating dose of luteinizing hormone (LH), were investigated. Human albumin and the peptic

  18. Composite reference interval for thyroid-stimulating hormone and free thyroxine, comparison with common cutoff values, and reconsideration of subclinical thyroid disease.

    NARCIS (Netherlands)

    Ross, H.A.; Heijer, M. den; Hermus, A.R.M.M.; Sweep, C.G.J.

    2009-01-01

    BACKGROUND: Examination of the 2-dimensional probability distribution of thyroid-stimulating hormone (TSH) and free thyroxine (FT(4)) shows that the widths of the TSH and FT(4) reference intervals derived from this bivariate distribution are mutually interdependent, an aspect commonly ignored when

  19. The value of routine creatine kinase and thyroid stimulating hormone testing in patients with suspected fibromyalgia: a cross-sectional study

    NARCIS (Netherlands)

    Lesuis, N.; Vliet, J. van; Boers, N.; Broeder, N. den; Cats, H.; Hulscher, M.E.J.L.; Verrips, A.; Broeder, A.A. den

    2016-01-01

    OBJECTIVE: The aim was to examine the prevalence of abnormal creatine kinase (CK) and thyroid stimulating hormone (TSH) values and previously unknown myopathy or thyroid disease in patients with suspected FM syndrome (FMS). METHODS: All adult patients with suspected FMS referred to the study

  20. The SUPER study: protocol for a randomised controlled trial comparing follicle-stimulating hormone and clomiphene citrate for ovarian stimulation in intrauterine insemination.

    Science.gov (United States)

    Danhof, N A; van Wely, M; Koks, C A M; Gianotten, J; de Bruin, J P; Cohlen, B J; van der Ham, D P; Klijn, N F; van Hooff, M H A; Broekmans, F J M; Fleischer, K; Janssen, C A H; Rijn van Weert, J M; van Disseldorp, J; Twisk, M; Traas, M; Verberg, M F G; Pelinck, M J; Visser, J; Perquin, D A M; Boks, D E S; Verhoeve, H R; van Heteren, C F; Mol, B W J; Repping, S; van der Veen, F; Mochtar, M H

    2017-05-25

    To study the effectiveness of four cycles of intrauterine insemination (IUI) with ovarian stimulation (OS) by follicle-stimulating hormone (FSH) or by clomiphene citrate (CC), and adherence to strict cancellation criteria. Randomised controlled trial among 22 secondary and tertiary fertility clinics in the Netherlands. 732 women from couples diagnosed with unexplained or mild male subfertility and an unfavourable prognosis according to the model of Hunault of natural conception. Four cycles of IUI-OS within a time horizon of 6 months comparing FSH 75 IU with CC 100 mg. The primary outcome is ongoing pregnancy conceived within 6 months after randomisation, defined as a positive heartbeat at 12 weeks of gestation. Secondary outcomes are cancellation rates, number of cycles with a monofollicular or with multifollicular growth, number of follicles >14 mm at the time of ovulation triggering, time to ongoing pregnancy, clinical pregnancy, miscarriage, live birth and multiple pregnancy. We will also assess if biomarkers such as female age, body mass index, smoking status, antral follicle count and endometrial aspect and thickness can be used as treatment selection markers. The study has been approved by the Medical Ethical Committee of the Academic Medical Centre and from the Dutch Central Committee on Research involving Human Subjects (CCMO NL 43131-018-13). Results will be disseminated through peer-reviewed publications and presentations at international scientific meetings. NTR4057. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  1. Biological Variability in Serum Cortisol Concentration Post-adrenocorticotropic Hormone Stimulation in Healthy Dogs.

    Science.gov (United States)

    Gal, A; Weidgraaf, K; Bowden, J P; Lopez-Villalobos, N; Cave, N J; Chambers, J P; Castillo-Alcala, F

    2017-05-01

    The ACTH stimulation has low sensitivity for the diagnosis of hypercortisolism possibly as a result of biological and analytical variability. To report the components of biological and analytical variability in serum cortisol concentration post-ACTH stimulation ([cortisol]) in healthy dogs. Fourteen healthy harrier hound dogs. The data were extracted from a separate, prospective, randomized, double-blinded, controlled discovery study in which dogs treated with vehicle control and 4 different doses of cortisone acetate (CA) for 7 days had an ACTH stimulation test performed to confirm the dose-dependent effect of CA. The index of individuality (IoI), the critical difference between sequential measurements (C D ), and the number of measurements required to assess the homeostatic set point (HSP) of [cortisol] with confidence intervals (CI) of 90 and 95% were estimated. The IoI was equal to 1.1 and the C D was 3.3 μg/dL (92 nmol/L). The number of measurements required to assess the HSP of [cortisol] with CI of 90 and 95% were 3 and 15, respectively. Additionally, mean [cortisol] was higher in males than in females (13.3 ± 4 μg/dL [366 ± 114 nmol/L] vs. 11.5 ± 2.5 μg/dL [318 ± 65 nmol/L], respectively; P = .046). As expected, treatment with CA resulted in a dose-dependent suppression of [cortisol]. False-negative test results in hypercortisolism could occur when [cortisol] is outside of the individual's HSP and within the reference interval. The large C D emphasizes the importance of assessing clinically relevant parameters in the diagnosis and monitoring of HC. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  2. Use of recombinant human thyroid-stimulating hormone for evaluation of thyroid function in guinea pigs (Cavia porcellus).

    Science.gov (United States)

    Mayer, Jörg; Wagner, Robert; Mitchell, Mark A; Fecteau, Kellie

    2013-02-01

    To evaluate the effects of administration of recombinant human (rh) thyroid-stimulating hormone (TSH) for evaluation of thyroid function in euthyroid guinea pigs (Cavia porcellus). Prospective, experimental study. 10 healthy, sexually intact, pet guinea pigs (approx 1 year of age). Guinea pigs were given rhTSH (100 μg, IM); plasma thyroxine concentrations were determined prior to and 3 and 4 hours after rhTSH injection. The animals were housed in 2 groups on the basis of sex and fed different commercial maintenance diets according to their husbandry. There was no significant difference in thyroxine concentrations between males and females before or after rhTSH injection. There was also no difference between thyroxine concentrations at 3 versus 4 hours after rhTSH injection. There was a significant difference between thyroxine concentrations before (median, 9.05 nmol/L [0.70 μg/dL]; 10% to 90% range, 7.39 to 16.99 nmol/L [0.57 to 1.32 μg/dL]) and after (mean ± SD, 23.95 ± 4.2 nmol/L) rhTSH injection. Euthyroid guinea pigs had plasma thyroxine concentrations of at least 7.30 nmol/L (0.57 μg/dL) and an increase of at least 2.6 times prestimulation thyroxine concentrations at 3 or 4 hours after stimulation. The results suggested that rhTSH administered IM can be used for the TSH stimulation testing in guinea pigs. We suggest thyroxine concentration in a euthyroid guinea pig should at least double 3 to 4 hours after rhTSH injection.

  3. Comparison of therapeutic efficacy and clinical parameters between recombinant human thyroid stimulating hormone and thyroid hormone withdrawal in high-dose radioiodine treatment with differentiated thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Se Hun; Na, Chang Ju; Kim, Jeong Hun; Han, Yeon Hee; KIm, Hee Kwon; Jeong, Hwan Jeong; Sohn, Myung Hee; Lim, Seok Tae [Dept. of Nuclear Medicine, Chonbuk National University Medical School and Hospital, Jeonju (Korea, Republic of)

    2015-06-15

    High-dose radioiodine treatment (HD-RIT) after injection of recombinant human thyroid stimulating hormone (rh-TSH) has become widely used. This study compared the therapeutic efficacy of HD-RIT and clinical parameters between rh-TSH supplement and thyroid hormone withdrawal (THW) after total thyroidectomy in patients with differentiated thyroid cancer. We retrospectively reviewed 266 patients (47 male and 219 female; age, 49.0 ± 10.9 years) with differentiated thyroid cancer detected from September 2011 to September 2012. Patients comprised THW (217, 81.6 %) and rh-TSH (49, 18.4 %). Inclusion criteria were: first HD-RIT; any TN stage; absence of distant metastasis. To evaluate the complete ablation of the remnant thyroid tissue or metastasis, we reviewed stimulated serum thyroglobulin (sTg), I-123 whole-body scan (RxWBS) on T4 off-state, and thyroid ultrasonography (US) or [F-18]-fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) 6–8 months after HD-RIT. We defined a complete ablation state when all three of the follow-up conditions were satisfied; <2.0 ng/ml of the sTg, I-123 RxWBS (−), and thyroid US or F-18 FDG PET/CT (−). If one of the three was positive, ablation was considered incomplete. We also compared various clinical biomarkers (body weight, body mass index, liver and kidney function) between THW and rh-TSH groups. The rates of complete ablation were 73.7 % (160/217) for the THW group and 73.5 % (36/49) for the rh-TSH group. There was no significant difference between the two groups (p = 0.970). The follow-up aspartate transaminase (p = 0.001) and alanine transaminase (p = 0.001) were significantly higher in the THW group. The renal function parameters of blood urea nitrogen (p = 0.001) and creatinine (p = 0.005) tended to increase in the THW group. The change of body weight was + Δ0.96 (±1.9) kg for the THW group and was decreased by -Δ1.39 (±1.5) kg for the rh-TSH group. The change

  4. Disruption of β-catenin binding to parathyroid hormone (PTH) receptor inhibits PTH-stimulated ERK1/2 activation.

    Science.gov (United States)

    Yang, Yanmei; Wang, Bin

    2015-08-14

    The type I parathyroid hormone receptor (PTH1R) mediates PTH and PTH-related protein (PTHrP) actions on extracellular mineral ion homeostasis and bone remodeling. These effects depend in part on the activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2). Sequences located within or at the carboxyl-terminus of PTH1R control its activation and trafficking. β-catenin regulates PTH1R signaling and promotes chondrocyte hypertrophy through binding to the intracellular carboxyl-terminal region of the receptor. How the interaction of PTH1R with β-catenin affects PTH-stimulated ERK1/2 is unknown. In the present study, human embryonic kidney 293 (HEK293) cells, which do not express the PTH1R, were used to investigate whether the disruption of β-catenin binding to PTH1R affects PTH-stimulated ERK1/2 activation. We demonstrated that β-catenin interacted with wild-type PTH1R but this interaction was markedly reduced with mutant PTH1R (L584A/L585A). PTH stimulated less cAMP formation and increased more intracellular calcium in HEK293 cells transfected with wild-type PTH1R compared with mutant PTH1R, indicating β-catenin switches PTH1R signaling from Gαs activation to Gαq signaling. In addition, ERK1/2 activation in HEK293 cells transfected with PTH1R exhibited time and concentration dependence. PTH-stimulated ERK1/2 activation was mostly mediated through Gαq/PLC signaling pathway. Importantly, transfection of mutant PTH1R decreased PTH-induced ERK1/2 activation by inhibiting Gαq-mediated signaling. This study shows for the first time that the interference of β-catenin binding to PTH1R inhibits PTH-stimulated ERK1/2 phosphorylation. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Human melanocytes form a PAX3-expressing melanocyte cluster on Matrigel by the cell migration process.

    Science.gov (United States)

    Choi, Hyunjung; Jin, Sun Hee; Han, Mi Hwa; Lee, Jinyoung; Ahn, Seyeon; Seong, Minjeong; Choi, Hyun; Han, Jiyeon; Cho, Eun-Gyung; Lee, Tae Ryong; Noh, Minsoo

    2014-10-01

    The interactions between human epidermal melanocytes and their cellular microenvironment are important in the regulation of human melanocyte functions or in their malignant transformation into melanoma. Although the basement membrane extracellular matrix (BM-ECM) is one of major melanocyte microenvironments, the effects of BM-ECM on the human melanocyte functions are not fully explained at a molecular level. This study was aimed to characterize the molecular and cellular interactions between normal human melanocytes (NHMs) and BM-ECM. We investigated cell culture models of normal human melanocytes or melanoma cells on three-dimensional (3D) Matrigel to understand the roles of the basement membrane microenvironment in human melanocyte functions. Melanogenesis and melanobast biomarker expression in both primary human melanocytes and melanoma cells on 3D Matrigel were evaluated. We found that NHMs migrated and formed reversible paired box 3 (PAX3) expressing cell clusters on three-dimensional (3D) Matrigel. The melanogenesis was significantly decreased in the PAX3 expressing cell cluster. The expression profile of PAX3, SOX10, and MITF in the melanocyte cluster on 3D Matrigel was similar to that of melanoblasts. Interestingly, PAX3 and SOX10 showed an inverse expression profile in NHMs, whereas the inverse expression pattern of PAX3 and SOX10 was disrupted in melanoma MNT1 and WM266-4 cells. The human melanocyte culture on 3D Matrigel provides an alternative model system to study functions of human melanoblasts. In addition, this system will contribute to the elucidation of PAX3-related tumorigenic mechanisms to understand human melanoma. Copyright © 2014 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  6. Lack of stimulation of 24-hour growth hormone release by hypocaloric diet in obesity

    DEFF Research Database (Denmark)

    Rasmussen, M H; Juul, A; Kjems, L L

    1995-01-01

    Obesity is associated with a marked reduction in the spontaneous secretion of GH. To investigate the effect of acute alterations in calorie intake on GH release, 24-hr spontaneous GH release was measured during habitual calorie intake as well as during a short term, very low calorie diet (VLCD......-I (IGF-I), IGF-binding protein-1 (IGFBP-1), IGF-binding protein-3 (IGFBP-3), insulin, pro-insulin, and blood glucose were measured during habitual energy intake as well as during the hypocaloric diet. Twenty-four-hour GH release profiles and IGFBP-1 were decreased, and insulin as well as proinsulin....... This suggests a reversible defect in GH release, rather than a persistent preexisting disorder. It is hypothesized that enhanced bioavailability of IGF-I, acting in concert with elevated proinsulin and insulin levels, may account for the lack of stimulation of 24-hr GH release by the hypocaloric diet in obese...

  7. Effects of thyroid hormone on Na+-K+ transport in resting and stimulated rat skeletal muscle

    International Nuclear Information System (INIS)

    Everts, M.E.; Clausen, T.

    1988-01-01

    The effects of hypothyroidism and 3,5,3'-triiodothyronine (T 3 ) treatment on passive Na + -K + fluxes and Na + -K + pump concentration were investigated in isolated rat muscle. Within 12 h after a single dose of T 3 (20 μg/100 g body wt), K + efflux had increased by 21% in soleus and by 20% in extensor digitorum longus muscle. In the presence of ouabain, even larger effects were observed. These changes were associated with a 12% rise in amiloride-suppressible Na + influx but no significant increase in [ 3 H]ouabain binding site concentration. After 3 days of T 3 treatment, the stimulating effect on K + efflux and Na + influx in soleus reached a plateau ∼80 and 40% above control levels, respectively, whereas the maximum increase in [ 3 H]ouabain binding site concentration (103%) was only fully developed after 8 days. Hypothyroidism decreased 86 Rb efflux by 30%. The efflux of K + and the influx of Na + per contraction (both ∼7 nmol/g wet wt) as well as the net loss of K + induced by electrical stimulation were unaffected by T 3 treatment. The rise in resting K + efflux after 12-24 h of T 3 treatment could be partly blocked by dantrolene or trifluoroperazine, indicating that an increase in the cytoplasmic Ca 2+ concentration may contribute to the early rise in K + efflux. It is concluded that the early rise in the resting passive leaks of Na + and K + induced by T 3 is a major driving force for Na + -K + pump synthesis

  8. Trajectories of estradiol and follicle-stimulating hormone over the menopause transition and early markers of atherosclerosis after menopause.

    Science.gov (United States)

    El Khoudary, Samar R; Santoro, Nanette; Chen, Hsiang-Yu; Tepper, Ping G; Brooks, Maria M; Thurston, Rebecca C; Janssen, Imke; Harlow, Sioban D; Barinas-Mitchell, Emma; Selzer, Faith; Derby, Carol A; Jackson, Elizabeth A; McConnell, Daniel; Matthews, Karen A

    2016-05-01

    The purpose of this study was to assess associations between distinct patterns of circulating estradiol (E2) and follicle-stimulating hormone (FSH) over the menopause transition (MT) and subclinical measures of atherosclerosis after menopause. Four temporal patterns of E2 decline (Low: low before and after final menstrual period (FMP); Medium: medium before and high after FMP; High-early decline: high prior to FMP and early decline thereafter; High-late decline: high prior to FMP and late decline thereafter) and three of FSH rise (Low, Medium, High) over 9.6 years across FMP were identified and linked to carotid intima-media-thickness (IMT), adventitial diameter (AD), and presence of carotid plaque (cPlaque) measured after menopause at the 12th annual visit (visit 12). Participants were 856 women (age at visit 12 = 59.5 ± 2.7 years) from the Study of Women's Health Across the Nation (SWAN), who never reported a stroke or a heart attack. In models adjusted for visit 12 or baseline cardiovascular disease (CVD) risk factors, odds of having any cPlaque were ∼43% lower among women with the High-early decline E2 trajectory compared to women with the Low E2 trajectory. In contrast, women with the Medium E2 trajectory had significantly higher IMT than those with the Low E2 trajectory adjusting for visit 12 CVD risk factors. Interestingly, adjusting for baseline CVD risk factors attenuated this association. The Low FSH group had lower IMT than the Medium and High FSH groups (p ≤ 0.05) in all models. During MT, women are subjected to hormonal alterations that could potentially increase their risk of developing CVD after menopause. © The European Society of Cardiology 2015.

  9. New radioimmunoassay for follicle-stimulating hormone in macaques: ovulatory menstrual cycles. [/sup 125/I tracer technique

    Energy Technology Data Exchange (ETDEWEB)

    Hodgen, G.D.; Wilks, J.W.; Vaitukaitis, J.L.; Chen, H.C.; Papkoff, H.; Ross, G.

    1976-07-01

    A sensitive and specific radioimmunoassay system for macaque follicle-stimulating hormone (mFSH) was developed utilizing an antiserum (H-31) prepared in a rabbit against purified ovine FSH as the immunogen. Sera from castrated female, adult male, and juvenile rhesus monkeys, as well as urinary extracts from castrated rhesus and bonnet monkeys, were used to demonstrate parallelism with a standard of partially purified monkey pituitary gonadotropins (LER-M-907-D). An extract of baboon pituitary tissue also showed parallelism with the reference standard. A highly purified pituitary extract (WP-X-105-28), containing approximately 75 percent macaque luteinizing hormone (mLH) and 1 percent mFSH, was used to demonstrate the specificity of this mFSH assay system. Sera and urinary extracts obtained from hypophysectomized monkeys did not show cross-reactivity in the assay. Macaque chorionic gonadotropin (mCG) did not produce an inhibition curve in the assay, as determined from serum samples and urinary extracts collected from pregnant monkeys at the time of peak mCG secretion. Serum concentrations of mFSH were suppressed in ovariectomized monkeys by the administration of ethinyl estradiol for 3 days, but returned to near pretreatment values by 96 h after the last estradiol administration. The determination of serum mFSH concentrations in daily blood samples obtained from 20 rhesus monkeys throughout ovulatory menstrual cycles revealed a pattern similar to that previously reported for the rhesus monkey and the woman. The peak value of serum mFSH during the menstrual cycle coincided with the midcycle surge of mLH in each case. The gonadotropin peaks were preceded by increasing serum concentrations of estradiol and followed by rises in the serum concentrations of progesterone.

  10. NR4A1 (Nur77 mediates thyrotropin-releasing hormone-induced stimulation of transcription of the thyrotropin β gene: analysis of TRH knockout mice.

    Directory of Open Access Journals (Sweden)

    Yasuyo Nakajima

    Full Text Available Thyrotropin-releasing hormone (TRH is a major stimulator of thyrotropin-stimulating hormone (TSH synthesis in the anterior pituitary, though precisely how TRH stimulates the TSHβ gene remains unclear. Analysis of TRH-deficient mice differing in thyroid hormone status demonstrated that TRH was critical for the basal activity and responsiveness to thyroid hormone of the TSHβ gene. cDNA microarray and K-means cluster analyses with pituitaries from wild-type mice, TRH-deficient mice and TRH-deficient mice with thyroid hormone replacement revealed that the largest and most consistent decrease in expression in the absence of TRH and on supplementation with thyroid hormone was shown by the TSHβ gene, and the NR4A1 gene belonged to the same cluster as and showed a similar expression profile to the TSHβ gene. Immunohistochemical analysis demonstrated that NR4A1 was expressed not only in ACTH- and FSH- producing cells but also in thyrotrophs and the expression was remarkably reduced in TRH-deficient pituitary. Furthermore, experiments in vitro demonstrated that incubation with TRH in GH4C1 cells increased the endogenous NR4A1 mRNA level by approximately 50-fold within one hour, and this stimulation was inhibited by inhibitors for PKC and ERK1/2. Western blot analysis confirmed that TRH increased NR4A1 expression within 2 h. A series of deletions of the promoter demonstrated that the region between bp -138 and +37 of the TSHβ gene was responsible for the TRH-induced stimulation, and Chip analysis revealed that NR4A1 was recruited to this region. Conversely, knockdown of NR4A1 by siRNA led to a significant reduction in TRH-induced TSHβ promoter activity. Furthermore, TRH stimulated NR4A1 promoter activity through the TRH receptor. These findings demonstrated that 1 TRH is a highly specific regulator of the TSHβ gene, and 2 TRH mediated induction of the TSHβ gene, at least in part by sequential stimulation of the NR4A1-TSHβ genes through a PKC and

  11. Basic dermoscopy of melanocytic lesions for beginners

    Directory of Open Access Journals (Sweden)

    Grażyna Kamińska-Winciorek

    2011-08-01

    Full Text Available Background. Dermoscopy is a safe, easy-to-repeat diagnostic method used especially in the diagnosis of melanocytic lesions and others. Performing dermoscopy for skin lesions on the whole body takes only one minute more than standard clinical examination. Therefore the knowledge of basic dermoscopy among multi-specialization doctors – from general practitioners, surgeons, oncologists to dermatologists – increases the possibility of detection of potential melanoma.Aim. To describe the basic aspects of dermoscopy of melanocytic lesions.Methods. Review of medical databases PubMed and Medline from the last 8 years and a retrospective analysis of own experience.Results. We report the fundamental principles of performing dermoscopy, basic dermoscopic features and diagnostic algorithms of selected melanocytic lesions. Conclusions. The knowledge base of dermoscopy is very important among doctors of many specializations. It increases melanoma detection in very early stages.

  12. Inhibition of renal brush border phosphate transport and stimulation of renal gluconeogenesis by cyclic amp and parathyroid hormone.

    Science.gov (United States)

    Kempson, S A; Kowalski, J C; Puschett, J B

    1983-05-01

    The aims of the study were to determine whether 8-bromo-cyclic AMP (8BcAMP) in vivo mimics the inhibitory action of parathyroid hormone (PTH) on phosphate transport across the brush border membrane (BBM) of the renal proximal tubule, and to examine whether changes in BBM transport are accompanied by changes in the rate of renal gluconeogenesis. Thyroparathyroidectomized dogs were anesthetized and equilibrated, and control urine collections were obtained prior to removing the left kidney. Subsequent intravenous infusion of 8BcAMP at 50 mg/hr for 2 hr increased fractional excretion of phosphate from 4 +/- 1 (controls) to 29 +/- 4% (P less than 0.001) without changing glomerular filtration. In BBM vesicles isolated from the renal cortex, the initial Na+-dependent transport of phosphate was decreased from 747 +/- 135 (controls) to 564 +/- 126 pmoles per mg per 0.25 min after 8BcAMP (P less than 0.025), but Na+-independent phosphate uptake and Na+-dependent L-proline uptake were not changed significantly. Renal gluconeogenesis in the same animals was increased from 2.5 +/- 0.3 (controls) to 5.3 +/- 0.5 mumoles glucose per g tissue per hr after infusion of 8BcAMP (P less than 0.001). Infusion of PTH, like 8BcAMP, inhibited BBM phosphate transport and stimulated renal gluconeogenesis. We conclude that the inhibitory action of cyclic AMP and PTH on BBM phosphate transport is accompanied by stimulation of gluconeogenesis which suggests, indirectly, that changes in gluconeogenesis may be part of the intracellular mechanism for regulating BBM phosphate uptake in response to certain stimuli.

  13. The use of anti-Müllerian hormone (AMH) for controlled ovarian stimulation in assisted reproductive technology and for fertility assessment and -counselling

    DEFF Research Database (Denmark)

    Pilsgaard, Fie; Grynnerup, Anna Garcia-Alix; Loessl, Kristine

    2018-01-01

    Ovarian reserve can be determined by serum anti-Müllerian hormone (AMH) level and/or antral follicle count prior to controlled ovarian stimulation. The aim of controlled ovarian stimulation is to achieve an appropriate number of mature follicles and avoid complications such as ovarian hyperstimul......Ovarian reserve can be determined by serum anti-Müllerian hormone (AMH) level and/or antral follicle count prior to controlled ovarian stimulation. The aim of controlled ovarian stimulation is to achieve an appropriate number of mature follicles and avoid complications such as ovarian....... Currently, no international standardised assays exist. AMH is a valid predictor of the ovarian response to controlled ovarian stimulation and to some extent the chance of pregnancy in relation to assisted reproductive technology, but AMH is less optimal in prediction of spontaneous pregnancy and live birth...... after assisted reproductive technology. Accordingly, AMH can be used to optimize gonadotrophin stimulation in fertility treatment, but is not recommended as a screening tool in the general population. This article is protected by copyright. All rights reserved....

  14. Carriers of a VEGFA enhancer polymorphism selectively binding CHOP/DDIT3 are predisposed to increased circulating levels of thyroid-stimulating hormone

    DEFF Research Database (Denmark)

    Ahluwalia, Tarun Veer Singh; Troelsen, Jesper Thorvald; Balslev-Harder, Marie

    2017-01-01

    BACKGROUND: Levels of serum thyroid-stimulating hormone (TSH) indicate thyroid function, because thyroid hormone negatively controls TSH release. Genetic variants in the vascular endothelial growth factor A (VEGFA) gene are associated with TSH levels. The aim of this study was to characterise...... the association of VEGFA variants with TSH in a Danish cohort and to identify and characterise functional variants. METHODS: We performed an association study of the VEGFA locus for circulating TSH levels in 8445 Danish individuals. Lead variants were tested for allele-specific effects in vitro using luciferase...

  15. Melanocyte-secreted fibromodulin promotes an angiogenic microenvironment.

    Science.gov (United States)

    Adini, Irit; Ghosh, Kaustabh; Adini, Avner; Chi, Zai-Long; Yoshimura, Takeru; Benny, Ofra; Connor, Kip M; Rogers, Michael S; Bazinet, Lauren; Birsner, Amy E; Bielenberg, Diane R; D'Amato, Robert J

    2014-01-01

    Studies have established that pigmentation can provide strong, protective effects against certain human diseases. For example, angiogenesis-dependent diseases such as wet age-related macular degeneration and infantile hemangioma are more common in light-skinned individuals of mixed European descent than in African-Americans. Here we found that melanocytes from light-skinned humans and albino mice secrete high levels of fibromodulin (FMOD), which we determined to be a potent angiogenic factor. FMOD treatment stimulated angiogenesis in numerous in vivo systems, including laser-induced choroidal neovascularization, growth factor-induced corneal neovascularization, wound healing, and Matrigel plug assays. Additionally, FMOD enhanced vascular sprouting during normal retinal development. Deletion of Fmod in albino mice resulted in a marked reduction in the amount of neovascularization induced by retinal vein occlusion, corneal growth factor pellets, and Matrigel plugs. Our data implicate the melanocyte-secreted factor FMOD as a key regulator of angiogenesis and suggest an underlying mechanism for epidemiological differences between light-skinned individuals of mixed European descent and African-Americans. Furthermore, inhibition of FMOD in humans has potential as a therapeutic strategy for treating angiogenesis-dependent diseases.

  16. Increasing thyroid-stimulating hormone is associated with impaired glucose metabolism in euthyroid obese children and adolescents.

    Science.gov (United States)

    Radhakishun, Nalini N E; van Vliet, Mariska; von Rosenstiel, Ines A; Weijer, Olivier; Beijnen, Jos H; Brandjes, Dees P M; Diamant, Michaela

    2013-01-01

    Contrasting data exist regarding the relationship between thyroid-stimulating hormone (TSH) and obesity-related risk factors in children. In the present study, we investigated the association between TSH, free T4 (fT4) and cardiometabolic risk factors in euthyroid obese children and adolescents. A retrospective analysis of patient records was performed on data from 703 multi-ethnic obese children and adolescents who visited an obesity-outpatient clinic. We performed anthropometric measurements, an oral glucose tolerance test, and measured serum TSH, fT4 and lipid levels. A positive association between TSH and the standard deviation score of the body mass index (BMI-Z) was found. After adjustment for ethnicity, sex, pubertal stage and BMI-Z, logistic regression analysis showed significant associations between TSH levels and impaired fasting glucose, impaired glucose tolerance, high total cholesterol, high low-density lipoprotein cholesterol and high triglycerides. No significant associations between fT4 levels and cardiometabolic risk factors were found in linear/logistic regression analysis. In our multi-ethnic cohort of euthyroid obese children and adolescents increasing TSH was associated with impaired glucose metabolism and dyslipidemia.

  17. Inter-laboratory validation of the measurement of follicle stimulating hormone (FSH after various lengths of frozen storage

    Directory of Open Access Journals (Sweden)

    Behr Barry

    2010-11-01

    Full Text Available Abstract Background Serum follicle stimulating hormone (FSH levels are used clinically to evaluate infertility, pituitary and gonadal disorders. With increased frequency of research collaborations across institutions, it is essential that inter-laboratory validation is addressed. Methods An inter-laboratory validation of three commercial FSH immunoassays was performed with human serum samples of varying frozen storage length (2 batches of 15 samples each at -25 degree C. Percentage differences and Bland-Altman limits of agreement were calculated. Results The inter- and intra-laboratory consistency of FSH values with the same assay manufacturer was much higher after shorter-term storage (frozen for less than 11 months, mean percentage degradation less than 4% than after long-term storage (2-3 years, mean percentage degradation = 23%. Comparing assay results from different manufacturers, there was similar overall long term degradation as seen with the same manufacturer (-25%, however the degradation was greater when the original FSH was greater than 20 mIU/mL relative to less than 10 mIU/mL (p Conclusion The findings suggest that degradation of serum samples stored between 11 months and 2-3 years at -25 degrees C can lead to unstable FSH measurements. Inter-laboratory variability due to frozen storage time and manufacturer differences in assay results should be accounted for when designing and implementing research or clinical quality control activities involving serum FSH at multiple study sites.

  18. Electron Capture Dissociation of Divalent Metal-adducted Sulfated N-Glycans Released from Bovine Thyroid Stimulating Hormone

    Science.gov (United States)

    Zhou, Wen; Håkansson, Kristina

    2013-11-01

    Sulfated N-glycans released from bovine thyroid stimulating hormone (bTSH) were ionized with the divalent metal cations Ca2+, Mg2+, and Co by electrospray ionization (ESI). These metal-adducted species were subjected to infrared multiphoton dissociation (IRMPD) and electron capture dissociation (ECD) and the corresponding fragmentation patterns were compared. IRMPD generated extensive glycosidic and cross-ring cleavages, but most product ions suffered from sulfonate loss. Internal fragments were also observed, which complicated the spectra. ECD provided complementary structural information compared with IRMPD, and all observed product ions retained the sulfonate group, allowing sulfonate localization. To our knowledge, this work represents the first application of ECD towards metal-adducted sulfated N-glycans released from a glycoprotein. Due to the ability of IRMPD and ECD to provide complementary structural information, the combination of the two strategies is a promising and valuable tool for glycan structural characterization. The influence of different metal ions was also examined. Calcium adducts appeared to be the most promising species because of high sensitivity and ability to provide extensive structural information.

  19. Oxytocin, vasopressin, prostaglandin F(2alpha), luteinizing hormone, testosterone, estrone sulfate, and cortisol plasma concentrations after sexual stimulation in stallions.

    Science.gov (United States)

    Veronesi, M C; Tosi, U; Villani, M; Govoni, N; Faustini, M; Kindahl, H; Madej, A; Carluccio, A

    2010-03-01

    This experiment was designed to determine the effects of sexual stimulation on plasma concentrations of oxytocin (OT), vasopressin (VP), 15-ketodihydro-PGF(2alpha) (PG-metabolite), luteinizing hormone (LH), testosterone (T), estrone sulfate (ES), and cortisol (C) in stallions. Semen samples were collected from 14 light horse stallions (Equus caballus) of proven fertility using a Missouri model artificial vagina. Blood samples were collected at 15, 12, 9, 6, and 3 min before estrous mare exposure, at erection, at ejaculation, and at 3, 6, and 9 min after ejaculation. Afterwards, blood sampling was performed every 10 min for the following 60 min. Sexual activity determined an increase in plasma concentrations of OT, VP, C, PG-metabolite, and ES and caused no changes in LH and T concentrations. The finding of a negative correlation between C and VP at erection, and between C and T before erection and at the time of erection, could be explained by a possible inhibitory role exerted by C in the mechanism of sexual arousal described for men. Copyright 2010 Elsevier Inc. All rights reserved.

