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Sample records for interstitial cell stimulating hormone

  1. 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.

  2. 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%....

  3. 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 ...

  4. 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.

  5. 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: ...

  6. Autocrine Human Growth Hormone Stimulates Oncogenicity of Endometrial Carcinoma Cells

    OpenAIRE

    Pandey, Vijay; Perry, Jo K.; Mohankumar, Kumarasamypet M.; Kong, Xiang-Jun; Liu, Shu-Min; Wu, Zheng-Sheng; Mitchell, Murray D.; Zhu, Tao; Lobie, Peter E.

    2008-01-01

    Recent published data have demonstrated elevated levels of human GH (hGH) in endometriosis and endometrial adenocarcinoma. Herein, we demonstrate that autocrine production of hGH can enhance the in vitro and in vivo oncogenic potential of endometrial carcinoma cells. Forced expression of hGH in endometrial carcinoma cell lines RL95-2 and AN3 resulted in an increased total cell number through enhanced cell cycle progression and decreased apoptotic cell death. In addition, autocrine hGH express...

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

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    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.

  8. Functional innervation of Guinea-pig bladder interstitial cells of cajal subtypes: neurogenic stimulation evokes in situ calcium transients.

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    Susannah M Gray

    Full Text Available Several populations of interstitial cells of Cajal (ICC exist in the bladder, associated with intramural nerves. Although ICC respond to exogenous agonists, there is currently no evidence of their functional innervation. The objective was to determine whether bladder ICC are functionally innervated. Guinea-pig bladder tissues, loaded with fluo-4AM were imaged with fluorescent microscopy and challenged with neurogenic electrical field stimulation (EFS. All subtypes of ICC and smooth muscle cells (SMC displayed spontaneous Ca(2+-oscillations. EFS (0.5 Hz, 2 Hz, 10 Hz evoked tetrodotoxin (1 µM-sensitive Ca(2+-transients in lamina propria ICC (ICC-LP, detrusor ICC and perivascular ICC (PICC associated with mucosal microvessels. EFS responses in ICC-LP were significantly reduced by atropine or suramin. SMC and vascular SMC (VSM also responded to EFS. Spontaneous Ca(2+-oscillations in individual ICC-LP within networks occurred asynchronously whereas EFS evoked coordinated Ca(2+-transients in all ICC-LP within a field of view. Non-correlated Ca(2+-oscillations in detrusor ICC and adjacent SMC pre-EFS, contrasted with simultaneous neurogenic Ca(2+ transients evoked by EFS. Spontaneous Ca(2+-oscillations in PICC were little affected by EFS, whereas large Ca(2+-transients were evoked in pre-EFS quiescent PICC. EFS also increased the frequency of VSM Ca(2+-oscillations. In conclusion, ICC-LP, detrusor ICC and PICC are functionally innervated. Interestingly, Ca(2+-activity within ICC-LP networks and between detrusor ICC and their adjacent SMC were synchronous under neural control. VSM and PICC Ca(2+-activity was regulated by bladder nerves. These novel findings demonstrate functional neural control of bladder ICC. Similar studies should now be carried out on neurogenic bladder to elucidate the contribution of impaired nerve-ICC communication to bladder pathophysiology.

  9. 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

  10. 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...

  11. 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.

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

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    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.

  13. 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

  14. 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

  15. 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...

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

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    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.

  17. 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 ...

  18. 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 ...

  19. 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

  20. 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.

  1. 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...

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

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    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.

  3. 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....

  4. 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)

  5. 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

  6. 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.

  7. 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...

  8. 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

  9. 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.

  10. Experimental depletion of different renal interstitial cell populations

    International Nuclear Information System (INIS)

    Bohman, S.O.; Sundelin, B.; Forsum, U.; Tribukait, B.

    1988-01-01

    To define different populations of renal interstitial cells and investigate some aspects of their function, we studied the kidneys of normal rats and rats with hereditary diabetes insipidus (DI, Brattleboro) after experimental manipulations expected to alter the number of interstitial cells. DI rats showed an almost complete loss of interstitial cells in their renal papillae after treatment with a high dose of vasopressin. In spite of the lack of interstitial cells, the animals concentrated their urine to the same extent as vasopressin-treated normal rats, indicating that the renomedullary interstitial cells do not have an important function in concentrating the urine. The interstitial cells returned nearly to normal within 1 week off vasopressin treatment, suggesting a rapid turnover rate of these cells. To further distinguish different populations of interstitial cells, we studied the distribution of class II MHC antigen expression in the kidneys of normal and bone-marrow depleted Wistar rats. Normal rats had abundant class II antigen-positive interstitial cells in the renal cortex and outer medulla, but not in the inner medulla (papilla). Six days after 1000 rad whole body irradiation, the stainable cells were almost completely lost, but electron microscopic morphometry showed a virtually unchanged volume density of interstitial cells in the cortex and outer medulla, as well as the inner medulla. Thus, irradiation abolished the expression of the class II antigen but caused no significant depletion of interstitial cells

  11. 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

  12. 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...

  13. 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.

  14. 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

  15. 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

  16. Advanced sickle cell associated interstitial lung disease presenting ...

    African Journals Online (AJOL)

    Previous studies have reported abnormal pulmonary function and pulmonary hypertension among Nigerians with sickle cell disease, but there is no report of interstitial lung disease among them. We report a Nigerian sickle cell patient who presented with computed tomography proven interstitial lung disease complicated by ...

  17. 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.

  18. CD34-positive interstitial cells of the human detrusor

    DEFF Research Database (Denmark)

    Rasmussen, Helle; Hansen, Alastair; Smedts, Frank

    2007-01-01

    Interstitial cells of Cajal (ICC) are well described in the bowel wall. They are c-kit positive and play a role as pacemaker cells. Similar c-kit-positive cells have recently been described in the human bladder. The aim of this study was to characterize interstitial cells of the bladder detrusor...... using a panel of antibodies directed against CD117/c-kit, CD34, CD31, S100, tryptase, neurofilament, NSE, Factor-VIII and GFAP. A striking finding was an interstitial type of cell which is CD34 immunoreactive (CD34-ir) but CD117/c-kit negative. The cells have a tentacular morphology, enveloping...... and intermingling with individual muscle fasicles. Morphologically and immunohistochemically, they show no neurogenic, endothelial or mast cell differentiation. Transmission electron microscopy (TEM) showed the presence of interstitial cells with a round-to-oval nucleus, sparse perinuclear cytoplasm and long...

  19. 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.

  20. 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

  1. W/kit gene required for interstitial cells of Cajal and for intestinal pacemaker activity

    DEFF Research Database (Denmark)

    Huizinga, J D; Thuneberg, L; Klüppel, M

    1995-01-01

    The pacemaker activity in the mammalian gut is responsible for generating anally propagating phasic contractions. The cellular basis for this intrinsic activity is unknown. The smooth muscle cells of the external muscle layers and the innervated cellular network of interstitial cells of Cajal......, which is closely associated with the external muscle layers of the mammalian gut, have both been proposed to stimulate pacemaker activity. The interstitial cells of Cajal were identified in the last century but their developmental origin and function have remained unclear. Here we show...... of Cajal associated with Auerbach's nerve plexus and intestinal pacemaker activity....

  2. 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...

  3. 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.

  4. 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...

  5. Interstitial cells in the musculature of the gastrointestinal tract

    DEFF Research Database (Denmark)

    Rumessen, Jüri J; Vanderwinden, Jean-Marie

    2003-01-01

    "non-Cajal" (including the FLC and possibly also other cell types) cell types in the interstitium of the smooth musculature of the gastrointestinal tract, is proposed. Furthermore, evidence is accumulating to suggest that, as postulated by Santiago Ramon y Cajal, the concept of interstitial cells......Expression of the receptor tyrosine kinase KIT on cells referred to as interstitial cells of Cajal (ICC) has been instrumental during the past decade in the tremendous interest in cells in the interstitium of the smooth muscle layers of the digestive tract. ICC generate the pacemaker component...

  6. 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...

  7. 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

  8. Crohn's disease: ultrastructure of interstitial cells in colonic myenteric plexus

    DEFF Research Database (Denmark)

    Rumessen, Jüri Johs.; Vanderwinden, Jean-Marie; Horn, Thomas

    2011-01-01

    -MP and other interstitial cells in the myenteric region of the colon are lacking for CD. In the present study, we characterized the ultrastructure of interstitial cells, nerves, and glial cells in the myenteric region in Crohn's colitis (CC). In comparison with controls, varicosities of the myenteric bundles...... were dilated and appeared to be empty. Lipid droplets and lipofuscin-bodies were prominent in glial cells and neurons. ICC-MP were scanty but, as in controls, had caveolae, prominent intermediate filaments, cytoplasmic dense bodies, and membrane-associated dense bands with a patchy basal lamina. ICC......The role of the interstitial cells of Cajal (ICC) in chronic inflammatory bowel disease, i.e., ulcerative colitis (UC) and Crohn's disease (CD), remains unclear. Ultrastructural alterations in ICC in the colonic myenteric plexus (ICC-MP) have been reported previously in UC, but descriptions of ICC...

  9. Interstitial cells in the musculature of the gastrointestinal tract

    DEFF Research Database (Denmark)

    Rumessen, Jüri J; Vanderwinden, Jean-Marie

    2003-01-01

    Expression of the receptor tyrosine kinase KIT on cells referred to as interstitial cells of Cajal (ICC) has been instrumental during the past decade in the tremendous interest in cells in the interstitium of the smooth muscle layers of the digestive tract. ICC generate the pacemaker component (e...

  10. Comparative proteomic analysis of kidney distal convoluted tubule and cortical collecting duct cells following long-term hormonal stimulation

    DEFF Research Database (Denmark)

    Wu, Qi; Moller, Hanne; Rosenbaek, Lena Lindtoft

    2017-01-01

    , both of which modulate DCT and CCD cells differently. Mass spectrometry based quantitative proteomics was used to profile the differential proteome between DCT and CCD. Mouse kidney distal convoluted tubule cells (mpkDCT) were cultured in heavy SILAC medium (Lys+6, Arg+10) while cortical collecting......The distal convoluted tubule (DCT) and the cortical collecting ducts (CCD) are portions of renal tubule that are partly responsible for maintaining the systemic concentrations of potassium, sodium, calcium and magnesium. Despite being structurally similar, DCT and CCD cells have different transport...... and deubiquitinating enzyme identification, and kinase and transcription factor predictions, with the aim to identify cell specific proteins that define tubule-specific biological processes. Preliminary data suggests that one specific gene CHIP in mpkCCD might be involved in the regulation of AQP2....