  20. Hormonal, follicular and endometrial dynamics in letrozole-treated versus natural cycles in patients undergoing controlled ovarian stimulation

    Directory of Open Access Journals (Sweden)

    Brunengraber Lisa N

    2011-06-01

    Full Text Available Abstract The objective of this study was to compare letrozole-stimulated cycles to natural cycles in 208 patients undergoing intrauterine insemination (IUI between July of 2004 and January of 2007. Group I (n = 47 received cycle monitoring only (natural group, Group II (n = 125 received letrozole 2.5 mg/day on cycle days three to seven, and Group III (n = 36 received letrozole 5 mg/day on cycle days three to seven. There were no differences between the groups in endometrial thickness or P4 on the day of hCG. Estradiol levels had higher variation in the second half of the follicular phase in both letrozole-treated groups compared to the control group. Estradiol per preovulatory follicle was similar in both letrozole cycles to that observed in the natural cycles. LH was lower on the day of hCG administration in the letrozole 2.5 mg/day group vs. the natural group. In summary, letrozole results in some minor changes in follicular, hormonal and endometrial dynamics compared to natural cycles. Increased folliculogenesis and pregnancy rates were observed in the letrozole-treated groups compared to the natural group. These findings need to be confirmed in larger, prospective studies.

  1. Featured Article: Transcriptional landscape analysis identifies differently expressed genes involved in follicle-stimulating hormone induced postmenopausal osteoporosis.

    Science.gov (United States)

    Maasalu, Katre; Laius, Ott; Zhytnik, Lidiia; Kõks, Sulev; Prans, Ele; Reimann, Ene; Märtson, Aare

    2017-01-01

    Osteoporosis is a disorder associated with bone tissue reorganization, bone mass, and mineral density. Osteoporosis can severely affect postmenopausal women, causing bone fragility and osteoporotic fractures. The aim of the current study was to compare blood mRNA profiles of postmenopausal women with and without osteoporosis, with the aim of finding different gene expressions and thus targets for future osteoporosis biomarker studies. Our study consisted of transcriptome analysis of whole blood serum from 12 elderly female osteoporotic patients and 12 non-osteoporotic elderly female controls. The transcriptome analysis was performed with RNA sequencing technology. For data analysis, the edgeR package of R Bioconductor was used. Two hundred and fourteen genes were expressed differently in osteoporotic compared with non-osteoporotic patients. Statistical analysis revealed 20 differently expressed genes with a false discovery rate of less than 1.47 × 10 -4 among osteoporotic patients. The expression of 10 genes were up-regulated and 10 down-regulated. Further statistical analysis identified a potential osteoporosis mRNA biomarker pattern consisting of six genes: CACNA1G, ALG13, SBK1, GGT7, MBNL3, and RIOK3. Functional ingenuity pathway analysis identified the strongest candidate genes with regard to potential involvement in a follicle-stimulating hormone activated network of increased osteoclast activity and hypogonadal bone loss. The differentially expressed genes identified in this study may contribute to future research of postmenopausal osteoporosis blood biomarkers.

  2. Reconsidering a lower level of follicle-stimulating hormone as abnormal in sub-fertile males of pakistan

    International Nuclear Information System (INIS)

    Arif, S.; Khan, A.

    2017-01-01

    To assess the association between Follicle-Stimulating Hormone (FSH) and semen parameters in order to evaluate whether the current laboratory reference for abnormal FSH levels should be readjusted. Study Design: Observational, cross-sectional study. Place and Duration of Study: Infertility Clinic of Gynecology Unit 1, Civil Hospital, Karachi, from May 2015 to April 2016. Methodology:The study included 100 sub-fertile males inducted from the clinic. Those above 45 years of age, with hypo gonadotrophic hypogonadism, and those on anabolic steroids were excluded. After history and examination, semen parameters and FSH levels were tested. Abnormal semen values were based on WHO 1999 criteria. Data was analyzed by SPSS 17 and mean, frequencies and percentages were calculated. Chi-square test was applied to check association between variables. Results: The FSH levels had a significant association with abnormal semen sperm concentration, motility and morphology but not with semen volume (p=0.246). The mean FSH level was 5.8 ±1.80 IU/L with two-thirds of individuals having value >4.5 IU/L. Frequency of semen abnormalities increased as the level of FSH increased. Conclusion: There is significantly an increased possibility of abnormal semen characteristics at FSH levels >4.5, so the current reference level should be lowered down and adjusted again. (author)

  3. Expression of Thyroid Stimulating Hormone Receptor mRNA in Mouse C2C12 Skeletal Muscle Cells

    Directory of Open Access Journals (Sweden)

    Jung Hun Ohn

    2013-06-01

    Full Text Available BackgroundWe analyzed whether thyroid stimulating hormone receptor (TSH-R is expressed in a skeletal muscle cell line and if TSH has influence on the differentiation of muscle cells or on the determination of muscle fiber types.MethodsTSH-R gene expression was detected with nested real-time polymerase chain reaction (RT-PCR in C2C12, a mouse skeletal muscle cell line. The effect of TSH on myotube differentiation was assessed by microscopic examination of myotube formation and through the measurement of expression of muscle differentiation markers, i.e., myogenin and myoD, and muscle type-specific genes, i.e., MyHC1, MyHC2a, and MyHC2b, with quantitative RT-PCR before and after incubation of C2C12 myotube with TSH.ResultsTSH-R was expressed in the mouse skeletal muscle cell line. However, treatment with TSH had little effect on the differentiation of muscle cells, although the expression of the muscle differention marker myogenin was significantly increased after TSH treatment. Treatment of TSH did not affect the expression of muscle type-specific genes.ConclusionTSH-R is expressed in a mouse skeletal muscle cell line, but the role of TSH receptor signaling in skeletal muscle needs further investigation.

  4. Thyroid-Stimulating Hormone (TSH) Concentration at Birth in Belgian Neonates and Cognitive Development at Preschool Age.

    Science.gov (United States)

    Trumpff, Caroline; De Schepper, Jean; Vanderfaeillie, Johan; Vercruysse, Nathalie; Van Oyen, Herman; Moreno-Reyes, Rodrigo; Tafforeau, Jean; Vanderpas, Jean; Vandevijvere, Stefanie

    2015-11-02

    The main objective of the study was to investigate the effect of MID during late pregnancy, assessed by the thyroid-stimulating hormone (TSH) concentration at neonatal screening, on cognitive development of preschool children. A retrospective cohort study including 311 Belgian preschool children of 4-6 years old was conducted. Children were selected at random from the total list of neonates screened in 2008, 2009, and 2010 by the Brussels new-born screening center. Infants with congenital hypothyroidism, low birth weight, and/or prematurity were excluded from the selection. The selected children were stratified by gender and TSH-range (0.45-15 mIU/L). Cognitive abilities were assessed using Wechsler Preschool and Primary Scale of Intelligence-third edition. In addition, several socioeconomic, parental, and child confounding factors were assessed. Neonatal TSH concentration-a surrogate marker for MID-was not associated with Full Scale and Performance IQ scores in children. Lower Verbal IQ scores were found in children with neonatal TSH values comprised between 10-15 mIU/L compared to lower TSH levels in univariate analysis but these results did not hold when adjusting for confounding factors. Current levels of iodine deficiency among pregnant Belgian women may not be severe enough to affect the neurodevelopment of preschool children.

  5. Thyroid-Stimulating Hormone (TSH Concentration at Birth in Belgian Neonates and Cognitive Development at Preschool Age

    Directory of Open Access Journals (Sweden)

    Caroline Trumpff

    2015-11-01

    Full Text Available The main objective of the study was to investigate the effect of MID during late pregnancy, assessed by the thyroid-stimulating hormone (TSH concentration at neonatal screening, on cognitive development of preschool children. A retrospective cohort study including 311 Belgian preschool children of 4–6 years old was conducted. Children were selected at random from the total list of neonates screened in 2008, 2009, and 2010 by the Brussels new-born screening center. Infants with congenital hypothyroidism, low birth weight, and/or prematurity were excluded from the selection. The selected children were stratified by gender and TSH-range (0.45–15 mIU/L. Cognitive abilities were assessed using Wechsler Preschool and Primary Scale of Intelligence—third edition. In addition, several socioeconomic, parental, and child confounding factors were assessed. Neonatal TSH concentration—a surrogate marker for MID—was not associated with Full Scale and Performance IQ scores in children. Lower Verbal IQ scores were found in children with neonatal TSH values comprised between 10–15 mIU/L compared to lower TSH levels in univariate analysis but these results did not hold when adjusting for confounding factors. Current levels of iodine deficiency among pregnant Belgian women may not be severe enough to affect the neurodevelopment of preschool children.

  6. Growth hormone induced stimulation of the T4 to T3 conversion in fed and fasting dwarf goats.

    Science.gov (United States)

    Iqbal, A; Cheema, A M; Kühn, E R

    1990-11-01

    Fed and food deprived (7 days) adult dwarf goats were injected intravenously with 75 micrograms/kg b. w. of ovine growth hormone (o-GH). Blood samples were collected from the jugular vein -2, -1 and 0 hr prior to and 30, 60, 90 and 120 min after injection and assayed for thyroxine (T4) and triiodothyronine (T3) concentrations. The 5'-monodeiodination (5'-D) activity was consequently determined in liver and kidney samples following slaughtering. Fasting alone increased plasma concentrations of T3 and T4, whereas injection of o-GH raised T3 additionally and more profoundly in food deprived animals compared to fed ones. A small increase in plasma T4 was also observed following o-GH injection, but only in starved goats. At the same time the hepatic, but not the kidney, 5'-D activity was stimulated in food deprived and GH injected animals. It is concluded that during prolonged fasting an increased peripheral T4 to T3 conversion is occurring contrary to the known decrease in T3 production during short periods of food deprivation. This increased conversion may be under the control of GH.

  7. Stimulation of calcium uptake by parathyroid hormone in renal brush-border membrane vesicles. Relationship to membrane phosphorylation.

    Science.gov (United States)

    Khalifa, S; Mills, S; Hruska, K A

    1983-12-10

    The effect of parathyroid hormone (PTH) on Ca2+ uptake was studied in brush-border membrane vesicles (BBMV) prepared from the kidneys of dogs administered 4-5 micrograms/kg of bovine PTH 1-84 in vivo. PTH stimulated Ca2+ uptake at 20 s of incubation from control values of 231 +/- 21 to 306 +/- 30 pmol/mg of protein, p less than 0.001. The stimulation of Ca2+ uptake by PTH was not reversed by incubation of the BBMV with the Ca2+ ionophore, despite the fact that Ca2+ uptake was several times greater than the expected uptake at equilibrium, indicating that most of the uptake represented Ca2+ binding to the BBMV. In BBMV from kidneys exposed to PTH, hypotonic lysis or increasing the osmolality of the solution external to the BBMV did not affect Ca2+ uptake. These data also indicated that the largest fraction of Ca2+ uptake in the presence of a chemical potential represented binding of Ca2+ to BBMV. Ca2+ binding was initially to the exterior of the BBMV, then translocated within the membrane and to the interior vesicular face as assessed by chelation of Ca2+ bound to the BBMV by ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid. Incubation of BBMV from kidneys exposed to PTH with gentamicin, which competes with Ca2+ for anionic phospholipid-binding sites, reversed the stimulatory effects of PTH on Ca2+ uptake. Phosphorylation of BBMV and PTH treatment in vivo had similar effects on BBMV phospholipid composition increasing the levels of anionic phospholipids. Phosphorylation of the BBMV also produced gentamicin-inhibitable increases in membrane Ca2+ binding. Phosphorylation of BBMV from kidneys exposed to PTH was inhibited suggesting a higher state of phosphorylation in vivo. The data demonstrate that PTH administered in vivo stimulated Ca2+ binding in BBMV that was gentamicin inhibitable and associated with an increase in the membrane content of anionic phospholipids.

  8. Characterisation of Population Pharmacokinetics and Endogenous Follicle Stimulating Hormone (FSH) Levels after Multiple Dosing of a Recombinant Human FSH, FE 999049, in Healthy Women

    DEFF Research Database (Denmark)

    Rose, Trine Høyer; Röshammer, Daniel; Erichsen, Lars

    2016-01-01

    Objective: The aim of this study was to characterise the population pharmacokinetics of FE 999049, a novel recombinant human follicle-stimulating hormone (FSH), after multiple dosing in healthy women, taking into account endogenous FSH levels and the reproductive hormone dynamics. Methods......: Longitudinal measurements of FSH, luteinising hormone, progesterone, estradiol, and inhibin B levels were collected after repeated subcutaneous dosing with 225 IU of FE 999049 in 24 gonadotropin downregulated healthy women. The FSH data were described using nonlinear mixed-effects modelling. Results......: The measured FSH levels were modelled as a sum of endogenous FSH and FE 999049. The FE 999049 population pharmacokinetics were best described using a one-compartment model with first-order absorption and elimination, and a transit model for delayed absorption. The apparent clearance and volume of distribution...

  9. Use of the granulosa cell aromatase bioassay for measurement of bioactive follicle-stimulating hormone in urine and serum samples of diverse species.

    Science.gov (United States)

    Dahl, K D; Hsueh, A J

    1987-01-01

    Ovarian steroids and growth factors are intragonadal modulators which augment a key endpoint of follicle-stimulating hormone (FSH) action in granulosa cells: the induction of aromatase activity. Studies of these paracrine hormones that enhance FSH-stimulated estrogen biosynthesis by cultured rat granulosa cells, have led to the development of a sensitive and specific in vitro bioassay for FSH. This newly developed granulosa cell aromatase bioassay (GAB) allows for the measurement of bioactive FSH levels in serum and urine of humans and animals with various physiological and pathological conditions. These studies have demonstrated that the GAB assay is useful in detecting possible changes in the molecular forms of FSH. The adaptation of this method for urine samples allows for the measurement of bio-FSH levels in situations where venipuncture is not practical or in species for which specific radioimmunoassays are not available.

  10. Lutropin alpha, recombinant human luteinizing hormone, for the stimulation of follicular development in profoundly LH-deficient hypogonadotropic hypogonadal women: a review

    Directory of Open Access Journals (Sweden)

    Bernd Th Krause

    2009-06-01

    Full Text Available Bernd Th Krause1, Ralf Ohlinger2, Annette Haase31Center for Endocrinology and Reproductive Medicine, MVZ Uhlandstr, Berlin, Germany; 2Ernst-Moritz-Arndt-University, Department of Gynecology and Obstetrics, Greifswald, Germany; 3Uhlandstr. 162, 10719 BerlinAbstract: Hypogonadotropic hypogonadism is defined as a medical condition with low or undetectable gonadotropin secretion, associated with a complete arrest of follicular growth and very low estradiol. The main cause can be traced back to an irregular or absent hypothalamic GnRH secretion, whereas only a minority suffers from a pituitary disorder. The choice of treatment to reverse this situation is a pulsatile GnRH application or a direct ovarian stimulation using gonadotropin injections. The goal is to achieve a proper ovarian function in these cases for a short time to allow ovulation and chance of pregnancy. Since the pulsatile GnRH treatment lost its former importance, several gonadotropins are in use to stimulate follicular growth, such as urine-derived human menopausal gonadotropin, highly purified follicle stimulating hormone (FSH or recombinant FSH, all with different success. The introduction of recombinant luteinizing hormone (LH and FSH provided an opportunity to investigate the distinct influences of LH and FSH alone and in combination on follicular growth in monofollicular ovulation induction cycles, and additionally on oocyte maturation, fertilization competence of the oocyte and embryo quality in downregulated IVF patients. Whereas FSH was known to be indispensable for normal follicular growth, the role of LH remained questionable. Downregulated IVF patients with this short-term gonadotropin depletion displayed no advance in stimulation success with the use of recombinant LH. Patients with hypogonadotropic hypogonadism undergoing monofollicular stimulation for ovulation induction showed clearly a specific role and need for both hormones in normal follicular growth. Therefore, a

  11. Immunoglobulin production induced in vitro by glucocorticoid hormones: T cell-dependent stimulation of immunoglobulin production without B cell proliferation in cultures of human peripheral blood lymphocytes

    International Nuclear Information System (INIS)

    Grayson, J.; Dooley, N.J.; Koski, I.R.; Blaese, R.M.

    1981-01-01

    The direct effects of steroid hormones on the production of immunoglobulins and DNA synthesis by human T and B lymphocytes was evaluated in cultures of peripheral blood mononuclear cells. As detected by a reverse hemolytic plaque assay, the addition of 0.1 mM to 10 nM hydrocortisone to lymphocytes in culture in the absence of other stimulants or mitogens, resulted in the dramatic induction of immunoglobulin production with responses comparable to those seen in similar cultures stimulated with pokeweed mitogen. Steroid-stimulated immunoglobulin production was first seen after 48 h and peaked at 8-10 d of culture. The production of IgG, IgA, and IgM was induced following incubation with steroid. Glucocorticoids, but not estrogens or androgens, were capable of mediating this effect, and only compounds with affinity for the glucocorticoid receptor were active. The induction of immunoglobulin production was dependent on both T cells and monocytes; cultures depleted of either cell type did not produce immunoglobulin when stimulated with glucocorticoid hormones. Proliferation of B cells or T cells could not be detected by [/sup 3/H]thymidine incorporation or total cell recovery from steroid-stimulated cultures, even though such cultures demonstrated marked increases in immunoglobulin production. The mechanism responsible for this functional maturation of B cells to become high rate immunoglobulin producing cells is as yet undefined, although it appears to involve more than merely steroid mediated inactivation of suppressor T cells

  12. Hypermetabolic Conversion of Plant Oil into Water: Endothermic Biochemical Process Stimulated by Juvenile Hormone in the European Firebug, L.

    Directory of Open Access Journals (Sweden)

    Karel Sláma

    2016-01-01

    difference between the warm and cold larvae of P. apterus was only some 30% (not a reported 10-fold difference, which was presumably due to their ability to drink. We conclude that a very important, though still largely neglected, epigenetic biochemical role of insect JH depends on switchover between the utilization of dietary lipid (+JH; production of metabolic water and carbohydrate (-JH; lipid storage in the fat body. The hypermetabolic water supply in insects fed on dry food, which is associated with enormous rates of O 2 consumption, liberates endothermic energy that heats the body and potentially influences the insect thermoregulation. A possibility that the JH-dependent lipolytic hormone stimulates the total metabolic breakdown of nutritional lipids may be absolutely different from the currently known adipokinetic peptides that have been emphasized.

  13. Effect of 30 mCi radioiodine on multinodular goiter previously treated with recombinant human thyroid-stimulating hormone

    Energy Technology Data Exchange (ETDEWEB)

    Paz-Filho, G.J.; Mesa-Junior, C.O.; Boguszewski, C.L.; Carvalho, G.A.; Graf, H. [Universidade Federal do Parana (UFPR), Curitiba, PR (Brazil). Hospital de Clinicas. Servico de Endocrinologia e Metabologia; Olandoski, M. [Pontificia Univ. Catolica do Parana, Curitiba, PR (Brazil). Nucleo de Bioestatistica; Woellner, L.C. [Centro de Medicina Nuclear, Curitiba, PR (Brazil); Goedert, C.A. [Centro de Tomografia Computadorizada, Curitiba, PR (Brazil)

    2007-12-15

    Recombinant human thyroid-stimulating hormone (rhTSH) enhances {sup 131}I uptake, permitting a decrease in radiation for the treatment of multinodular goiter (MNG). Our objective was to evaluate the safety and efficacy of a single 0.1-mg dose of rhTSH, followed by 30 mCi {sup 131}I, in patients with MNG. Seventeen patients (15 females, 59.0 {+-} 13.1 years), who had never been submitted to {sup 131}I therapy, received a single 0.1-mg injection of rhTSH followed by 30 mCi {sup 131}I on the next day. Mean basal thyroid volume measured by computed tomography was 106.1 {+-} 64.4 mL. {sup 131}I 24-h uptake, TSH, free-T4, T3, thyroglobulin, anti-thyroid antibodies, and thyroid volume were evaluated at regular intervals of 12 months. Mean {sup 131}I 24-h uptake increased from 18.1 {+-} 9.7 to 49.6 {+-} 13.4% (P < 0.001), a median 2.6-fold increase (1.2 to 9.2). Peak hormonal levels were 10.86 {+-} 5.44 mU/L for TSH (a median 15.5-fold increase), 1.80 {+-} 0.48 ng/dL for free-T4, 204.61 {+-} 58.37 ng/dL for T3, and a median of 557.0 ng/mL for thyroglobulin. The adverse effects observed were hyperthyroidism (17.6%), painful thyroiditis (29.4%) and hypothyroidism (52.9%). Thyroid volume was reduced by 34.3 {+-} 14.3% after 6 months (P < 0.001) and by 46.0 {+-} 14.6% after 1 year (P < 0.001). Treatment of MNG with a single 0.1-mg dose of rhTSH, followed by a fixed amount of radioactivity of {sup 131}I, leads to an efficacious decrease in thyroid volume for the majority of the patients, with a moderate incidence of non-serious and readily treatable adverse effects. (author)

  14. Comparative assessment of quality of immunoradiometric assay (IRMA) and chemiluminescence immunometric assay (CHEIMA) for estimation of thyroid stimulating hormone (TSH)

    International Nuclear Information System (INIS)

    Sajid, K.M.

    2009-01-01

    Biological substances like hormones, vitamins and enzymes are found in minute quantities in blood. Their estimation requires very sensitive and specific methods. The most modern method for estimation of thyroid stimulating hormone in serum is non-isotopic enzyme enhanced chemiluminescence immunometric method. In our laboratory immunoradiometric assay is in routine for the last many years. Recently interest has grown to establish non-isotopic techniques in laboratories of PAEC. However, the main requirement to adopt the new procedures is to compare their results, cost and other benefits with the existing method. Immunoassay laboratory of MINAR, therefore, conducted a study to compare the two methods. A total of 173 (males: 34 females: 139 age: between 1 and 65 years) cases of clinically confirmed thyroid status were included in the study. Serum samples of these cases were analyzed by two methods and results were compared by plotting precision profiles, correlation plots and calculating sensitivities and specificities of the methods. As the results in all the samples were not normally distributed Wilcoxon rank sum test was applied to compare the analytical results of two methods. The comparison shows that the results obtained in two methods are not completely similar (p=0.0003293), although analysis of samples in groups shows that some similarity exists between the results of hypo and hyperthyroid patients (p<=0.156 and p<=0.6138). This shows that results obtained in these two methods could sometimes disagree in final diagnosis. Although TSH-CHEIMA is analytically more sensitive than TSH-IRMA the clinical sensitivities and specificities of two methods are not significantly different. TSH-CHEIMA test completes in almost 2 hours whereas TSH-IRMA takes about 6 hours to complete. Comparison of costs shows that TSH-CHIEMA is almost 5 times more expensive than TSH-IRMA. We conclude that the two methods could sometimes disagree but the two techniques have almost same

  15. Molecular cloning of the cDNA encoding follicle-stimulating hormone beta subunit of the Chinese soft-shell turtle Pelodiscus sinensis, and its gene expression.

    Science.gov (United States)

    Chien, Jung-Tsun; Shen, San-Tai; Lin, Yao-Sung; Yu, John Yuh-Lin

    2005-04-01

    Follicle-stimulating hormone (FSH) is a member of the pituitary glycoprotein hormone family. These hormones are composed of two dissimilar subunits, alpha and beta. Very little information is available regarding the nucleotide and amino acid sequence of FSHbeta in reptilian species. For better understanding of the phylogenetic diversity and evolution of FSH molecule, we have isolated and sequenced the complementary DNA (cDNA) encoding the Chinese soft-shell turtle (Pelodiscus sinensis, Family of Trionychidae) FSHbeta precursor molecule by reverse transcription-polymerase chain reaction (RT-PCR) and rapid amplification of cDNA end (RACE) methods. The cloned Chinese soft-shell turtle FSHbeta cDNA consists of 602-bp nucleotides, including 34-bp nucleotides of the 5'-untranslated region (UTR), 396-bp of the open reading frame, and 3'-UTR of 206-bp nucleotides. It encodes a 131-amino acid precursor molecule of FSHbeta subunit with a signal peptide of 20 amino acids followed by a mature protein of 111 amino acids. Twelve cysteine residues, forming six disulfide bonds within beta-subunit and two putative asparagine-linked glycosylation sites, are also conserved in the Chinese soft-shell turtle FSHbeta subunit. The deduced amino acid sequence of the Chinese soft-shell turtle FSHbeta shares identities of 97% with Reeves's turtle (Family of Bataguridae), 83-89% with birds, 61-70% with mammals, 63-66% with amphibians and 40-58% with fish. By contrast, when comparing the FSHbeta with the beta-subunits of the Chinese soft-shell turtle luteinizing hormone and thyroid stimulating hormone, the homologies are as low as 38 and 39%, respectively. A phylogenetic tree including reptilian species of FSHbeta subunits, is presented for the first time. Out of various tissues examined, FSHbeta mRNA was only expressed in the pituitary gland and can be up-regulated by gonadotropin-releasing hormone in pituitary tissue culture as estimated by fluorescence real-time PCR analysis.

  16. Melanocyte stem cells: biology and current aspects.

    Science.gov (United States)

    Gola, Monika; Czajkowski, Rafał; Bajek, Anna; Dura, Aleksander; Drewa, Tomasz

    2012-10-01

    Epidermal stem cells have become an object of intensive research. The epidermis constitutes one of the main sources of stem cells and is a tissue of choice for use in exploring their biology. Stratified squamous epithelium (epidermis) possesses the capacity for self-renewal and repair due to the presence of epidermal stem cells (ESC). They have been identified within basal layer of the interfollicular epidermis (IFE), in the "bulge" of the hair follicles of rodents, and also in the human follicular bulge. Melanocyte stem cells (MSC) from hair follicles (precisely from the bulge region, which also contains epidermal stem cells) provide an attractive model for the study of stem cells and their regulation at the niche. This review summarizes the rapidly developing field of epidermal stem cell research and their application in regenerative medicine, paying particular attention to melanocyte stem cells, their biology and some of the processes that occur during hair graying and regeneration of the pigmentary system, as well as discussing how aged-associated changes in the melanocyte stem cells compartment impact hair graying. This review also includes differentiation of human skin stem cells into functional epidermal melanocytes.

  17. Keratinocyte-melanocyte interactions during melanosome transfer.

    Science.gov (United States)

    Seiberg, M

    2001-08-01

    The epidermal-melanin unit is composed of one melanocyte and approximately 36 neighboring keratinocytes, working in synchrony to produce and distribute melanin. Melanin is synthesized in melanosomes, transferred to the dendrite tips, and translocated into keratinocytes, forming caps over the keratinocyte nuclei. The molecular and cellular mechanisms involved in melanosome transfer and the keratinocyte-melanocyte interactions required for this process are not yet completely understood. Suggested mechanisms of melanosome transfer include melanosome release and endocytosis, direct inoculation ('injection'), keratinocyte-melanocyte membrane fusion, and phagocytosis. Studies of the keratinocyte receptor protease-activated receptor-2 (PAR-2) support the phagocytosis theory. PAR-2 controls melanosome ingestion and phagocytosis by keratinocytes and exerts a regulatory role in skin pigmentation. Modulation of PAR-2 activity can enhance or decrease melanosome transfer and affects pigmentation only when there is keratinocyte-melanocyte contact. Moreover, PAR-2 is induced by UV irradiation and inhibition of PAR-2 activation results in the prevention of UVB-induced tanning. The role of PAR-2 in mediating UV-induced responses remains to be elucidated.

  18. Melanocytic Nevus of the Tarsal Conjunctiva

    Directory of Open Access Journals (Sweden)

    Bülent Yazıcı

    2016-08-01

    Full Text Available Background: Melanocytic nevus is a rare occurrence in the tarsal conjunctiva and only 7 well-described cases have been reported previously in the English literature. Case Report: The medical records of 4 patients with tarsal conjunctival melanocytic nevus were reviewed, together with the relevant literature. All patients (3 women and 1 man; age range: 17 - 40 years had been referred with a suspicion of melanoma. There was one tarsal nevus in the lower eyelid in 3 patients and 2 nevi in the upper eyelid in 1 patient. All lesions were darkly pigmented with irregular borders and were associated with a history of a recent growth in size. An intralesional cyst was present in 1 nevus only. After surgical excision, no recurrence or complication occurred during the follow-up period (range: 7 - 48 months. Conclusion: Tarsal melanocytic nevus has been described in detail in 11 cases, including these 4 cases, in the English literature. The lesion arose from the lower eyelid in all cases except one. Tarsal melanocytic nevi may frequently display clinical features suggesting melanoma, such as advanced patient age, recent growth, dark and irregular pigmentation, nodularity, hypervascularity, and the absence of an intralesional cyst. After total excision, nevus recurrence or malignant trans-formation has not been reported.

  19. Growth hormone binding to specific receptors stimulates growth and function of cloned insulin-producing rat insulinoma RIN-5AH cells

    DEFF Research Database (Denmark)

    Billestrup, Nils; Martin, J M

    1985-01-01

    Binding of 125I-labeled human GH (hGH) to a cloned rat insulin-producing cell line RIN-5AH in monolayer culture was studied along with some physiological effects of the hormone on these cells. Binding was time and temperature dependent, and steady state binding was observed in 60 min at 37 C...... in the cell membrane, directly stimulates proliferation and function of pancreatic beta-cells....

  20. Generation of human melanocytes from induced pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Shigeki Ohta

    Full Text Available Epidermal melanocytes play an important role in protecting the skin from UV rays, and their functional impairment results in pigment disorders. Additionally, melanomas are considered to arise from mutations that accumulate in melanocyte stem cells. The mechanisms underlying melanocyte differentiation and the defining characteristics of melanocyte stem cells in humans are, however, largely unknown. In the present study, we set out to generate melanocytes from human iPS cells in vitro, leading to a preliminary investigation of the mechanisms of human melanocyte differentiation. We generated iPS cell lines from human dermal fibroblasts using the Yamanaka factors (SOX2, OCT3/4, and KLF4, with or without c-MYC. These iPS cell lines were subsequently used to form embryoid bodies (EBs and then differentiated into melanocytes via culture supplementation with Wnt3a, SCF, and ET-3. Seven weeks after inducing differentiation, pigmented cells expressing melanocyte markers such as MITF, tyrosinase, SILV, and TYRP1, were detected. Melanosomes were identified in these pigmented cells by electron microscopy, and global gene expression profiling of the pigmented cells showed a high similarity to that of human primary foreskin-derived melanocytes, suggesting the successful generation of melanocytes from iPS cells. This in vitro differentiation system should prove useful for understanding human melanocyte biology and revealing the mechanism of various pigment cell disorders, including melanoma.

  1. Ultraviolet Radiation and the Slug Transcription Factor Induce Proinflammatory and Immunomodulatory Mediator Expression in Melanocytes

    Directory of Open Access Journals (Sweden)

    Stephanie H. Shirley

    2012-01-01

    Full Text Available Despite extensive investigation, the precise contribution of the ultraviolet radiation (UVR component of sunlight to melanoma etiology remains unclear. UVR induces keratinocytes to secrete proinflammatory and immunomodulatory mediators that promote inflammation and skin tumor development; expression of the slug transcription factor in keratinocytes is required for maximal production of these mediators. In the present studies we examined the possibility that UVR-exposed melanocytes also produce proinflammatory mediators and that Slug is important in this process. Microarray studies revealed that both UVR exposure and Slug overexpression altered transcription of a variety of proinflammatory mediators by normal human melanocytes; some of these mediators are also known to stimulate melanocyte growth and migration. There was little overlap in the spectra of cytokines produced by the two stimuli. However IL-20 was similarly induced by both stimuli and the NFκB pathway appeared to be important in both circumstances. Further exploration of UVR-induced and Slug-dependent pathways of cytokine induction in melanocytes may reveal novel targets for melanoma therapy.

  2. Ultraviolet Radiation and the Slug Transcription Factor Induce Pro inflammatory and Immunomodulatory Mediator Expression in Melanocytes

    International Nuclear Information System (INIS)

    Shirley, S. H.; Kusewitt, D. F.; Grimm, E. A.

    2012-01-01

    Despite extensive investigation, the precise contribution of the ultraviolet radiation (UVR) component of sunlight to melanoma etiology remains unclear. UVR induces keratinocytes to secrete pro inflammatory and immunomodulatory mediators that promote inflammation and skin tumor development; expression of the slug transcription factor in keratinocytes is required for maximal production of these mediators. In the present studies we examined the possibility that UVR-exposed melanocytes also produce pro inflammatory mediators and that Slug is important in this process. Micro array studies revealed that both UVR exposure and Slug overexpression altered transcription of a variety of pro inflammatory mediators by normal human melanocytes; some of these mediators are also known to stimulate melanocyte growth and migration. There was little overlap in the spectra of cytokines produced by the two stimuli. However IL-20 was similarly induced by both stimuli and the NFκB pathway appeared to be important in both circumstances. Further exploration of UVR-induced and Slug-dependent pathways of cytokine induction in melanocytes may reveal novel targets for melanoma therapy.

  3. Clinical Association of Thyroid Stimulating Hormone Receptor Antibody Levels with Disease Severity in the Chronic Inactive Stage of Graves' Orbitopathy.