  11. 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

  12. 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 ...

  13. Perivascular Interstitial Cells of Cajal in Human ColonSummary

    Directory of Open Access Journals (Sweden)

    Yuan-An Liu

    2015-01-01

    Full Text Available Background & Aims: Interstitial cells of Cajal (ICC closely associate with nerves and smooth muscles to modulate gut motility. In the ICC microenvironment, although the circulating hormones/factors have been shown to influence ICC activities, the association between ICC and microvessels in the gut wall has not been described. We applied three-dimensional (3D vascular histology with c-kit staining to identify the perivascular ICC and characterize their morphologic and population features in the human colon wall. Methods: Full-thickness colons were obtained from colectomies performed for colorectal cancer. We targeted the colon wall away from the tumor site. Confocal microscopy with optical clearing (use of immersion solution to reduce scattering in optical imaging was performed to simultaneously reveal the ICC and vascular networks in space. 3D image rendering and projection were digitally conducted to illustrate the ICC–vessel contact patterns. Results: Perivascular ICC were identified in the submucosal border, myenteric plexus, and circular and longitudinal muscles via high-definition 3D microscopy. Through in-depth image projection, we specified two contact patterns—the intimate cell body-to-vessel contact (type I, 18% of ICC in circular muscle and the long-distance process-to-vessel contact (type II, 16%—to classify perivascular ICC. Particularly, type I perivascular ICC were detected with elevated c-kit staining levels and were routinely found in clusters, making them readily distinguishable from other ICC in the network. Conclusions: We propose a new subclass of ICC that closely associates with microvessels in the human colon. Our finding suggests a functional relationship between these mural ICC and microvessels based on the morphologic proximity. Keywords: 3D Histology, c-kit, ICC, Mural Cells

  14. 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

  15. 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...

  16. Interstitial cells in the musculature of the gastrointestinal tract

    DEFF Research Database (Denmark)

    Rumessen, Jüri J; Vanderwinden, Jean-Marie

    2003-01-01

    , the ultrastructure and light microscopic morphology, as well as the functions and the development of ICC and of neighboring fibroblast-like cells (FLC), are critically reviewed. Directions for future research are considered and a unifying concept of mesenchymal cells, either KIT positive (the "ICC") or KIT negative......Expression of the receptor tyrosine kinase KIT on cells referred to as interstitial cells of Cajal (ICC) has been instrumental during the past decade in the tremendous interest in cells in the interstitium of the smooth muscle layers of the digestive tract. ICC generate the pacemaker component...... "non-Cajal" (including the FLC and possibly also other cell types) cell types in the interstitium of the smooth musculature of the gastrointestinal tract, is proposed. Furthermore, evidence is accumulating to suggest that, as postulated by Santiago Ramon y Cajal, the concept of interstitial cells...

  17. 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 ...

  18. 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 ...

  19. Differences in gene expression of granulosa cells from women undergoing controlled ovarian hyperstimulation with either recombinant follicle-stimulating hormone or highly purified human menopausal gonadotropin

    DEFF Research Database (Denmark)

    Grøndahl, Marie Louise; Borup, Rehannah; Lee, Young Bae

    2009-01-01

    groups of granulosa cells. Expression level of luteinizing hormone/human chorionic gonadotropin (LH/hCG) receptor gene and genes involved in biosynthesis of cholesterol and steroids were expressed at lower levels in the hMG-treated cells; inositol 1,4,5-triphosphate-3-kinase-A and S100-calcium....... Granulosa cells were collected from follicular fluid after oocyte retrieval, and mRNA were isolated for gene expression analysis. MAIN OUTCOME MEASURE(S): General gene expression profile. RESULT(S): Ninety-six probe sets (85 genes) showed statistically significant differences in expression level in the two......-binding-protein-P (anti-apoptosis protein) were expressed at higher levels in hMG than in recombinant FSH. CONCLUSION(S): The different hormone compositions of the two drugs used for COH had a statistically significant impact on the gene expression profile of preovulatory granulosa cells. Some of these genes may...

  20. Whey proteins have beneficial effects on intestinal enteroendocrine cells stimulating cell growth and increasing the production and secretion of incretin hormones.

    Science.gov (United States)

    Gillespie, Anna L; Calderwood, Danielle; Hobson, Laura; Green, Brian D

    2015-12-15

    Whey protein has been indicated to curb diet-induced obesity, glucose intolerance and delay the onset of type 2 diabetes mellitus. Here the effects of intact crude whey, intact individual whey proteins and beta-lactoglobulin hydrolysates on an enteroendocrine (EE) cell model were examined. STC-1 pGIP/neo cells were incubated with several concentrations of yogurt whey (YW), cheese whey (CW), beta-lactoglobulin (BLG), alpha-lactalbumin (ALA) and bovine serum albumin (BSA). The findings demonstrate that BLG stimulates EE cell proliferation, and also GLP-1 secretion (an effect which is lost following hydrolysis with chymotrypsin or trypsin). ALA is a highly potent GLP-1 secretagogue which also increases the intracellular levels of GLP-1. Conversely, whey proteins and hydrolysates had little impact on GIP secretion. This appears to be the first investigation of the effects of the three major proteins of YW and CW on EE cells. The anti-diabetic potential of whey proteins should be further investigated. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. 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...

  2. Interstitial cells of Cajal in human gut and gastrointestinal disease

    DEFF Research Database (Denmark)

    Vanderwinden, J M; Rumessen, J J

    1999-01-01

    This paper reviews the distribution of interstitial cells of Cajal (ICC) in the human gastrointestinal (GI) tract, based on ultrastructural and immunohistochemical evidence. The distribution and morphology of ICC at each level of the normal GI tracts is addressed from the perspective of their fun...

  3. 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....

  4. Autocrine human growth hormone (hGH) regulation of human mammary carcinoma cell gene expression. Identification of CHOP as a mediator of hGH-stimulated human mammary carcinoma cell survival.

    Science.gov (United States)

    Mertani, H C; Zhu, T; Goh, E L; Lee, K O; Morel, G; Lobie, P E

    2001-06-15

    By use of cDNA array technology we have screened 588 genes to determine the effect of autocrine production of human growth hormone (hGH) on gene expression in human mammary carcinoma cells. We have used a previously described cellular model to study autocrine hGH function in which the hGH gene or a translation-deficient hGH gene was stably transfected into MCF-7 cells. Fifty two of the screened genes were regulated, either positively () or negatively (), by autocrine production of hGH. We have now characterized the role of one of the up-regulated genes, chop (gadd153), in the effect of autocrine production of hGH on mammary carcinoma cell number. The effect of autocrine production of hGH on the level of CHOP mRNA was exerted at the transcriptional level as autocrine hGH increased chloramphenicol acetyltransferase production from a reporter plasmid containing a 1-kilobase pair fragment of the chop promoter. The autocrine hGH-stimulated increase in CHOP mRNA also resulted in an increase in CHOP protein. As a consequence, autocrine hGH stimulation of CHOP-mediated transcriptional activation was increased. Stable transfection of human CHOP cDNA into mammary carcinoma cells demonstrated that CHOP functioned not as a mediator of hGH-stimulated mitogenesis but rather enhanced the protection from apoptosis afforded by hGH in a p38 MAPK-dependent manner. Thus transcriptional up-regulation of chop is one mechanism by which hGH regulates mammary carcinoma cell number.

  5. Interstitial cells in the musculature of the gastrointestinal tract

    DEFF Research Database (Denmark)

    Rumessen, Jüri J; Vanderwinden, Jean-Marie

    2003-01-01

    , the ultrastructure and light microscopic morphology, as well as the functions and the development of ICC and of neighboring fibroblast-like cells (FLC), are critically reviewed. Directions for future research are considered and a unifying concept of mesenchymal cells, either KIT positive (the "ICC") or KIT negative...... "non-Cajal" (including the FLC and possibly also other cell types) cell types in the interstitium of the smooth musculature of the gastrointestinal tract, is proposed. Furthermore, evidence is accumulating to suggest that, as postulated by Santiago Ramon y Cajal, the concept of interstitial cells...

  6. 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.

  7. 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.

  8. 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.

  9. 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 ...

  10. Stimulation by parathyroid hormone of sup 45 Ca sup 2+ uptake in osteoblast-like cells: Possible involvement of alkaline phosphatase

    Energy Technology Data Exchange (ETDEWEB)

    Fukayama, S.; Tashjian, A.H. Jr. (Harvard School of Public Health, Boston, MA (USA))

    1990-04-01

    We have investigated the actions of human PTH (hPTH-(1-34)) on the association of 45Ca2+ with two human (SaOS-2 and MG-63) and two rat (ROS 17/2.8 and UMR-106) osteoblast-like cell types. In SaOS-2 cells, hPTH-(1-34) binds to specific membrane receptors to activate adenylate cyclase. Treatment of SaOS-2 cells with hPTH-(1-34) resulted in an increase in 45Ca2+ uptake, in a dose-dependent fashion, up to 2- to 4-fold above control values. The increase was first evident at 10 min and persisted for at least 30 min. Treatment with nimodipine, a calcium channel antagonist, was without effect on the stimulatory action of PTH. A similar enhancement of cell-associated 45Ca2+ was observed when the cells were incubated with vasoactive intestinal peptide, which acts via different receptors to activate adenylate cyclase in SaOS-2 cells. Treatment with (Bu)2cAMP also induced an increase in cell-associated 45Ca2+. Pretreatment of SaOS-2 cells with hPTH-(1-34) for 4 h, which induced homologous desensitization to a second challenge with the same peptide for stimulation of cAMP production, did not attenuate the further enhancement of cell-associated 45Ca2+ by a second treatment with hPTH-(1-34). We then examined a possible relationship between alkaline phosphatase (ALPase) and 45Ca2+ uptake. SaOS-2 cells contained high levels of alkaline phosphatase activity and continuously released the enzyme into the medium. Release was enhanced by treatment with hPTH-(1-34) for 10 min. Incubation of cells with levamisole (an inhibitor of the liver/bone/kidney type of ALPase) resulted in a rapid decrease in basal and PTH-stimulated 45Ca2+ uptake, while treatment with L-Phe-Gly-Gly was without effect. Treatment of the cells with ALPase (bovine kidney) enhanced 45Ca2+ uptake. In MG-63 cells, a stimulatory effect of hPTH-(1-34) on cell-associated 45Ca2+ was also observed; however, hPTH-(1-34) did not stimulate cAMP production in MG-63 cells.