    Science.gov (United States)

    Woo, Young Jae; Jang, Sun Young; Lim, Tyler Hyung Taek; Yoon, Jin Sook

    2015-08-01

    To investigate associations between serum thyroid stimulating hormone (TSH) receptor antibody (TRAb) levels and Graves' orbitopathy (GO) activity/severity in chronic-stage GO and compare the performance of two newly-developed TRAb assays (third-generation TSH-binding inhibition immunoglobulin [TBII] assay versus Mc4 thyroid-stimulating immunoglobulin [TSI] bioassay). This study is a retrospective review of medical charts and blood tests from Korean GO patients who first visited the departments of ophthalmology and endocrinology, Yonsei University College of Medicine from January 2008 to December 2011, were diagnosed with GO and Graves' hyperthyroidism, and were followed up for ≥18 months. Third-generation M22-TBII and Mc4-TSI assays were performed in the chronic-inactive GO patients in whom euthyroidism status was restored. Patients' GO activity/severity clinical activity scores (CAS), and modified NOSPECS scores were examined for a correlation with TRAb assays. Fifty patients (mean age, 41.3 years; 41 females) were analyzed. The mean duration of Graves' hyperthyroidism symptom was 63 months (range, 18 to 401 months) and that of GO was 46 months (range, 18 to 240 months). All patients had been treated previously with anti-thyroid drugs for a median period of 52.3 months, and two patients underwent either radioiodine therapy or total thyroidectomy. Mean CAS and NOSPECS scores were 0.5 ± 0.9 (standard deviation) and 4.8 ± 3.1, respectively. Mean M22-TBII and Mc4-TSI values were 7.5 ± 10.2 IL/L and 325.9 ± 210.1 specimen-to-reference control ratio. TSI was significantly correlated with NOSPECS score (R = 0.479, p 0.05), because GO inflammatory activity subsided in the chronic stages of GO. In chronic-inactive GO after euthyroid restoration, GO activity score did not associate with serum levels of TRAb or TBII. However, levels of the functional antibody Mc4-TSI did correlate with GO severity. Therefore, the TSI bioassay is a clinically relevant measure of disease

  4. Serum follicle-stimulating hormone level is associated with human epidermal growth factor receptor type 2 and Ki67 expression in post-menopausal females with breast cancer.

    Science.gov (United States)

    Zhou, Jun; Chen, Yiding; Huang, Yiting; Long, Jinpei; Wan, Fang; Zhang, Suzhan

    2013-10-01

    The present study aimed to determine the association between levels of the gender hormones, follicle-stimulating hormone (FSH), luteinizing hormone (LH), progesterone (P) and prolactin (PRL), and two breast cancer molecular markers, human epidermal growth factor receptor 2 (Her-2) and Ki67, in post-menopausal patients with breast cancer. A retrospective study of the serum hormone levels of FSH, LH, P and PRL and the expression status of Her-2 and Ki67 was performed using 187 post-menopausal females with breast cancer. Her-2 + breast cancer patients exhibited higher serum FSH levels compared with Her-2 - patients (69.47±3.219 vs. 58.56±1.516 IU/l). The patients with high Ki67 expression [immunohistochemistry (IHC), 3+] displayed higher FSH (72.51±4.616 vs. 60.53±1.476 IU/l) and LH (32.33±1.916 vs. 26.98±0.8852 IU/l) levels than those with lower Ki67 expression. No correlation was identified between the FSH, LH, P and PRL hormone levels, tumor stages and lymphovascular invasion (LVI). In conclusion, a higher serum FSH level was identified in Her-2 + post-menopausal patients with breast cancer. Higher serum FSH and LH levels were also observed in breast cancer patients with high Ki67 expression. FSH and LH may function in the progression of breast cancer.

  5. The Common Follicle-Stimulating Hormone Receptor (FSHR Promoter Polymorphism FSHR −29G > A Affects Androgen Production in Normal Human Small Antral Follicles

    Directory of Open Access Journals (Sweden)

    Tanni Borgbo

    2017-06-01

    Full Text Available Follicle-stimulating hormone receptors (FSHRs are almost exclusively expressed on granulosa cells, and FSH action is probably most clearly reflected in intrafollicular hormone milieu of antral follicles. Little is known about the possible effects of the common single nucleotide polymorphism (SNP FSHR −29G > A (rs1394205 on hormonal conditions in humsan small antral follicles (hSAFs obtained from women in the natural menstrual cycle. This study investigated the follicle fluid (FF concentrations of anti-Müllerian hormone, estradiol, progesterone, androstenedione, and testosterone in hSAF in relation to the different genotypes of FSHR −29G > A. FF from 362 follicles was collected in 95 women undergoing fertility preservation, who did not suffer from a disease that directly affected ovarian function. The testosterone levels of the minor A/A genotype were significantly increased compared to the A/G and the G/G genotype. Furthermore, significantly reduced androstenedione levels were observed for the G/G genotype, as compared to the A/G genotype, while the other hormones did not show statistical significant differences. In conclusion, the androgen levels of hSAF were significantly elevated in the minor SNP genotype in the FSHR promoter polymorphism FSHR −29G > A.

  6. The association between soya consumption and serum thyroid-stimulating hormone concentrations in the Adventist Health Study-2.

    Science.gov (United States)

    Tonstad, Serena; Jaceldo-Siegl, Karen; Messina, Mark; Haddad, Ella; Fraser, Gary E

    2016-06-01

    Consumers may choose soya foods as healthful alternatives to animal products, but concern has arisen that eating large amounts of soya may adversely affect thyroid function. The present study aimed to examine the association between soya food consumption and serum thyroid-stimulating hormone (TSH) concentrations in North American churchgoers belonging to the Seventh-day Adventist denomination that encourages vegetarianism. Participants completed six repeated 24 h dietary recalls within a 6-month period. Soya protein and soya isoflavone intakes were estimated, and their relationships to TSH concentrations measured at the end of 6 months were calculated using logistic regression analyses. Calibration sub-study of the Adventist Health Study-2. Women (n 548) and men (n 295) who were not taking thyroid medications. In men, age and urinary iodine concentrations were associated with high serum TSH concentrations (>5 mIU/l), while among women White ethnicity was associated with high TSH. In multivariate models adjusted for age, ethnicity and urinary iodine, soya isoflavone and protein intakes were not associated with high TSH in men. In women higher soya isoflavone consumption was associated with higher TSH, with an adjusted odds ratio (highest v. lowest quintile) of 4·17 (95 % CI 1·73, 10·06). Likewise, women with high consumption of soya protein (midpoint of highest quintile, 11 g/d) v. low consumption (midpoint of lowest quintile, 0 g/d) carried increased odds of high TSH (OR=2·69; 95 % CI 1·34, 5·30). In women high consumption of soya was associated with elevated TSH concentrations. No associations between soya intake and TSH were found in men.

  7. Impacts of incorporation of follicle stimulating hormone into an estrous synchronization protocol for timed artificial insemination of crossbred beef cattle.

    Science.gov (United States)

    Gentry, G T; Walker, R S; Gentry, L R

    2016-05-01

    One-hundred-eighty crossbred beef cows and 66 crossbred beef heifers across three locations were stratified by body weight (BW), body condition score (BCS), and age (within location) to evaluate administration of follicle stimulating hormone (FSH) on Day 2 using a modified 7-day CO-Synch plus CIDR(®) protocol (Day 0=CIDR insertion) with timed-artificial insemination (TAI) at 72 h (cows) or 54 h (heifers) following CIDR removal. Estrous response following CIDR removal was determined using an Estrotect patch and TAI and final pregnancy rates were determined by transrectal ultrasonography 42-45 days following TAI and ≥ 45 days following removal of clean-up bulls. Estrous response rate, TAI and final pregnancy rates for cows were not affected (P ≥ 0.65) by treatment. Cows that exhibited estrus had greater (P<0.01) TAI pregnancy rate (66%) than cows not exhibiting estrus (38%). There was an estrous response by postpartum length interaction (P=0.02) where cows exhibiting estrus and ≥ 55 days postpartum had greater TAI pregnancy rates (75%) compared to cows not exhibiting estrus and < 55 days postpartum (39%) or ≥ 55 days postpartum (28%). For heifers, timed AI (P=0.46) and final pregnancy rates (P=0.45) were similar across treatments and estrous response had no effect (P=0.30) on TAI pregnancy rates. In conclusion, the addition of FSH to the CO-Synch plus CIDR estrous synchronization protocol did not increase TAI pregnancy rates in beef cows or heifers. However, a positive estrous response to the synchronization protocol was associated with increased TAI pregnancy rates in cows. Copyright © 2016. Published by Elsevier B.V.

  8. Mother's menopausal age is associated with her daughter's early follicular phase urinary follicle-stimulating hormone level.

    Science.gov (United States)

    Steiner, Anne Z; Baird, Donna D; Kesner, James S

    2008-01-01

    Early follicular phase follicle-stimulating hormone (FSH), a marker of ovarian reserve, has been used to predict time to menopause. A mother's age at menopause is related to her daughter's age at menopause, possibly because of genetic factors. In this study we sought to determine the relationship between maternal age at menopause and early follicular phase FSH of premenopausal daughters. The Uterine Fibroid Study enrolled women randomly selected from a prepaid health plan, collected questionnaire data, and obtained early follicular phase urine samples for a subset of participants. For this secondary analysis, premenopausal women between the ages of 35 and 46 years, who provided a urine sample on cycle day 2, 3, 4, or 5 and their mother's age at natural menopause (n = 182) were selected from the original cohort. Initially bivariate analysis and subsequently regression modeling were performed to assess the independent relationship between maternal age at menopause and urinary creatinine-corrected FSH. Unadjusted analyses and those adjusting for age (mean +/- SD, 40.5 +/- 3.2 y), smoking status (16% current smokers), and body mass index (26.8 +/- 6.9 kg/m) showed a significant association between maternal age at menopause and daughter's urinary FSH level (P menopause had higher urinary FSH levels. The significantly increased FSH values among women whose mothers experienced early menopause is consistent with previously reported associations between mother's and daughter's age of menopause. FSH, a marker of ovarian reserve, is influenced by both genetic and environmental factors. Future epidemiologic studies on FSH should include collection of information on maternal age at menopause.

  9. Follicle-Stimulating Hormone Receptor Is Expressed by Most Ovarian Cancer Subtypes and Is a Safe and Effective Immunotherapeutic Target.

    Science.gov (United States)

    Perales-Puchalt, Alfredo; Svoronos, Nikolaos; Rutkowski, Melanie R; Allegrezza, Michael J; Tesone, Amelia J; Payne, Kyle K; Wickramasinghe, Jayamanna; Nguyen, Jenny M; O'Brien, Shane W; Gumireddy, Kiranmai; Huang, Qihong; Cadungog, Mark G; Connolly, Denise C; Tchou, Julia; Curiel, Tyler J; Conejo-Garcia, Jose R

    2017-01-15

    To define the safety and effectiveness of T cells redirected against follicle-stimulating hormone receptor (FSHR)-expressing ovarian cancer cells. FSHR expression was determined by Western blotting, immunohistochemistry, and qPCR in 77 human ovarian cancer specimens from 6 different histologic subtypes and 20 human healthy tissues. The effectiveness of human T cells targeted with full-length FSH in vivo was determined against a panel of patient-derived xenografts. Safety and effectiveness were confirmed in immunocompetent tumor-bearing mice, using constructs targeting murine FSHR and syngeneic T cells. FSHR is expressed in gynecologic malignancies of different histologic types but not in nonovarian healthy tissues. Accordingly, T cells expressing full-length FSHR-redirected chimeric receptors mediate significant therapeutic effects (including tumor rejection) against a panel of patient-derived tumors in vivo In immunocompetent mice growing syngeneic, orthotopic, and aggressive ovarian tumors, fully murine FSHR-targeted T cells also increased survival without any measurable toxicity. Notably, chimeric receptors enhanced the ability of endogenous tumor-reactive T cells to abrogate malignant progression upon adoptive transfer into naïve recipients subsequently challenged with the same tumor. Interestingly, FSHR-targeted T cells persisted as memory lymphocytes without noticeable PD-1-dependent exhaustion during end-stage disease, in the absence of tumor cell immunoediting. However, exosomes in advanced tumor ascites diverted the effector activity of this and other chimeric receptor-transduced T cells away from targeted tumor cells. T cells redirected against FSHR + tumor cells with full-length FSH represent a promising therapeutic alternative against a broad range of ovarian malignancies, with negligible toxicity even in the presence of cognate targets in tumor-free ovaries. Clin Cancer Res; 23(2); 441-53. ©2016 AACR. ©2016 American Association for Cancer Research.

  10. Harmonization of Serum Thyroid-Stimulating Hormone Measurements Paves the Way for the Adoption of a More Uniform Reference Interval.

    Science.gov (United States)

    Thienpont, Linda M; Van Uytfanghe, Katleen; De Grande, Linde A C; Reynders, Dries; Das, Barnali; Faix, James D; MacKenzie, Finlay; Decallonne, Brigitte; Hishinuma, Akira; Lapauw, Bruno; Taelman, Paul; Van Crombrugge, Paul; Van den Bruel, Annick; Velkeniers, Brigitte; Williams, Paul

    2017-07-01

    The IFCC Committee for Standardization of Thyroid Function Tests developed a global harmonization approach for thyroid-stimulating hormone measurements. It is based on a multiassay method comparison study with clinical serum samples and target setting with a robust factor analysis method. Here we describe the Phase IV method comparison and reference interval (RI) studies conducted with the objective to recalibrate the participating assays and demonstrate the proof-of-concept. Fourteen manufacturers measured the harmonization and RI panel; 4 of them quantified the harmonization and first follow-up panel in parallel. All recalibrated their assays to the statistically inferred targets. For validation, we used desirable specifications from the biological variation for the bias and total error (TE). The RI measurements were done with the assays' current calibrators, but data were also reported after transformation to the new calibration status. We estimated the pre- and postrecalibration RIs with a nonparametric bootstrap procedure. After recalibration, 14 of 15 assays met the bias specification with 95% confidence; 8 assays complied with the TE specification. The CV of the assay means for the harmonization panel was reduced from 9.5% to 4.2%. The RI study showed improved uniformity after recalibration: the ranges (i.e., maximum differences) exhibited by the assay-specific 2.5th, 50th, and 97.5th percentile estimates were reduced from 0.27, 0.89, and 2.13 mIU/L to 0.12, 0.29, and 0.77 mIU/L. We showed that harmonization increased the agreement of results from the participating immunoassays, and may allow them to adopt a more uniform RI in the future. © 2017 American Association for Clinical Chemistry.

  11. Using Hashimoto thyroiditis as gold standard to determine the upper limit value of thyroid stimulating hormone in a Chinese cohort.

    Science.gov (United States)

    Li, Yu; Chen, Dong-Ning; Cui, Jing; Xin, Zhong; Yang, Guang-Ran; Niu, Ming-Jia; Yang, Jin-Kui

    2016-11-06

    Subclinical hypothyroidism, commonly caused by Hashimoto thyroiditis (HT), is a risk factor for cardiovascular diseases. This disorder is defined as merely having elevated serum thyroid stimulating hormone (TSH) levels. However, the upper limit of reference range for TSH is debated recently. This study was to determine the cutoff value for the upper normal limit of TSH in a cohort using the prevalence of Hashimoto thyroiditis as "gold" calibration standard. The research population was medical staff of 2856 individuals who took part in health examination annually. Serum free triiodothyronine (FT3), free thyroxine (FT4), TSH, thyroid peroxidase antibody (TPAb), thyroglobulin antibody (TGAb) and other biochemistry parameters were tested. Meanwhile, thyroid ultrasound examination was performed. The diagnosis of HT was based on presence of thyroid antibodies (TPAb and TGAb) and abnormalities of thyroid ultrasound examination. We used two different methods to estimate the cutoff point of TSH based on the prevalence of HT. Joinpoint regression showed the prevalence of HT increased significantly at the ninth decile of TSH value corresponding to 2.9 mU/L. ROC curve showed a TSH cutoff value of 2.6 mU/L with the maximized sensitivity and specificity in identifying HT. Using the newly defined cutoff value of TSH can detect patients with hyperlipidemia more efficiently, which may indicate our approach to define the upper limit of TSH can make more sense from the clinical point of view. A significant increase in the prevalence of HT occurred among individuals with a TSH of 2.6-2.9 mU/L made it possible to determine the cutoff value of normal upper limit of TSH.

  12. Serum thyroid stimulating hormone, total and free T4 during the neonatal period: Establishing regional reference intervals

    Directory of Open Access Journals (Sweden)

    Sara Sheikhbahaei

    2014-01-01

    Full Text Available Context: Congenital hypothyroidism (CH, the most common etiology of preventable mental retardation in children, is estimated to be more prevalent among Asian population. Aims: Since thyroid function tests (TFTs varied among different ages and geographical regions, in this study, the neonatal thyroid reference intervals in a healthy neonatal population is determined for the first time in Iran. Settings and Design: A cross-sectional study performed on 246 healthy term newborns aged between 2 days and 1 month. Materials and Methods: Blood samples were obtained by venipuncture from all subjects. The median, 2.5 th , 5 th , 95 th , and 97.5 th percentile of serum thyroid-stimulating hormone (TSH, as well as the total and free T4 were assessed among different age groups. Statistical Analysis Used: Predictive Analytics Software (PASW Statistics 18 was used for the analysis. Results: Serum TSH, total and free T4 concentration peaked in 5 th to 7 th days of life, continued over 2 weeks, then decreased and started reaching to adult reference range. A significant negative correlation between age and serum concentration of TSH (P = 0.02, total T4 (P = 0.01 and free T4 (P = 0.01 was found. Conclusion: This study yielded fairly different values for TFTs compared compared values found in other countries and also different from values reported for laboratory kits we used. These differences were assumed to be due to variations in ethnicity, age, and laboratory methods used. Due to the lack of international standardization, conducting multicenter studies helps in making a more precise evaluation of thyroid status in neonates.

  13. How well does the capillary thyroid-stimulating hormone test for newborn thyroid screening predict the venous free thyroxine level?

    Science.gov (United States)

    Pokrovska, Tzveta; Jones, Jeremy; Shaikh, M Guftar; Smith, Sarah; Donaldson, Malcolm D C

    2016-06-01

    To determine, in newborn infants referred with elevated capillary thyroid-stimulating hormone (TSH), a threshold below which a frankly subnormal venous free thyroxine (fT4) level of 10 days after capillary sampling (13, 10)), leaving 286 eligible for analysis (208 definite/probable hypothyroidism, 61 transient TSH elevation, 17 of uncertain thyroid status). Capillary TSH and venous T4 were strongly correlated (Spearman's rank correlation coefficient -0.707355). The optimal capillary TSH threshold for predicting a venous fT4 of 40 mU/L (90.3% sensitivity and 65.9% specificity compared with 90.25% and 59.1% for >35 mU/L and 88.3% and 68.2% for >45 mU/L). 93 infants (32.5%) had capillary TSH ≤40 mU/L at referral of whom 15 (9.7%) had venous fT4 <10 pmol/L, comprising seven with true congenital hypothyroidism, five with transient TSH elevation and three with uncertain status, two of whom died. For infants in whom capillary TSH is ≤40 mU/L, it is reasonable to defer L-T4 treatment until venous TFT results are known provided that the latter become available quickly. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  14. Constitutive activation of the thyroid-stimulating hormone receptor (TSHR by mutating Ile691 in the cytoplasmic tail segment.

    Directory of Open Access Journals (Sweden)

    Zheng Liu

    Full Text Available BACKGROUND: Autosomal dominant non-autoimmune hyperthyroidism (ADNAH is a rare genetic disorder of the endocrine system. Molecular genetic studies in ADNAH have revealed heterozygous germline mutations in the TSHR. To data, mutations leading to an increase in the constitutive activation of the TSHR have been described in the transmembrane segments, exoloops and cytoplasmic loop of TSHR. These mutations result in constitutive activation of the G(αs/cAMP or G(αq/11/inositol phosphate (IP pathways, which stimulate thyroid hormone production and thyroid proliferation. METHODOLOGY/PRINCIPAL FINDINGS: In a previous study, we reported a new TSHR mutation located in the C-terminal domain of TSHR, which results in a substitution of the conserved Ile(691 for Phe. In this study, to address the question of whether the I691F mutated receptor could be responsible for G(αs/cAMP or G(αq/11/IP constitutive activity, wild-type and TSHR mutants were expressed in COS-7 cells to determine cAMP constitutive activity and IP formation. Compared to the cell surface with expression of the A623V mutated receptor as positive control, the I691F mutated receptor showed a slight increase of cAMP accumulation. Furthermore, I691F resulted in constitutive activation of the G(αq/11/IP signaling pathway. CONCLUSIONS/SIGNIFICANCE: Our results indicate that Ile(691 not only contributes to keeping TSHR inactive in the G(αs/cAMP pathways but also in the G(αq/11/IP cascade.

  15. FSHB-211 and FSHR 2039 are associated with serum levels of follicle-stimulating hormone and antimüllerian hormone in healthy girls

    DEFF Research Database (Denmark)

    Hagen, Casper P; Aksglæde, Lise; Sørensen, Kaspar

    2013-01-01

    To investigate whether genetic polymorphisms in the FSH pathway (FSHB-211 G→T and FSHR 2039 A→G) affect serum levels of FSH, antimüllerian hormone (AMH), and age at pubertal onset. FSH secretion and FSH signal transduction are enhanced in carriers of FSHB GG and FSHR AA, respectively. Furthermore...

  16. In vitro effect of Δ9-tetrahydrocannabinol to stimulate somatostatin release and block that of luteinizing hormone-releasing hormone by suppression of the release of prostaglandin E2

    International Nuclear Information System (INIS)

    Rettori, V.; Aguila, M.C.; McCann, S.M.; Gimeno, M.F.; Franchi, A.M.

    1990-01-01

    Previous in vivo studies have shown that Δ 9 -tetrahydrocannabinol (THC), the principal active ingredient in marijuana, can suppress both luteinizing hormone (LH) and growth hormone (GH) secretion after its injection into the third ventricle of conscious male rats. The present studies were deigned to determine the mechanism of these effects. Various doses of THC were incubated with either stalk median eminence fragments (MEs) or mediobasal hypothalamic (MBH) fragments in vitro. Although THC (10 nM) did not alter basal release of LH-releasing hormone (LHRH) from MEs in vitro, it completely blocked the stimulatory action of dopamine or nonrepinephrine on LHRH release. The effective doses to block LHRH release were associated with a blockade of synthesis and release of prostaglandin E 2 (PGE 2 ) from MBH in vitro. In contrast to the suppressive effect of THC on LHRH release, somatostatin release from MEs was enhanced in a dose-related manner with a minimal effective dose of 1 nM. Since PGE 2 suppresses somatostatin release, this enhancement may also be related to the suppressive effect of THC on PGE 2 synthesis and release. The authors speculate that these actions are mediated by the recently discovered THC receptors in the tissue. The results indicate that the suppressive effect of THC on LH release is mediated by a blockade of LHRH release, whereas the suppressive effect of the compound on growth hormone release is mediated, at least in part, by a stimulation of somatostatin release

  17. Internal jugular vein: Peripheral vein adrenocorticotropic hormone ratio in patients with adrenocorticotropic hormone-dependent Cushing′s syndrome: Ratio calculated from one adrenocorticotropic hormone sample each from right and left internal jugular vein during corticotrophin releasing hormone stimulation test

    Directory of Open Access Journals (Sweden)

    Sachin Chittawar

    2013-01-01

    Full Text Available Background: Demonstration of central: Peripheral adrenocorticotropic hormone (ACTH gradient is important for diagnosis of Cushing′s disease. Aim: The aim was to assess the utility of internal jugular vein (IJV: Peripheral vein ACTH ratio for diagnosis of Cushing′s disease. Materials and Methods: Patients with ACTH-dependent Cushing′s syndrome (CS patients were the subjects for this study. One blood sample each was collected from right and left IJV following intravenous hCRH at 3 and 5 min, respectively. A simultaneous peripheral vein sample was also collected with each IJV sample for calculation of IJV: Peripheral vein ACTH ratio. IJV sample collection was done under ultrasound guidance. ACTH was assayed using electrochemiluminescence immunoassay (ECLIA. Results: Thirty-two patients participated in this study. The IJV: Peripheral vein ACTH ratio ranged from 1.07 to 6.99 ( n = 32. It was more than 1.6 in 23 patients. Cushing′s disease could be confirmed in 20 of the 23 cases with IJV: Peripheral vein ratio more than 1.6. Four patients with Cushing′s disease and 2 patients with ectopic ACTH syndrome had IJV: Peripheral vein ACTH ratio less than 1.6. Six cases with unknown ACTH source were excluded for calculation of sensitivity and specificity of the test. Conclusion: IJV: Peripheral vein ACTH ratio calculated from a single sample from each IJV obtained after hCRH had 83% sensitivity and 100% specificity for diagnosis of CD.

  18. l-tyrosine induces melanocyte differentiation in novel pink-eyed dilution castaneus mouse mutant showing age-related pigmentation.

    Science.gov (United States)

    Hirobe, Tomohisa; Ishikawa, Akira

    2015-12-01

    The mouse pink-eyed dilution (oculocutaneous albinism II; p/Oca2(p)) locus is known to control tyrosinase activity, melanin content, and melanosome development in melanocytes. Pink-eyed dilution castaneus (p(cas)/Oca2(p-cas)) is a novel mutant allele on mouse chromosome 7 that arose spontaneously in Indonesian wild mice, Mus musculus castaneus. Mice homozygous for Oca2(p-cas) usually exhibit pink eyes and beige-colored coat on nonagouti C57BL/6 (B6) background. Recently, a novel spontaneous mutation occurred in the progeny between this mutant and B6 mice. The eyes of this novel mutant progressively become black from pink and the coat becomes dark gray from beige with aging. The aim of this study is to clarify whatever differences exist in melanocyte proliferation and differentiation between the ordinary (pink-eyed) and novel (black-eyed) mutant using serum-free primary culture system. The characteristics of melanocyte proliferation and differentiation were investigated by serum-free primary culture system using melanocyte-proliferation medium (MDMD). The proliferation of melanoblasts in MDMD did not differ between the two mice. However, when the epidermal cell suspensions were cultured with MDMD supplemented with l-tyrosine (Tyr), the differentiation of black-eyed melanocytes was greatly induced in a concentration-dependent manner compared with pink-eyed melanocytes. Immunocytochemistry demonstrated that the expression of tyrosinase and tyrosinase-related protein-1 (Tyrp1) was greatly induced or stimulated both in pink-eyed and black-eyed melanocytes, whereas the expression of microphthalmia-associated transcription factor (Mitf) was stimulated only in black-eyed melanocytes. These results suggest that the age-related coat darkening in black-eyed mutant may be caused by the increased ability of melanocyte differentiation dependent on l-Tyr through the upregulation of tyrosinase, Tyrp1, and Mitf. This mutant mouse may be useful for animal model to clarify the

  19. Luteinizing hormone (LH) blood test

    Science.gov (United States)

    ICSH - blood test; Luteinizing hormone - blood test; Interstitial cell stimulating hormone - blood test ... Chernecky CC, Berger BJ. Luteinizing hormone - blood. In: Chernecky ... Jeelani R, Bluth MH. Reproductive function and pregnancy. In: ...

  20. Alterations of serum concentrations of thyroid hormones and sex hormone-binding globulin, nuclear binding of tri-iodothyronine and thyroid hormone-stimulated cellular uptake of oxygen and glucose in mononuclear blood cells from patients with non-thyroidal illness

    DEFF Research Database (Denmark)

    Kvetny, J; Matzen, L

    1990-01-01

    Nuclear tri-iodothyronine (T3) binding and thyroid hormone-stimulated oxygen consumption and glucose uptake were examined in mononuclear blood cells from patients with non-thyroidal illness (NTI) in which serum T3 was significantly (P less than 0.05) depressed (0.62 +/- 0.12 (S.D.) nmol/l) compared...

  1. Thyroid stimulating hormone and serum, plasma, and platelet brain-derived neurotrophic factor during a 3-month follow-up in patients with major depressive disorder.

    Science.gov (United States)

    Baek, Ji Hyun; Kang, Eun-Suk; Fava, Maurizio; Mischoulon, David; Nierenberg, Andrew A; Lee, Dongsoo; Heo, Jung-Yoon; Jeon, Hong Jin

    2014-12-01

    Thyroid dysfunction and elevated thyroid stimulating hormone (TSH) are common in patients with depression. TSH might exert its function in the brain through blood levels of brain-derived neurotrophic factor (BDNF). BDNF decreases during depressed states and normalize after treatment. The gap is that the association between TSH and BDNF in patients with major depressive disorder (MDD) is unknown. We studied 105 subjects ≥18 years of age with MDD and measured serum, plasma, and platelet BDNF at baseline, 1 month and 3 months during antidepressant treatment. Other baseline measurements included hypothalamic-pituitary-thyroid axis hormones such as TSH, triiodothyronine (T3) and thyroxine (T4); hypothalamic-pituitary-adrenal (HPA) axis hormones and hypothalamic-pituitary-gonadal (HPG) axis hormones and prolactin. Linear mixed model effect analyses revealed that baseline TSH level was negatively associated with changes of serum BDNF from baseline to 3 months (F=7.58, p=0.007) after adjusting for age, sex, and body mass index, but was not associated with plasma and platelet BDNF. In contrast, T3 and T4, HPA axis hormones, HPG axis hormones, and prolactin were not associated with serum, plasma, or platelet BDNF levels. Patients in the highest quartile of TSH showed significantly lower serum BDNF than in the other quartiles (F=4.54, p=0.038), but no significant differences were found based on T3 and T4 levels. TSH was only measured at baseline. Higher TSH is associated with lower baseline and reduced the increase of serum BDNF levels during antidepressant treatment in patients with MDD. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Dose-dependent effects of luteinizing hormone and follicle ...

    African Journals Online (AJOL)

    Dose-dependent effects of luteinizing hormone and follicle stimulating hormone on in vitro maturation, apoptosis, secretion function and expression of follicle stimulating hormone receptor and luteinizing hormone receptor of sheep oocytes.

  3. Association of Exon 10A and 10B inactivating mutation of follicle stimulating hormone receptor gene (FSHR) and Polycystic Ovarian Syndrome in Vellore cohort

    Science.gov (United States)

    Sekar, Nishu; Kulkarni, Rucha; Ozalkar, Sharvari; Prabhu, Yogamaya D.; Renu, Kaviyarasi; Ramgir, Shalaka S.; Abilash, V. G.

    2017-11-01

    Polycystic ovarian syndrome is the most common heterogenous endocrine disorder in women. Follicle stimulating hormone receptor is associated with normal development as well as maturation of follicles and triggers estrogen production in granulosa cells of the ovary. Inactivating mutation in FSHR gene correlated with reduction of ovarian function in women is due to damage to receptor function. This study aims to investigate whether inactivating mutations, in follicle stimulating hormone receptor gene is related to polycystic ovarian morphology in women with PCOS. Genomic DNA isolated from 15 subjects from Sandhya Hospital, Vellore (10 patients with PCOS and 5 healthy controls) was taken for this study. Patient data included a clinical report, hormonal levels, and ovarian morphological details. DNA isolation was followed by DNA amplification by polymerase chain reaction using Exon 10 A and Exon 10 B primers. The PCR-RFLP analysis was performed using Dde1 restriction enzyme. Here we discuss inactivating mutation found in Exon 10 of FSHR gene in patients with PCOS.The absence of inactivating mutation was observed through PCR-RFLP study on Exon 10A and Exon 10B.

  4. Increases in Intracellular Zinc Enhance Proliferative Signaling as well as Mitochondrial and Endolysosomal Activity in Human Melanocytes.

    Science.gov (United States)

    Rudolf, Emil; Rudolf, Kamil

    2017-01-01

    Zinc (Zn) is an important microelement required by skin cells for a variety of biological processes. The role of Zn in melanocyte proliferation and homeostasis has to date not been investigated. Human dermal melanocytes were isolated from patients and their proliferative activity determined along with both total and labile Zn content. Subsequently, changes in proliferation as well as in Zn content were determined upon exposure of the dermal melanocytes to external Zn. Further in-depth analyses were undertaken aimed at measuring the expression of proliferation-related proteins (determined by immunoblotting and densitometry), as well as changes in mitochondrial biogenesis and membrane potential (assessed by fluorescence-based cellometry) along with endolysosomal activity (determined by spectrofluorimetrically-measured elevation in fluorescence of lysosomal-aimed non-fuorescent substrate). Human skin melanocytes accumulate externally added Zn, a process which dose-dependently enhances their injury or proliferative activity. Enhanced proliferation is accompanied by an increased expression of the proteins AKT3, ERK1/2, c-MYC and CYCD. In addition, Zn-enriched melanocytes exhibit enhanced mitochondrial biogenesis, with individual mitochondria possessing stabilized mitochondrial membrane potential as well as showing elevated ATP and superoxide levels. Moreover, upon external exposure, Zn enters lysosomes/melanosomes, the activity of which is stimulated along with the process of autophagy. The determination of the unique Zn-dependent stimulation of melanocytes and in particular the enhancement of the cells' mitochondrial as well as lysosomal/melanosomal activities may prove important in tracing the sequence of steps in the process of melanomagenesis. © 2017 The Author(s). Published by S. Karger AG, Basel.

  5. Increases in Intracellular Zinc Enhance Proliferative Signaling as well as Mitochondrial and Endolysosomal Activity in Human Melanocytes

    Directory of Open Access Journals (Sweden)

    Emil Rudolf

    2017-08-01

    Full Text Available Background/Aims: Zinc (Zn is an important microelement required by skin cells for a variety of biological processes. The role of Zn in melanocyte proliferation and homeostasis has to date not been investigated. Methods: Human dermal melanocytes were isolated from patients and their proliferative activity determined along with both total and labile Zn content. Subsequently, changes in proliferation as well as in Zn content were determined upon exposure of the dermal melanocytes to external Zn. Further in-depth analyses were undertaken aimed at measuring the expression of proliferation-related proteins (determined by immunoblotting and densitometry, as well as changes in mitochondrial biogenesis and membrane potential (assessed by fluorescence-based cellometry along with endolysosomal activity (determined by spectrofluorimetrically-measured elevation in fluorescence of lysosomal-aimed non-fuorescent substrate. Results: Human skin melanocytes accumulate externally added Zn, a process which dose-dependently enhances their injury or proliferative activity. Enhanced proliferation is accompanied by an increased expression of the proteins AKT3, ERK1/2, c-MYC and CYCD. In addition, Zn-enriched melanocytes exhibit enhanced mitochondrial biogenesis, with individual mitochondria possessing stabilized mitochondrial membrane potential as well as showing elevated ATP and superoxide levels. Moreover, upon external exposure, Zn enters lysosomes/melanosomes, the activity of which is stimulated along with the process of autophagy. Conclusion: The determination of the unique Zn-dependent stimulation of melanocytes and in particular the enhancement of the cells’ mitochondrial as well as lysosomal/melanosomal activities may prove important in tracing the sequence of steps in the process of melanomagenesis.