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

    Directory of Open Access Journals (Sweden)

    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

  12. 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...

  13. Gonadotrophins, testosterone and spermatogenesis in neonatally irradiated male rates: evidence for a role of the Sertoli cell in follicle-stimulating hormone feedback

    International Nuclear Information System (INIS)

    De Jong, F.H.; Sharpe, R.M.

    1977-01-01

    Peripheral concentrations of FSH in the male rat seem to be regulated in parts by a protein hormone, inhibin, which originates from the testes. In an attempt to ascertain which type of testicular cell secretes inhibin, groups of male rats were irradiated prenatally or on days 4, 6 or 8 of postnatal life, and killed at 21, 51 or 81 days of age together with castrated and intact controls. The concentrations of FSH and LH in the pituitary gland, and FSH, LH and testosterone in the plasma were estimated for each animal, and the numbers of each class of intratubular cell in the testes were calculated. Rats irradiated neonatally had fewer Sertoli cells than controls at all ages studied, while the numbers of Sertoli cells in rats irradiated prenatally were higher than those in controls on day 21. The number of spermatogenic cells was usually decreased in rats irradiated postnatally. In the rats irradiated prenatally normal numbers of spermatogenic cells were found at day 51. Numbers of spermatogenic cells were significantly correlated with the number of Sertoli cells at the ages of 51 and 81 days. The concentration of FSH in the plasma usually increased in the postnatally irradiated animals on days 21 and 51, but not on day 81; prenatal irradiation did not result in altered levels of FSH at any age. Peripheral levels of LH and testosterone were not affected by irradiation. The concentration of FSH in the plasma was negatively correlated with the number of Sertoli cells in all age groups, whereas significant correlations between the levels of FSH and the number of spermatogenic cells were only found at days 51 and 81. It is concluded from these data that the Sertoli cell is the most likely source of inhibin. (author)

  14. 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

  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. 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.

  17. Hormonal treatment may harm the germ cells in 1 to 3-year-old boys with cryptorchidism

    DEFF Research Database (Denmark)

    Cortes, Dina; Thorup, Jørgen Mogens; Visfeldt, J

    2000-01-01

    Hormonal treatment with human chorionic gonadotropin (HCG) or gonadotropin releasing hormone may be given initially for cryptorchidism. We evaluated whether hormonal treatment is safe for the germ cells in boys with cryptorchidism 1 to 3 years old in whom follicle-stimulating hormone, luteinizing...... hormone and testosterone values are normally low....

  18. Interstitial cells of Cajal mediate mechanosensitive responses in the stomach

    Science.gov (United States)

    Won, Kyung-Jong; Sanders, Kenton M.; Ward, Sean M.

    2005-10-01

    Changes in motor activity are a basic response to filling of smooth muscle organs. Responses to gastric filling, for example, are thought to be regulated by neural reflexes. Here, we demonstrate a previously uncharacterized aspect of stretch-dependent responses in visceral smooth muscles that is mediated by mechanosensitive interstitial cells of Cajal. Length ramps were applied to the murine antral muscles while recording intracellular electrical activity and isometric force. Stretching muscles by an average of 27 ± 1% of resting length resulted in 5 mN of force. Increasing length caused membrane depolarization and increased slow-wave frequency. The responses were dependent on the rate of stretch. Stretch-dependent responses were not inhibited by neuronal antagonists or nifedipine. Increases in slow-wave frequency, but not membrane depolarization, were inhibited by reducing external Ca2+ (100 μM) and by Ni2+ (250 μM). Responses to stretch were inhibited by indomethacin (1 μM) and were absent in cyclooxygenase II-deficient mice, suggesting that cyclooxygenase II-derived eicosanoids may mediate these responses. Dual microelectrode impalements of muscle cells within the corpus and antrum showed that stretch-induced changes in slow-wave frequency uncoupled proximal-to-distal propagation of slow waves. This uncoupling could interfere with gastric peristalsis and impede gastric emptying. Stretch of antral muscles of W/WV mice, which lack intramuscular interstitial cells of Cajal, did not affect membrane depolarization or slow-wave frequency. These data demonstrate a previously uncharacterized nonneural stretch reflex in gastric muscles and provide physiological evidence demonstrating a mechanosensitive role for interstitial cells of Cajal in smooth muscle tissues. gastric compliance | pacemaker | stretch | slow waves | propagation

  19. Interstitial Fluid Flow: The Mechanical Environment of Cells and Foundation of Meridians

    Directory of Open Access Journals (Sweden)

    Wei Yao

    2012-01-01

    Full Text Available Using information from the deep dissection, microobservation, and measurement of acupoints in the upper and lower limbs of the human body, we developed a three-dimensional porous medium model to simulate the flow field using FLUENT software and to study the shear stress on the surface of interstitial cells (mast cells caused by interstitial fluid flow. The numerical simulation results show the following: (i the parallel nature of capillaries will lead to directional interstitial fluid flow, which may explain the long interstitial tissue channels or meridians observed in some experiments; (ii when the distribution of capillaries is staggered, increases in the velocity alternate, and the velocity tends to be uniform, which is beneficial for substance exchange; (iii interstitial fluid flow induces a shear stress, with magnitude of several Pa, on interstitial cell membranes, which will activate cells and lead to a biological response; (iv capillary and interstitial parameters, such as capillary density, blood pressure, capillary permeability, interstitial pressure, and interstitial porosity, affect the shear stress on cell surfaces. The numerical simulation results suggest that in vivo interstitial fluid flow constitutes the mechanical environment of cells and plays a key role in guiding cell activities, which may explain the meridian phenomena and the acupuncture effects observed in experiments.

  20. 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 presence of 3.0 X 10(-10) M unlabeled hGH. Rat GH as well as human placental lactogen were able to compete for binding sites, but with less affinity. Other non-GH peptides at 6.7 micrograms/ml did not affect [125I]hGH binding. Scatchard analysis revealed curvilinear plots, and approximately 2700 high...... affinity binding sites were calculated. Culture of RIN-5AH in the presence of 1 microgram/ml hGH for 4 days resulted in an 80% increase in insulin content as well as an 18% increase in cell number and DNA and protein content compared to those in cells cultured in the absence of hGH. The dose dependence...

  1. 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.

  2. 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.

  3. 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

  4. The Mystery of the Interstitial Cells in the Urinary Bladder.

    Science.gov (United States)

    Koh, Sang Don; Lee, Haeyeong; Ward, Sean M; Sanders, Kenton M

    2018-01-06

    Intrinsic mechanisms to restrain smooth muscle excitability are present in the bladder, and premature contractions during filling indicate a pathological phenotype. Some investigators have proposed that c-Kit + interstitial cells (ICs) are pacemakers and intermediaries in efferent and afferent neural activity, but recent findings suggest these cells have been misidentified and their functions have been misinterpreted. Cells reported to be c-Kit + cells colabel with vimentin antibodies, but vimentin is not a specific marker for c-Kit + cells. A recent report shows that c-Kit + cells in several species coexpress mast cell tryptase, suggesting that they are likely to be mast cells. In fact, most bladder ICs labeled with vimentin antibodies coexpress platelet-derived growth factor receptor α (PDGFRα). Rather than an excitatory phenotype, PDGFRα + cells convey inhibitory regulation in the detrusor, and inhibitory mechanisms are activated by purines and stretch. PDGFRα + cells restrain premature development of contractions during bladder filling, and overactive behavior develops when the inhibitory pathways in these cells are blocked. PDGFRα + cells are also a prominent cell type in the submucosa and lamina propria, but little is known about their function in these locations. Effective pharmacological manipulation of bladder ICs depends on proper identification and further study of the pathways in these cells that affect bladder functions.

  5. Biphasic action of cyclic adenosine 3',5'- monophosphate in gonadotropin-releasing hormone (GnRH) analog-stimulated hormone release from GH3 cells stably transfected with GnRH receptor complementary deoxyribonucleic acid.

    Science.gov (United States)

    Stanislaus, D; Arora, V; Awara, W M; Conn, P M

    1996-03-01

    GH3 cells are a PRL-secreting adenoma cell line derived from pituitary lactotropes. These cells have been stably transfected with rat GnRH receptor complementary DNA to produce four cell lines: GGH(3)1', GGH(3)2', GGH(3)6', and GGH(3)12'. In response to either GnRH or Buserelin (a metabolically stable GnRH agonist), these cell lines synthesize PRL in a cAMP-dependent manner. Only GGH(3)6' cells desensitize in response to persistent treatment with 10(-7) g/ml Buserelin. GGH(3)1', GGH(3)2', and GGH(3)12' cells, however, can be made refractory to Buserelin stimulation by raising cAMP levels either by the addition of (Bu)2cAMP to the medium or by treatment with cholera toxin. In GGH(3) cells, low levels of cAMP fulfill the requirements for a second messenger, whereas higher levels appear to mediate the development of desensitization. The observation that in GGH(3)6' cells, cAMP production persists after the onset of desensitization is consistent with the view that the mechanism responsible for desensitization is distal to the production of cAMP. Moreover, the absence of any significant difference in the amount of cAMP produced per cell in GGH(3)2', GGH(3)6', or GGH(3)12' cells suggests that elevated cAMP production per cell does not explain the development of desensitization in GGH(3)6' cells. We suggest that Buserelin-stimulated PRL synthesis in GGH(3)6' cells is mediated by a different cAMP-dependent protein kinase pool(s) than that in nondesensitizing GGH(3) cells. Such a protein kinase A pool(s) may be more susceptible to degradation via cAMP-mediated mechanisms than the protein kinase pools mediating the Buserelin response in nondesensitizing GGH(3) cells. A similar mechanism has been reported in other systems.

  6. Ultrastructure of interstitial cells of Cajal in myenteric plexus of human colon

    DEFF Research Database (Denmark)

    Rumessen, Jüri Johs.; Vanderwinden, Jean-Marie; Rasmussen, Helle

    2009-01-01

    The role of the interstitial cells of Cajal (ICC) associated with the myenteric plexus (ICC-MP) as regulators of the motility of the colonic external muscle remains unclear. Ultrastructural studies of myenteric interstitial cells are lacking in human colon. We therefore characterized the distinct......The role of the interstitial cells of Cajal (ICC) associated with the myenteric plexus (ICC-MP) as regulators of the motility of the colonic external muscle remains unclear. Ultrastructural studies of myenteric interstitial cells are lacking in human colon. We therefore characterized...

  7. Central hypogonadism due to a giant, "silent" FSH-secreting, atypical pituitary adenoma: effects of adenoma dissection and short-term Leydig cell stimulation by luteinizing hormone (LH) and human chorionic gonadotropin (hCG).

    Science.gov (United States)

    Santi, Daniele; Spaggiari, Giorgia; Casarini, Livio; Fanelli, Flaminia; Mezzullo, Marco; Pagotto, Uberto; Granata, Antonio R M; Carani, Cesare; Simoni, Manuela

    2017-06-01

    We present a case report of an atypical giant pituitary adenoma secreting follicle-stimulating hormone (FSH). A 55-year-old patient presented for erectile dysfunction, loss of libido and fatigue. The biochemical evaluation showed very high FSH serum levels in the presence of central hypogonadism. Neither testicular enlargement nor increased sperm count was observed, thus a secretion of FSH with reduced biological activity was supposed. The histological examination after neuro-surgery showed an atypical pituitary adenoma with FSH-positive cells. Hypogonadism persisted and semen analyses impaired until azoospermia in conjunction with the reduction in FSH levels suggesting that, at least in part, this gonadotropin should be biologically active. Thus, we hypothesized a concomitant primary testicular insufficiency. The patient underwent short-term treatment trials with low doses of either recombinant luteinizing hormone (LH) or human chorionic gonadotropin (hCG) in three consecutive treatment schemes, showing an equal efficacy in stimulating testosterone (T) increase. This is the first case of atypical, giant FSH-secreting pituitary adenoma with high FSH serum levels without signs of testicular hyperstimulation, in presence of hypogonadism with plausible combined primary and secondary etiology. Hypophysectomized patients may represent a good model to assess both pharmacodynamics and effective dose of LH and hCG in the male.

  8. 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

  9. Digital quantitative analysis of mast cell infiltration in interstitial cystitis.

    Science.gov (United States)

    Akiyama, Yoshiyuki; Maeda, Daichi; Morikawa, Teppei; Niimi, Aya; Nomiya, Akira; Yamada, Yukio; Igawa, Yasuhiko; Goto, Akiteru; Fukayama, Masashi; Homma, Yukio

    2018-02-01

    To evaluate the significance of mast cell infiltration in interstitial cystitis (IC) by comparison with equally inflamed controls using a digital quantification technique. Bladder biopsy specimens from 31 patients with Hunner type IC and 38 patients with non-Hunner type IC were analyzed. Bladder biopsy specimens from 37 patients without IC, including 19 non-specific chronic cystitis ("non-IC cystitis") specimens and 18 non-inflamed bladder ("normal bladder") specimens, were used as controls. Mast cell tryptase-, CD3-, CD20-, and CD138-immunoreactive cells were quantified using digital image analysis software to evaluate both mast cell and lymphoplasmacytic cell densities. Mast cell and lymphoplasmacytic cell densities were counted independently in the entire lamina propria and detrusor areas and compared among the four groups. In the lamina propria, there were no significant differences in mast cell and lymphoplasmacytic cell densities between Hunner type IC and non-IC cystitis or between non-Hunner type IC and normal bladder specimens. In the detrusor, the mast cell densities were not significantly different among the four groups. Mast cell density was correlated with lymphoplasmacytic cell density, but not with clinical parameters. Mast cell density is not significantly different between IC specimens and non-IC control specimens with a similar degree of background inflammation. The intensity of mast cell infiltration generally correlated with that of lymphoplasmacytic cells. We conclude that mast cell count is of no value in the differential diagnosis between IC and other etiologies. © 2017 The Authors. Neurourology and Urodynamics Published by Wiley Periodicals, Inc.

  10. 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.

  11. Lipoprotein(a Induces Human Aortic Valve Interstitial Cell Calcification

    Directory of Open Access Journals (Sweden)

    Bin Yu, PhD

    2017-08-01

    Full Text Available Lipoprotein(a, or Lp(a, significantly increased alkaline phosphatase activity, release of phosphate, calcium deposition, hydroxyapatite, cell apoptosis, matrix vesicle formation, and phosphorylation of signal transduction proteins; increased expression of chondro-osteogenic mediators; and decreased SOX9 and matrix Gla protein (p < 0.001. Inhibition of MAPK38 and GSK3β significantly reduced Lp(a-induced calcification of human aortic valve interstitial cells (p < 0.001. There was abundant presence of Lp(a and E06 immunoreactivity in diseased human aortic valves. The present study demonstrates a causal effect for Lp(a in aortic valve calcification and suggests that interfering with the Lp(apathway could provide a novel therapeutic approach in the management of this debilitating disease.

  12. Ovotoxic Effects of Galactose Involve Attenuation of Follicle-Stimulating Hormone Bioactivity and Up-Regulation of Granulosa Cell p53 Expression

    Science.gov (United States)

    Banerjee, Sayani; Chakraborty, Pratip; Saha, Piyali; Bandyopadhyay, Soma Aditya; Banerjee, Sutapa; Kabir, Syed N.

    2012-01-01

    Clinical evidence suggests an association between galactosaemia and premature ovarian insufficiency (POI); however, the mechanism still remains unresolved. Experimental galactose toxicity in rats produces an array of ovarian dysfunction including ovarian development with deficient follicular reserve and follicular resistance to gonadotrophins that characterize the basic tenets of human POI. The present investigation explores if galactose toxicity in rats attenuates the bioactivity of gonadotrophins or interferes with their receptor competency, and accelerates the rate of follicular atresia. Pregnant rats were fed isocaloric food-pellets supplemented with or without 35% D-galactose from day-3 of gestation and continuing through weaning of the litters. The 35-day old female litters were autopsied. Serum galactose-binding capacity, galactosyltransferase (GalTase) activity, and bioactivity of FSH and LH together with their receptor competency were assessed. Ovarian follicular atresia was evaluated in situ by TUNEL. The in vitro effects of galactose were studied in isolated whole follicles in respect of generation of reactive oxygen species (ROS) and expression of caspase 3, and in isolated granulosa cells in respect of mitochondrial membrane potential, expression of p53, and apoptosis. The rats prenatally exposed to galactose exhibited significantly decreased serum GalTase activity and greater degree of galactose-incorporation capacity of sera proteins. LH biopotency and LH-FSH receptor competency were comparable between the control and study population, but the latter group showed significantly attenuated FSH bioactivity and increased rate of follicular atresia. In culture, galactose increased follicular generation of ROS and expression of caspase 3. In isolated granulosa cells, galactose disrupted mitochondrial membrane potential, stimulated p53 expression, and induced apoptosis in vitro; however co-treatment with either FSH or estradiol significantly prevented

  13. 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.

  14. Thyroid Hormones as Renal Cell Cancer Regulators

    OpenAIRE

    Szyma?ski, ?ukasz; Matak, Damian; Bartnik, Ewa; Szczylik, Cezary; Czarnecka, Anna M.

    2016-01-01

    It is known that thyroid hormone is an important regulator of cancer development and metastasis. What is more, changes across the genome, as well as alternative splicing, may affect the activity of the thyroid hormone receptors. Mechanism of action of the thyroid hormone is different in every cancer; therefore in this review thyroid hormone and its receptor are presented as a regulator of renal cell carcinoma.

  15. Advanced sickle cell associated interstitial lung disease presenting with cor pulmonale in a Nigerian.

    Science.gov (United States)

    Fawibe, Ademola Emmanuel; Kolo, Philip Manman; Ogunmodede, James Ayodele; Desalu, Olufemi Olumuyiwa; Salami, Kazeem Alakija

    2012-04-01

    Previous studies have reported abnormal pulmonary function and pulmonary hypertension among Nigerians with sickle cell disease, but there is no report of interstitial lung disease among them. We report a Nigerian sickle cell patient who presented with computed tomography proven interstitial lung disease complicated by pulmonary hypertension and cor pulmonale.

  16. Turnover time of Leydig cells and other interstitial cells in testes of adult rats

    NARCIS (Netherlands)

    Teerds, K. J.; de rooij, D. G.; Rommerts, F. F.; van der Tweel, I.; Wensing, C. J.

    1989-01-01

    The aim of this study was to investigate the turnover of Leydig cells and other interstitial cells in the adult rat testis. Normal adult rats received injections of [3H]thymidine at 9:00 and 21:00 for 2, 5, or 8 days. The percentage of labeled Leydig cells, which was initially low (0.8% +/- 0.2%),

  17. Interstitial cells of Cajal and Auerbach's plexus. A scanning electron microscopical study of guinea-pig small intestine

    DEFF Research Database (Denmark)

    Jessen, Harry; Thuneberg, Lars

    1991-01-01

    Anatomy, interstitial cells of Cajal, myenteric plexus, small intestine, guinea-pig, scanning electron microscopy......Anatomy, interstitial cells of Cajal, myenteric plexus, small intestine, guinea-pig, scanning electron microscopy...

  18. Sirtuin 1 is a negative regulator of parathyroid hormone stimulation of matrix metalloproteinase 13 expression in osteoblastic cells: role of sirtuin 1 in the action of PTH on osteoblasts.