  6. Cadmium, follicle-stimulating hormone, and effects on bone in women age 42-60 years, NHANES III

    Energy Technology Data Exchange (ETDEWEB)

    Gallagher, Carolyn M., E-mail: 2crgallagher@optonline.net [PhD Program in Population Health and Clinical Outcomes Research, Stony Brook University, Health Sciences Center L3-R071, Stony Brook, New York 11794-8338 (United States); Department of Preventive Medicine, Stony Brook University Medical Center, Stony Brook, New York (United States); Moonga, Baljit S. [Stony Brook University School of Dental Medicine, New York (United States); Kovach, John S. [Department of Preventive Medicine, Stony Brook University Medical Center, Stony Brook, New York (United States)

    2010-01-15

    Background: Increased body burden of environmental cadmium has been associated with greater risk of decreased bone mineral density (BMD) and osteoporosis in middle-aged and older women, and an inverse relationship has been reported between follicle-stimulating hormone (FSH) and BMD in middle-aged women; however, the relationships between cadmium and FSH are uncertain, and the associations of each with bone loss have not been analyzed in a single population. Objectives: The objective of this study was to evaluate the associations between creatinine-adjusted urinary cadmium (UCd) and FSH levels, and the associations between UCd and FSH with BMD and osteoporosis, in postmenopausal and perimenopausal women aged 42-60 years. Methods: Data were obtained from the Third National Health Examination and Nutrition Survey, 1988-1994 (NHANES III). Outcomes evaluated were serum FSH levels, femoral bone mineral density measured by dual energy X-ray absorptiometry, and osteoporosis indicated by femoral BMD cutoffs based on the international standard. Urinary cadmium levels were analyzed for association with these outcomes, and FSH levels analyzed for association with bone effects, using multiple regression. Subset analysis was conducted by a dichotomous measure of body mass index (BMI) to proxy higher and lower adipose-synthesized estrogen effects. Results: UCd was associated with increased serum FSH in perimenopausal women with high BMI (n=642; {beta}=0.45; p{<=}0.05; R{sup 2}=0.35) and low BMI (n=408; {beta}=0.61; p{<=}0.01; R{sup 2}=0.34). Among perimenopausal women with high BMI, BMD was inversely related to UCd ({beta}=-0.04; p{<=}0.05) and FSH ({beta}=-0.03; p{<=}0.05). In postmenopausal women with low BMI, an incremental increase in FSH was associated with 2.78 greater odds for osteoporosis (109 with and 706 without) (OR=2.78; 95% CI=1.43, 5.42; p{<=}0.01). Conclusion: Long-term cadmium exposure at environmental levels is associated with increased serum FSH, and both FSH

  7. Follicle-stimulating hormone to substitute equine chorionic gonadotropin in the synchronization of ovulation in Santa Inês ewes

    Directory of Open Access Journals (Sweden)

    Bianor Matias Cardoso Neto

    2012-03-01

    Full Text Available The substitution of equine chorionic gonadotropin (eCG by follicle-stimulating hormone (FSH in protocols for synchronization of ovulation in Santa Inês ewes was assessed. Ten females were submitted to the insertion of intravaginal sponges containing 60 mg medroxyprogesterone acetate for 10 days; after this period sponges were withdrawn and the animals were randomly divided into two groups. Group 1 (n = 5: intramuscular injection of 0.5 mL d-cloprostenol and 300 UI eCG; Group 2 (n = 5: intramuscular injection of 0.5 mL d-cloprostenol and 20 mg FSH. Interval between sponge withdrawal and estrus beginning was 27.7 h and 35.9 h for eCG and FSH, respectively. Interval between sponge withdrawal and the end of estrus was 55.8 h for eCG treatment and 55.6 h for FSH treatment. Estrus length was 29.3 h and 19.6 h, for eCG and FSH treatments, respectively. The biggest follicle and the second in size measured 0.74 cm and 0.54 cm for eCG treatment, whereas for the FSH treatment they measured 0.73 and 0.50 cm. The interval between the beginning of estrus and ovulation was similar within all groups: 21.0 h for eCG treated ewes and 25.2 h for the ones treated with FSH. Ewes treated with eCG presented an interval of 47.5 h between sponge withdrawal and ovulation, while the ones treated with FSH presented a 61.1 h interval. Ovulation occurred 8.3 h before the end of estrus in the eCG group. On the other hand, ewes treated with FSH ovulated 5.5 h after the end of estrus. Estrus and ovulation were efficiently synchronized in Santa Inês ewes by using long-term progestogen protocol associated to the administration of 20 mg FSH, along with Prostaglandin F2α (PGF2α at the moment of sponge withdrawal, thus substituting the use of eCG.

  8. Pulse Width-Dependent Effects of Intestinal Electrical Stimulation for Obesity: Role of Gastrointestinal Motility and Hormones.

    Science.gov (United States)

    Li, Shiying; Chen, Jiande D Z

    2017-01-01

    The goals of this experiment were to study therapeutic potential of intestinal electrical stimulation (IES) for obesity, its mechanisms involving gastrointestinal motility and hormones, and role of pulse width in diet-induced obese rats. In a 4-week study, rats equipped with one pair of electrodes at the duodenum were assigned to receive either a sham or IES of varied pulse widths in a sequential way. Food intake was measured daily and body weight measured weekly. Blood samples were collected for the measurement of glucagon-like peptide-1 (GLP-1). Solid gastric emptying (GE) and small bowel transit (SIT) tests were performed at the end of the experiment. The results of the study were as follows: (1) Daily food intake, not affected by IES of 0.3 ms, was pulse width-dependently reduced by 1.9 g with 1 ms and by 5.7 g with 3 ms. Accordingly, body weight was pulse width-dependently reduced by 2.4 g with 1 ms and by 12.8 g with 3 ms compared to a gain of 5.6 g in sham. (2) GLP-1 level was elevated by both 0.3 and 3 ms at 15 min, but was elevated only with 3 ms at 60 min. (3) GE was delayed to 52.3 % by IES of 3 ms but not 0.3 ms, compared to that at 64.4 % with sham IES. (4) Compared to the geometric center of 7.0 with sham IES, SIT was accelerated by 3 ms to 7.8 but not by 0.3 ms. IES pulse width-dependently reduces food intake and body weight, attributed to the delay of gastric emptying and the acceleration of small bowel transit, as well as the enhancement of GLP-1 secretion.

  9. Aging, graying and loss of melanocyte stem cells.

    Science.gov (United States)

    Sarin, Kavita Y; Artandi, Steven E

    2007-01-01

    Hair graying is one of the prototypical signs of human aging. Maintenance of hair pigmentation is dependent on the presence and functionality of melanocytes, neural crest derived cells which synthesize pigment for growing hair. The melanocytes, themselves, are maintained by a small number of stem cells which reside in the bulge region of the hair follicle. The recent characterization of the melanocyte lineage during aging has significantly accelerated our understanding of how age-related changes in the melanocyte stem cell compartment contribute to hair graying. This review will discuss our current understanding of hair graying, drawing on evidence from human and mouse studies, and consider the contribution of melanocyte stem cells to this process. Furthermore, using the melanocyte lineage as an example, it will discuss common theories of tissue and stem cell aging.

  10. Melanocytic nevi and melanoma: unraveling a complex relationship.

    Science.gov (United States)

    Damsky, W E; Bosenberg, M

    2017-10-19

    Approximately 33% of melanomas are derived directly from benign, melanocytic nevi. Despite this, the vast majority of melanocytic nevi, which typically form as a result of BRAF V600E -activating mutations, will never progress to melanoma. Herein, we synthesize basic scientific insights and data from mouse models with common observations from clinical practice to comprehensively review melanocytic nevus biology. In particular, we focus on the mechanisms by which growth arrest is established after BRAF V600E mutation. Means by which growth arrest can be overcome and how melanocytic nevi relate to melanoma are also considered. Finally, we present a new conceptual paradigm for understanding the growth arrest of melanocytic nevi in vivo termed stable clonal expansion. This review builds upon the canonical hypothesis of oncogene-induced senescence in growth arrest and tumor suppression in melanocytic nevi and melanoma.

  11. Can anti-Müllerian hormone concentrations be used to determine gonadotrophin dose and treatment protocol for ovarian stimulation?

    DEFF Research Database (Denmark)

    Fleming, R; Broekmans, F; Calhaz-Jorge, C

    2013-01-01

    The ability to predict the response potential of women to ovarian stimulation may allow the development of individualized ovarian stimulation protocols. This tailored approach to ovarian stimulation could reduce the incidence of ovarian hyperstimulation syndrome in women predicted to have an exce...

  12. Kisspeptin Stimulates Growth Hormone Release by Utilizing Neuropeptide Y Pathways and Is Dependent on the Presence of Ghrelin in the Ewe.

    Science.gov (United States)

    Foradori, Chad D; Whitlock, Brian K; Daniel, Jay A; Zimmerman, Arthur D; Jones, Melaney A; Read, Casey C; Steele, Barbara P; Smith, Jeremy T; Clarke, Iain J; Elsasser, Theodore H; Keisler, Duane H; Sartin, James L

    2017-10-01

    Although kisspeptin is the primary stimulator of gonadotropin-releasing hormone secretion and therefore the hypothalamic-pituitary-gonadal axis, recent findings suggest kisspeptin can also regulate additional neuroendocrine processes including release of growth hormone (GH). Here we show that central delivery of kisspeptin causes a robust rise in plasma GH in fasted but not fed sheep. Kisspeptin-induced GH secretion was similar in animals fasted for 24 hours and those fasted for 72 hours, suggesting that the factors involved in kisspeptin-induced GH secretion are responsive to loss of food availability and not the result of severe negative energy balance. Pretreatment with the neuropeptide Y (NPY) Y1 receptor antagonist, BIBO 3304, blocked the effects of kisspeptin-induced GH release, implicating NPY as an intermediary. Kisspeptin treatment induced c-Fos in NPY and GH-releasing hormone (GHRH) cells of the arcuate nucleus. The same kisspeptin treatment resulted in a reduction in c-Fos in somatostatin (SS) cells in the periventricular nucleus. Finally, blockade of systemic ghrelin release or antagonism of the ghrelin receptor eliminated or reduced the ability of kisspeptin to induce GH release, suggesting the presence of ghrelin is required for kisspeptin-induced GH release in fasted animals. Our findings support the hypothesis that during short-term fasting, systemic ghrelin concentrations and NPY expression in the arcuate nucleus rise. This permits kisspeptin activation of NPY cells. In turn, NPY stimulates GHRH cells and inhibits SS cells, resulting in GH release. We propose a mechanism by which kisspeptin conveys reproductive and hormone status onto the somatotropic axis, resulting in alterations in GH release. Copyright © 2017 Endocrine Society.

  13. Phosphorylation of JAK2 at serine 523: a negative regulator of JAK2 that is stimulated by growth hormone and epidermal growth factor

    DEFF Research Database (Denmark)

    Mazurkiewicz-Munoz, Anna M.; Argetsinger, Lawrence S.; Kouadio, Jean-Louis K.

    2006-01-01

    spectrometry identified serine 523 (Ser523) in JAK2 as a site of phosphorylation. A phosphoserine 523 antibody revealed that Ser523 is rapidly but transiently phosphorylated in response to growth hormone (GH). MEK1 inhibitor UO126 suppresses GH-dependent phosphorylation of Ser523, suggesting that extracellular...... signal-regulated kinases (ERKs) 1 and/or 2 or another kinase downstream of MEK1 phosphorylate Ser523 in response to GH. Other ERK activators, phorbol 12-myristate 13-acetate and epidermal growth factor, also stimulate phosphorylation of Ser523. When Ser523 in JAK2 was mutated, JAK2 kinase activity...

  14. Gaps, limitations and new insights on endogenous estrogen and follicle stimulating hormone as related to risk of cardiovascular disease in women traversing the menopause: A narrative review.

    Science.gov (United States)

    El Khoudary, Samar R

    2017-10-01

    While it is known that estrogen protects heart health in women prior to menopause, its role after menopause and during the menopause transition is far less apparent. Previous reviews summarizing the literature on the impact of endogenous estrogen on risk of cardiovascular disease (CVD) have focused on postmenopausal women and have not come to a clear conclusion. No previous review has summarized the associations between follicle stimulating hormone (FSH), a proxy measure of the menopause transition, and CVD risk. The main purpose of this narrative review is to highlight gaps and limitations in the literature on endogenous estrogen and FSH as related to CVD risk. Future directions are addressed in light of recent findings in the field. When studying the relationship of estrogen to cardiovascular risk, it is critical to separate endogenously produced estrogen from exogenously administered estrogen. Moreover, other reproductive hormones such as FSH should be assessed, since growing evidence suggests a potential contribution of this hormone. Evaluation of estrogen changes over time allows a separation of women based on their hormone trajectories. These individual trajectories correlate with subclinical CVD and thus indicate that it is much more important to observe a woman over time rather than ascribe risk to a single determination at a single time point. As women progress through menopause and the ovary stops producing estradiol, the nature of the relationship between estrogens and subclinical CVD markers also appears to undergo a switch. Studies are needed to examine the midlife course of endogenous estradiol, FSH and CVD risk. These studies should also consider other hormones, including androgens, with an eye towards helping women modify their cardiovascular risk in midlife, when prevention is most likely possible. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. In vitro effect of. Delta. sup 9 -tetrahydrocannabinol to stimulate somatostatin release and block that of luteinizing hormone-releasing hormone by suppression of the release of prostaglandin E sub 2

    Energy Technology Data Exchange (ETDEWEB)

    Rettori, V.; Aguila, M.C.; McCann, S.M. (Univ. of Texas Southwestern Medical Center at Dallas (United States)); Gimeno, M.F.; Franchi, A.M. (Centro de Estudios Farmacologicos y de Principios Naturales, Buenos Aires (Argentina))

    1990-12-01

    Previous in vivo studies have shown that {Delta}{sup 9}-tetrahydrocannabinol (THC), the principal active ingredient in marijuana, can suppress both luteinizing hormone (LH) and growth hormone (GH) secretion after its injection into the third ventricle of conscious male rats. The present studies were deigned to determine the mechanism of these effects. Various doses of THC were incubated with either stalk median eminence fragments (MEs) or mediobasal hypothalamic (MBH) fragments in vitro. Although THC (10 nM) did not alter basal release of LH-releasing hormone (LHRH) from MEs in vitro, it completely blocked the stimulatory action of dopamine or nonrepinephrine on LHRH release. The effective doses to block LHRH release were associated with a blockade of synthesis and release of prostaglandin E{sub 2} (PGE{sub 2}) from MBH in vitro. In contrast to the suppressive effect of THC on LHRH release, somatostatin release from MEs was enhanced in a dose-related manner with a minimal effective dose of 1 nM. Since PGE{sub 2} suppresses somatostatin release, this enhancement may also be related to the suppressive effect of THC on PGE{sub 2} synthesis and release. The authors speculate that these actions are mediated by the recently discovered THC receptors in the tissue. The results indicate that the suppressive effect of THC on LH release is mediated by a blockade of LHRH release, whereas the suppressive effect of the compound on growth hormone release is mediated, at least in part, by a stimulation of somatostatin release.

  16. Effects of sub-lethal heroin administration on thyroid stimulating hormone (TSH), thyroid hormones (T3, T4) and thyroid gland of Mus norvegicus.

    Science.gov (United States)

    Bhoir, Kaminidevi K; Suryawanshi, S A; Pandey, A K

    2009-11-01

    Serum TSH level of control Mus norvegicus fluctuated between 498.20 +/- 21.92 and 506.80 +/- 22.35 ng ml(-1), thyroxine (T4) between 68.17 +/- 3.46 and 69.03 +/- 4.12 microg dl(-1) and triiodothyronine (T3) between 4.76 +/- 0.52 and 5.00 +/- 0.66 microg dl(-1). Sub-lethal heroin administration induced a significant decline in the levels of all the three hormones at 24 hr and 15 days post-administration. Decline in the levels of these hormones registered the lowest values (pThyroid gland of control rat consisted of spherical, round follicles lined with low cuboidal and columnar epithelial cells and lumina filled with eosinophilic colloid. Ultrastructurally, the thyroid follicular cells showed the presence of round nuclei, polymorphic mitochondria, Golgi complex as well as lysosomes located on the apical side of the nucleus and cytoplasm with different sizes of lipid droplets and smooth along with rough endoplasmic reticulum. Basal lamina of the follicular cells was often in association with the endothelium of the capillaries. Sub-lethal heroin administration for 30 days elicited degenerative changes in the follicular epithelial cells as evident by the vacuolization of cytoplasm, pycnotic nuclei and reduced colloidal content. Ultrastructurally, the thyroid follicular cells showed indented nuclei with heavy deposition of chromatin material on the inner membrane of nucleus and dilated rough endoplasmic reticulum. Along with RBC infiltration, vesiculated mitochondria owing to the loss of cristae were also seen. Diffused electron-dense material was seen at the periphery of the cell body. Heroin treatment caused cellular necrosis as revealed by the fragmentation of cytoplasmic materials in follicular epithelial cells of the gland.

  17. Estradiol-Dependent Stimulation and Suppression of Gonadotropin-Releasing Hormone Neuron Firing Activity by Corticotropin-Releasing Hormone in Female Mice.

    Science.gov (United States)

    Phumsatitpong, Chayarndorn; Moenter, Suzanne M

    2018-01-01

    Gonadotropin-releasing hormone (GnRH) neurons are the final central regulators of reproduction, integrating various inputs that modulate fertility. Stress typically inhibits reproduction but can be stimulatory; stress effects can also be modulated by steroid milieu. Corticotropin-releasing hormone (CRH) released during the stress response may suppress reproduction independent of downstream glucocorticoids. We hypothesized CRH suppresses fertility by decreasing GnRH neuron firing activity. To test this, mice were ovariectomized (OVX) and either implanted with an estradiol capsule (OVX+E) or not treated further to examine the influence of estradiol on GnRH neuron response to CRH. Targeted extracellular recordings were used to record firing activity from green fluorescent protein-identified GnRH neurons in brain slices before and during CRH treatment; recordings were done in the afternoon when estradiol has a positive feedback effect to increase GnRH neuron firing. In OVX mice, CRH did not affect the firing rate of GnRH neurons. In contrast, CRH exhibited dose-dependent stimulatory (30 nM) or inhibitory (100 nM) effects on GnRH neuron firing activity in OVX+E mice; both effects were reversible. The dose-dependent effects of CRH appear to result from activation of different receptor populations; a CRH receptor type-1 agonist increased firing activity in GnRH neurons, whereas a CRH receptor type-2 agonist decreased firing activity. CRH and specific agonists also differentially regulated short-term burst frequency and burst properties, including burst duration, spikes/burst, and/or intraburst interval. These results indicate that CRH alters GnRH neuron activity and that estradiol is required for CRH to exert both stimulatory and inhibitory effects on GnRH neurons. Copyright © 2018 Endocrine Society.

  18. Medium Sized Congenital Melanocytic Nevus with Suspected Progression to Melanoma during Pregnancy: What’s the Best for the Patient?

    Directory of Open Access Journals (Sweden)

    Georgi Tchernev

    2018-01-01

    Full Text Available BACKGROUND: Congenital melanocytic nevi (CMN are pigmented skin lesions usually present at birth. Rare varieties can develop and become clinically very large. Although they are benign nevomelanocytic neoplasms, all CMN may be precursors of the melanoma, regardless of their size. Individual risk of malignant transformation of melanocyte is determined by simultaneous action of exogenous and endogenous factors. The major exogenous risk factor is ultraviolet radiation. Leading roles among the endogenous factors are attributed to skin phenotype, gene mutation, sex hormones and their significance. CASE REPORT: We present a case of a 27 – year - old pregnant female patient with a congenital melanocytic nevus, which increased significantly in size, during her pregnancy. Estrogen levels increase during pregnancy and clinical evidence has suggested that melanocytes are estrogen - responsive. Nevi in a pregnant patient would exhibit increased expression of estrogen receptor β (ERβ and thus enhanced the potential to respond to altered estrogen levels. CONCLUSION: All pigmented skin lesions should be carefully observed during pregnancy by a dermatologist due to the increased risk of malignant transformation, associated with the endocrine dependence. All lesions with visible changes should be removed surgically with appropriative anaesthesia.

  19. Resurgence of Minimal Stimulation In Vitro Fertilization with A Protocol Consisting of Gonadotropin Releasing Hormone-Agonist Trigger and Vitrified-Thawed Embryo Transfer

    Directory of Open Access Journals (Sweden)

    Zhang John

    2016-07-01

    Full Text Available Minimal stimulation in vitro fertilization (mini-IVF consists of a gentle controlled ovarian stimulation that aims to produce a maximum of five to six oocytes. There is a misbelief that mini-IVF severely compromises pregnancy and live birth rates. An appraisal of the literature pertaining to studies on mini-IVF protocols was performed. The advantages of minimal stimulation protocols are reported here with a focus on the use of clomiphene citrate (CC, gonadotropin releasing hormone (GnRH ago- nist trigger for oocyte maturation, and freeze-all embryo strategy. Literature review and the author’s own center data suggest that minimal ovarian stimulation protocols with GnRH agonist trigger and freeze-all embryo strategy along with single embryo transfer produce a reasonable clinical pregnancy and live birth rates in both good and poor responders. Additionally, mini-IVF offers numerous advantages such as: i. Reduction in cost and stress with fewer office visits, needle sticks, and ultrasounds, and ii. Reduction in the incidence of ovarian hyperstimulation syndrome (OHSS. Mini-IVF is re-emerging as a solution for some of the problems associated with conventional IVF, such as OHSS, cost, and patient discomfort.

  20. Analysis of the Relationship between Estradiol and Follicle-Stimulating Hormone Concentrations and Polymorphisms of Apolipoprotein E and LeptinGenes in Women Post-Menopause.

    Science.gov (United States)

    Rył, Aleksandra; Jasiewicz, Andrzej; Grzywacz, Anna; Adler, Grażyna; Skonieczna-Żydecka, Karolina; Rotter, Iwona; Sipak-Szmigiel, Olimpia; Rumianowski, Bogdan; Karakiewicz, Beata; Jurczak, Anna; Parczewski, Miłosz; Urbańska, Anna; Grabowska, Marta; Laszczyńska, Maria

    2016-05-28

    Menopause is the permanent cessation of menstruation due to loss of ovarian follicular activity. A review of the available literature indicates that correlations between the changes that take place in a woman's body after menopause and different genetic variants are still being sought. The study was conducted in 252 women who had completed physiological menopause. The women were divided into groups according to the time elapsed since menopause. The total concentrations of estradiol and follicle-stimulating hormone were determined by means of electrochemiluminescence. The apolipoprotein E (APOE) and lepitn (LEP) genotypes were determined by real-time PCR and polymerase chain reaction-restriction fragment length polymorphism, respectively. We observed that people with the APOE3/E3 genotype entered menopause insignificantly later compared to other genotypes. Additionally, in the group of patients with the APOE3/E3 genotypes, differences in the E2 concentration were significantly related to the time since their last menstruation. There is no association found in the literature between these polymorphisms of the LEP gene and hormones. To date, attempts to formulate a model describing the association between E2 and FSH concentration with the polymorphisms of various genes of menopause in women have not been successful. This relationship is difficult to study because of the number of nongenetic factors. Environmental factors can explain variation in postmenopausal changes in hormone levels.

  1. Analysis of the Relationship between Estradiol and Follicle-Stimulating Hormone Concentrations and Polymorphisms of Apolipoprotein E and LeptinGenes in Women Post-Menopause

    Directory of Open Access Journals (Sweden)

    Aleksandra Rył

    2016-05-01

    Full Text Available Background: Menopause is the permanent cessation of menstruation due to loss of ovarian follicular activity. A review of the available literature indicates that correlations between the changes that take place in a woman’s body after menopause and different genetic variants are still being sought. Methods: The study was conducted in 252 women who had completed physiological menopause. The women were divided into groups according to the time elapsed since menopause. The total concentrations of estradiol and follicle-stimulating hormone were determined by means of electrochemiluminescence. The apolipoprotein E (APOE and lepitn (LEP genotypes were determined by real-time PCR and polymerase chain reaction–restriction fragment length polymorphism, respectively. Results: We observed that people with the APOE3/E3 genotype entered menopause insignificantly later compared to other genotypes. Additionally, in the group of patients with the APOE3/E3 genotypes, differences in the E2 concentration were significantly related to the time since their last menstruation. There is no association found in the literature between these polymorphisms of the LEP gene and hormones. Conclusions: To date, attempts to formulate a model describing the association between E2 and FSH concentration with the polymorphisms of various genes of menopause in women have not been successful. This relationship is difficult to study because of the number of nongenetic factors. Environmental factors can explain variation in postmenopausal changes in hormone levels.

  2. Critical evaluation of the radioiodination of follicle-stimulating-and luteinizing hormones by lactoperoxidase and its comparison with chloramine-T classical method

    International Nuclear Information System (INIS)

    Pinto, H.

    1978-01-01

    A method is described for the enzymatic radioiodination of human gonadotropins by a system consisting of lactoperoxidase, hydrogen peroxide and Na 125 I. A comparison witth the clhloramine-T modified technique was done a satisfactory specific activity (100 μCi/μg) of the labeled hormone was obtained with the enzymatic iodination, with much greater immunoreactivity and stability than after chloramine-T. As aqueous polyethylene glycol causes precipitation of antibody-bound peptide hormones with radioactive iodine with little or no precipitation of free hormones, a method of separation was developed and applied to radioimmunoassay of gonadotropins, providing several advantages over te double-antibody precipitation method. It was demonstrated that, in humans, the intravenous administration of synthetic LH-FSH/RH, stimulates the pituitary release of both LH and FSH. Results are reported now for normal women, infused with an acute load of 25μg of synthetic LH/FSH-RH and 8 hours infusion of 100μg, during the mid-follicular and luteal phases. The greatest gonadotropin responsiveness to LH/FSH-RH are found in the luteal phase during acute testing. No differences were noticed during chronic infusion as well as acute post-chronic, performed in both phases of the menstrual cycle. The possible modulating effects of steroidal secretion by the ovaries are discussed. (Author) [pt

  3. High-definition optical coherence tomography imaging of melanocytic lesions

    DEFF Research Database (Denmark)

    Boone, Marc A L M; Norrenberg, Sarah; Jemec, Gregor B E

    2014-01-01

    and cytologic features of melanocytic lesions. All lesions were examined by one observer clinically and using dermoscopy. Cross-sectional HD-OCT images were compared with histopathology. En face HD-OCT images were compared with reflectance confocal microscopy (RCM). Twenty-six melanocytic lesions of 26 patients...

  4. Cytotoxic T lymphocyte responses against melanocytes and melanoma

    Directory of Open Access Journals (Sweden)

    Schwartz Erich J

    2011-07-01

    Full Text Available Abstract Background Vitiligo is a common toxicity associated with immunotherapy for melanoma. Cytotoxic T lymphocytes (CTLs against melanoma commonly target melanoma-associated antigens (MAAs which are also expressed by melanocytes. To uncouple vitiligo from melanoma destruction, it is important to understand if CTLs can respond against melanoma and melanocytes at different levels. Methods To understand the dichotomous role of MAA-specific CTL, we characterized the functional reactivities of established CTL clones directed to MAAs against melanoma and melanocyte cell lines. Results CTL clones generated from melanoma patients were capable of eliciting MHC-restricted, MAA-specific lysis against melanocyte cell lines as well as melanoma cells. Among the tested HLA-A*0201-restricted CTL clones, melanocytes evoked equal to slightly higher degranulation and cytolytic responses as compared to melanoma cells. Moreover, MAA-specific T cells from vaccinated patients responded directly ex vivo to melanoma and melanocytes. Melanoma cells express slightly higher levels of MART-1 and gp100 than melanocytes as measured by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR and immunohistochemistry. Conclusions Our data suggest that CTLs respond to melanoma and melanocytes equally in vitro and directly ex vivo.

  5. Organotypic culture of human skin to study melanocyte migration

    NARCIS (Netherlands)

    Le Poole, I. C.; van den Wijngaard, R. M.; Westerhof, W.; Dormans, J. A.; van den Berg, F. M.; Verkruisen, R. P.; Dingemans, K. P.; Das, P. K.

    1994-01-01

    An ex vivo model system was developed to investigate melanocyte migration. Within this model system, melanocytes migrate among other epidermal cells in the epibolic outgrowth of skin explants. This process is initiated by loss of contact inhibition of epidermal cells at the rim of the explants and

  6. Can a glucagon stimulation test characterized by lower GH cut-off value be used for the diagnosis of growth hormone deficiency in adults?

    Science.gov (United States)

    Diri, Halit; Karaca, Zuleyha; Simsek, Yasin; Tanriverdi, Fatih; Unluhizarci, Kursad; Selcuklu, Ahmet; Kelestimur, Fahrettin

    2015-12-01

    The aim of this study was to assess diagnostic values of insulin tolerance test (ITT), glucagon stimulation test (GST), and insulin like growth factor-I (IGF-I) level, to find optimal GH cut-off values for GST, and to evaluate efficiencies of patient age, gender, body-mass index (BMI), and additional pituitary hormone deficiencies (PHDs) in the diagnosis of growth hormone deficiency (GHD). This retrospective study involved 216 patients with a pituitary disease and 26 healthy controls. Age, gender, BMI, medical histories, and hormonal data including baseline and stimulated hormone values were evaluated. Three cut-off values for peak GH responses to stimulation tests were evaluated: (a) 3.00 µg/L on ITT, (b) 3.00 µg/L on GST, and (c) 1.07 µg/L on GST. According to the ITT, GST with 3.00 µg/L cut-off, and GST with 1.07 µg/L cut-off, GHD was present in 86.1, 74.5, and 54.2 % patients, respectively. Patient age, BMI, and number of PHDs, but not gender, were found to be correlated with IGF-I and peak GH concentrations. All patients with an IGF-I concentration ≤95 ng/ml or ≥3 PHD had GHD. None of the patients with adequate GH response to the GST with 1.07 µg/L cut-off, but blunted responses to ITT and GST with 3.00 µg/L cut-off, had ≥3 PHDs. 12 out of 26 (46.2 %) healthy subjects failed the GST with 3.00 µg/L cut-off, but not with 1.07 µg/L cut-off. Patient age, IGF-I, BMI, and number of PHDs are efficient factors associated with the diagnosis of GHD. A 4 h GST with a diagnostic GH threshold of 1.07 µg/L seems to be a good diagnostic method for GHD.

  7. Intracellular mechanism of the action of inhibin on the secretion of follicular stimulating hormone and of luteinizing hormone induced by LH-RH in vitro

    Science.gov (United States)

    Lecomte-Yerna, M. J.; Hazee-Hagelstein, M. T.; Charlet-Renard, C.; Franchimont, P.

    1982-01-01

    The FSH secretion-inhibiting action of inhibin in vitro under basal conditions and also in the presence of LH-RH is suppressed by the addition of MIX, a phosphodiesterase inhibitor. In the presence of LH-RH, inhibin reduces significantly the intracellular level of cAMP in isolated pituitary cells. In contrast, the simultaneous addition of MIX and inhibin raises the cAMP level, and this stimulation is comparable to the increase observed when MIX is added alone. These observations suggest that one mode of action of inhibin could be mediated by a reduction in cAMP within the pituitary gonadotropic cell.

  8. Role of the thyrotropin-releasing hormone stimulation test in diagnosis of congenital central hypothyroidism in infants

    NARCIS (Netherlands)

    van Tijn, David A.; de Vijlder, Jan J. M.; Vulsma, Thomas

    2008-01-01

    CONTEXT: A shortage of thyroid hormone during prenatal life and the first years after birth results in a spectrum of neuropsychological disorders, depending on the duration and severity of the deficiency. In the case of congenital hypothyroidism of central origin (CH-C), the majority of patients

  9. Requirement of tyrosine residues 333 and 338 of the growth hormone (GH) receptor for selected GH-stimulated function

    DEFF Research Database (Denmark)

    Lobie, P E; Allevato, G; Norstedt, G

    1995-01-01

    We have examined the involvement of tyrosine residues 333 and 338 of the growth hormone (GH) receptor in the cellular response to GH. Stable Chinese hamster ovary (CHO) cell clones expressing a receptor with tyrosine residues at position 333 and 338 of the receptor substituted for phenylalanine (...

  10. Variation in levels of serum inhibin B, testosterone, estradiol, luteinizing hormone, follicle-stimulating hormone, and sex hormone-binding globulin in monthly samples from healthy men during a 17-month period

    DEFF Research Database (Denmark)

    Andersson, Anna-Maria; Carlsen, Elisabeth; Petersen, Jørgen Holm

    2003-01-01

    To obtain information on the scale of the intraindividual variation in testicular hormone, blood samples for inhibin B determination were collected monthly in 27 healthy male volunteers during a 17-month period. In addition, the traditional reproductive hormones FSH, LH, testosterone, estradiol....... A seasonal variation was observed in LH and testosterone levels, but not in the levels of the other hormones. The seasonal variation in testosterone levels could be explained by the variation in LH levels. The seasonal variation in LH levels seemed to be related to the mean air temperature during the month...... before blood sampling, but not to the length of daylight or the hours of sunshine. In conclusion, our data showed that day to day levels of inhibin B are relatively constant in men and do not seem to be influenced by seasonal factors. In contrast, we found a seasonal variation in LH and testosterone...