    Science.gov (United States)

    Fei, Yurong; Shimizu, Emi; McBurney, Michael W; Partridge, Nicola C

    2015-03-27

    Parathyroid hormone (PTH) is the only current anabolic treatment for osteoporosis in the United States. PTH stimulates expression of matrix metalloproteinase 13 (MMP13) in bone. Sirtuin 1 (SIRT1), an NAD-dependent deacetylase, participates in a variety of human diseases. Here we identify a role for SIRT1 in the action of PTH in osteoblasts. We observed increased Mmp13 mRNA expression and protein levels in bone from Sirt1 knock-out mice compared with wild type mice. PTH-induced Mmp13 expression was significantly blocked by the SIRT1 activator, resveratrol, in osteoblastic UMR 106-01 cells. In contrast, the SIRT1 inhibitor, EX527, significantly enhanced PTH-induced Mmp13 expression. Two h of PTH treatment augmented SIRT1 association with c-Jun, a component of the transcription factor complex, activator protein 1 (AP-1), and promoted SIRT1 association with the AP-1 site of the Mmp13 promoter. This binding was further increased by resveratrol, implicating SIRT1 as a feedback inhibitor regulating Mmp13 transcription. The AP-1 site of the Mmp13 promoter is required for PTH stimulation of Mmp13 transcriptional activity. When the AP-1 site was mutated, EX527 was unable to increase PTH-stimulated Mmp13 promoter activity, indicating a role for the AP-1 site in SIRT1 inhibition. We further showed that SIRT1 deacetylates c-Jun and that the cAMP pathway participates in this deacetylation process. These data indicate that SIRT1 is a negative regulator of MMP13 expression, SIRT1 activation inhibits PTH stimulation of Mmp13 expression, and this regulation is mediated by SIRT1 association with c-Jun at the AP-1 site of the Mmp13 promoter. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. About the presence of interstitial cells of Cajal outside the musculature of the gastrointestinal tract.

    Science.gov (United States)

    Huizinga, Jan D; Faussone-Pellegrini, Maria-Simonetta

    2005-01-01

    Santiago Ramon y Cajal observed a special cell type that appeared to function as endstructures of the intrinsic nervous system in several organs. These cells were structurally and functionally further characterized in the gut musculature and named interstitial cells of Cajal (ICC). In recent years, interstitial cells have been identified in the vasculature, urinary tract, glands and other organs. Their morphologies and functions are just beginning to be clarified. It is likely that amongst them, subtypes will be discovered that warrant the classification of interstitial cells of Cajal. This "point of view" continues the discussion on the criteria that should be used to identify ICC outside the musculature of the gut.

  20. Are mast cells still good biomarkers for bladder pain syndrome/interstitial cystitis?

    Science.gov (United States)

    Gamper, Marianne; Regauer, Sigrid; Welter, JoEllen; Eberhard, Jakob; Viereck, Volker

    2015-06-01

    ESSIC identifies mast cell infiltrates of detrusor muscle as a diagnostic criterion for bladder pain syndrome/interstitial cystitis. However, an increased mast cell count is also characteristic of overactive bladder syndrome. The lack of uniformity in mast cell detection methods hampers data comparison. Using state-of-the-art techniques we investigated whether mast cells differ among bladder conditions. We analyzed bladder biopsies from 56 patients, including 31 with bladder pain syndrome/interstitial cystitis with (12) or without (19) Hunner lesions, 13 with overactive bladder syndrome and 12 without bladder symptoms to determine the quantity, location, distribution and activation of mast cells using immunohistochemistry with anti-mast cell tryptase. Patients were allocated to study groups by key bladder symptoms commonly used to define conditions (pain and major urgency). Subepithelial mast cell localization (p interstitial cystitis with Hunner lesions. The optimal cutoff of 32 detrusor mast cells per mm(2) achieved only 68% accuracy with 38% positive predictive value. No difference was observed between bladder pain syndrome/interstitial cystitis without Hunner lesions and overactive bladder syndrome. Patient groups differed in lymphocyte infiltration (p = 0.001), nodular lymphocyte aggregates (p interstitial cystitis with Hunner lesions. Detrusor mastocytosis had poor predictive value for bladder pain syndrome/interstitial cystitis. Mast cell assessment did not distinguish bladder pain syndrome/interstitial cystitis without Hunner lesions from overactive bladder syndrome. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  1. Appearance of interstitial cells of Cajal in the human midgut.

    Science.gov (United States)

    Abramovic, Mirjana; Radenkovic, Goran; Velickov, Aleksandra

    2014-04-01

    Several subtypes of the interstitial cells of Cajal (ICC) form networks that play a role in gastrointestinal motor control. ICC express c-kit and depend on signaling via Kit receptors for development and phenotype maintenance. At 7-8 weeks of development, c-kit-immunoreactive (c-kit-IR) cells are present in the human oesophagus, stomach and proximal duodenum wall. In the remaining small and large bowel, c-kit-IR cells appear later. The object of the present study is to determine the timing of the appearance of c-kit-IR ICC in the parts of the digestive tube originating from the midgut (distal duodenum, jejunum, ileum and proximal colon). Specimens were obtained from eight human embryos and 11 fetuses at 7-12 weeks of gestational age. The specimens were exposed to anti-c-kit antibodies to investigate ICC differentiation. The differentiation of enteric neurons and smooth muscle cells was immunohistochemically examined by using anti-PGP9,5 and anti-desmin antibodies, respectively. In the distal duodenum, jejunum and ileum, c-kit-IR cells emerged at week 9 at the level of the myenteric plexus in the form of a thin row of cells encircling the inception of the ganglia. These cells were multipolar or spindle-shaped with two long processes and corresponded to the ICC of the myenteric plexus. In the proximal colon, c-kit-IR cells emerged at week 9-10 in the form of two parallel belts of cells extending at the submucosal plexus and the myenteric plexus levels. We conclude that ICC develop following two different patterns in the human midgut.

  2. Follicle-stimulating hormone receptor-mediated uptake of 45Ca2+ by proteoliposomes and cultured rat sertoli cells: Evidence for involvement of voltage-activated and voltage-independent calcium channels

    International Nuclear Information System (INIS)

    Grasso, P.; Reichert, L.E. Jr.

    1989-01-01

    We have previously reported incorporation into liposomes of Triton X-100-solubilized FSH receptor-G-protein complexes derived from purified bovine calf testis membranes. In the present study we have used this model system to show that FSH induces flux of 45Ca2+ into such proteoliposomes in a hormone-specific concentration-dependent manner. FSH, inactivated by boiling, had no stimulatory effect on 45Ca2+ flux, nor did isolated alpha- or beta-subunits of FSH. Addition of GTP (or its analogs 5'-guanylylimidodiphosphate and guanosine-5'-O-[3-thiotriphosphate]) or sodium fluoride (in the presence or absence of GTP or its analogs) failed to induce 45Ca2+ flux into proteoliposomes, suggesting that the uptake of 45Ca2+ was receptor, and not G-protein, related. Voltage-independent (ruthenium red and gadolinium chloride) and voltage-activated (methyoxyverapamil and nifedipine) calcium channel-blocking agents reduced FSH-stimulated 45Ca2+ flux into proteoliposomes to control levels. FSH also induced uptake of 45Ca2+ by cultured rat Sertoli cells. Ruthenium red and gadolinium chloride had no effect on basal levels of 45Ca2+ uptake or estradiol secretion by cultured rat Sertoli cells, nor did methoxyverapamil or nifedipine. All four calcium channel blockers, however, were able to reduce FSH-induced 45Ca2+ uptake to basal levels and FSH-stimulated conversion of androstenedione to estradiol by up to 50%, indicating an involvement of Ca2+ in FSH-stimulated steroidogenesis. Our results suggest that the well documented changes in intracellular calcium levels consequent to FSH binding may be due, at least in part, to an influx of calcium through FSH receptor-regulated calcium channels

  3. Hormonal treatment may harm the germ cells in 1 to 3-year-old boys with cryptorchidism

    DEFF Research Database (Denmark)

    Cortes, Dina; Thorup, Jørgen Mogens; Visfeldt, J

    2000-01-01

    Hormonal treatment with human chorionic gonadotropin (HCG) or gonadotropin releasing hormone may be given initially for cryptorchidism. We evaluated whether hormonal treatment is safe for the germ cells in boys with cryptorchidism 1 to 3 years old in whom follicle-stimulating hormone, luteinizing...

  4. 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.

  5. Plexus muscularis profundus and associated interstitial cells. I. Light microscopical studies of mouse small intestine

    DEFF Research Database (Denmark)

    Rumessen, J J; Thuneberg, L

    1982-01-01

    interstitial cells (ICC-II) in the subserous layer. (2) Auerbach's plexus with an associated extensive plexus of interstitial cells (ICC-I) in close contact with tertiary fasciculi. (3) Nerve fasciculi of the outer division of the circular muscle layer. These formed a nerve plexus in a well-defined plane...... in the outermost cell layers (plexus muscularis superficialis), with few fasciculi located internal to this plexus. A few bipolar interstitial cells (ICC-IV) were associated with nerve fasciculi of this region. (4) A nerve plexus located in the region between the two subdivisions of the circular muscle, plexus...

  6. Stem Cell Therapy for Interstitial Cystitis/Bladder Pain Syndrome.

    Science.gov (United States)

    Kim, Aram; Shin, Dong-Myung; Choo, Myung-Soo

    2016-01-01

    Interstitial cystitis/bladder pain syndrome (IC/BPS) is a disease characterized by pelvic pain, usually with urinary frequency. These symptoms make patients suffer from a poor quality of life. However, there is still a lack of consensus on the pathophysiology and curable treatment of IC/BPS. We have reviewed several candidates for the pathophysiology of this disease and also treatments that have been used. Although several oral medications, bladder instillation therapies, fulguration for Hunner's lesion, and hydrodistention have been tried as IC/BPS treatments, their outcomes have not been satisfactory. As the application of stem cell therapy is expanding into the urologic field, innovative strategies have been tested with animal models of IC/BPS and have shown promising therapeutic effects for reversing the symptoms of this disorder. Although several concerns about stem cell sources and their safety should be addressed before initiating human clinical trials, we introduce stem cell therapy as a valuable future treatment approach for IC/BPS.

  7. 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, ...

  8. Interstitial cells of Cajal in the vermiform appendix in childhood.

    Science.gov (United States)

    Richter, A; Wit, C; Vanderwinden, J-M; Wit, J; Barthlen, W

    2009-02-01

    The interstitial cells of Cajal (ICC) have not yet been investigated in the vermiform appendix. They are important for the peristalsis of the gastrointestinal tract and have been found to be altered in various motility disorders. Motor disturbance has been suggested as a possible contributor in the unclear etiology of appendicitis. We wanted to examine the distribution of the ICC in the vermiform appendix. Furthermore we investigated whether ICC are altered in persons with appendicitis. We investigated the ICC distribution in 28 appendices of children using immunohistochemistry and anti-c-kit antibodies. Cells and processes were quantified in normal, acute and chronic inflamed appendices. IC(C)-CM and IC(C)-LM were found in the circular and longitudinal muscle layers, respectively. IC(C)-LM, however, were scarce and inhomogeneous in contrast to the IC(C)-CM. The functionally important subgroups of the colon, the IC(C)-SM and IC(C)-MP, however, could not be detected in the appendix with the used antibody. There was no difference in the distribution of detected ICC between normal and inflamed appendices. IC(C)-LM are altered and IC(C)-SM and IC(C)-MP are lost in the vermiform appendix with no differences between healthy and inflamed tissue and without a correlation to appendicitis. Thus, other factors must be considered in the etiology of appendicitis.

  9. The Glycoprofile Patterns of Endothelial Cells in Usual Interstitial Pneumonia

    Directory of Open Access Journals (Sweden)

    A Barkhordari

    2014-09-01

    Full Text Available [THIS ARTICLE HAS BEEN RETRACTED FOR DUPLICATE PUBLICATION] Background: The pathological classification of cryptogenic fibrosing alveolitis has been a matter of debate and controversy for histopathologists. Objective: To identify and specify the glycotypes of capillary endothelial cells in usual interstitial pneumonia (UIP compared to those found in normal tissue. Methods: Sections of formalin-fixed, paraffin-embedded blocks from 16 cases of UIP were studied by lectin histochemistry with a panel of 27 biotinylated lectins and an avidin-peroxidase revealing system. Results: High expression of several classes of glycan was seen de novo in capillary endothelial cells from patients with UIP including small complex and bi/tri-antennary bisected complex N-linked sequences bolund by Concanavalin A and erythro-phytohemagglutinin, respectively, GalNAca1 residues bound by Helix pomatia and Maclura pomifera agglutinins, and L-fucosylated derivatives of type II glycan chains recognized by Ulex europaeus agglutinin-I. Glycans bound by agglutinins from Lycopersicon esculentum (β1,4GlcNAc and Wisteria floribunda (GalNAc as well as GlcNAc oligomers bound by Phytolacca americana and succinylated Wheat Germ agglutinin were also seen in the capillary endothelial cells of UIP. In contrast, L-fucosylated derivatives of type I glycan chains were absent in cells from cases of UIP when Anguilla anguilla agglutinin was applied, unlike the situation in normal tissue. Conclusion: These results may indicate existence of two distinct populations of endothelial cell in UIP with markedly different patterns of glycosylation, reflecting a pattern of differentiation and angiogenesis, which is not detectable morphologically.

  10. 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.

  11. 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)

  12. 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

  13. 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.

  14. Muscarinic activation of Ca2+-activated Cl- current in interstitial cells of Cajal.

    Science.gov (United States)

    Zhu, Mei Hong; Sung, In Kyung; Zheng, Haifeng; Sung, Tae Sik; Britton, Fiona C; O'Driscoll, Kate; Koh, Sang Don; Sanders, Kenton M

    2011-09-15

    Interstitial cells of Cajal (ICC) provide pacemaker activity and functional bridges between enteric motor nerve terminals and gastrointestinal smooth muscle cells. The ionic conductance(s) in ICC that are activated by excitatory neural inputs are unknown. Transgenic mice (Kit(copGFP/+)) with constitutive expression of a bright green fluorescent protein were used to investigate cellular responses of ICC to cholinergic stimulation. ICC displayed spontaneous transient inward currents (STICs) under voltage clamp that corresponded to spontaneous transient depolarizations (STDs) under current clamp. STICs reversed at 0 mV when E(Cl) = 0 mV and at -40 mV when E(Cl) was -40 mV, suggesting the STICs were due to a chloride conductance. Carbachol (CCh, 100 nm and 1 μm) induced a sustained inward current (depolarization in current clamp) and increased the amplitude and frequency of STICs and STDs. CCh responses were blocked by atropine (10 μm) or 4-DAMP (100 nm), an M(3) receptor antagonist. STDs were blocked by niflumic acid and 5-nitro-2-(3-phenylpropylamino)-benzoic acid (both 100 μm), and CCh had no effect in the presence of these drugs. The responses of intact circular muscles to CCh and stimulation of intrinsic excitatory nerves by electrical field stimulation (EFS) were also compared. CCh (1 μm) caused atropine-sensitive depolarization and increased the maximum depolarization of slow waves. Similar atropine-sensitive responses were elicited by stimulation of intrinsic excitatory neurons. Niflumic acid (100 μm) blocked responses to EFS but had minor effect on responses to exogenous CCh. These data suggest that different ionic conductances are responsible for electrical responses elicited by bath-applied CCh and cholinergic nerve stimulation.

  15. Muscarinic activation of Ca2+-activated Cl− current in interstitial cells of Cajal

    Science.gov (United States)

    Zhu, Mei Hong; Sung, In Kyung; Zheng, Haifeng; Sung, Tae Sik; Britton, Fiona C; O'Driscoll, Kate; Koh, Sang Don; Sanders, Kenton M

    2011-01-01

    Abstract Interstitial cells of Cajal (ICC) provide pacemaker activity and functional bridges between enteric motor nerve terminals and gastrointestinal smooth muscle cells. The ionic conductance(s) in ICC that are activated by excitatory neural inputs are unknown. Transgenic mice (KitcopGFP/+) with constitutive expression of a bright green fluorescent protein were used to investigate cellular responses of ICC to cholinergic stimulation. ICC displayed spontaneous transient inward currents (STICs) under voltage clamp that corresponded to spontaneous transient depolarizations (STDs) under current clamp. STICs reversed at 0 mV when ECl = 0 mV and at –40 mV when ECl was –40 mV, suggesting the STICs were due to a chloride conductance. Carbachol (CCh, 100 nm and 1 μm) induced a sustained inward current (depolarization in current clamp) and increased the amplitude and frequency of STICs and STDs. CCh responses were blocked by atropine (10 μm) or 4-DAMP (100 nm), an M3 receptor antagonist. STDs were blocked by niflumic acid and 5-nitro-2-(3-phenylpropylamino)-benzoic acid (both 100 μm), and CCh had no effect in the presence of these drugs. The responses of intact circular muscles to CCh and stimulation of intrinsic excitatory nerves by electrical field stimulation (EFS) were also compared. CCh (1 μm) caused atropine-sensitive depolarization and increased the maximum depolarization of slow waves. Similar atropine-sensitive responses were elicited by stimulation of intrinsic excitatory neurons. Niflumic acid (100 μm) blocked responses to EFS but had minor effect on responses to exogenous CCh. These data suggest that different ionic conductances are responsible for electrical responses elicited by bath-applied CCh and cholinergic nerve stimulation. PMID:21768263

  16. 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.

  17. 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.

  18. 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

  19. 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

  20. 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

  1. 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...

  2. 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.

  3. 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

  4. 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...

  5. Influence of in vitro elaidic acid or trans-vaccenic acid uptake and lactogenic hormone stimulation on fatty acid content of mouse mammary cells

    OpenAIRE

    Baughman, Curtis Andrew

    1996-01-01

    The objective of the study was to examine the effects of trans-9-octadecenoic acid (elaidic) and trans-II-octadecenoic acid (trans-vaccenic) on uptake and alteration of exogenous fatty acids by mouse mammary epithelial cells. Cells from a subclone of the COMMA-D cell line were plated on uncoated plastic petri dishes and grown to confluence. Supplemental fatty acids bound to bovine serum albumin were added to the medium applied to the confluent cell cultures. Treatments included 200 JlM ...

  6. Nephron progenitor cell death elicits a limited compensatory response associated with interstitial expansion in the neonatal kidney

    Directory of Open Access Journals (Sweden)

    Sree Deepthi Muthukrishnan

    2018-01-01

    Full Text Available The final nephron number in an adult kidney is regulated by nephron progenitor cell availability and collecting duct branching in the fetal period. Fetal environmental perturbations that cause reductions in cell numbers in these two compartments result in low nephron endowment. Previous work has shown that maternal dietary factors influence nephron progenitor cell availability, with both caloric restriction and protein deprivation leading to reduced cell numbers through apoptosis. In this study, we evaluate the consequences of inducing nephron progenitor cell death on progenitor niche dynamics and on nephron endowment. Depletion of approximately 40% of nephron progenitor cells by expression of diphtheria toxin A at embryonic day 15 in the mouse results in 10-20% nephron reduction in the neonatal period. Analysis of cell numbers within the progenitor cell pool following induction of apoptosis reveals a compensatory response in which surviving progenitor cells increase their proliferation and replenish the niche. The proliferative response is temporally associated with infiltration of macrophages into the nephrogenic zone. Colony stimulating factor 1 (CSF1 has a mitogenic effect on nephron progenitor cells, providing a potential explanation for the compensatory proliferation. However, CSF1 also promotes interstitial cell proliferation, and the compensatory response is associated with interstitial expansion in recovering kidneys which can be pharmacologically inhibited by treatment with clodronate liposomes. Our findings suggest that the fetal kidney employs a macrophage-dependent compensatory regenerative mechanism to respond to acute injury caused by death of nephron progenitor cells, but that this regenerative response is associated with neonatal interstitial expansion.

  7. 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.

  8. 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

  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. Changes in Sexual Behavior of Orchidectomized Rats Under Influence of Allotransplantation of Testicular Interstitial Cell Suspension.