  11. Incidence of congenital melanocytic nevi in newborn babies in Denmark.

    Science.gov (United States)

    Kroon, S; Clemmensen, O J; Hastrup, N

    1987-09-01

    Three hundred fourteen unselected babies were examined within 96 hours of delivery. Three (1%) of the infants had clinically recognizable pigmented lesions. Two of the lesions (mean, 0.6%; range, 0.1%-2.3%; 95% confidence limits) proved histologically to be compound melanocytic nevi. The histology displayed almost identical patterns, with large nests of melanocytes at the dermoepidermal junction and only few nevus cells in the papillary dermis. A 0.6% incidence rate corresponds to 330 congenital melanocytic nevi in Denmark each year (range, 55-1265; 95% confidence limits). Because histology does not seem to be an accurate diagnostic tool to sort out the malignant potential of the small congenital melanocytic nevi, prospective studies are needed to characterize the premalignant melanocytic nevi, whether congenital or acquired.

  12. Histopathological diagnosis of small melanocytic lesions suspicious for malignant melanoma*

    Science.gov (United States)

    Quintella, Danielle Carvalho; Campos-do-Carmo, Gabriella; Quintella, Leonardo Pereira; Cuzzi, Tullia

    2017-01-01

    The concern about malignant skin neoplasms leads to the excision of smaller lesions. This study on small melanocytic lesions aims to evaluate the range of possible histopathological diagnoses, describe histopathological aspects, and assess the usefulness of serial histological sections. We performed a cross-sectional descriptive histopathological study examining 76 pigmented skin lesions up to 6 mm in diameter. Histopathological diagnoses included atypical melanocytic nevi (n=38), common melanocytic nevi (n=18), atypical lentiginous melanocytic hyperplasia with architectural features of atypical melanocytic nevi (n=7), lentigo simplex (n=2), and malignant melanoma (n=1). Ten cases were non-diagnostic. Cytological atypia was not an exclusive finding of atypical lesions. Examination of serial sections did not change histopathological impression. Early detection of malignant melanoma is important, but clinical and dermoscopy exams may be leading to the resection of a great number of benign lesions. Strict attention to histopathological criteria results in a large number of non-diagnostic cases. PMID:29186251

  13. Histopathological diagnosis of small melanocytic lesions suspicious for malignant melanoma.

    Science.gov (United States)

    Quintella, Danielle Carvalho; Campos-do-Carmo, Gabriella; Quintella, Leonardo Pereira; Cuzzi, Tullia

    2017-01-01

    The concern about malignant skin neoplasms leads to the excision of smaller lesions. This study on small melanocytic lesions aims to evaluate the range of possible histopathological diagnoses, describe histopathological aspects, and assess the usefulness of serial histological sections. We performed a cross-sectional descriptive histopathological study examining 76 pigmented skin lesions up to 6 mm in diameter. Histopathological diagnoses included atypical melanocytic nevi (n=38), common melanocytic nevi (n=18), atypical lentiginous melanocytic hyperplasia with architectural features of atypical melanocytic nevi (n=7), lentigo simplex (n=2), and malignant melanoma (n=1). Ten cases were non-diagnostic. Cytological atypia was not an exclusive finding of atypical lesions. Examination of serial sections did not change histopathological impression. Early detection of malignant melanoma is important, but clinical and dermoscopy exams may be leading to the resection of a great number of benign lesions. Strict attention to histopathological criteria results in a large number of non-diagnostic cases.

  14. Effect of litter separation on 24-hour rhythmicity of plasma prolactin, follicle-stimulating hormone and luteinizing hormone levels in lactating rabbit does

    Directory of Open Access Journals (Sweden)

    Cardinali Daniel P

    2005-06-01

    Full Text Available Abstract Background This work describes the effect of a 48-h litter separation on 24-h patterns of plasma prolactin, FSH and LH concentration in female lactating rabbits kept under a 16:8 light-dark photoperiod (lights on at 0800 h. Methods Groups of 6–7 female lactating rabbits maintained with their litters or separated from them for 48 h were killed by decapitation on day 11 post-partum, at 6 different time points throughout a 24-h cycle, starting at 0900 h. Plasma levels of prolactin, FSH and LH were measured by specific double antibody radio-immunoassays. Results Plasma level of prolactin in control and separated does changed in a similar way throughout the day, showing two maxima, at 0500–0900 h and at 1700–2100 h, respectively. Litter separation significantly augmented plasma FSH and LH and disrupted their 24-h rhythmicity. Conclusion Since previous studies had shown that litter separation for short periods of time augmented sexual receptivity and fertility of the doe, the changes in FSH and LH reported may influence the massive release of gonadotropin releasing hormone, LH and FSH triggered by mating or artificial insemination in litter-separated mothers.

  15. SOX9 is a key player in ultraviolet B-induced melanocyte differentiation and pigmentation.

    Science.gov (United States)

    Passeron, Thierry; Valencia, Julio C; Bertolotto, Corine; Hoashi, Toshihiko; Le Pape, Elodie; Takahashi, Kaoruko; Ballotti, Robert; Hearing, Vincent J

    2007-08-28

    SOX (SRY type HMG box) proteins are transcription factors that are predominantly known for their roles during development. During melanocyte development from the neural crest, SOX10 regulates microphthalmia-associated transcription factor, which controls a set of genes critical for pigment cell development and pigmentation, including dopachrome tautomerase and tyrosinase. We report here that another SOX factor, SOX9, is expressed by melanocytes in neonatal and adult human skin and is up-regulated by UVB exposure. We demonstrate that this regulation is mediated by cAMP and protein kinase. We also show that agouti signal protein, a secreted factor known to decrease pigmentation, down-regulates SOX9 expression. In adult and neonatal melanocytes, SOX9 regulates microphthalmia-associated transcription factor, dopachrome tautomerase, and tyrosinase promoters, leading to an increase in the expression of these key melanogenic proteins and finally to a stimulation of pigmentation. SOX9 completes the complex and tightly regulated process leading to the production of melanin by acting at a very upstream level. This role of SOX9 in pigmentation emphasizes the poorly understood impact of SOX proteins in adult tissues.

  16. [Repigmentation of gray hair after thyroid hormone treatment].

    Science.gov (United States)

    Redondo, P; Guzmán, M; Marquina, M; Pretel, M; Aguado, L; Lloret, P; Gorrochategui, A

    2007-11-01

    Darkening of gray and white hairs occurred in 2 patients with increased exogenous triiodothyronine (T3) due to treatment of myxedema coma in one case and iatrogenic hyperthyroidism in the other. We hypothesized that thyroid hormone may affect the homeostasis of hair follicles. To test our hypothesis and investigate the influence of thyroid hormone on the hair cycle, we used an in vivo murine model and an in vitro model based on culture of follicular units. We used the standard C57BL/6 murine model of the hair cycle. T3 (0.5 microg) dissolved in ethanol was applied topically once daily for 10 days to a depilated area in the telogen phase on the backs of the mice. Follicular units, obtained from hair transplant interventions, were cultured in vitro with different concentrations of T3. On day 5, all T3-treated mice entered the anagen phase, whereas the anagen phase started spontaneously in control mice on day 9, and not until day 15 had all controls entered this phase. In the in vitro experiment, follicular units treated with 100 nmol/L T3 grew significantly larger compared to the control group. These data suggest that follicles in the telogen phase can be induced to enter the anagen phase by the topical application of T3. This thyroid hormone may reverse graying of the terminal hair. In the in vitro experiments, T3 stimulated hair shaft growth. Follicular melanocytes may be the target cell for these actions.

  17. Melanocyte Transformation Associated with Substrate Adhesion Impediment

    Directory of Open Access Journals (Sweden)

    Sueli M. Oba-Shinjo

    2006-03-01

    Full Text Available Exclude experimental models of malignant transformation employ chemical and physical carcinogens or genetic manipulations to study tumor progression. In this work, different melanoma cell lines were established after submitting a nontumorigenic melanocyte lineage (melan-a to sequential cycles of forced anchorage impediment. The great majority of these cells underwent anoikis when maintained in suspension. After one deadhesion cycle, phenotypic alterations were noticeable in the few surviving cells, which became more numerous and showed progressive alterations after each adhesion impediment step. No significant differences in cell surface expression of integrins were detected, but a clear electrophoretic migration shift, compatible with an altered glycosylation pattern, was observed for β1 chain in transformed cell lines. In parallel, a progressive enrichment of tri- and tetra-antennary N-glycans was apparent, suggesting increased N-acetylglucosaminyl-transferase V activity. Alterations both in proteoglycan glycosylation pattern and core protein expression were detected during the transformation process. In conclusion, this model corroborates the role of adhesion state as a promoting agent in transformation process and demonstrates that cell adhesion disturbances may act as carcinogenic stimuli, at least for a nontumorigenic immortalized melanocyte lineage. These findings have intriguing implications for in vivo carcinogenesis, suggesting that anchorage independence may precede, and contribute to, neoplastic conversion.

  18. Melanocyte transformation associated with substrate adhesion impediment.

    Science.gov (United States)

    Oba-Shinjo, Sueli M; Correa, Mariangela; Ricca, Tatiana I; Molognoni, Fernanda; Pinhal, Maria A; Neves, Izabel A; Marie, Sueli K; Sampaio, Lúcia O; Nader, Helena B; Chammas, Roger; Jasiulionis, Miriam G

    2006-03-01

    Exclude experimental models of malignant transformation employ chemical and physical carcinogens or genetic manipulations to study tumor progression. In this work, different melanoma cell lines were established after submitting a nontumorigenic melanocyte lineage (melan-a) to sequential cycles of forced anchorage impediment. The great majority of these cells underwent anoikis when maintained in suspension. After one deadhesion cycle, phenotypic alterations were noticeable in the few surviving cells, which became more numerous and showed progressive alterations after each adhesion impediment step. No significant differences in cell surface expression of integrins were detected, but a clear electrophoretic migration shift, compatible with an altered glycosylation pattern, was observed for beta1 chain in transformed cell lines. In parallel, a progressive enrichment of tri- and tetra-antennary N-glycans was apparent, suggesting increased N-acetylglucosaminyltransferase V activity. Alterations both in proteoglycan glycosylation pattern and core protein expression were detected during the transformation process. In conclusion, this model corroborates the role of adhesion state as a promoting agent in transformation process and demonstrates that cell adhesion disturbances may act as carcinogenic stimuli, at least for a nontumorigenic immortalized melanocyte lineage. These findings have intriguing implications for in vivo carcinogenesis, suggesting that anchorage independence may precede, and contribute to, neoplastic conversion.

  19. Analysis of clinical factors for the determination of optimal serum level of thyrotropin after recombinant human thyroid-stimulating hormone administration

    International Nuclear Information System (INIS)

    Son, Seung Hyun; Lee, Sang Woo; Jung, Ji Hoon; Kim, Choon Young; Kim, Do Hoon; Jeong, Shin Young; Ahn, Byeong Cheol; Lee, Jae Tae

    2015-01-01

    To determine the optimal levels of thyroid-stimulating hormone (TSH) levels after administration of recombinant human TSH (rhTSH) to patients with differentiated thyroid cancer (DTC), we have analyzed the clinical parameters that affected the degree of the increase in serum levels of TSH. We retrospectively analyzed 276 patients with differentiated thyroid cancer (DTC), post-thyroidectomy and remnant ablation. Pearson’s correlation coefficient test was used to evaluate the correlation between serum levels of TSH after rhTSH stimulation and various clinical factors, including age, sex, height, weight, body mass index (BMI), body surface area (BSA), serum blood urea nitrogen, creatinine, and estimated glomerular filtration rate (GFR). Linear regression analysis was used to determine the predictors of the degree of increase in serum TSH level after rhTSH stimulation. After the rhTSH injections, all subjects achieved TSH levels of >30 μU/mL, with a mean of 203.8 ± 83.4 μU/mL. On univariate analysis, age (r = 0.255) and serum creatinine (r = 0.169) level were positive predictors for higher levels of serum TSH after rhTSH stimulation, while weight (r = –0.239), BMI (r = –0.223), BSA (r = –0.217), and estimated GFR (r = –0.199) were negative predictors. Multiple linear regression analysis revealed that serum creatinine was the most powerful independent predictor for serum levels of TSH, followed by age, BSA, and BMI. An increment in serum TSH after rhTSH stimulation was significantly affected by age, BSA, BMI, and creatinine, with creatinine being the most powerful predictor. By understanding the difference in the increased levels of TSH in various subjects, their dose of rhTSH can be adjusted during scheduling for radioiodine ablation, or during follow-up (recurrence surveillance) after surgery and ablation

  20. Analysis of clinical factors for the determination of optimal serum level of thyrotropin after recombinant human thyroid-stimulating hormone administration

    Energy Technology Data Exchange (ETDEWEB)

    Son, Seung Hyun; Lee, Sang Woo; Jung, Ji Hoon; Kim, Choon Young; Kim, Do Hoon; Jeong, Shin Young; Ahn, Byeong Cheol; Lee, Jae Tae [Dept. of Nuclear Medicine, Kyungpook National University Medical Center and School of Medicine, Daegu (Korea, Republic of)

    2015-12-15

    To determine the optimal levels of thyroid-stimulating hormone (TSH) levels after administration of recombinant human TSH (rhTSH) to patients with differentiated thyroid cancer (DTC), we have analyzed the clinical parameters that affected the degree of the increase in serum levels of TSH. We retrospectively analyzed 276 patients with differentiated thyroid cancer (DTC), post-thyroidectomy and remnant ablation. Pearson’s correlation coefficient test was used to evaluate the correlation between serum levels of TSH after rhTSH stimulation and various clinical factors, including age, sex, height, weight, body mass index (BMI), body surface area (BSA), serum blood urea nitrogen, creatinine, and estimated glomerular filtration rate (GFR). Linear regression analysis was used to determine the predictors of the degree of increase in serum TSH level after rhTSH stimulation. After the rhTSH injections, all subjects achieved TSH levels of >30 μU/mL, with a mean of 203.8 ± 83.4 μU/mL. On univariate analysis, age (r = 0.255) and serum creatinine (r = 0.169) level were positive predictors for higher levels of serum TSH after rhTSH stimulation, while weight (r = –0.239), BMI (r = –0.223), BSA (r = –0.217), and estimated GFR (r = –0.199) were negative predictors. Multiple linear regression analysis revealed that serum creatinine was the most powerful independent predictor for serum levels of TSH, followed by age, BSA, and BMI. An increment in serum TSH after rhTSH stimulation was significantly affected by age, BSA, BMI, and creatinine, with creatinine being the most powerful predictor. By understanding the difference in the increased levels of TSH in various subjects, their dose of rhTSH can be adjusted during scheduling for radioiodine ablation, or during follow-up (recurrence surveillance) after surgery and ablation.

  1. Requirement of tyrosine residues 333 and 338 of the growth hormone (GH) receptor for selected GH-stimulated function

    DEFF Research Database (Denmark)

    Lobie, P E; Allevato, G; Norstedt, G

    1995-01-01

    We have examined the involvement of tyrosine residues 333 and 338 of the growth hormone (GH) receptor in the cellular response to GH. Stable Chinese hamster ovary (CHO) cell clones expressing a receptor with tyrosine residues at position 333 and 338 of the receptor substituted for phenylalanine...... (CHO-GHR1-638 Y333F, Y338F) were generated by cDNA transfection. Compared with the wild type receptor the Y333F,Y338F mutant possessed normal high affinity ligand binding, hormone internalization, and ligand-induced receptor down-regulation. GH activation of mitogen-associated protein kinase was also...... similar in CHO clones expressing similar wild type and Y333F,Y338F receptor number. However, two GH-regulated cellular events (lipogenesis, and protein synthesis) were deficient in the tyrosine substituted receptor. In contrast, transcriptional regulation by GH (as evidenced by chloramphenicol...

  2. Higher Thyroid-Stimulating Hormone, Triiodothyronine and Thyroxine Values Are Associated with Better Outcome in Acute Liver Failure.

    Directory of Open Access Journals (Sweden)

    Olympia Anastasiou

    Full Text Available Changes in thyroid hormone levels, mostly as non-thyroidal illness syndrome (NTIS, have been described in many diseases. However, the relationship between acute liver failure (ALF and thyroid hormone levels has not yet been clarified. The present study evaluates potential correlations of select thyroid functional parameters with ALF.84 consecutively recruited ALF patients were grouped according to the outcome of ALF (spontaneous recovery: SR; transplantation or death: NSR. TSH, free thyroxine (fT4, free triiodothyronine (fT3, T4, and T3 were determined.More than 50% of patients with ALF presented with abnormal thyroid parameters. These patients had greater risk for an adverse outcome than euthyroid patients. SR patients had significantly higher TSH, T4, and T3 concentrations than NSR patients. Albumin concentrations were significantly higher in SR than in NSR. In vitro T3 treatment was not able to rescue primary human hepatocytes from acetaminophen induced changes in mRNA expression.In patients with ALF, TSH and total thyroid hormone levels differed significantly between SR patients and NSR patients. This might be related to diminished liver-derived transport proteins, such as albumin, in more severe forms of ALF. Thyroid parameters may serve as additional indicators of ALF severity.

  3. Multicenter, noninterventional, post-marketing surveillance study to evaluate dosing of recombinant human follicle-stimulating hormone using the redesigned follitropin alfa pen in women undergoing ovulation induction

    Directory of Open Access Journals (Sweden)

    Nawroth F

    2015-04-01

    Full Text Available Frank Nawroth,1 Andreas Tandler-Schneider,2 Wilma Bilger3 1Centre for Reproductive and Prenatal Medicine, Endocrinology and Osteology, Hamburg, Germany; 2Center for Reproductive Medicine, Fertility Center Berlin, Berlin, Germany; 3Medical Affairs, Fertility, Endocrinology and General Medicine, Merck Serono GmbH, Darmstadt, Germany (an affiliate of Merck KGaA, Darmstadt, Germany Abstract: This prospective, noninterventional, post-marketing surveillance study evaluated doses of recombinant human follicle-stimulating hormone (r-hFSH using the redesigned follitropin alfa pen in women who were anovulatory or oligomenorrheic and undergoing ovulation induction (OI alone or OI with intrauterine insemination. The primary endpoint was the proportion of patients who achieved monofollicular or bifollicular development (defined as one or two follicles 15 mm. Secondary endpoints included characteristics of ovulation stimulation treatment, such as mean total and mean daily r-hFSH doses. Data were analyzed for 3,193 patients from 30 German fertility centers. The proportion of patients with monofollicular or bifollicular development was 71.1% (n=2,270 of a total of 3,193 patients; intent-to-treat population. The mean±standard deviation total and daily doses of r-hFSH were 696.9±542.5 IU and 61.7±29.4 IU, respectively. The three doses prescribed most frequently were: 37.5 IU (n=703 from N=3,189; 22.0%, 50.0 IU (n=1,056 from N=3,189; 33.1%, and 75.0 IU (n=738 from N=3,189; 23.1% on the first day of stimulation; and 37.5 IU (n=465 from N=3,189; 14.6%, 50.0 IU (n=922 from N=3,189; 28.9%, and 75.0 IU (n=895 from N=3,189; 28.1% on the last day of stimulation. This noninterventional, post-marketing surveillance study found that monofollicular or bifollicular development was achieved in 71% of patients studied and the small dose increment (12.5 IU of the redesigned follitropin alfa pen allowed individualized treatment of women undergoing OI. Keywords: ovulation

  4. The effect of the intracervical application of follicle-stimulating hormone or luteinizing hormone on the pattern of expression of gonadotrophin receptors in the cervix of non-pregnant ewes.

    Science.gov (United States)

    Leethongdee, S; Khalid, M; Scaramuzzi, R J

    2014-08-01

    During the periovulatory period, the cervix relaxes in response to changes in circulating concentrations of reproductive hormones. The present study investigated the role of gonadotrophins in cervical function by examining the expression of follicle-stimulating hormone receptor (FSHR) and luteinizing hormone receptor (LHR) and their mRNAs following intracervical treatment with either FSH or LH. Eighteen ewes were assigned to four groups, and they were then treated with progestagen sponges and PMSG to synchronize their oestrous cycles. Intracervical treatments were given 24 h after sponge removal as follows: Group 1: FSH 2 mg; Group 2: LH 2 mg; Group 3: Vehicle and Group 4: Control. Cervices were collected 54 h after sponge removal and then divided into three regions. The expression of FSHR and LHR was determined by immunohistochemistry and FSHR mRNA and LH mRNA by in situ hybridization. The expression of LHR, FSHR and their respective mRNAs was compared in six tissue layers (luminal epithelium, subepithelial stroma, circular, longitudinal and transverse muscle and serosa) and in three cervical regions (vaginal, mid and uterine). The results showed that FSH increased transcription of the FSHR gene and the levels of its receptor, but only in subepithelial stroma of the cervix. FSH also increased the levels of LHR in the cervix, but only in the muscle layers. LH had no effect on the levels of FSHR despite the fact that it did increase the level of transcription of the FSHR gene and LH also increased the levels of its own receptor in the cervix, but only in the muscle layers, and this action was independent of increased levels of transcription of the LHR gene. These findings suggest multiple levels of regulation of cervical LH and FSH receptors and that the gonadotrophins may have a role in relaxation of the cervix during oestrus by regulating their own receptors. © 2014 Blackwell Verlag GmbH.

  5. Efficacy of Follicle-Stimulating Hormone (FSH) Alone, FSH + Luteinizing Hormone, Human Menopausal Gonadotropin or FSH + Human Chorionic Gonadotropin on Assisted Reproductive Technology Outcomes in the "Personalized" Medicine Era: A Meta-analysis.

    Science.gov (United States)

    Santi, Daniele; Casarini, Livio; Alviggi, Carlo; Simoni, Manuela

    2017-01-01

    Luteinizing hormone (LH) and human chorionic gonadotropin (hCG) act on the same receptor, activating different signal transduction pathways. The role of LH or hCG addition to follicle-stimulating hormone (FSH) as well as menopausal gonadotropins (human menopausal gonadotropin; hMG) in controlled ovarian stimulation (COS) is debated. To compare FSH + LH, or FSH + hCG or hMG vs. FSH alone on COS outcomes. A meta-analysis according to PRISMA statement and Cochrane Collaboration was performed, including prospective, controlled clinical trials published until July 2016, enrolling women treated with FSH alone or combined with other gonadotropins. Trials enrolling women with polycystic ovarian syndrome were excluded (PROSPERO registration no. CRD42016048404). Considering 70 studies, the administration of FSH alone resulted in higher number of oocytes retrieved than FSH + LH or hMG. The MII oocytes number did not change when FSH alone was compared to FSH + LH, FSH + hCG, or hMG. Embryo number and implantation rate were higher when hMG was used instead of FSH alone. Pregnancy rate was significantly higher in FSH + LH-treated group vs. others. Only 12 studies reported live birth rate, not providing protocol-dependent differences. Patients' stratification by GnRH agonist/antagonist identified patient subgroups benefiting from specific drug combinations. In COS, FSH alone results in higher oocyte number. HMG improves the collection of mature oocytes, embryos, and increases implantation rate. On the other hand, LH addition leads to higher pregnancy rate. This study supports the concept of a different clinical action of gonadotropins in COS, reflecting previous in vitro data.

  6. Predictors of in vitro fertilization outcomes in women with highest follicle-stimulating hormone levels ≥ 12 IU/L: a prospective cohort study.

    Directory of Open Access Journals (Sweden)

    Lina N Huang

    Full Text Available The purpose of this study is to evaluate factors predictive of outcomes in women with highest follicle-stimulating hormone (FSH levels ≥ 12 IU/L on basal testing, undergoing in vitro fertilization (IVF.A prospective cohort study was conducted at Stanford University Hospital in the Reproductive Endocrinology and Infertility Center for 12 months. Women age 21 to 43 undergoing IVF with highest FSH levels on baseline testing were included. Donor/Recipient and frozen embryo cycles were excluded from this study. Prognostic factors evaluated in association with clinical pregnancy rates were type of infertility diagnosis and IVF stimulation parameters.The current study found that factors associated with clinical pregnancy were: increased number of mature follicles on the day of triggering, number of oocytes retrieved, number of Metaphase II oocytes if intracytoplasmic sperm injection was done, and number of embryos developed 24 hours after retrieval.Our findings suggest that it would be beneficial for women with increased FSH levels to attempt a cycle of IVF. Results of ovarian stimulation, especially embryo quantity appear to be the best predictors of IVF outcomes and those can only be obtained from a cycle of IVF. Therefore, increased basal FSH levels should not discourage women from attempting a cycle of IVF.

  7. Melanin-Concentrating Hormone acts through hypothalamic kappa opioid system and p70S6K to stimulate acute food intake.

    Science.gov (United States)

    Romero-Picó, Amparo; Sanchez-Rebordelo, Estrella; Imbernon, Monica; González-Touceda, David; Folgueira, Cintia; Senra, Ana; Fernø, Johan; Blouet, Clémence; Cabrera, Roberto; van Gestel, Margriet; Adan, Roger A; López, Miguel; Maldonado, Rafael; Nogueiras, Ruben; Diéguez, Carlos

    2018-03-01

    Melanin-Concentrating Hormone (MCH) is one of the most relevant orexigenic factors specifically located in the lateral hypothalamic area (LHA), with its physiological relevance demonstrated in studies using several genetically manipulated mice models. However, the central mechanisms controlling MCH-induced hyperphagia remain largely uncharacterized. Here, we show that central injection of MCH in mice deficient for kappa opoid receptor (k-OR) failed to stimulate feeding. To determine the hypothalamic area responsible for this MCH/k-OR interaction, we performed virogenetic studies and found that downregulation of k-OR by adeno-associated viruses (shOprk1-AAV) in LHA, but not in other hypothalamic nuclei, was sufficient to block MCH-induced food intake. Next, we sought to investigate the molecular signaling pathway within the LHA that mediates acute central MCH stimulation of food intake. We found that MCH activates k-OR and that increased levels of phosphorylated extracellular signal regulated kinase (ERK) are associated with downregulation of phospho-S6 Ribosomal Protein. This effect was prevented when a pharmacological inhibitor of k-OR was co-administered with MCH. Finally, the specific activation of the direct upstream regulator of S6 (p70S6K) in the LHA attenuated MCH-stimulated food consumption. Our results reveal that lateral hypothalamic k-OR system modulates the orexigenic action of MCH via the p70S6K/S6 pathway. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Hormonal changes in secondary impotence

    International Nuclear Information System (INIS)

    Salama, F.M.; El-Shabrawy, N.O.; Nosseir, S.A.; Abo El-Azayem, Naglaa.

    1985-01-01

    Impotence is one of the problems which is still obscure both in its aetiology and treatment. The present study deals with the possible hormonal changes in cases of secondary infertility. The study involved 25 patients diagnosed as secondary impotence. Hormonal assay was performed for the following hormones: 1. Prolaction hormone. 2. Luteinising hormone (L.H.). 3. Testosterone. 4. Follicle stimulating hormone (F.S.H.). The assay was carried out by radioimmunoassay using double antibody technique. Results are discussed

  9. Pregnancy and live birth after follicle-stimulating hormone treatment for an infertile couple including a male affected by Sertoli cell-only syndrome

    Directory of Open Access Journals (Sweden)

    Paulis G

    2017-10-01

    Full Text Available Gianni Paulis,1,2 Luca Paulis,3 Gennaro Romano,4 Carmen Concas,5 Marika Di Sarno,5 Renata Pagano,5 Antonio Di Filippo,5 Maria Luisa Di Petrillo5 1Andrology Center, Regina Apostolorum Hospital, Rome, Italy; 2Department of Uro-Andrology, Castelfidardo Medical Team, Peyronie’s Disease Care Center, Rome, Italy; 3Section of Pharmacology and Research, Department of Uro-Andrology, Castelfidardo Medical Team, Peyronie’s Disease Care Center, Rome, Italy; 4Department of Urologic Oncology, Italian League Against Cancer, Avellino, Italy; 5Department of Reproductive Medicine and Biology, Caran Center, Caserta, Italy Abstract: In males with nonobstructive azoospermia, one of the main histopathologic patterns of the testis is Sertoli cell-only syndrome (SCOS, in which no germ cells are present and only Sertoli cells are contained in the seminiferous tubules. There is not any formal treatment for this pathological condition. However, several studies reported the possibility to perform testicular sperm extraction in patients with SCOS, although, according to some authors, sperm retrieval is possible only in the presence of focal spermatogenesis. We report the case of an infertile couple in whom the 30-year-old male was azoospermic. After the diagnosis, the patient underwent multiple bilateral testicular biopsies, which showed a histological pattern corresponding to SCOS. We administered a cycle of hormone stimulation followed by medically assisted procreation procedures to the male patient. Therefore, the male patient was treated with follicle-stimulating hormone gonadotropin for a total of 7 months (150 IU recombinant human follicle stimulating hormone three times per week. After carrying out a new multiple testicular sperm extraction, several spermatozoa were microscopically observed, and it was then possible to perform an intracytoplasmic sperm injection with subsequent embryo transfer of the blastocyst into the wife’s uterus, and so pregnancy was

  10. Variation in levels of serum inhibin B, testosterone, estradiol, luteinizing hormone, follicle-stimulating hormone, and sex hormone-binding globulin in monthly samples from healthy men during a 17-month period

    DEFF Research Database (Denmark)

    Andersson, Anna-Maria; Carlsen, Elisabeth; Petersen, Jørgen Holm

    2003-01-01

    To obtain information on the scale of the intraindividual variation in testicular hormone, blood samples for inhibin B determination were collected monthly in 27 healthy male volunteers during a 17-month period. In addition, the traditional reproductive hormones FSH, LH, testosterone, estradiol......, and SHBG were measured. The intraindividual variation in inhibin B over the study period was, on the average, 10%, corresponding to the assay variation of the inhibin B assay, indicating that most of the observed day to day variation in inhibin B levels in men could be explained by assay variation...... before blood sampling, but not to the length of daylight or the hours of sunshine. In conclusion, our data showed that day to day levels of inhibin B are relatively constant in men and do not seem to be influenced by seasonal factors. In contrast, we found a seasonal variation in LH and testosterone...

  11. Influence of nitric oxide on in vitro growth, survival, steroidogenesis, and apoptosis of follicle stimulating hormone stimulated buffalo (Bubalus bubalis) preantral follicles.

    Science.gov (United States)

    Dubey, Pawan K; Tripathi, Vrajesh; Singh, Ram Pratap; Sharma, G Taru

    2011-09-01

    Effect of sodium nitroprusside (SNP), a nitric oxide (NO) donor, on in vitro survival, growth, steroidogenesis, and apoptosis of buffalo preantral follicles (PFs) was investigated. PFs (200~250 µm) were isolated by micro-dissection and cultured in 0 (control), 10(-3), 10(-5), 10(-7), and 10(-9) M SNP. To examine the reversible effect of SNP, PFs were cultured with 10(-5) M SNP + 1 mM N(ω)-nitro-L-arginine methyl ester (L-NAME) or 1.0 µg hemoglobin (Hb). The results showed that greater concentrations of SNP (10(-3), 10(-5), 10(-7) M) inhibited (p growth, antrum formation, estradiol production, and oocyte apoptosis in a dose-dependent manner. However, a lower dose of SNP (10(-9) M) significantly stimulated (p growth, antrum formation, follicular oocyte maturation, and stimulated progesterone secretion compared to the control. A combination of SNP + L-NAME promoted the inhibitor effect of SNP while a SNP + Hb combination reversed this effect. Nitrate and nitrite concentrations in the culture medium increased (p < 0.05) in a dose-dependent manner according to SNP concentration in the culture medium. At higher concentrations, SNP had a cytotoxic effect leading to follicular oocyte apoptosis whereas lower concentrations have stimulatory effects. In conclusion, NO exerts a dual effect on its development of buffalo PFs depending on the concentration in the culture medium.

  12. Meningeal melanocytes in the mouse: Distribution and dependence on Mitf

    Directory of Open Access Journals (Sweden)

    Stefan Arni Hafsteinsson Gudjohnsen

    2015-11-01

    Full Text Available Melanocytes are pigment producing cells derived from the neural crest. They are primarily found in the skin and hair follicles, but can also be found in other tissues including the eye, ear and heart. Here we describe the distribution of pigmented cells in C57BL/6J mouse meninges, the membranes that envelope the brain. These cells contain melanosomes of all four stages of development and they depend on MITF, the master regulator of melanocyte development, suggesting that they are bona-fide melanocytes. The location of these pigmented cells is consistent with the location of meningeal melanomas in humans and animal models.

  13. Growth hormone and prolactin stimulate the expression of rat preadipocyte factor-1/delta-like protein in pancreatic islets

    DEFF Research Database (Denmark)

    Carlsson, C; Tornehave, D; Lindberg, Karen

    1997-01-01

    GH and PRL have been shown to stimulate proliferation and insulin production in islets of Langerhans. To identify genes regulated by GH/PRL in islets, we performed differential screening of a complementary DNA library from neonatal rat islets cultured for 24 h with human GH (hGH). One hGH-induced...

  14. Single vagus nerve stimulation reduces early postprandial C-peptide levels but not other hormones or postprandial metabolism

    NARCIS (Netherlands)

    Tang, M. W.; van Nierop, F. S.; Koopman, F. A.; Eggink, H. M.; Gerlag, D. M.; Chan, M. W.; Zitnik, R.; Vaz, F. M.; Romijn, J. A.; Tak, P. P.; Soeters, M. R.