    Science.gov (United States)

    Deng, Bo; Bondarenko, Tatyana; Pakhomov, Oleksandr

    2017-05-09

    Transplantation of hormone-producing cells is an experimental endocrine dysfunction treatment. The present study investigated the effects of orchidectomy (OE) and transplantation of interstitial cell suspension (ICS) on rat sexual behavior. Adult experimental animals were divided into two populations. One of these populations had sexual experience before the experiment and the other did not. Each population was divided into three groups: control group and two orchidectomized groups. One of the orchidectomized groups was treated with ICS, and the other was treated with the vehicle. The changes in the sexual behavior were investigated on the following parameters: mount latency (ML), intromission latency (IL), ejaculation latency (EL), mount frequency (MF), intromission frequency (IF), copulatory efficacy (CE), and IF/EL ratio. The investigation of these changes lasted 4 weeks after ICS transplantation. The parameters of sexual behavior reflected a decrease in sexual function after OE at the beginning of the observation, especially for the animals that did not have a sexual experience. However, it was shown that sexual activity increased in the following 4 weeks. We have indicated that the loss of gonads attenuated the capacity to acquire sexual experience; nonetheless, it did not mean that the animals completely lost this capacity. Transplantation of ICS facilitated the maintenance of male sexual behavior after OE, fractionally enlarged the size of regressed seminal vesicles of the animals, and increased the free testosterone (T) level. These findings suggest the ICS can be considered as a temporal source of androgens, which can facilitate a restoration of sexual activity.

  11. Valvular interstitial cells suppress calcification of valvular endothelial cells

    NARCIS (Netherlands)

    Hjortnaes, Jesper; Shapero, Kayle; Goettsch, Claudia; Hutcheson, Joshua D; Keegan, Joshua; Kluin, J; Mayer, John E; Bischoff, Joyce; Aikawa, Elena

    BACKGROUND: Calcific aortic valve disease (CAVD) is the most common heart valve disease in the Western world. We previously proposed that valvular endothelial cells (VECs) replenish injured adult valve leaflets via endothelial-to-mesenchymal transformation (EndMT); however, whether EndMT contributes

  12. 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

  13. A new role for follicle-stimulating hormone in the regulation of calcium flux in Sertoli cells: Inhibition of Na+/Ca++ exchange

    International Nuclear Information System (INIS)

    Grasso, P.; Joseph, M.P.; Reichert, L.E. Jr.

    1991-01-01

    Elucidation of mechanisms regulating intracellular calcium levels in steroidogenic tissues is important for understanding control of cellular function. We have previously described FSH receptor-mediated flux of 45Ca++ into cultured rat Sertoli cells and receptor-enriched proteoliposomes via voltage-sensitive and voltage-independent calcium channels. In the present study, we report heretofore unrecognized inhibitory effects of FSH on Na+/Ca++ exchange in these two systems. An outwardly directed Na+ gradient, developed by preincubating Sertoli cell monolayers in buffer made hypertonic with NaCl, resulted in uptake of 45Ca++ that was unaffected by calcium channel blocking agents, ruthenium red or methoxyverapamil, but was enhanced by ouabain, a specific inhibitor of Na+/K(+)-ATPase. Sodium-dependent 45Ca++ flux into Sertoli cells was inhibited in a concentration-related manner by increased extracellular Na+ (up to 135 mM). FSH consistently and reproducibly (28.9 +/- 3.8%, 10 separate assays) reduced sodium-dependent 45Ca++ influx in the absence or presence of ouabain. A lesser effect on Na+/Ca++ exchange was seen when Li+ replaced Na+ in the preincubation buffer, and a marked reduction occurred when Sertoli cells were incubated in buffer containing KCl, presumably due to membrane depolarization. FSH-sensitive Na+/45Ca++ exchange was also observed when using FSH receptor-enriched proteoliposomes. Our earlier calcium channel studies indicated that FSH affects Ca++ entry into Sertoli cells via a receptor-mediated process. The results reported here demonstrate that the interaction of FSH with its receptor is associated with changes in Na+/Ca++ exchange as well, and suggest that this activity may also be involved in regulating intracellular free Ca++ levels in the Sertoli cell

  14. 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

  15. 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...

  16. Shear stress induced by an interstitial level of slow flow increases the osteogenic differentiation of mesenchymal stem cells through TAZ activation.

    Directory of Open Access Journals (Sweden)

    Kyung Min Kim

    Full Text Available Shear stress activates cellular signaling involved in cellular proliferation, differentiation, and migration. However, the mechanisms of mesenchymal stem cell (MSC differentiation under interstitial flow are not fully understood. Here, we show the increased osteogenic differentiation of MSCs under exposure to constant, extremely low shear stress created by osmotic pressure-induced flow in a microfluidic chip. The interstitial level of shear stress in the proposed microfluidic system stimulated nuclear localization of TAZ (transcriptional coactivator with PDZ-binding motif, a transcriptional modulator of MSCs, activated TAZ target genes such as CTGF and Cyr61, and induced osteogenic differentiation. TAZ-depleted cells showed defects in shear stress-induced osteogenic differentiation. In shear stress induced cellular signaling, Rho signaling pathway was important forthe nuclear localization of TAZ. Taken together, these results suggest that TAZ is an important mediator of interstitial flow-driven shear stress signaling in osteoblast differentiation of MSCs.

  17. Expression of Nestin, Vimentin, and NCAM by Renal Interstitial Cells after Ischemic Tubular Injury

    Directory of Open Access Journals (Sweden)

    David Vansthertem

    2010-01-01

    Full Text Available This work explores the distribution of various markers expressed by interstitial cells in rat kidneys after ischemic injury (35 minutes during regeneration of S3 tubules of outer stripe of outer medulla (OSOM. Groups of experimental animals (n=4 were sacrificed every two hours during the first 24 hours post-ischemia as well as 2, 3, 7, 14 days post-ischemia. The occurrence of lineage markers was analyzed on kidney sections by immunohistochemistry and morphometry during the process of tubular regeneration. In postischemic kidneys, interstitial cell proliferation, assessed by 5-bromo-2′-deoxyuridine (BrdU and Proliferating Cell Nuclear Antigen (PCNA labeling, was prominent in outer medulla and reach a maximum between 24 and 72 hours after reperfusion. This population was characterized by the coexpression of vimentin and nestin. The density of -Neural Cell Adhesion Molecule (NCAM positive interstitial cells increased transiently (18–72 hours in the vicinity of altered tubules. We have also localized a small population of α-Smooth Muscle Actin (SMA-positive cells confined to chronically altered areas and characterized by a small proliferative index. In conclusion, we observed in the postischemic kidney a marked proliferation of interstitial cells that underwent transient phenotypical modifications. These interstitial cells could be implicated in processes leading to renal fibrosis.

  18. In vitro effect of 4-nonylphenol on human chorionic gonadotropin (hCG) stimulated hormone secretion, cell viability and reactive oxygen species generation in mice Leydig cells.

    Science.gov (United States)

    Jambor, Tomáš; Tvrdá, Eva; Tušimová, Eva; Kováčik, Anton; Bistáková, Jana; Forgács, Zsolt; Lukáč, Norbert

    2017-03-01

    Nonylphenol is considered an endocrine disruptor and has been reported to affect male reproductive functions. In our in vitro study, we evaluated the effects of 4-nonylphenol (4-NP) on cholesterol levels, hormone formation and viability in cultured Leydig cells from adult ICR male mice. We also determined the potential impact of 4-NP on generation of reactive oxygen species (ROS) after 44 h of cultivation. The cells were cultured with addition of 0.04; 0.2; 1.0; 2.5 and 5.0 μg/mL of 4-NP in the present of 1 IU/mL human chorionic gonadotropin (hCG) and compared to the control. The quantity of cholesterol was determined from culture medium using photometry. Determination of hormone production was performed by enzyme-linked immunosorbent assay. Metabolic activity assay was used for quantification of cell viability. The chemiluminescence technique, which uses a luminometer to measure reactive oxygen species, was employed. Applied doses of 4-NP (0.04-5.0 μg/mL) slight increase cholesterol levels and decrease production of dehydroepiandrosterone after 44 h of cultivation, but not significantly. Incubation of 4-NP treated cells with hCG significantly (P < 0.001) inhibited androstenedione, but not testosterone, formation at the highest concentration (5.0 μg/mL). The viability was significantly (P < 0.05); (P < 0.001) increased at 1.0; 2.5 and 5.0 μg/mL of 4-NP after 44 h treatment. Furthermore, 44 h treatment of 4-NP (0.04-5.0 μg/mL) caused significant (P < 0.001) intracellular accumulation of ROS in exposed cells. Taken together, the results of our in vitro study reported herein is consistent with the conclusion that 4-nonylphenol is able to influence hormonal profile, cell viability and generate ROS. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. 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

  20. Gastrointestinal peristalsis: joint action of enteric nerves, smooth muscle, and interstitial cells of Cajal.

    Science.gov (United States)

    Huizinga, J D

    1999-11-15

    Peristalsis is a propulsive motor pattern orchestrated by neuronal excitation and inhibition in cooperation with intrinsic muscular control mechanisms, including those residing in interstitial cells of Cajal (ICC). Interstitial cells of Cajal form a network of cells in which electrical slow waves originate and then propagate into the musculature initiating rhythmic contractile activity upon excitaton by enteric nerves. Interstitial cells of Cajal have now been isolated and their intrinsic properties reveal the presence of rhythmic inward currents not found in smooth muscle cells. In tissues where classical slow waves are not present, enteric cholinergic excitation will evoke slow wave-like activity that forces action potentials to occur in a rhythmic manner. Intrinsic and induced slow wave activity directs many of the peristaltic motor patterns in the gut. Copyright 1999 Wiley-Liss, Inc.

  1. Interstitial cells of Cajal in the striated musculature of the mouse esophagus

    DEFF Research Database (Denmark)

    Rumessen, J J; de Kerchove d'Exaerde, A; Mignon, S

    2001-01-01

    Interstitial cells of Cajal (ICC) are important regulatory cells in the smooth muscle coats of the digestive tract. Expression of the Kit receptor tyrosine kinase was used in this study as a marker to study their distribution and development in the striated musculature of the mouse esophagus...... scarce in both muscle layers of the thoracic esophagus, while their number increased steeply toward the cardia in the striated portion of the intraabdominal esophagus. They did not form networks and had no relationship with intrinsic myenteric ganglia and motor end-plates. They were often close to nerve...... but absent in adult ICC-deficient KitW-lacZ/KitWv mice. Interstitial cells of Cajal were identified by electron microscopy by their ultrastructure in the striated muscle of the esophagus and exhibited Xgal labeling, while fibroblasts and muscle cells were unlabeled. Interstitial cells of Cajal are scattered...