    2018-01-01

    A recent study in rheumatoid arthritis (RA) patients using electrical vagus nerve stimulation (VNS) to activate the inflammatory reflex has shown promising effects on disease activity. Innervation by the autonomic nerve system might be involved in the regulation of many endocrine and metabolic

  15. Role of Gonadotropin-releasing Hormone Stimulation Test in Diagnosing Gonadotropin Deficiency in Both Males and Females with Delayed Puberty

    Directory of Open Access Journals (Sweden)

    Qi-Hong Sun

    2015-01-01

    Conclusions: Our data suggest that isolated use of the gonadorelin stimulation test is almost sufficient to discriminate between HH and CDP in males, but unnecessary in females. The most useful predictor is serum basal or peak LH to differentiate these two disorders in males, but serum basal LH or FSH in females.

  16. Ghrelin stimulation of growth hormone isoforms: parallel secretion of total and 20-kDa growth hormone and relation to insulin sensitivity in healthy humans.

    Science.gov (United States)

    Tong, Jenny; D'Alessio, David; Ramisch, Juliane; Davis, Harold W; Stambrook, Elizabeth; Tschöp, Matthias H; Bidlingmaier, Martin

    2012-09-01

    The 20-kDa human GH (hGH) is produced in the pituitary by alternative splicing of the hGH-N gene. The 20-kDa hGH promotes growth similarly to 22-kDa or total hGH, the predominant form in circulation, but the relative effects of these isoforms on glucose metabolism have been debated. To investigate the effect of ghrelin on 20-kDa and total hGH secretion in healthy, nonobese subjects. We also studied associations between basal GH concentration and fasting glucose and insulin as well as between dynamic GH secretion and insulin sensitivity. Synthetic human acyl ghrelin (0.2 or 0.6 nmol/kg · h) or saline was infused in random order in 14 healthy subjects (six males, eight females; age 27.7 ± 6.3 yr; body mass index 22.0 ± 2.7 kg/m(2), mean ± SEM) on 3 separate days. Ghrelin was infused for 45 min to achieve steady-state levels and continued through a 3-h frequently sampled i.v. glucose tolerance test. Insulin sensitivity index was quantified using the minimal model of glucose kinetics. Basal 20-kDa and total GH concentrations were 0.4 ± 0.1 and 2.2 ± 0.4 ng/ml, respectively, with a 20-kDa to total GH ratio of 0.13 ± 0.02. Females had significantly higher baseline GH levels. Ghrelin administration increased 20-kDa and total GH levels in a parallel and dose-dependent fashion, with no significant change in the ratio of the isoforms. Basal 20-kDa and total GH levels were negatively correlated with fasting glucose, insulin, and homeostasis model assessment of insulin resistance. During the frequently sampled iv glucose tolerance test, GH secretion was positively correlated with insulin sensitivity index with saline infusion. Ghrelin dose-dependently increases endogenous 20-kDa and total GH secretion in a parallel fashion in healthy subjects. Both basal and stimulated levels of the different GH isoforms were positively associated with insulin sensitivity in this cohort of healthy men and women.

  17. From Melanocyte to Metastatic Malignant Melanoma

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    Bizhan Bandarchi

    2010-01-01

    Full Text Available Malignant melanoma is one of the most aggressive malignancies in human and is responsible for almost 60% of lethal skin tumors. Its incidence has been increasing in white population in the past two decades. There is a complex interaction of environmental (exogenous and endogenous, including genetic, risk factors in developing malignant melanoma. 8–12% of familial melanomas occur in a familial setting related to mutation of the CDKN2A gene that encodes p16. The aim of this is to briefly review the microanatomy and physiology of the melanocytes, epidemiology, risk factors, clinical presentation, historical classification and histopathology and, more in details, the most recent discoveries in biology and genetics of malignant melanoma. At the end, the final version of 2009 AJCC malignant melanoma staging and classification is presented.

  18. Peroxisome proliferator-activated receptor gamma agonism reduces the insulin-stimulated increase in circulating interleukin-6 in growth hormone (GH) replaced GH-deficient adults

    DEFF Research Database (Denmark)

    Krag, Morten B; Rasmussen, Lars M; Hansen, Troels K

    2008-01-01

    SUMMARY Context: Peroxisome proliferator-activated receptor gamma (PPARgamma) agonists modify cardiovascular risk factors and inflammatory markers in patients with type 2 diabetes. Growth hormone (GH) treatment in GH-deficient (GHD) patients may cause insulin resistance and exerts ambiguous effects...... on inflammatory markers. Objective: To investigate circulating markers of inflammation and endothelial function in GH replaced GHD patients before and after 12 weeks administration of either pioglitazone 30 mg/day (N=10) or placebo (N=10) in a randomized double-blind parallel design. Methods: Circulating levels...... abrogated this insulin-stimulated increment in IL-6 levels compared to placebo (P = 0.01). Furthermore PPARgamma agonist treatment significantly lowered basal IL-4 levels (PGH replaced patients, 2) This increase in IL-6...

  19. Sperm counts and serum follicle-stimulating hormone levels before and after radiotherapy and chemotherapy in men with testicular germ cell cancer

    Energy Technology Data Exchange (ETDEWEB)

    Berthelsen, J.G.

    1984-02-01

    Sperm counts were low (median, 15 X 10(6) per ejaculate) and serum follicle-stimulating hormone (FSH) levels were moderately elevated (median, 31 IU/l) after unilateral orchiectomy and immediately before radiotherapy and chemotherapy in 34 patients with seminomas and 20 patients with nonseminomatous germ cell tumors. The scattered radiation (0.2 to 1.3 Gray (Gy)) reaching the remaining testicle during radiotherapy caused azoospermia in more than two thirds of the patients. A median of 540 days elapsed after the end of treatment before spermatozoa were again found in semen samples, while a median of 1250 days passed before the pretreatment sperm count was reached. One to 5 years after treatment, sperm counts were still low (median, 6 X 10(6) per ejaculate) and serum FSH was elevated (median, 61 IU/l). The adjuvant chemotherapy given to the 20 patients with nonseminomatous tumors did not appear to affect restitution appreciably.

  20. Multicenter, noninterventional, post-marketing surveillance study to evaluate dosing of recombinant human follicle-stimulating hormone using the redesigned follitropin alfa pen in women undergoing ovulation induction

    Science.gov (United States)

    Nawroth, Frank; Tandler-Schneider, Andreas; Bilger, Wilma

    2015-01-01

    This prospective, noninterventional, post-marketing surveillance study evaluated doses of recombinant human follicle-stimulating hormone (r-hFSH) using the redesigned follitropin alfa pen in women who were anovulatory or oligomenorrheic and undergoing ovulation induction (OI) alone or OI with intrauterine insemination. The primary endpoint was the proportion of patients who achieved monofollicular or bifollicular development (defined as one or two follicles ≥15 mm). Secondary endpoints included characteristics of ovulation stimulation treatment, such as mean total and mean daily r-hFSH doses. Data were analyzed for 3,193 patients from 30 German fertility centers. The proportion of patients with monofollicular or bifollicular development was 71.1% (n=2,270 of a total of 3,193 patients; intent-to-treat population). The mean±standard deviation total and daily doses of r-hFSH were 696.9±542.5 IU and 61.7±29.4 IU, respectively. The three doses prescribed most frequently were: 37.5 IU (n=703 from N=3,189; 22.0%), 50.0 IU (n=1,056 from N=3,189; 33.1%), and 75.0 IU (n=738 from N=3,189; 23.1%) on the first day of stimulation; and 37.5 IU (n=465 from N=3,189; 14.6%), 50.0 IU (n=922 from N=3,189; 28.9%), and 75.0 IU (n=895 from N=3,189; 28.1%) on the last day of stimulation. This noninterventional, post-marketing surveillance study found that monofollicular or bifollicular development was achieved in 71% of patients studied and the small dose increment (12.5 IU) of the redesigned follitropin alfa pen allowed individualized treatment of women undergoing OI. PMID:25926755

  1. Follicle-stimulating hormone (FSH activates extracellular signal-regulated kinase phosphorylation independently of beta-arrestin- and dynamin-mediated FSH receptor internalization

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    Crepieux Pascale

    2006-06-01

    Full Text Available Abstract Background The follicle-stimulating hormone receptor (FSH-R is a seven transmembrane spanning receptor (7TMR which plays a crucial role in male and female reproduction. Upon FSH stimulation, the FSH-R activates the extracellular signal-regulated kinases (ERK. However, the mechanisms whereby the agonist-stimulated FSH-R activates ERK are poorly understood. In order to activate ERK, some 7 TMRs require beta-arrestin-and dynamin-dependent internalization to occur, whereas some others do not. In the present study, we examined the ability of the FSH-activated FSH-R to induce ERK phosphorylation, in conditions where its beta-arrestin- and dynamin-mediated internalization was impaired. Methods Human embryonic kidney (HEK 293 cells were transiently transfected with the rat FSH-R. Internalization of the FSH-R was manipulated by co-expression of either a beta-arrestin (319–418 dominant negative peptide, either an inactive dynamin K44A mutant or of wild-type beta-arrestin 1 or 2. The outcomes on the FSH-R internalization were assayed by measuring 125I-FSH binding at the cell surface when compared to internalized 125I-FSH binding. The resulting ERK phosphorylation level was visualized by Western blot analysis. Results In HEK 293 cells, FSH stimulated ERK phosphorylation in a dose-dependent manner. Co-transfection of the beta- arrestin (319–418 construct, or of the dynamin K44A mutant reduced FSH-R internalization in response to FSH, without affecting ERK phosphorylation. Likewise, overexpression of wild-type beta-arrestin 1 or 2 significantly increased the FSH-R internalization level in response to FSH, without altering FSH-induced ERK phosphorylation. Conclusion From these results, we conclude that the FSH-R does not require beta-arrestin- nor dynamin-mediated internalization to initiate ERK phosphorylation in response to FSH.

  2. The preparation and application of N-terminal 57 amino acid protein of the follicle-stimulating hormone receptor as a candidate male contraceptive vaccine

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    Cheng Xu

    2014-08-01

    Full Text Available Follicle-stimulating hormone receptor (FSHR, which is expressed only on Sertoli cells and plays a key role in spermatogenesis, has been paid attention for its potential in male contraception vaccine research and development. This study introduces a method for the preparation and purification of human FSHR 57-amino acid protein (FSHR-57aa as well as determination of its immunogenicity and antifertility effect. A recombinant pET-28a(+-FSHR-57aa plasmid was constructed and expressed in Escherichia coli strain BL21 Star TM (DE3 and the FSHR-57aa protein was separated and collected by cutting the gel and recovering activity by efficient refolding dialysis. The protein was identified by Western blot and high-performance liquid chromatography analysis with a band of nearly 7 kDa and a purity of 97.4%. Male monkeys were immunized with rhFSHR-57aa protein and a gradual rising of specific serum IgG antibody was found which reached a plateau on day 112 (16 weeks after the first immunization. After mating of one male with three female monkeys, the pregnancy rate of those mated with males immunized against FSHR-57aa was significantly decreased while the serum hormone levels of testosterone and estradiol were not disturbed in the control or the FSHR-57aa groups. By evaluating pathological changes in testicular histology, we found that the blood-testis barrier remained intact, in spite of some small damage to Sertoli cells. In conclusion, our study demonstrates that the rhFSHR-57aa protein might be a feasible male contraceptive which could affect sperm production without disturbing hormone levels.

  3. Cost-effectiveness of using recombinant human thyroid-stimulating hormone before radioiodine ablation for thyroid cancer treatment in Spanish hospitals.

    Science.gov (United States)

    Vallejo, J A; Muros, M A

    In thyroid cancer treatment, the thyroid-stimulating hormone (TSH) must be elevated before radioiodine ablation, either by exogenous (with recombinant human thyrotropin [rhTSH]) or endogenous stimulation by thyroid hormone withdrawal (THW). The use of rhTSH avoids hypothyroidism and favours the subsequent elimination of radioiodine, but involves the cost of the product. For this reason, a cost-effectiveness analysis was performed, taking into account all costs involved and the benefits associated with the use of this therapy. Using a Markov modelling with two analysis arms (rhTSH and THW), stratified into high (100mCi/3700 MBq) and low (30mCi/1110 MBq) radioiodine doses, and using 17 weekly cycles, the incremental cost per quality-adjusted life-year (QALY) related to the use of rhTSH was determined. The clinical inputs included in the model were based on published studies and in a treatment survey conducted in Spain. Radioablation preparation with rhTSH is superior to THW, showing additional benefits (0.048 AVAC), as well as cost savings (-€614.16), with an incremental cost-effectiveness rate (ICER) of -€12,795/QALY. The univariate and multivariate sensitivity analyses showed the result to be robust. The use of rhTSH previous to radioablation in Spain has cost savings, as well as a series of health benefits for the patient, making it highly cost-effective. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

  4. Adrenal steroid, cortisol, adrenocorticotropin, and beta-endorphin responses to human corticotropin-releasing hormone stimulation test in normal children and children with premature pubarche.

    Science.gov (United States)

    Ghizzoni, L; Virdis, R; Ziveri, M; Lamborghini, A; Alberini, A; Volta, C; Bernasconi, S

    1989-10-01

    To determine whether CRH affects adrenal androgen, beta-endorphin (B-E), and ACTH secretion in normal children during sexual maturation, 17-hydroxyprogesterone (17-OHP), androstenedione (D4-A), dehydroepiandrosterone (DHEA), DHEA sulfate (DS), cortisol, B-E, and ACTH were measured after an iv injection of 1 microgram/kg human CRH. Children with premature pubarche were similarly analyzed to establish whether this condition is accompanied by altered hormonal responses to CRH. CRH produced consistent increases in ACTH, B-EP, and cortisol blood levels, which were comparable at all age intervals in all groups. 17-OHP increased after CRH injection, but its response linearly with age. D4-A levels were not influenced, while DHEA and DS levels were only partially influenced by CRH. The stimulated D4-A to 17-OHP ratio increased with sexual maturation, whereas ratios of cortisol to 17-OHP and D4-A to DHEA remained constant. Children with premature pubarche had hormonal responses similar in magnitude to those of prepubertal children of comparable age. In conclusion, an increase in 17,20-desmolase efficiency occurs with postnatal maturation after CRH challenge. Moreover, CRH does not appear to play an important role in premature pubarche.

  5. Follicle-stimulating hormone is associated with non-alcoholic fatty liver disease in Chinese women over 55 years old.

    Science.gov (United States)

    Wang, Ningjian; Li, Qin; Han, Bing; Chen, Yi; Zhu, Chunfang; Chen, Yingchao; Xia, Fangzhen; Lu, Meng; Meng, Ying; Guo, Yuyu; Ye, Lin; Sui, Chunhua; Kuang, Lin; Lin, Dongping; Lu, Yingli

    2016-06-01

    Obesity and diabetes are related to non-alcoholic fatty liver disease (NAFLD). A reduction in follicle-stimulating hormone (FSH) is associated with obesity and diabetes in postmenopausal women. Thus, we aim to investigate whether FSH is associated with NAFLD in women over 55 who were postmenopausal with a high probability. Our data were obtained from the 2014 Survey on Prevalence in East China for Metabolic Diseases and Risk Factors. A total of 1635 women at the age of 55-89 years were selected. The degrees of fatty liver were categorized into mild and moderate-severe hepatic steatosis groups by ultrasonography. FSH and other sex hormones were measured by chemiluminescence. A total of 366 (22.4%) and 417 (25.5%) women had mild and moderate-severe hepatic steatosis, respectively. FSH was negatively correlated with waist circumference, homeostasis model assessment of insulin resistance (HOMA-IR), and other metabolic factors (all P hepatic steatosis. The association of FSH with moderate-severe hepatic steatosis was attenuated by waist circumference and HOMA-IR but persisted in the fully adjusted model (P for trend hepatic steatosis and partially explained the association of moderate-severe hepatic steatosis with FSH. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  6. Evaluation of the effect of follicular stimulating hormone on the in vitro bovine spermatogonial stem cells self-renewal: An experimental study

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    Masoome Jabarpour

    2017-12-01

    Full Text Available Background: Spermatogonial stem cells (SSCs are undifferentiated cells which are highly reproducible and expandable. Several studies have been conducted to reproduce these cells in culture. They used growth factors, hormones and different feeder cells to improve survival and proliferation of SSCs. Objective: This study was conducted to evaluate the effects of follicular stimulating hormone (FSH on gene expression of fibroblast growth factor (FGF2 and glial cell-derived neurotrophic factor (GDNF in Sertoli cells. Materials and Methods: Sertoli cells and SSCs were isolated from 3-5 month-old calves. Bovine testicular cells were cultured for 15 days with or without FSH. Identification of these cells was confirmed by immunocytochemistry analysis. Colony formation of SSCs was evaluated using an inverted microscope. The gene expression of FGF2 and GDNF and the gene markers bcl6b, thy-1, and C-kit were evaluated using the quantitative RT-PCR technique. Results: The results indicated that FSH increased colonization of SSCs. the expression of GDNF, FGF2, and markers of undifferentiated spermatogonia was increased following culture in control and FSH groups (p<0.05, this increase was more in FSH group. Conversely, the expression of C-kit was decreased in both groups (p<0.05. Conclusion: The results showed that FSH can increase the self-renewal of SSCs in vitro via upregulation of GDNF and FGF2 expression in Sertoli cells.

  7. Characterization of Inhibitor of Growth 2 tumor suppressor in Alligator mississippiensis, its conservation in Archosauria, and response to thyroid stimulating hormone.

    Science.gov (United States)

    Helbing, Caren C; Crump, Kate; Bailey, Carmen M; Kohno, Satomi; Veldhoen, Nik; Song, Yue; Bryan, Teresa; Bermudez, Dieldrich S; Ausió, Juan; Guillette, Louis J

    2007-02-01

    Inhibitor of growth 2 (ING2) belongs to a family of tumor suppressors that are important regulators of a wide range of cellular processes including proliferation, apoptosis, and DNA repair. ING family members are found in yeast, plants, invertebrates and many vertebrate species. However, to date, ING has not been characterized in reptiles. Herein we describe the isolation of expressed ING2 sequence in the American alligator, Alligator mississippiensis, and compare this sequence with that isolated in the chicken. We identify features that are unique to these two representatives of the Archosaurs including conservation of specific amino acid residues and the absence of an adenylate residue in the 5' end of the nucleotide sequence relative to frogs and mammals. The latter feature results in an alteration of the coding potential leading to distinctive N-termini. Injection of juvenile alligators with thyroid stimulating hormone (TSH), which increases endogenous thyroid hormones, results in the modulation of ING2 transcript levels. Quantitative real time polymerase chain reaction analyses revealed a reduction in the steady-state levels of ING2 mRNA in the phallus/cliterophallus, lung, and liver by 48 h after TSH injection. ING2 expression in the thyroid gland, gonad, and heart was unaffected by TSH treatment. These data indicate that control of ING2 expression by the thyroid axis may be conserved among species and is tissue-dependent.

  8. Macimorelin (AEZS-130)-stimulated growth hormone (GH) test: validation of a novel oral stimulation test for the diagnosis of adult GH deficiency.

    Science.gov (United States)

    Garcia, J M; Swerdloff, R; Wang, C; Kyle, M; Kipnes, M; Biller, B M K; Cook, D; Yuen, K C J; Bonert, V; Dobs, A; Molitch, M E; Merriam, G R

    2013-06-01

    In the absence of panhypopituitarism and low serum IGF-I levels, the diagnosis of adult GH deficiency (AGHD) requires confirmation with a GH stimulation test. Macimorelin is a novel, orally active ghrelin mimetic that stimulates GH secretion. The objective of the study was to determine the diagnostic efficacy and safety of macimorelin in AGHD. This was a multicenter open-label study comparing the diagnostic accuracy of oral macimorelin with that of arginine+GHRH in AGHD patients and healthy, matched controls. After 43 AGHD patients and 10 controls were tested, the GHRH analog Geref Diagnostic [GHRH(1-29)NH2] became unavailable in the United States. The study was completed by testing 10 additional AGHD patients and 38 controls with macimorelin alone. Peak GH area under the receiver operating characteristic curve after macimorelin was measured. Fifty AGHD subjects and 48 controls were evaluated. Peak GH levels in AGHD patients and controls after macimorelin were 2.36 ± 5.69 and 17.71 ± 19.11 ng/mL, respectively (P GH cut point of 2.7 ng/mL, with 82% sensitivity, 92% specificity, and 13% misclassification rate. For subjects receiving both tests, macimorelin showed discrimination comparable with arginine+GHRH (area under the receiver operating characteristic curve 0.99 vs 0.94, respectively, P = .29). Obesity (body mass index > 30 kg/m(2)) was present in 58% of subjects, and peak GH levels were inversely associated with body mass index in controls (r = -0.37, P = .01). Using the separate cut points of 6.8 ng/mL for nonobese and 2.7 for obese subjects reduced the misclassification rate to 11%. Only 1 drug-related serious adverse event, an asymptomatic QT interval prolongation on the electrocardiogram, was reported. Oral macimorelin is safe, convenient, and effective in diagnosing AGHD with accuracy comparable with the arginine+GHRH test.

  9. Atrial fibrillation associated with a thyroid stimulating hormone-secreting adenoma of the pituitary gland leading to a presentation of acute cardiac decompensation: A case report

    Directory of Open Access Journals (Sweden)

    George Jyothis T

    2008-02-01

    Full Text Available Abstract Introduction Hyperthyroidism is a well established cause of atrial fibrillation (AF. Thyroid Stimulating Hormone-secreting pituitary tumours are rare causes of pituitary hyperthyroidism. Whilst pituitary causes of hyperthyroidism are much less common than primary thyroid pathology, establishing a clear aetiology is critical in minimising complications and providing appropriate treatment. Measuring Thyroid Stimulating Hormone (TSH alone to screen for hyperthyroidism may be insufficient to appropriately evaluate the thyroid status in such cases. Case presentation A 63-year-old Caucasian man, previously fit and well, presented with a five-day history of shortness of breath associated with wheeze and dry cough. He denied symptoms of hyperthyroidism and his family, social and past history were unremarkable. Initial investigation was in keeping with a diagnosis of atrial fibrillation (AF with fast ventricular response leading to cardiac decompensation. TSH 6.2 (Normal Range = 0.40 – 4.00 mU/L, Free T3 of 12.5 (4.00 – 6.8 pmol/L and Free T4 51(10–30 pmol/L. Heterophilic antibodies were ruled out. Testosterone was elevated at 43.10 (Normal range: 10.00 – 31.00 nmol/L with an elevated FSH, 18.1 (1.0–7.0 U/L and elevated LH, 12.4 (1.0–8.0 U/L. Growth Hormone, IGF-1 and prolactin were normal. MRI showed a 2.4 cm pituitary macroadenoma. Visual field tests showed a right inferotemporal defect. While awaiting neurosurgical removal of the tumour, the patient was commenced on antithyroid medication (carbimazole and maintained on this until successful trans-sphenoidal excision of the macroadenoma had been performed. AF persisted post-operatively, but was electrically cardioverted subsequently and he remains in sinus rhythm at twelve months follow-up off all treatment. Conclusion This case reiterates the need to evaluate thyroid function in all patients presenting with atrial fibrillation. TSH-secreting pituitary adenomas must be considered

  10. Frequently Asked Questions about Congenital Melanocytic Nevus (CMN)

    Science.gov (United States)

    ... or Giant Congenital Melanocytic Nevus are not hereditary, meaning you did not "pass it on" to your ... are the signs of melanoma? Changes in size, color, surface texture, pain, bleeding, or itching are all ...

  11. MC1R stimulation by alpha-MSH induces catalase and promotes its re-distribution to the cell periphery and dendrites.

    Science.gov (United States)

    Maresca, Vittoria; Flori, Enrica; Bellei, Barbara; Aspite, Nicaela; Kovacs, Daniela; Picardo, Mauro

    2010-04-01

    We demonstrated a direct correlation between melanogenic and catalase activities on in vitro and ex vivo models. Here, we investigated whether the stimulation of Melanocortin-1 Receptor (MC1R) could influence catalase expression, activity and cellular localization. For this purpose, we treated B16-F0 melanoma cells with alpha-Melanocyte Stimulating Hormone (alpha-MSH) and we showed a rapid induction of catalase through a cAMP/PKA-dependent, microphthalmia-associated transcription factor (MITF) independent mechanism, acting at post-transcriptional level. Moreover, alpha-MSH promoted a partial re-distribution of catalase to the cell periphery and dendrites. This work strengthens the correlation between melanogenesis and anti-oxidants, demonstrating the induction of catalase in response to a melanogenic stimulation, such as alpha-MSH-dependent MC1R activation. Moreover, this study highlights catalase regulatory mechanisms poorly known, and attributes to alpha-MSH a protective role in defending melanocytes, and possibly keratinocytes, not only on the basis of its pigmentary action, but also for its capacity to stimulate a quick anti-oxidant defence.

  12. Effect of transcutaneous electric nerve stimulation (TENS on hormones profile in subjects with primary dysmenorrhoea - a preliminary study

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    S. R. A. Akinbo

    2007-02-01

    Full Text Available Background & Objective: Primary dysmenorrhoea (PD is definedas the occurrence of painful menstrual cramps of uterine origin which occurs in the absence of any underlying disease. The pathogenesis is unclear, but uterine hyperactivity, elevated prostaglandin and leukotrienes levels, and hormonal level fluctuations have all been implicated. The objective of this study was to evaluate the effect of TENS on the hormones cortisol and prolactin in individuals with PD.Methods: Plasma levels of cortisol and prolactin were studied in twenty-one (21 subjects with PD by obtaining blood samples from each subject pre-and post-TENS therapy on the first day of menstruation. The mean age of subjects was 23 (+ 2 years.  The Visual Analogue Scale (VAS was used to assess the pre-and post-treatment pain intensity.  The TENS unit was applied for a duration of 30 minutes.Results: A paired t-test showed that there was an overall reduction in the mean cortisol and prolactin from  pre treatment values of 28.45µg/dl ((5.27 and 56.81ng/ml ((31.86 to post treatment values of 27.33µg/dl ((5.13 and 53.23ng/ml ((37.63 respectively. However, these differences were not statistically significant (P>0.05.  Pain intensity was significantly reduced comparing pre and post treatment VAS scores (P = 0.001.Conclusion: The probable mechanism by which TENS effected alterations in cortisol and prolactin levels and pain reduction in subjects with PD might be through the opioid-modulating analgesia system, which releases B-endorphins and other endogenous opiates in response to pain.  This is because there is a close relationship between B-endorphin, cortisol and neurons, which secrete dopamine into the hypothalamic-pituitary-portal system.

  13. Effect of transcutaneous electric nerve stimulation (TENS on hormones profile in subjects with primary dysmenorrhoea - a preliminary study

    Directory of Open Access Journals (Sweden)

    S. R. A. Akinbo

    2007-01-01

    as the occurrence of painful menstrual cramps of uterine origin which occurs in the absence of any underlying disease. The pathogenesis is unclear, but uterine hyperactivity, elevated prostaglandin and leukotrienes levels, and hormonal level fluctuations have all been implicated. The objective of this study was to evaluate the effect of TENS on the hormones cortisol and prolactin in individuals with PD. Methods: Plasma levels of cortisol and prolactin were studied in twenty-one (21 subjects with PD by obtaining blood samples from each subject pre-and post-TENS therapy on the first day of menstruation. The mean age of subjects was 23 (+ 2 years.  The Visual Analogue Scale (VAS was used to assess the pre-and post-treatment pain intensity.  The TENS unit was applied for a duration of 30 minutes. Results: A paired t-test showed that there was an overall reduction in the mean cortisol and prolactin from  pre treatment values of 28.45µg/dl ((5.27 and 56.81ng/ml ((31.86 to post treatment values of 27.33µg/dl ((5.13 and 53.23ng/ml ((37.63 respectively. However, these differences were not statistically significant (P>0.05.  Pain intensity was significantly reduced comparing pre and post treatment VAS scores (P = 0.001. Conclusion: The probable mechanism by which TENS effected alterations in cortisol and prolactin levels and pain reduction in subjects with PD might be through the opioid-modulating analgesia system, which releases B-endorphins and other endogenous opiates in response to pain.  This is because there is a close relationship between B-endorphin, cortisol and neurons, which secrete dopamine into the hypothalamic-pituitary-portal system.

  14. Relationship of adiponectin to endogenous GH pulse secretion parameters in response to stimulation with a growth hormone releasing factor.

    Science.gov (United States)

    Makimura, H; Stanley, T L; Chen, C Y; Branch, K L; Grinspoon, S K

    2011-06-01

    Obesity is associated with both reduced growth hormone (GH) and adiponectin. However, the relationship between adiponectin and parameters of endogenous GH secretion remains unknown. The aim of this study was to determine the relationship between total and high molecular weight (HMW) adiponectin and parameters of endogenous pulsatile GH secretion and the effects of tesamorelin, a synthetic GH releasing hormone (GHRH(1-44)), on total and HMW adiponectin. A 2-week interventional study with tesamorelin was conducted at an academic medical center in 13 men with BMI 20-35 kg/m(2). Overnight frequent blood sampling and measurement of total and HMW adiponectin at baseline and after treatment were performed to assess the effects of augmenting endogenous pulsatile GH secretion. Total, but not HMW, adiponectin was positively associated with log(10)Peak GH area (r=+0.73; P=0.005), basal GH secretion (r=+0.67; P=0.01), and total GH production (r=+0.57; P=0.04), but was not associated with the number of secretion events (P=0.85). Two-week treatment with tesamorelin increased endogenous GH release and IGF-1, but neither total (change -0.16±0.64; P=0.40), nor HMW (change +0.03±0.70; P=0.87) adiponectin changed significantly with treatment. Sub-analyses in overweight and obese men yielded similar results. Our study demonstrates a strong relationship between specific parameters of endogenous GH pulsatility and adiponectin. However, short-term augmentation of GH pulsatility over 2-weeks does not change adiponectin. Therefore, the relationship between GH and adiponectin is most likely mediated by specific covariates related to adiposity or other factors. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Intradermal Melanocytic Nevus Containing Bone Metaplasia: A Case Report

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    Recep Bedir

    2013-06-01

    Full Text Available Melanocytic nevi in the bone metaplasia is not a common case. The majority of these lesions tend to be located in the upper part of the body, as in our case. There is a higher incidence of females. In the pathogenesis usually is thought to develop seconder damage of the hair follicles. We report a 46-year-old woman who presented a case of osseous metaplasia within a benign intradermal melanocytic nevus was excised from the face.

  16. Classifying Melanocytic Tumors Based on DNA Copy Number Changes

    OpenAIRE

    Bastian, Boris C.; Olshen, Adam B.; LeBoit, Philip E.; Pinkel, Daniel

    2003-01-01

    Melanoma and benign melanocytic nevi can overlap significantly in their histopathological presentation and misdiagnoses are common. To determine whether genetic criteria can be of diagnostic help we determined DNA copy number changes in 186 melanocytic tumors (132 melanomas and 54 benign nevi) using comparative genomic hybridization. We found highly significant differences between melanomas and nevi. Whereas 127 (96.2%) of the melanomas had some form of chromosomal aberration, only 7 (13.0%) ...

  17. Fertilization promoting peptide, a tripeptide similar to thyrotrophin-releasing hormone, stimulates the capacitation and fertilizing ability of human spermatozoa in vitro.

    Science.gov (United States)

    Green, C M; Cockle, S M; Watson, P F; Fraser, L R

    1996-04-01

    Recent studies have demonstrated that a prostatic tripeptide similar in structure to thyrotrophin-releasing hormone (TRH) can stimulate the in-vitro capacitation and fertilizing ability of epididymal mouse spermatozoa. Therefore we have proposed that this tripeptide be referred to as fertilization promoting peptide (FPP). Using chlortetracycline fluorescence analysis and the hamster oocyte penetration test (HOPT), we have obtained evidence that FPP can also promote the capacitation and fertilizing ability of ejaculated human spermatozoa in vitro. FPP (25-200 nM) caused a significant increase in the proportion of B-pattern uncapacitated cells, with no significant stimulation of acrosomal exocytosis. Comparison of FPP with two structurally similar tripeptides, TRH and pyroglutamyl phenylalanylprolineamide, at 50 nM revealed that only FPP could significantly promote capacitation. Finally, after a brief exposure to progesterone to induce acrosomal exocytosis in capacitated cells, FPP-treated suspensions penetrated a significantly higher proportion of oocytes than the untreated controls when assessed in the HOPT. The presence of FPP in human seminal plasma at concentrations similar to those used here suggests that, in vivo, FPP may play a positive role in promoting human sperm function.

  18. Growth hormone-releasing peptide-biotin conjugate stimulates myocytes differentiation through insulin-like growth factor-1 and collagen type I.

    Science.gov (United States)

    Lim, Chae Jin; Jeon, Jung Eun; Jeong, Se Kyoo; Yoon, Seok Jeong; Kwon, Seon Deok; Lim, Jina; Park, Keedon; Kim, Dae Yong; Ahn, Jeong Keun; Kim, Bong-Woo

    2015-09-01

    Based on the potential beneficial effects of growth hormone releasing peptide (GHRP)-6 on muscle functions, a newly synthesized GHRP-6-biotin conjugate was tested on cultured myoblast cells. Increased expression of myogenic marker proteins was observed in GHRP-6-biotin conjugate-treated cells. Additionally, increased expression levels of insulin-like growth factor-1 and collagen type I were observed. Furthermore, GHRP-6-biotin conjugate-treated cells showed increased metabolic activity, as indicated by increased concentrations of energy metabolites, such as ATP and lactate, and increased enzymatic activity of lactate dehydrogenase and creatine kinase. Finally, binding protein analysis suggested few candidate proteins, including desmin, actin, and zinc finger protein 691 as potential targets for GHRP6-biotin conjugate action. These results suggest that the newly synthesized GHRP-6-biotin conjugate has myogenic stimulating activity through, at least in part, by stimulating collagen type I synthesis and several key proteins. Practical applications of the GHRP-6-biotin conjugate could include improving muscle condition.

  19. Mathematical model of human growth hormone (hGH)-stimulated cell proliferation explains the efficacy of hGH variants as receptor agonists or antagonists.

    Science.gov (United States)

    Haugh, Jason M

    2004-01-01

    Human growth hormone (hGH) is a therapeutically important endocrine factor that signals various cell types. Structurally and functionally, the interactions of hGH with its receptor have been resolved in fine detail, such that hGH and hGH receptor variants can be practically engineered by either random or rational approaches to achieve significant changes in the free energies of binding. A somewhat unique feature of hGH action is its homodimerization of two hGH receptors, which is required for intracellular signaling and stimulation of cell proliferation, yet the potencies of hGH mutants in cell-based assays rarely correlate with their overall receptor-binding avidities. Here, a mathematical model of hGH-stimulated cell signaling is posed, accounting not only for binding interactions at the cell surface but induction of receptor endocytosis and downregulation as well. Receptor internalization affects ligand potency by imposing a limit on the lifetime of an active receptor complex, irrespective of ligand-receptor binding properties. The model thus explains, in quantitative terms, the numerous published observations regarding hGH receptor agonism and antagonism and challenges the interpretations of previous studies that have not considered receptor trafficking as a central regulatory mechanism in hGH signaling.

  20. Anti-Müllerian hormone serum values and ovarian reserve: can it predict a decrease in fertility after ovarian stimulation by ART cycles?

    Directory of Open Access Journals (Sweden)

    Tito Silvio Patrelli

    Full Text Available BACKGROUND: A variety of indicators of potentially successful ovarian stimulation cycles are available, including biomarkers such as anti-Mullerian hormone. The aim of our study was to confirm the usefulness of serum anti-Mullerian hormone assay in predicting ovarian response and reproductive outcome in women eligible for ART cycles. MATERIALS: Forty-six women undergoing ART cycles at the Centre for Reproductive Medicine in Parma were recruited from March-to-June 2010. INCLUSION CRITERIA: age<42 years; body-mass-index = 20-25; regular menstrual cycles; basal serum FSH concentration <12 IU/L and basal serum estradiol concentration <70 pg/mL. The couples included in our study reported a variety of primary infertility causes. All women underwent FSH stimulation and pituitary suppression (GnRH-agonist/GnRH-antagonist protocols. Women were considered poor-responders if they had ≤ 3 oocytes; normal-responders 4-9 oocytes and high-responders ≥ 10 oocytes. Serum samples for the AMH assays were obtained on the first and last days of stimulation. A P value ≤ 0.05 was considered statistically significant. RESULT: FSH levels increased significantly when AMH levels decreased. The total dose of r-FSH administered to induce ovulation was not correlated to AMH. The number of follicles on the hCG, serum estradiol levels on the hCG-day, and the number of retrieved oocytes were significantly correlated to AMH. The number of fertilized oocytes was significantly correlated to the AMH levels. No significant correlation was found between obtained embryos or transferred embryos and AMH. Basal serum AMH levels were significantly higher than those measured on the hCG-day, which appeared significantly reduced. There was a significant correlation between AMH in normal responders and AMH in both high and poor responders. CONCLUSIONS: Our data confirm the clinical usefulness of AMH in ART-cycles to customize treatment protocols and suggest the necessity of verifying an

  1. Melanocyte stem cells as potential therapeutics in skin disorders.

    Science.gov (United States)

    Lee, Ju Hee; Fisher, David E

    2014-11-01

    Melanocytes produce pigment granules that color both skin and hair. In the hair follicles melanocytes are derived from stem cells (MelSCs) that are present in hair bulges or sub-bulge regions and function as melanocyte reservoirs. Quiescence, maintenance, activation and proliferation of MelSCs are controlled by specific activities in the microenvironment that can influence the differentiation and regeneration of melanocytes. Therefore, understanding MelSCs and their niche may lead to use of MelSCs in new treatments for various pigmentation disorders. We describe here pathophysiological mechanisms by which melanocyte defects lead to skin pigmentation disorders such as vitiligo and hair graying. The development, migration and proliferation of melanocytes and factors involved in the survival, maintenance and regeneration of MelSCs are reviewed with regard to the biological roles and potential therapeutic applications in skin pigmentation diseases. MelSC biology and niche factors have been studied mainly in murine experimental models. Human MelSC markers or methods to isolate them are much less well understood. Identification, isolation and culturing of human MelSCs would represent a major step toward new biological therapeutic options for patients with recalcitrant pigmentary disorders or hair graying. By modulating the niche factors for MelSCs, it may one day be possible to control skin pigmentary disorders and prevent or reverse hair graying.

  2. Role of Melanin in Melanocyte Dysregulation of Reactive Oxygen Species

    Directory of Open Access Journals (Sweden)

    Noah C. Jenkins

    2013-01-01

    Full Text Available We have recently reported a potential alternative tumor suppressor function for p16 relating to its capacity to regulate oxidative stress and observed that oxidative dysregulation in p16-depleted cells was most profound in melanocytes, compared to keratinocytes or fibroblasts. Moreover, in the absence of p16 depletion or exogenous oxidative insult, melanocytes exhibited significantly higher basal levels of reactive oxygen species (ROS than these other epidermal cell types. Given the role of oxidative stress in melanoma development, we speculated that this increased susceptibility of melanocytes to oxidative stress (and greater reliance on p16 for suppression of ROS may explain why genetic compromise of p16 is more commonly associated with predisposition to melanoma rather than other cancers. Here we show that the presence of melanin accounts for this differential oxidative stress in normal and p16-depleted melanocytes. Thus the presence of melanin in the skin appears to be a double-edged sword: it protects melanocytes as well as neighboring keratinocytes in the skin through its capacity to absorb UV radiation, but its synthesis in melanocytes results in higher levels of intracellular ROS that may increase melanoma susceptibility.

  3. Identification and characterization of muscarinic receptors potentiating the stimulation of adenylyl cyclase activity by corticotropin-releasing hormone in membranes of rat frontal cortex.

    Science.gov (United States)

    Onali, P; Olianas, M C

    1998-08-01

    In membranes of the rat frontal cortex, acetylcholine (ACh) and other cholinergic agonists were found to potentiate the stimulation of adenylyl cyclase activity elicited by corticotropin-releasing hormone (CRH). Oxotremorine-M, carbachol and methacholine were as effective as ACh, whereas oxotremorine and arecoline were much less effective. The facilitating effect of Ach was potently blocked by the M1 antagonists R-trihexyphenidyl, telenzepine and pirenzepine and by the M3 antagonists hexahydro-sila-difenidol and p-fluorohexahydro-sila-difenidol, whereas the M2 and M4 antagonists himbacine, methoctramine, AF-DX 116 and AQ-RA 741 were less potent. The mamba venom toxin MT-1, which binds with high affinity to M1 receptors, was also a potent blocker. The pharmacological profile of the muscarinic potentiation of CRH receptor activity was markedly different from that displayed by the muscarinic inhibition of forskolin-stimulated adenylyl cyclase, which could be detected in the same membrane preparations. Moreover, the intracerebral injection of pertussis toxin impaired the muscarinic inhibition of cyclic AMP formation and reduced the Ach stimulation of [35S]GTPgammaS binding to membrane G proteins but failed to affect the facilitating effect on CRH receptor activity. The latter response was also insensitive to the phospholipase C inhibitor U-73122, the protein kinase inhibitor staurosporine and to the inhibitors of arachidonic acid metabolism indomethacin and nordihydroguaiaretic acid. These data demonstrate that in the rat frontal cortex, muscarinic receptors of the M1 subtype potentiate CRH transmission by interacting with pertussis toxin-insensitive G proteins.

  4. Growth hormone and prolactin stimulate the expression of rat preadipocyte factor-1/delta-like protein in pancreatic islets

    DEFF Research Database (Denmark)

    Carlsson, C; Tornehave, D; Lindberg, Karen

    1997-01-01

    GH and PRL have been shown to stimulate proliferation and insulin production in islets of Langerhans. To identify genes regulated by GH/PRL in islets, we performed differential screening of a complementary DNA library from neonatal rat islets cultured for 24 h with human GH (hGH). One hGH-induced......GH and PRL have been shown to stimulate proliferation and insulin production in islets of Langerhans. To identify genes regulated by GH/PRL in islets, we performed differential screening of a complementary DNA library from neonatal rat islets cultured for 24 h with human GH (hGH). One h......RNA was up-regulated 3- to 4-fold in neonatal rat islets of Langerhans after 48-h culture with hGH, as found also with bovine GH or ovine PRL. During the development of pancreas from embryonic day 12 (E12) to postnatal day 4, we observed a 2-fold increase in Pref-1 mRNA on E17 and a 5-fold increase at birth...

  5. Parathyroid hormone-related protein stimulates plasma renin activity via its anorexic effects on sodium chloride intake.

    Science.gov (United States)

    Atchison, Douglas K; Westrick, Elizabeth; Szandzik, David L; Gordish, Kevin L; Beierwaltes, William H

    2012-08-15

    Parathyroid hormone-related protein (PTHrP) increases renin release from isolated perfused kidneys and may act as an autacoid regulator of renin secretion, but its effects on renin in vivo are unknown. In vivo, PTHrP causes hypercalcemia and anorexia, which may affect renin. We hypothesized that chronically elevated PTHrP would increase plasma renin activity (PRA) indirectly via its anorexic effects, reducing sodium chloride (NaCl) intake and causing NaCl restriction. We infused male Sprague-Dawley rats with the vehicle (control) or 125 μg PTHrP/day (PTHrP) via subcutaneous osmotic minipumps for 5 days. To replenish NaCl consumption, a third group of PTHrP-infused rats received 0.3% NaCl (PTHrP + NaCl) in their drinking water. PTHrP increased PRA from a median control value of 3.68 to 18.4 ng Ang I·ml(-1)·h(-1) (P anorexic effects, reducing NaCl intake and causing NaCl restriction.

  6. TFAP2 paralogs regulate melanocyte differentiation in parallel with MITF.

    Directory of Open Access Journals (Sweden)

    Hannah E Seberg

    2017-03-01

    Full Text Available Mutations in the gene encoding transcription factor TFAP2A result in pigmentation anomalies in model organisms and premature hair graying in humans. However, the pleiotropic functions of TFAP2A and its redundantly-acting paralogs have made the precise contribution of TFAP2-type activity to melanocyte differentiation unclear. Defining this contribution may help to explain why TFAP2A expression is reduced in advanced-stage melanoma compared to benign nevi. To identify genes with TFAP2A-dependent expression in melanocytes, we profile zebrafish tissue and mouse melanocytes deficient in Tfap2a, and find that expression of a small subset of genes underlying pigmentation phenotypes is TFAP2A-dependent, including Dct, Mc1r, Mlph, and Pmel. We then conduct TFAP2A ChIP-seq in mouse and human melanocytes and find that a much larger subset of pigmentation genes is associated with active regulatory elements bound by TFAP2A. These elements are also frequently bound by MITF, which is considered the "master regulator" of melanocyte development. For example, the promoter of TRPM1 is bound by both TFAP2A and MITF, and we show that the activity of a minimal TRPM1 promoter is lost upon deletion of the TFAP2A binding sites. However, the expression of Trpm1 is not TFAP2A-dependent, implying that additional TFAP2 paralogs function redundantly to drive melanocyte differentiation, which is consistent with previous results from zebrafish. Paralogs Tfap2a and Tfap2b are both expressed in mouse melanocytes, and we show that mouse embryos with Wnt1-Cre-mediated deletion of Tfap2a and Tfap2b in the neural crest almost completely lack melanocytes but retain neural crest-derived sensory ganglia. These results suggest that TFAP2 paralogs, like MITF, are also necessary for induction of the melanocyte lineage. Finally, we observe a genetic interaction between tfap2a and mitfa in zebrafish, but find that artificially elevating expression of tfap2a does not increase levels of

  7. Effects of thyroid hormone on Na sup + -K sup + transport in resting and stimulated rat skeletal muscle

    Energy Technology Data Exchange (ETDEWEB)

    Everts, M.E.; Clausen, T. (Aarhus Univ. (Denmark))

    1988-11-01

    The effects of hypothyroidism and 3,5,3{prime}-triiodothyronine (T{sub 3}) treatment on passive Na{sup +}-K{sup +} fluxes and Na{sup +}-K{sup +} pump concentration were investigated in isolated rat muscle. Within 12 h after a single dose of T{sub 3} (20 {mu}g/100 g body wt), K{sup +} efflux had increased by 21% in soleus and by 20% in extensor digitorum longus muscle. In the presence of ouabain, even larger effects were observed. These changes were associated with a 12% rise in amiloride-suppressible Na{sup +} influx but no significant increase in ({sup 3}H)ouabain binding site concentration. After 3 days of T{sub 3} treatment, the stimulating effect on K{sup +} efflux and Na{sup +} influx in soleus reached a plateau {approximately}80 and 40% above control levels, respectively, whereas the maximum increase in ({sup 3}H)ouabain binding site concentration (103%) was only fully developed after 8 days. Hypothyroidism decreased {sup 86}Rb efflux by 30%. The efflux of K{sup +} and the influx of Na{sup +} per contraction (both {approximately}7 nmol/g wet wt) as well as the net loss of K{sup +} induced by electrical stimulation were unaffected by T{sub 3} treatment. The rise in resting K{sup +} efflux after 12-24 h of T{sub 3} treatment could be partly blocked by dantrolene or trifluoroperazine, indicating that an increase in the cytoplasmic Ca{sup 2+} concentration may contribute to the early rise in K{sup +} efflux. It is concluded that the early rise in the resting passive leaks of Na{sup +} and K{sup +} induced by T{sub 3} is a major driving force for Na{sup +}-K{sup +} pump synthesis.

  8. Mechanisms of hair graying: incomplete melanocyte stem cell maintenance in the niche.

    Science.gov (United States)

    Nishimura, Emi K; Granter, Scott R; Fisher, David E

    2005-02-04

    Hair graying is the most obvious sign of aging in humans, yet its mechanism is largely unknown. Here, we used melanocyte-tagged transgenic mice and aging human hair follicles to demonstrate that hair graying is caused by defective self-maintenance of melanocyte stem cells. This process is accelerated dramatically with Bcl2 deficiency, which causes selective apoptosis of melanocyte stem cells, but not of differentiated melanocytes, within the niche at their entry into the dormant state. Furthermore, physiologic aging of melanocyte stem cells was associated with ectopic pigmentation or differentiation within the niche, a process accelerated by mutation of the melanocyte master transcriptional regulator Mitf.

  9. Zearalenone and alpha-zearalenol inhibit the synthesis and secretion of pig follicle stimulating hormone via the non-classical estrogen membrane receptor GPR30.

    Science.gov (United States)

    He, Jing; Wei, Chao; Li, Yueqin; Liu, Ying; Wang, Yue; Pan, Jirong; Liu, Jiali; Wu, Yingjie; Cui, Sheng

    2018-02-05

    Zearalenone (ZEA) is one of the most popular endocrine-disrupting chemicals and is mainly produced by fungi of the genus Fusarium. The excessive intake of ZEA severely disrupts human and animal fertility by affecting the reproductive axis. However, most studies on the effects of ZEA and its metabolite α-zearalenol (α-ZOL) on reproductive systems have focused on gonads. Few studies have investigated the endocrine-disrupting effects of ZEA and α-ZOL on pituitary gonadotropins, including follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The present study was designed to investigate the effects of ZEA and α-ZOL on the synthesis and secretion of FSH and LH and related mechanisms in female pig pituitary. Our in vivo and in vitro results demonstrated that ZEA significantly inhibited the synthesis and secretion of FSH in the pig pituitary gland, but ZEA and α-ZOL had no effects on LH. Our study also showed that ZEA and α-ZOL decreased FSH synthesis and secretion through non-classical estrogen membrane receptor GPR30, which subsequently induced protein kinase cascades and the phosphorylation of PKC, ERK and p38MAPK signaling pathways in pig pituitary cells. Furthermore, our study showed that the LIM homeodomain transcription factor LHX3 was involved in the mechanisms of ZEA and α-ZOL actions on gonadotropes in the female pig pituitary. These findings elucidate the mechanisms behind the physiological alterations resulting from endocrine-disrupting chemicals and further show that the proposed key molecules of the α-ZOL signaling pathway could be potential pharmacological targets. Copyright © 2017. Published by Elsevier B.V.

  10. Weight Changes in Patients with Differentiated Thyroid Carcinoma during Postoperative Long-Term Follow-up under Thyroid Stimulating Hormone Suppression

    Directory of Open Access Journals (Sweden)

    Seo Young Sohn

    2015-09-01

    Full Text Available BackgroundThere are limited data about whether patients who receive initial treatment for differentiated thyroid cancer (DTC gain or lose weight during long-term follow-up under thyroid stimulating hormone (TSH suppression. This study was aimed to evaluate whether DTC patients under TSH suppression experience long-term weight gain after initial treatment. We also examined the impact of the radioactive iodine ablation therapy (RAIT preparation method on changes of weight, comparing thyroid hormone withdrawal (THW and recombinant human TSH (rhTSH.MethodsWe retrospectively reviewed 700 DTC patients who underwent a total thyroidectomy followed by either RAIT and levothyroxine (T4 replacement or T4 replacement alone. The control group included 350 age-matched patients with benign thyroid nodules followed during same period. Anthropometric data were measured at baseline, 1 to 2 years, and 3 to 4 years after thyroidectomy. Comparisons were made between weight and body mass index (BMI at baseline and follow-up.ResultsSignificant gains in weight and BMI were observed 3 to 4 years after initial treatment for female DTC but not in male patients. These gains among female DTC patients were also significant compared to age-matched control. Women in the THW group gained a significant amount of weight and BMI compared to baseline, while there was no increase in weight or BMI in the rhTSH group. There were no changes in weight and BMI in men according to RAIT preparation methods.ConclusionFemale DTC patients showed significant gains in weight and BMI during long-term follow-up after initial treatment. These changes were seen only in patients who underwent THW for RAIT.

  11. Kinetic study of internalization and degradation of sup 131 I-labeled follicle-stimulating hormone in mouse Sertoli cells and its relevance to other systems

    Energy Technology Data Exchange (ETDEWEB)

    Shimizu, A.; Kawashima, S. (Hayashibara Biochemical Lab., Okayama (Japan))

    1989-08-15

    The behavior of 131I-labeled follicle-stimulating hormone (FSH) after binding to cell-surface receptors in cultured Sertoli cells of C57BL/6NCrj mice was investigated. Sertoli cells cultured in F12/DME were pulse-labeled with 131I-FSH for 10 min at 4 degrees C, followed by cold chase for various periods of time. After the cold chase Sertoli cells were treated with 0.2 M acetate (pH 2.5) to dissociate membrane-bound 131I-FSH (surface radioactivity). The medium containing radioactivity after cold chase was mixed with 20% trichloroacetic acid, centrifuged, and the radioactivity of the supernatant was measured (degraded hormone). The radiolabeled materials associated with each process (surface binding, internalization, and degradation) were concentrated with ultrafiltration and characterized with gel filtration and/or thin layer chromatography. The effects of lysosomotropic agents, NH4Cl and chloroquine, were studied. The cold chase study at 32 degrees C showed that the surface radioactivity was the largest among the three kinds of radioactivities associated with each process immediately after pulse labeling, but the surface radioactivity rapidly decreased, while the internalized radioactivity increased. The cold chase study at 4 degrees C did not show such time-related changes in radioactivities, and a high level of surface radioactivity constantly persisted. The surface and internalized radioactivities were due to 131I-FSH, and the degraded radioactivity was mainly due to (131I)monoiodotyrosine. When Sertoli cells were cultured with lysosomotropic agents, the internalized radioactivity increased, while the degraded radioactivity decreased. Based on these observations, a kinetic model was proposed and the relationships among the surface, internalized, and degraded radioactivities and cold chase time were calculated algebraically.

  12. Kinetic study of internalization and degradation of 131I-labeled follicle-stimulating hormone in mouse Sertoli cells and its relevance to other systems

    International Nuclear Information System (INIS)

    Shimizu, A.; Kawashima, S.

    1989-01-01

    The behavior of 131I-labeled follicle-stimulating hormone (FSH) after binding to cell-surface receptors in cultured Sertoli cells of C57BL/6NCrj mice was investigated. Sertoli cells cultured in F12/DME were pulse-labeled with 131I-FSH for 10 min at 4 degrees C, followed by cold chase for various periods of time. After the cold chase Sertoli cells were treated with 0.2 M acetate (pH 2.5) to dissociate membrane-bound 131I-FSH (surface radioactivity). The medium containing radioactivity after cold chase was mixed with 20% trichloroacetic acid, centrifuged, and the radioactivity of the supernatant was measured (degraded hormone). The radiolabeled materials associated with each process (surface binding, internalization, and degradation) were concentrated with ultrafiltration and characterized with gel filtration and/or thin layer chromatography. The effects of lysosomotropic agents, NH4Cl and chloroquine, were studied. The cold chase study at 32 degrees C showed that the surface radioactivity was the largest among the three kinds of radioactivities associated with each process immediately after pulse labeling, but the surface radioactivity rapidly decreased, while the internalized radioactivity increased. The cold chase study at 4 degrees C did not show such time-related changes in radioactivities, and a high level of surface radioactivity constantly persisted. The surface and internalized radioactivities were due to 131I-FSH, and the degraded radioactivity was mainly due to [131I]monoiodotyrosine. When Sertoli cells were cultured with lysosomotropic agents, the internalized radioactivity increased, while the degraded radioactivity decreased. Based on these observations, a kinetic model was proposed and the relationships among the surface, internalized, and degraded radioactivities and cold chase time were calculated algebraically

  13. Gonadotropin inhibitory hormone and RF9 stimulate hypothalamic-pituitary-adrenal axis in adult male rhesus monkeys.

    Science.gov (United States)

    Ullah, Rahim; Batool, Aalia; Wazir, Madiha; Naz, Rabia; Rahman, Tanzil Ur; Wahab, Fazal; Shahab, Muhammad; Fu, Junfen

    2017-12-01

    Stress activates gonadotropin inhibitory hormone (GnIH), hypothalamic-pituitary-adrenal axis (HPA-axis) and represses hypothalamic-pituitary-gonadal axis (HPG-axis) but RF9 administration relieves stress-induced repression of the HPG-axis. Importantly, it was not known whether GnIH signaling and RF9 synthetic peptide modulate the HPA axis. To assess this, mammalian orthologs of GnIH (RFRP-1 and RFRP-3) and RF9 were administered to intact adult male rhesus monkeys. RFRP-1 (125μg/animal), RFRP-3 (250μg/animal) and RF9 (0.1mg/kg BW) were intravenously (iv) injected into normal fed (n=4) monkeys. Additionally, a single bolus iv injection of RF9 (0.1mg/kg BW) was also administered to 48h fasted monkeys (n=4) to check the effects of RF9 signaling on an activated HPA-axis. Serial blood samples were collected, centrifuged and the obtained plasma was used for the analysis of cortisol by specific enzyme immunoassay. RFRP-1 treatment significantly increased cortisol levels while RFRP-3 increased the plasma cortisol, but the effect was non-significant. RF9 treatment significantly increased cortisol levels in normal fed animals. In contrast, RF9 injection did not significantly alter circulating cortisol in fasted monkeys. In conclusion, our results suggest stimulatory action of RFRPs and RF9 on the HPA axis in the adult male monkeys. However, the mechanism and site of action of RFRP-1 and RF9 along the HPA-axis is still unknown. Therefore, further studies are needed to decipher the mechanism and site of action of RFRPs and RF9 on the HPA axis in primates. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Generation of a double binary transgenic zebrafish model to study myeloid gene regulation in response to oncogene activation in melanocytes.

    Science.gov (United States)

    Kenyon, Amy; Gavriouchkina, Daria; Zorman, Jernej; Chong-Morrison, Vanessa; Napolitani, Giorgio; Cerundolo, Vincenzo; Sauka-Spengler, Tatjana

    2018-04-06

    A complex network of inflammatory genes is closely linked to somatic cell transformation and malignant disease. Immune cells and their associated molecules are responsible for detecting and eliminating cancer cells as they establish themselves as the precursors of a tumour. By the time a patient has a detectable solid tumour, cancer cells have escaped the initial immune response mechanisms. Here, we describe the development of a double binary zebrafish model that enables regulatory programming of the myeloid cells as they respond to oncogene-activated melanocytes to be explored, focussing on the initial phase when cells become the precursors of cancer. A hormone-inducible binary system allows for temporal control of expression of different Ras oncogenes ( NRas Q61K , HRas G12V and KRas G12V ) in melanocytes, leading to proliferation and changes in morphology of the melanocytes. This model was coupled to binary cell-specific biotagging models allowing in vivo biotinylation and subsequent isolation of macrophage or neutrophil nuclei for regulatory profiling of their active transcriptomes. Nuclear transcriptional profiling of neutrophils, performed as they respond to the earliest precursors of melanoma in vivo , revealed an intricate landscape of regulatory factors that may promote progression to melanoma, including Serpinb1l4, Fgf1, Fgf6, Cathepsin H, Galectin 1 and Galectin 3. The model presented here provides a powerful platform to study the myeloid response to the earliest precursors of melanoma. © 2018. Published by The Company of Biologists Ltd.

  15. The role of the Hippo pathway in melanocytes and melanoma

    Directory of Open Access Journals (Sweden)

    Bruce Charles Baguley

    2013-05-01

    Full Text Available The Hippo signalling pathway comprises a series of cytoplasmic tumour suppressor proteins including Merlin and the Lats1/2 and MST1/2 kinases, and is thought to play a critical role in determining the sizes of organs and tissues. The Hippo pathway is regulated upstream by extracellular mechanosensory signalling arising from cell shape and polarity, as well as by a variety of extracellular signalling molecules. When active, the pathway maintains the transcriptional activators YAP and TAZ in phosphorylated forms in the cytoplasm, preventing cell proliferation. When the Hippo pathway is inactivated, YAP and TAZ are translocated to the nucleus and induce the expression of a variety of proteins concerned with entry into the cell division cycle, such as cyclin D1 and Fox M1, as well as the inhibition of apoptosis. The failure of the Hippo pathway has been implicated in the development of many different types of cancer but there is limited information available as to its involvement in melanoma. We hypothesise here firstly that the Hippo pathway is involved in maintaining density of cutaneous melanocytes on the basement membrane at the junction of the epidermis and the dermis, and secondly, that its function is disturbed in melanoma. We have analysed a series of 23 low passage human melanoma lines as well as in cultures of normal melanocytes, and find that melanocytes, as well as all melanoma cell lines examined express TAZ. Melanocytes and most melanoma lines also express YAP. E-cadherin, an upstream regulator of the Hippo pathway, and Axl, a receptor tyrosine kinase regulated by the Hippo pathway, are expressed in melanocytes and in several melanoma cell lines. These observations, together with published evidence for the presence of Merlin, Lats1/2 and MST1/2 in melanocytes and melanoma cells, support the hypothesis that the Hippo pathway is an important component of melanocyte and melanoma behaviour.

  16. The follicle-stimulating hormone (FSH) and luteinizing hormone (LH) response to a gonadotropin-releasing hormone analogue test in healthy prepubertal girls aged 10 months to 6 years

    DEFF Research Database (Denmark)

    Vestergaard, Esben T; Schjørring, Mia Elbek; Kamperis, Konstantinos

    2017-01-01

    of age is challenging, as no reference interval exists for this age group. The objective is to determine the normal FSH and LH response to a GnRH test in healthy prepubertal girls below 6 years of age. DESIGN AND METHODS: A standardized GnRH test, baseline reproductive hormones, clinical evaluation...... and bone age were determined in all participants. Forty-eight healthy normal-weight girls aged 3.5 ± 0.2 years (range: 0.8-5.9 years) were included. Serum concentrations of LH and FSH were measured before and 30 min after the gonadorelin injection. RESULTS: The 30-min LH responses (mean ± 2 s.d.) were 5.......2 ± 4.0 and 2.9 ± 2.5 IU/L and the FSH responses were 23.3 ± 16.2 and 14.5 ± 10.3 IU/L in girls aged 0.8-3.0 years and 3.0-5.9 years respectively. This corresponds to upper cut-off limits for LH of 9.2 IU/L (FSH ratio was 0.23 ± 0.19 (range 0...

  17. Prediction of Dermoscopy Patterns for Recognition of both Melanocytic and Non-Melanocytic Skin Lesions

    Directory of Open Access Journals (Sweden)

    Qaisar Abbas

    2016-06-01

    Full Text Available A differentiation between all types of melanocytic and non-melanocytic skin lesions (MnM–SK is a challenging task for both computer-aided diagnosis (CAD and dermatologists due to the complex structure of patterns. The dermatologists are widely using pattern analysis as a first step with clinical attributes to recognize all categories of pigmented skin lesions (PSLs. To increase the diagnostic accuracy of CAD systems, a new pattern classification algorithm is proposed to predict skin lesions patterns by integrating the majority voting (MV–SVM scheme with multi-class support vector machine (SVM. The optimal color and texture features are also extracted from each region-of-interest (ROI dermoscopy image and then these normalized features are fed into an MV–SVM classifier to recognize seven classes. The overall system is evaluated using a dataset of 350 dermoscopy images (50 ROIs per class. On average, the sensitivity of 94%, specificity of 84%, 93% of accuracy and area under the receiver operating curve (AUC of 0.94 are achieved by the proposed MnM–SK system compared to state-of-the-art methods. The obtained result indicates that the MnM–SK system is successful for obtaining the high level of diagnostic accuracy. Thus, it can be used as an alternative pattern classification system to differentiate among all types of pigmented skin lesions (PSLs.

  18. MULTIPLE STABLE PERIODIC SOLUTIONS IN A MODEL FOR THE HORMONAL REGULATION OF THE MENSTRUAL CYCLE

    Science.gov (United States)

    ABSTRACTThe pituitary hormones, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and the ovarian hormones, estradiol (E2), progesterone (P4), and inhibin (Ih), are five hormones important for the regulation and maintenance of the human menstrual cycle. The...

  19. Relationship Between Genotype Variants Follicle-stimulating Hormone Receptor Gene Polymorphisms (FSHR) and Morphology of Oocytes Prior to ICSI Procedures

    Science.gov (United States)

    Gashi, Zafer; Elezaj, Shkelzen; Zeqiraj, Afrim; Grabanica, Driton; Shabani, Isak; Gruda, Bujar; Gashi, Fitore

    2016-01-01

    Introduction: This study investigated association of Asn680Ser FSHR polymorphism with the ovarian response in 104 women of Albanian ethnic population enrolled in ICSI program. The reason of infertility in all cases has been identified as male factor. Methods: Analysis of the Asn680Ser polymorphism was performed using TaqMan® SNP Genotyping Assay. Clinical and endocrinologic parameters were analyzed based on the genotype, age, BMI, oocyte yield, number of transferred embryos and pregnancy rate. Results: The frequencies of the Asn680 Ser genotype variants were as follows: Asn/Asn 22.1%, Asn/Ser 47.1%, and Ser/Ser 30.8%, respectively. BMI was significantly higher in the Ser/Ser group as compared to those from the Asn/Ser or the Asn/Asn group (p= 0.0010). The genotype variants Ser/Ser indicates a higher rate of oocyte retrieval (25.9%) in the immature form, metaphase I (MI) as opposed to the other two groups (Asn/Asn 23.7 % vs. Asn/Ser 21.9%), which was statistically significant (p = 0.3020). Conclusions: FSH receptor polymorphism is associated with different ovarian response to controlled ovarian stimulation (COS), but is not an important factor in increasing the degree of pregnancy. Polymorphisms of the FSH receptor is associated with normal morphology and genetic maturation (metaphase II) oocytes in dependence of genotypic variation polymorphisms. PMID:27994298

  20. G/sub o/ protein of fat cells: role in hormonal regulation of agonist-stimulated phosphatidyl inositol breakdown

    International Nuclear Information System (INIS)

    Rapiejko, P.J.; Northup, J.K.; Malbon, C.C.

    1986-01-01

    Incubating rat fat cell membranes in the presence of [ 32 P]NAD + and pertussis toxin (PT) results in the ADP-ribosylation of two peptides (M/sub r/ = 41,000 and 40,000). The 41,000-M/sub r/ peptide is the inhibitory G-protein of adenylate cyclase (G/sub i/). The 40,000-M/sub r/ peptide radiolabeled in the presence of [ 32 P]NAD + and PT has been purified from rabbit heart and bovine brain, but has not been identified uniformly in membranes of fat cells. Two rabbit polyclonal antisera raised against the alpha-subunit of bovine brain G/sub o/ were used to probe the nature of the 40,000-M/sub r/ peptide in rat fat cell membranes that had been separated by gel electrophoresis in the presence of sodium dodecyl sulfate and transferred electrophoretically to nitrocellulose. Both antisera specific for the alpha-subunit of G/sub o/ recognized the M/sub r/ = 40,000 peptide of fat cells that is ADP-ribosylated in the presence of PT. PT treatment of rat fat cells blocks epinephrine-stimulated inositol 1,4,5 trisphosphate (IP 3 ) generation. The inhibition of IP 3 generation by PT suggests a role for either G/sub i/ or G/sub o/ in receptor-mediated phosphatidyl inositol breakdown in the rat fat cell

  1. Does Melanoma Begin in a Melanocyte Stem Cell?

    Directory of Open Access Journals (Sweden)

    James D. Hoerter

    2012-01-01

    Full Text Available What is the cellular origin of melanoma? What role do melanocyte stem cells (MSC and other melanocyte precursors play in the development of melanoma? Are MSCs and other latent melanocyte precursors more susceptible to solar radiation? These and many other questions can be very effectively addressed using the zebrafish model. Zebrafish have a robust regenerative capability, permitting the study of how MSCs are regulated and recruited at specific times and places to generate the pigment pattern following fin amputation or melanocyte ablation. They can be used to determine the effects of environmental radiation on the proliferation, survival, repair, and differentiation of MSCs. Our lab is using zebrafish to investigate how UVA- (320–400 nm and UVB- (290–320 nm induced damage to MSCs may contribute to the development of melanoma. A review is given of MSCs in zebrafish as well as experimental techniques and drugs for manipulating MSC populations. These techniques can be used to design experiments to help answer many questions regarding the role of MSCs or melanocyte precursors in the formation of melanoma stem cells and tumors following exposure to UVA/UVB radiation.

  2. The effects of simvastatin on the serum concentrations of thyroid stimulating hormone and free thyroxine in hypothyroid patients treated with levothyroxine.

    Science.gov (United States)

    Abbasinazari, Mohammad; Nakhjavani, Manouchehr; Gogani, Sima

    2011-06-01

    Statins, such as simvastatin, are the drugs of choice for the treatment of hypercholesterolemia. On the other hand hypercholesterolmia can occur in hypothyroid patients, who receive levothyroxine. There are few clinical case reports in regards to drug interaction between levothyroxine and lovastatin or simvastatin, indicating decreased levothyroxine effects. This study aimed at determining possible interaction between simvastatin and levothyroxine in hypothyroid patients by assessing serum levels of thyroid stimulating hormone (TSH) and free thyroxine (FT4), the two important laboratory indices for levothyroxine therapy. In a cross sectional study, 41 eligible hypothyroid patients receiving levothyroxine (50-150 µg/d) were selected. Blood samples were taken before and after three months of simultaneous treatment with simvastatin (20 mg/d) and levothyroxine to determine the serum levels of TSH and FT4. There was no significant difference between the serum levels of TSH (P=0.77) or FT4 (P=0.76) before and after three months of simultaneous treatment. Also, there was no aggravation or initiation of any sign or symptom of hypothyroidism in the patients during the study period. Considering that FT(4) and TSH are the most reliable indicators for the levothyroxine treatment, the findings of the present study suggest that there may not be any significant interaction between simvastatin and levothyroxine.

  3. Effect of sequential medium with fibroblast growth factor-10 and follicle stimulating hormone on in vitro development of goat preantral follicles.

    Science.gov (United States)

    Almeida, A P; Magalhães-Padilha, D M; Araújo, V R; Costa, S L; Chaves, R N; Lopes, C A P; Donato, M A M; Peixoto, C A; Campello, C C; Junior, J Buratini; Figueiredo, J R

    2015-01-01

    A sequential medium with fibroblast growth factor-10 (FGF-10) and follicle stimulating hormone (FSH) was evaluated on the survival, ultrastructure, activation and growth rate of caprine preantral follicles submitted to long-term culture, aiming to establish an ideal in vitro culture system. Ovarian fragments were cultured for 16 days in α-MEM(+) alone or supplemented with FGF-10 and/or FSH added sequentially on different days of culture. Ovarian fragments were cultured during the first (days 0-8) and second (days 8-16) halves of the culture period, generating 10 treatments: α-MEM(+)/α-MEM(+) (cultured control), FSH/FSH, FSH/FGF-10, FSH/FSH+FGF-10, FGF-10/FGF-10, FGF-10/FSH, FGF-10/FSH+FGF-10, FSH+FGF-10/FSH+FGF-10, FSH+FGF-10/FSH and FSH+FGF-10/FGF-10. Follicle morphology, viability and ultrastructure were analyzed. The FSH/FGF-10 treatment showed a higher (Pmedium with FSH followed by FGF-10 (FSH/FGF-10 and FSH/FSH) maintains follicular viability and ultrastructure and promotes transition from the primordial to primary stage (activation) and growth in goat preantral follicles cultured in vitro. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Review of the safety, efficacy, costs and patient acceptability of recombinant follicle-stimulating hormone for injection in assisting ovulation induction in infertile women

    Directory of Open Access Journals (Sweden)

    Marleen Nahuis

    2009-11-01

    Full Text Available Marleen Nahuis1,2,3, Fulco van der Veen1, Jur Oosterhuis2, Ben Willem Mol1, Peter Hompes3, Madelon van Wely11Center for Reproductive Medicine, Department of Obstetrics and Gynaecology (H4-205, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; 2Department of Obstetrics and Gynaecology, Medisch Spectrum Twente, Enschede, The Netherlands; 3Department of Obstetrics and Gynaecology, Free Medical University, Amsterdam, The NetherlandsAbstract: Anovulation is a common cause of female subfertility. Treatment of anovulation is aimed at induction of ovulation. In women with clomiphene-citrate resistant WHO group II anovulation, one of the treatment options is ovulation induction with exogenous follicle-stimulating hormone (FSH or follitropin. FSH is derived from urine or is produced as recombinant FSH. Two forms of recombinant FSH are available – follitropin alpha and follitropin beta. To evaluate the efficacy, safety, costs and acceptability of recombinant FSH, we performed a review to compare recombinant FSH with urinary-derived FSH products. Follitropin alpha, beta and urinary FSH products appeared to be equally effective in terms of pregnancy rates. Patient safety was also found to be comparable, as the incidence of side effects including multiple pregnancies was similar for all FSH products. In practice follitropin alpha and beta may be more convenient to use due to the ease of self-administration, but they are also more expensive than the urinary products.Keywords: follitropin apha, follitropin beta, urinary gonadotropins, polycystic ovary syndrome

  5. An innovative sample-to-answer polymer lab-on-a-chip with on-chip reservoirs for the POCT of thyroid stimulating hormone (TSH).

    Science.gov (United States)

    Jung, Wooseok; Han, Jungyoup; Kai, Junhai; Lim, Ji-Youn; Sul, Donggeun; Ahn, Chong H

    2013-12-07

    A new sample-to-answer polymer lab-on-a-chip, which can perform immunoassay with minimum user intervention through on-chip reservoirs for reagents and single-channel assay system, has been designed, developed and successfully characterized as a point-of-care testing (POCT) cartridge for the detection of thyroid stimulating hormone (TSH). Test results were obtained within 30 minutes after a sample was dropped into the POCT cartridge. The analyzed results of TSH showed a linear range of up to 55 μIU mL(-1) with the limit of detection (LOD) of 1.9 μIU mL(-1) at the signal-to-noise ratio (SNR) of 3. The reagents stored in the on-chip reservoirs maintained more than 97% of their initial volume for 120 days of storage time while the detection antibody retained its activity above 98% for 120 days. The sample-to-answer polymer lab-on-a-chip developed in this work using the mass-producible and low-cost polymer is well suited for the point-of-care testing of rapid in vitro diagnostics (IVD) of TSH.

  6. Molecular cytogenetics of cutaneous melanocytic lesions - diagnostic, prognostic and therapeutic aspects

    NARCIS (Netherlands)

    Blokx, Willeke Am M.; van Dijk, Marcory C. R. F.; Ruiter, Dirk J.

    This review intends to update current knowledge regarding molecular cytogenetics in melanocytic tumours with a focus on cutaneous melanocytic lesions. Advantages and limitations of diverse, already established methods, such as (fluorescence) in situ hybridization and mutation analysis, to detect

  7. Molecular cytogenetics of cutaneous melanocytic lesions - diagnostic, prognostic and therapeutic aspects.

    NARCIS (Netherlands)

    Blokx, W.A.M.; Dijk, M.C.R.F. van; Ruiter, D.J.

    2010-01-01

    This review intends to update current knowledge regarding molecular cytogenetics in melanocytic tumours with a focus on cutaneous melanocytic lesions. Advantages and limitations of diverse, already established methods, such as (fluorescence) in situ hybridization and mutation analysis, to detect

  8. Immortalization of human melanocytes does not alter the de novo properties of nitric oxide to induce cell detachment from extracellular matrix components via cGMP.

    Science.gov (United States)

    Ivanova, Krassimira; Lambers, Britta; van den Wijngaard, Rene; Le Poole, I Caroline; Grigorieva, Olga; Gerzer, Rupert; Das, Pranab K

    2008-01-01

    Nitric oxide (NO) is an important mediator in many (patho)physiological processes including inflammation and skin cancer. A key transducer in NO signaling is the soluble guanylyl cyclase (sGC) that catalyzes the formation of guanosine 3',5'-cyclic monophosphate (cGMP). The basic mechanism of NO-cGMP signaling in melanocytic cells is, however, not well elucidated. A setback for such studies is the limited availability of patient-derived melanocytes. Here, we report that immortalized human normal and vitiliginous cell lines generated via cell transfection with human papilloma virus 16 genes E6 and E7 express NO synthase and guanylyl cyclase isoforms and the multidrug resistance-associated proteins 4 and 5 as selective cGMP exporters. Donors of NO (e.g., the NONOate (Z)-1-[N-(3-ammoniopropyl)-N-(n-propyl)amino]diazen-1-ium-1,2-diolate (PAPA-NO) and reactive nitrogen oxygen species (RNOS) like 3-morpholino-sydnonimine (SIN-1) as a donor of peroxynitrite as well as YC-1 as a NO-independent sGC stimulator increased intracellular cGMP levels in immortalized melanocytes (up to eightfold over controls), indicating the expression of functional sGC in these cells. PAPA-NO and SIN-1 also reduced the attachment of immortalized melanocytes to extracellular matrix (ECM) components like fibronectin which was dependent on cellular melanin content and cGMP. Such effects on melanoma cells were positively related to metastatic potential and were cGMP independent. Intriguingly, nonpigmented metastatic melanoma cells were more sensitive to exogenous sources of RNOS than of NO. Thus, immortalized melanocytes can be used as a tool for further research on differences in cell signaling between the different melanocytic lineages in particular towards impairment of cell-ECM adhesion by NO or RNOS, which may be important in metastasis and vitiligo pathogenesis.

  9. The epidermal melanocyte system in individuals of Scandinavian origin, determined by DOPA-staining and TEM

    DEFF Research Database (Denmark)

    Drzewiecki, K T; Piltz-Drzewiecka, J

    1979-01-01

    The quantitative evaluation of DOPA-positive epidermal melanocytes in 16 patients of Scandinavian origin showed both individual and regional differences in the melanocyte count. Our data is in agreement with other published studies. The distribution in the number of melanocytes varies significant...... concerning the presence of the epidermal melanin unit....

  10. The epidermal melanocyte system in individuals of Scandinavian origin, determined by DOPA-staining and TEM

    DEFF Research Database (Denmark)

    Drzewiecki, K T; Piltz-Drzewiecka, J

    1979-01-01

    The quantitative evaluation of DOPA-positive epidermal melanocytes in 16 patients of Scandinavian origin showed both individual and regional differences in the melanocyte count. Our data is in agreement with other published studies. The distribution in the number of melanocytes varies significantly...

  11. Carriers of aVEGFAenhancer polymorphism selectively binding CHOP/DDIT3 are predisposed to increased circulating levels of thyroid-stimulating hormone.

    Science.gov (United States)

    Ahluwalia, Tarunveer Singh; Troelsen, Jesper Thorvald; Balslev-Harder, Marie; Bork-Jensen, Jette; Thuesen, Betina Heinsbæk; Cerqueira, Charlotte; Linneberg, Allan; Grarup, Niels; Pedersen, Oluf; Hansen, Torben; Dalgaard, Louise Torp

    2017-03-01

    Levels of serum thyroid-stimulating hormone (TSH) indicate thyroid function, because thyroid hormone negatively controls TSH release. Genetic variants in the vascular endothelial growth factor A ( VEGFA ) gene are associated with TSH levels. The aim of this study was to characterise the association of VEGFA variants with TSH in a Danish cohort and to identify and characterise functional variants. We performed an association study of the VEGFA locus for circulating TSH levels in 8445 Danish individuals. Lead variants were tested for allele-specific effects in vitro using luciferase reporter and gel-shift assays. Four SNPs in VEGFA were associated with circulating TSH (rs9472138, rs881858, rs943080 and rs4711751). For rs881858, the presence of each G-allele was associated with a corresponding decrease in TSH levels of 2.3% (p=8.4×10 -9 ) and an increase in circulating free T4 levels (p=0.0014). The SNP rs881858 is located in a binding site for CHOP (C/EBP homology protein) and c/EBPβ (ccaat enhancer binding protein β). Reporter-gene analysis showed increased basal enhancer activity of the rs881858 A-allele versus the G-allele (34.5±9.9% (average±SEM), p=0.0012), while co-expression of CHOP effectively suppressed the rs881858 A-allele activity. The A-allele showed stronger binding to CHOP in gel-shift assays. VEGF is an important angiogenic signal required for tissue expansion. We show that VEGFA variation giving allele-specific response to transcription factors with overlapping binding sites associate closely with circulating TSH levels. Because CHOP is induced by several types of intracellular stress, this indicates that cellular stress could be involved in the normal or pathophysiological response of the thyroid to TSH. NCT00289237, NCT00316667; Results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  12. Effectiveness of a recombinant human follicle stimulating hormone on the ovarian follicles, peripheral progesterone, estradiol-17β, and pregnancy rate of dairy cows

    Directory of Open Access Journals (Sweden)

    Mohamed Ali

    2016-07-01

    Full Text Available Aims: This study aimed at elucidating the effects of recombinant human follicle stimulating hormone (r-hFSH on the ovarian follicular dynamics, progesterone, estradiol-17β profiles, and pregnancy of dairy cows. Materials and Methods: Three groups (G, n=5 cows of multiparous dairy cows were used. G1 (C control cows were given controlled internal drug release (CIDR and prostaglandin F2α; G2 (L cows were given low dose (525 IU and G3 (H cows were given high dose (1800 IU of r-hFSH on twice daily basis at the last 3 days before CIDR removal. All cows were ultrasonically scanned for follicular growth and dynamics, and blood samples were collected every other day for two consecutive estrus cycles for the determination of estradiol-17β and progesterone. Results: Estrus was observed in all C and L but not in H cows. Dominant follicle was bigger in L compared to C and H cows. Dominant follicle in C (16.00±2.5 mm and L cows (17.40±2.3 mm disappeared at 72 h after CIDR removal. However, in H cows, no ovulation has occurred during 7 days post-CIDR removal. Progesterone was not different (p>0.10 among groups, whereas estradiol-17β revealed significant (p<0.01 reduction in H (15.96±2.5 pg/ml cows compared to C (112.26±26.1 pg/ml and L (97.49±15.9 pg/ml cows. Pregnancy rate was higher in L cows (60% compared with C cows (20%. However, H cows were not artificially inseminated due to non-ovulation. Only a cow of C group has calved one calf, however, 2 of the L cows gave birth of twins and a cow gave single calf. Conclusion: Administration of a low dose (525 IU of r-hFSH resulted in an optimal size of dominant follicle, normal values of progesterone and estradiol-17β, and 40% twinning rate, howeverusing 1800 IU of r-hFSH, have adverse effects on ovarian follicular dynamics and hormonal profiles with non-pregnancy of dairy cows raised under hot climate.

  13. Dose-Exposure Proportionality of a Novel Recombinant Follicle-Stimulating Hormone (rFSH), FE 999049, Derived from a Human Cell Line, with Comparison Between Caucasian and Japanese Women After Subcutaneous Administration

    OpenAIRE

    Olsson, H?kan; Sandstr?m, Rikard; Bagger, Yu

    2015-01-01

    Background and Objectives FE 999049 is a novel recombinant follicle-stimulating hormone (rFSH) preparation expressed by a human cell line (PER.C6?), in contrast to existing rFSH preparations expressed by Chinese hamster ovary (CHO) cell lines. Since the individual dose of rFSH may be altered depending on the response in women undergoing assisted reproductive technologies, knowledge on the dose-exposure linearity and proportionality is important. The purpose of these studies was to investigate...

  14. Light stimulation of iris tyrosinase in vivo

    International Nuclear Information System (INIS)

    Dryja, T.P.; Kimball, G.P.; Albert, D.M.

    1980-01-01

    This paper presents evidence that light stimulates tyrosinase activity in iris melanocytes in rabbits. Levels of iris tyrosinase were found to be greater in eyes of rabbits exposed to light for 6 weeks than in eyes of rabbits maintained in darkness. Despite increasing tyrosinase levels, exposure to light produced no clinically observable change in iris color

  15. Individualized recombinant human follicle-stimulating hormone dosing using the CONSORT calculator in assisted reproductive technology: a large, multicenter, observational study of routine clinical practice.

    Science.gov (United States)

    Naether, Olaf Gj; Tandler-Schneider, Andreas; Bilger, Wilma

    2015-01-01

    This postmarketing surveillance survey was conducted to investigate the utility of the CONsistency in r-FSH Starting dOses for individualized tReatmenT (CONSORT) calculator for individualizing recombinant human follicle-stimulating hormone (r-hFSH) starting doses for controlled ovarian stimulation (COS) in routine clinical practice. This was a 3-year, open-label, observational study evaluating data from women undergoing COS for assisted reproductive technology at 31 German fertility centers. Physicians stated their recommended r-hFSH starting dose, then generated a CONSORT-recommended r-hFSH starting dose. Physicians could prescribe any r-hFSH starting dose. The primary objective was to compare the r-hFSH starting dose recommended by the physician with the CONSORT-calculated dose and that prescribed. Statistical analyses were conducted post hoc. Data were collected from 2,579 patients; the mean (standard deviation [SD]) age was 30.5 (2.93) years (range: 19-40 years). The mean (SD) CONSORT-calculated r-hFSH starting dose was significantly lower than the physician-recommended dose (134.5 [38.0] IU versus 164.6 [47.1] IU; PCONSORT-calculated doses were prescribed for 27.3% (number [n] =677) of patients, and non-CONSORT-calculated doses prescribed for 72.7% (n=1,800). The mean (SD) number of oocytes retrieved per patient was 10.6 (6.15) and 11.4 (6.66) in the CONSORT and non-CONSORT groups, respectively; the mean (SD) number of embryos transferred per patient was 1.98 (0.41) and 2.03 (0.45), respectively. Clinical pregnancy rates per COS cycle were 38.8% (CONSORT) and 34.8% (non-CONSORT) (P=0.142); clinical pregnancy rates per embryos transferred were 45.0% and 39.5%, respectively (P=0.049). Miscarriage occurred in 14.8% of all clinical pregnancies ( 12.5%; non- 15.3%). The rate of grade 3 ovarian hyperstimulation syndrome (OHSS) was 0.3% (n=2) in the CONSORT group and 0.6% (n=11) in the non-CONSORT group. OHSS led to hospitalization in 0.81% (n=21) of cases (CONSORT

  16. Autocrine/Paracrine Human Growth Hormone-stimulated MicroRNA 96-182-183 Cluster Promotes Epithelial-Mesenchymal Transition and Invasion in Breast Cancer*

    Science.gov (United States)

    Zhang, Weijie; Qian, Pengxu; Zhang, Xiao; Zhang, Min; Wang, Hong; Wu, Mingming; Kong, Xiangjun; Tan, Sheng; Ding, Keshuo; Perry, Jo K.; Wu, Zhengsheng; Cao, Yuan; Lobie, Peter E.; Zhu, Tao

    2015-01-01

    Human growth hormone (hGH) plays critical roles in pubertal mammary gland growth, development, and sexual maturation. Accumulated studies have reported that autocrine/paracrine hGH is an orthotopically expressed oncoprotein that promotes normal mammary epithelial cell oncogenic transformation. Autocrine/paracrine hGH has also been reported to promote mammary epithelial cell epithelial-mesenchymal transition (EMT) and invasion. However, the underlying mechanism remains largely obscure. MicroRNAs (miRNAs) are reported to be involved in regulation of multiple cellular functions of cancer. To determine whether autocrine/paracrine hGH promotes EMT and invasion through modulation of miRNA expression, we performed microarray profiling using MCF-7 cells stably expressing wild type or a translation-deficient hGH gene and identified miR-96-182-183 as an autocrine/paracrine hGH-regulated miRNA cluster. Forced expression of miR-96-182-183 conferred on epithelioid MCF-7 cells a mesenchymal phenotype and promoted invasive behavior in vitro and dissemination in vivo. Moreover, we observed that miR-96-182-183 promoted EMT and invasion by directly and simultaneously suppressing BRMS1L (breast cancer metastasis suppressor 1-like) gene expression. miR-96 and miR-182 also targeted GHR, providing a potential negative feedback loop in the hGH-GHR signaling pathway. We further demonstrated that autocrine/paracrine hGH stimulated miR-96-182-183 expression and facilitated EMT and invasion via STAT3 and STAT5 signaling. Consistent with elevated expression of autocrine/paracrine hGH in metastatic breast cancer tissue, miR-96-182-183 expression was also remarkably enhanced. Hence, we delineate the roles of the miRNA-96-182-183 cluster and elucidate a novel hGH-GHR-STAT3/STAT5-miR-96-182-183-BRMS1L-ZEB1/E47-EMT/invasion axis, which provides further understanding of the mechanism of autocrine/paracrine hGH-stimulated EMT and invasion in breast cancer. PMID:25873390

  17. Association between a serum thyroid-stimulating hormone concentration within the normal range and indices of obesity in Japanese men and women.

    Science.gov (United States)

    Sakurai, Masaru; Nakamura, Koshi; Miura, Katsuyuki; Yoshita, Katsushi; Takamura, Toshinari; Nagasawa, Shin-ya; Morikawa, Yuko; Ishizaki, Masao; Kido, Teruhiko; Naruse, Yuchi; Nakashima, Motoko; Nogawa, Kazuhiro; Suwazono, Yasushi; Nakagawa, Hideaki

    2014-01-01

    This cross-sectional study investigated the associations between the serum thyroid-stimulating hormone (TSH) concentration and indices of obesity in middle-aged Japanese men and women. The participants were 2,037 employees (1,044 men and 993 women; age, 36-55 yr) of a metal products factory in Japan. Clinical examinations were conducted in 2009. We obtained a medical history and anthropometric measurements (body weight, body mass index [BMI] and waist circumference) and measured the serum TSH concentrations. The anthropometric indices were compared across serum TSH quartiles. The associations were evaluated separately according to the smoking status in men. The mean body weight (kg), BMI (kg/m(2)) and waist circumference (cm) were 69.2, 23.7 and 83.2 in men and 55.3, 22.3 and 74.3 in women, respectively. Men with a higher TSH concentration had higher body weight and BMI values (p for trend=0.016 and 0.019, respectively), and these significant associations were observed even after adjusting for age, smoking status and other potential confounders. The TSH level was not associated with waist circumference. We found a significant interaction between the TSH level and the smoking status on body weight (p for interaction=0.013) and a significant association between the TSH level and body weight in nonsmokers, but not in current smokers. No significant associations were observed between the TSH level and the anthropometric indices in women. Significant positive associations between the serum TSH concentration, body weight and BMI were detected in men only, and an interaction with the smoking status was observed for this association.

  18. In vitro fertilisation with recombinant follicle stimulating hormone requires less IU usage compared with highly purified human menopausal gonadotrophin: results from a European retrospective observational chart review

    Directory of Open Access Journals (Sweden)

    Blackmore Stuart

    2010-11-01

    Full Text Available Abstract Background Previous studies have reported conflicting results for the comparative doses of recombinant follicle stimulating hormone (rFSH and highly purified human menopausal gonadotrophin (hMG-HP required per cycle of in vitro fertilisation (IVF; the aim of this study was to determine the average total usage of rFSH versus hMG-HP in a 'real-world' setting using routine clinical practice. Methods This retrospective chart review of databases from four European countries investigated gonadotrophin usage, oocyte and embryo yield, and pregnancy outcomes in IVF cycles (± intra-cytoplasmic sperm injection using rFSH or hMG-HP alone. Included patients met the National Institute for Health and Clinical Excellence (NICE guideline criteria for IVF and received either rFSH or hMG-HP. Statistical tests were conducted at 5% significance using Chi-square or t-tests. Results Of 30,630 IVF cycles included in this review, 74% used rFSH and 26% used hMG-HP. A significantly lower drug usage per cycle for rFSH than hMG-HP (2072.53 +/- 76.73 IU vs. 2540.14 +/- 883.08 IU, 22.6% higher for hMG-HP; p Conclusions Based on these results, IVF treatment cycles with rFSH yield statistically more oocytes (and more mature oocytes, using significantly less IU per cycle, versus hMG-HP. The incidence of all OHSS and hospitalisations due to OHSS was significantly higher in the rFSH cycles compared to the hMG-HP cycles. However, the absolute incidence of hospitalisations due to OHSS was similar to that reported previously. These results suggest that the perceived required dosage with rFSH is currently over-estimated, and the higher unit cost of rFSH may be offset by a lower required dosage compared with hMG-HP.

  19. Application of europium(III) chelates-bonded silica nanoparticle in time-resolved immunofluorometric detection assay for human thyroid stimulating hormone

    Energy Technology Data Exchange (ETDEWEB)

    Zhou Yulin [Xiamen Branch of Fujian Newborn Screening Centre and Xiamen Prenatal Diagnosis Centre, Xiamen Maternal and Children' s Health Care Hospital, Xiamen, Fujian 361003 (China); Xia Xiaohu; Xu Ye; Ke Wei [Engineering Research Centre of Molecular Diagnostics Laboratory, MOE, Department of Biomedical Sciences and the Key Laboratory of the Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005 (China); Yang Wei, E-mail: weiyang@xmu.edu.cn [Engineering Research Centre of Molecular Diagnostics Laboratory, MOE, Department of Biomedical Sciences and the Key Laboratory of the Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005 (China); Li Qingge, E-mail: qgli@xmu.edu.cn [Engineering Research Centre of Molecular Diagnostics Laboratory, MOE, Department of Biomedical Sciences and the Key Laboratory of the Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005 (China)

    2012-04-13

    Highlights: Black-Right-Pointing-Pointer A rapid and ultrasensitive TSH immunoassay was developed using fluorescent silica nanoparticles-based TrIFA. Black-Right-Pointing-Pointer The assay is of high sensitivity with short period time request. Black-Right-Pointing-Pointer method can be potentially used at hospitals for daily clinical practice in hTSH screening. - Abstract: Eu(III) chelate-bonded silica nanoparticle was used as a fluorescent label to develop a highly sensitive time-resolved immunofluorometric assay (TrIFA) for human thyroid stimulating hormone (hTSH). The limit of detection of the assay calculated according to the 2SD method was 0.0007 mIU L{sup -1} and became 0.003 mIU L{sup -1} when serum-based matrix was used for calibrators, indicating that this TrIFA is comparable with the most sensitive assays. The linear range was from 0.005 to 100 mIU L{sup -1} of hTSH with coefficient of variation between 1.9% and 8.3%. The correlation study using 204 blood spot samples from newborns showed that the results from this new method were coincident with that of the commercial dissociation-enhanced lanthanide fluorescence immunoassay (DELFIA) system, with a correlation coefficient of 0.938. The fluorescent nanoparticle label allows directly reading the fluorescent signal, omitting the signal development step required for the DELFIA system, and the whole procedure of this assay is fulfilled within 2 h. Thus, we developed a novel, sensitive, quantitative and simple nanoparticle label-based TrIFA assay, suitable for routine application in hTSH screening of neonatal hypothyroidism.

  20. Cytogenetic and dosimetric effects of {sup 131}I in patients with differentiated thyroid carcinoma: comparison between stimulation with rhTSH and thyroid hormone withdrawal treatments

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Marcia Augusta da; Gomes Silva Valgode, Flavia; Carvalho Pinto Ribela, Maria Teresa; Bartolini, Paolo; Okazaki, Kayo [Instituto de Pesquisas Energeticas e Nucleares (IPEN), Comissao Nacional de Energia Nuclear (CNEN), IPEN-CNEN/SP, Centro de Biotecnologia, Sao Paulo (Brazil); Armiliato Gonzalez, Julia; Calil Cury Guimaraes, Maria Ines; Buchpiguel, Carlos Alberto [Faculdade de Medicina da Universidade de Sao Paulo, Centro de Medicina Nuclear, Sao Paulo (Brazil); Yoriyaz, Helio [Instituto de Pesquisas Energeticas e Nucleares, IPEN-CNEN/SP, Centro de Engenharia Nuclear, Sao Paulo (Brazil)

    2016-08-15

    A study directed to the cytogenetic and dosimetric aspects of radionuclides of medical interest is very valuable, both for an accurate evaluation of the dose received by the patients, and consequently of the genetic damage, and for the optimization of therapeutic strategies. Cytogenetic and dosimetric effects of {sup 131}I in lymphocytes of thyroidectomized differentiated thyroid cancer (DTC) patients were evaluated through chromosome aberration (CA) technique: Euthyroid patients submitted to recombinant human thyroid-stimulating hormone (rhTSH) therapy (group A) were compared with hypothyroid patients left without levothyroxine treatment (group B). CA analysis was carried out prior to and 24 h, 1 week, 1 month and 1 year after radioiodine administration (4995-7030 MBq) in both groups. An activity-response curve of {sup 131}I (0.074-0.740 MBq/mL) was elaborated, comparing dicentric chromosomes in vivo and in vitro in order to estimate the absorbed dose through Monte Carlo simulations. In general, radioiodine therapy induced a higher total CA rate in hypothyroid patients as compared to euthyroid patients. The frequencies of dicentrics obtained in DTC patients 24 h after treatment were equivalent to those induced in vitro (0.2903 ± 0.1005 MBq/mL in group A and 0.2391 ± 0.1019 MBq/mL in group B), corresponding to absorbed doses of 0.65 ± 0.23 Gy and 0.53 ± 0.23 Gy, respectively. The effect on lymphocytes of internal radiation induced by {sup 131}I therapy is minimal when based on the frequencies of CA 1 year after the treatment, maintaining a higher quality of life for DTC patients receiving rhTSH-aided therapy. (orig.)

  1. Basal follicle stimulating hormone and leptin on the day of hCG administration predict successful fertilization in in vitro fertilization

    Directory of Open Access Journals (Sweden)

    Andon Hestiantoro

    2016-04-01

    Full Text Available Background: Successful pregnancy in in vitro fertilization (IVF program depends on multiple factors. This study aimed to determine whether age, body mass index (BMI, basal follicle stimulating hormone (FSH, estradiol, and leptin on the day of trigger ovulation with human chorionic gonadotropin (hCG might be used as predictor for successful oocyte fertilization in in vitro fertilization (IVF program.Methods: This is a cross sectional study conducted in Yasmin Fertility Clinic, Cipto Mangunkusumo Hospital, Jakarta, Indonesia. Forty participating patients underwent IVF program, excluding smokers, patients with diabetic, morbid obesity, and severe oligospermia or azoospermia. Age, BMI, basal FSH, estradiol, leptin on the day of hCG administration, oocyte count on oocyte retrieval, the number of mature oocyte, and fertility rate were analyzed using bivariate and multivariate analysis to determine which eligible factors play role in predicting the successful of fertilization.Results: Significant correlation was found between basal FSH level and serum leptin/oocyte ratio on the day of hCG administration with successful fertilization. We found probability formula as follows: 1/(1+exp –(6.2 - 0.4(leptin serum/oocyte ratio - 0.8(basal FSH, with 77.8% sensitivity, 77.8% specificity, and AUC levels of 85.6% indicating strong predictability. Probability of successful fertilization related to basal FSH level of 5.90 mIU/mL and leptin serum/oocyte ratio of 3.98.Conclusion: The formula consisting of basal FSH and leptin serum/oocyte ratio on the day of trigger ovulation was capable in predicting the probability of successful fertilization in IVF procedure.

  2. Evaluating melanocytic lesions with single nucleotide polymorphism (SNP) chromosomal microarray.

    Science.gov (United States)

    Hedayat, Amin A; Linos, Konstantinos; Jung, Hou-Sung; Tafe, Laura J; Yan, Shaofeng; LeBlanc, Robert E; Lefferts, Joel A

    2017-12-01

    Histopathology is the gold standard for diagnosing melanocytic lesions; however, distinguishing benign versus malignant is not always clear histologically. Single nucleotide polymorphism (SNP) microarray analysis may help in making a definitive diagnosis. Here, we share our experience with the Oncoscan FFPE Assay and demonstrate its diagnostic utility in the context of ambiguous melanocytic lesions. Eleven archival melanocytic lesions, including three benign nevi, four melanomas, three BAP1-deficient Spitzoid nevi and one nevoid melanoma were selected for validation. SNP-array was performed according to the manufacturer's protocol, using the recommended 80ng of DNA; however, as little as 15ng was used if the extraction yield was lower. Concordance was assessed with H&E and various combinations of BAP1 and p16 immunohistochemical stains (IHC) and external reference laboratory chromosomal microarray results. After validation, the SNP array was utilized to make definitive diagnoses in four challenging cases. Oncoscan SNP array findings were in concordance with H&E, IHC, and reference laboratory chromosomal microarray testing. The SNP-based microarray can accurately detect copy number changes and aid in making a more definitive diagnosis of challenging melanocytic lesions. This can be accomplished using significantly less DNA than is required by other microarray technologies. Copyright © 2017. Published by Elsevier Inc.

  3. Conditions for the differentiation of melanocyte- precursor cells from ...

    African Journals Online (AJOL)

    ONOS

    2010-09-06

    Sep 6, 2010 ... The loss of skin pigmentation can induce compromised cutaneous immunity, which can result in conditions such as vitiligo. In this study, we evaluated various agents that are able to induce the differentiation of stem cells into melanocytes. We found that a mixture of forskolin (FK), stem cell factor. (SCF) and ...

  4. Conditions for the differentiation of melanocyte-precursor cells from ...

    African Journals Online (AJOL)

    In a