  2. Dienogest, a selective progestin, reduces plasma estradiol level through induction of apoptosis of granulosa cells in the ovarian dominant follicle without follicle-stimulating hormone suppression in monkeys.

    Science.gov (United States)

    Sasagawa, S; Shimizu, Y; Nagaoka, T; Tokado, H; Imada, K; Mizuguchi, K

    2008-07-01

    Dienogest is a selective progestin that has been shown to arrest ovarian follicular development in women, without affecting gonadotropin secretion. As luteal progesterone or exogeneous progestins are known to suppress ovarian folliculogenesis via the inhibition of gonadotropin secretion, this action of dienogest on ovaries seems to be unique. To examine the underlying mechanism of the antifolliculogenic effect of dienogest, female cynomolgus monkeys were treated with a single oral dose of 0.1 mg/kg dienogest on day 7 of the menstrual cycle. Plasma FSH, estradiol (E2), and progesterone levels were measured up to 15 days after dosing. In an additional experiment, ovaries were excised 24 h after dosing for histological examinations. As a result, plasma E2 level declined within 24 h after dosing, while dienogest did not decreased FSH level prior to E2 decline. After decline of E2 level, the low level of E2 was sustained for more than 11 days. It is considered that a single oral dose of dienogest induced atresia of the dominant follicle. In the histological examination, two out of three animals showed decline in E2 level. The ovarian dominant follicles from these animals showed apoptotic changes in granulosa cells with scattered aromatase expression within 24 h after dosing. These results indicate that the induction of atresia of the ovarian dominant follicle by direct action would be a possible mechanism of dienogest to inhibit plasma E2 level.

  3. Hormonal regulation of Na -K -ATPase in cultured epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, J.P.; Jones, D.; Wiesmann, W.P.

    1986-08-01

    Aldosterone and insulin stimulate Na transport through mechanisms involving protein synthesis. Na -K -ATPase has been implicated in the action of both hormones. The authors examined the effect of aldosterone and insulin on Na -K -ATPase in epithelial cells in culture derived from toad urinary bladder (TB6C) and toad kidney (A6). Aldosterone, but not insulin, increases short-circuit current (I/sub sc/) in TB6C cells. Aldosterone increases Na -K -(TSP)ATPase activity after 18 h of incubation, but no effect can be seen at 3 and 6 h. Amiloride, which inhibits aldosterone-induced increases in I/sub sc/, has no effect on either basal or aldosterone stimulated enzyme activity. Both aldosterone and insulin increase I/sub sc/ in A6 cells and when added together are synergistic. Aldosterone stimulates enzyme activity in A6 cells, but insulin alone has no effect. However, aldosterone and insulin together stimulate enzyme activity more than aldosterone alone. It appears that stimulation of Na -K -ATPase activity is involved in aldosterone action in both cell lines but does not appear to be due to increased Na entry, since enhanced enzyme activity is not inhibited by amiloride. In contrast, insulin alone has no direct effect on Na -K -ATPase, although the increased enzyme activity following both agents in combination may explain their synergism on I/sub sc/.

  4. Mechanisms of action of nonpeptide hormones on resveratrol-induced antiproliferation of cancer cells.

    Science.gov (United States)

    Lin, Hung-Yun; Hsieh, Meng-Ti; Cheng, Guei-Yun; Lai, Hsuan-Yu; Chin, Yu-Tang; Shih, Ya-Jung; Nana, André Wendindondé; Lin, Shin-Ying; Yang, Yu-Chen S H; Tang, Heng-Yuan; Chiang, I-Jen; Wang, Kuan

    2017-09-01

    Nonpeptide hormones, such as thyroid hormone, dihydrotestosterone, and estrogen, have been shown to stimulate cancer proliferation via different mechanisms. Aside from their cytosolic or membrane-bound receptors, there are receptors on integrin α v β 3 for nonpeptide hormones. Interaction between hormones and integrin α v β 3 can induce signal transduction and eventually stimulate cancer cell proliferation. Resveratrol induces inducible COX-2-dependent antiproliferation via integrin α v β 3 . Resveratrol and hormone-induced signals are both transduced by activated extracellular-regulated kinases 1 and 2 (ERK1/2); however, hormones promote cell proliferation, while resveratrol induces antiproliferation in cancer cells. Hormones inhibit resveratrol-stimulated phosphorylation of p53 on Ser15, resveratrol-induced nuclear COX-2 accumulation, and formation of p53-COX-2 nuclear complexes. Subsequently, hormones impair resveratrol-induced COX-2-/p53-dependent gene expression. The inhibitory effects of hormones on resveratrol action can be blocked by different antagonists of specific nonpeptide hormone receptors but not integrin α v β 3 blockers. Results suggest that nonpeptide hormones inhibit resveratrol-induced antiproliferation in cancer cells downstream of the interaction between ligand and receptor and ERK1/2 activation to interfere with nuclear COX-2 accumulation. Thus, the surface receptor sites for resveratrol and nonpeptide hormones are distinct and can induce discrete ERK1/2-dependent downstream antiproliferation biological activities. It also indicates the complex pathways by which antiproliferation is induced by resveratrol in various physiological hormonal environments. . © 2017 New York Academy of Sciences.

  5. 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.

  6. 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

  7. 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

  8. 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

  9. Effects of growth hormone-releasing hormone on sleep and brain interstitial fluid amyloid-β in an APP transgenic mouse model.

    Science.gov (United States)

    Liao, Fan; Zhang, Tony J; Mahan, Thomas E; Jiang, Hong; Holtzman, David M

    2015-07-01

    Alzheimer's disease (AD) is a neurodegenerative disorder characterized by impairment of cognitive function, extracellular amyloid plaques, intracellular neurofibrillary tangles, and synaptic and neuronal loss. There is substantial evidence that the aggregation of amyloid β (Aβ) in the brain plays a key role in the pathogenesis of AD and that Aβ aggregation is a concentration dependent process. Recently, it was found that Aβ levels in the brain interstitial fluid (ISF) are regulated by the sleep-wake cycle in both humans and mice; ISF Aβ is higher during wakefulness and lower during sleep. Intracerebroventricular infusion of orexin increased wakefulness and ISF Aβ levels, and chronic sleep deprivation significantly increased Aβ plaque formation in amyloid precursor protein transgenic (APP) mice. Growth hormone-releasing hormone (GHRH) is a well-documented sleep regulatory substance which promotes non-rapid eye movement sleep. GHRHR(lit/lit) mice that lack functional GHRH receptor have shorter sleep duration and longer wakefulness during light periods. The current study was undertaken to determine whether manipulating sleep by interfering with GHRH signaling affects brain ISF Aβ levels in APPswe/PS1ΔE9 (PS1APP) transgenic mice that overexpress mutant forms of APP and PSEN1 that cause autosomal dominant AD. We found that intraperitoneal injection of GHRH at dark onset increased sleep and decreased ISF Aβ and that delivery of a GHRH antagonist via reverse-microdialysis suppressed sleep and increased ISF Aβ. The diurnal fluctuation of ISF Aβ in PS1APP/GHRHR(lit/lit) mice was significantly smaller than that in PS1APP/GHRHR(lit/+) mice. However despite decreased sleep in GHRHR deficient mice, this was not associated with an increase in Aβ accumulation later in life. One of several possibilities for the finding is the fact that GHRHR deficient mice have GHRH-dependent but sleep-independent factors which protect against Aβ deposition. Copyright © 2014

  10. 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…

  11. 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

  12. Inherent rhythmcity and interstitial cells of Cajal in a frog vein

    Indian Academy of Sciences (India)

    Interstitial cells of Cajal are responsible for rhythmic contractions of the musculature of the gastrointestinal tract and blood vessels. The existence of these cells and spontaneous rhythmicity were noticed in amphibian vein and the findings are reported in this paper. The postcaval vein was identified in the frog, Rana tigrina ...

  13. Inherent rhythmcity and interstitial cells of Cajal in a frog vein

    Indian Academy of Sciences (India)

    PRAKASH KUMAR

    substance(s), which depolarizes the smooth muscle cells of the blood vessel. While the role of the ICC ... Interstitial cells of Cajal are responsible for rhythmic contractions of the musculature of the gastrointestinal tract and blood vessels. ... decreased, while warm Ringer increased, the rate of contraction. Adrenaline caused ...

  14. Interstitial cells of Cajal in the striated musculature of the mouse esophagus

    DEFF Research Database (Denmark)

    Rumessen, J J; de Kerchove d'Exaerde, A; Mignon, S

    2001-01-01

    Interstitial cells of Cajal (ICC) are important regulatory cells in the smooth muscle coats of the digestive tract. Expression of the Kit receptor tyrosine kinase was used in this study as a marker to study their distribution and development in the striated musculature of the mouse esophagus. Sec...

  15. Ultrastructural and immunocytochemical characterization of interstitial cells in pre- and postnatal developing sheep pineal gland

    Directory of Open Access Journals (Sweden)

    E Redondo

    2009-12-01

    Full Text Available Pineal gland interstitial cells from 32 sheep embryos (from day 54 of gestation until birth and 18 sheep (from 1 month to >2 years were analysed using ultrastructural and immunohistochemical techniques. From day 98 of gestation and throughout postnatal development, a second cell type was observed in addition to pinealocytes; these cells displayed uniform ultrastructural features similar to those of CNS astrocytes. Ultrastructural homogeneity was not matched by the results of histochemical and immunohistochemical analysis. Expression of phosphotungstic acid hematoxylin, glial fibrillary acidic protein and vimentin indicates that the second cell population in the developing ovine pineal gland is, in fact, a combination of glial-astrocyte cells at varying stages of maturity. Pineal interstitial cells started to show signs of functional activity evident in vascular tropism; such activity, evident from around day 98 of gestation, appeared to relate to the exchange of substances between the pineal parenchyma and blood vessels and, though it continued throughout postnatal development, was most evident in animals slaughtered between 9 months and 2 years of age (group II. Morphologically, functional activi- ty in interstitial cells in this age-group was apparent in: 1, formation of specific contact sites between interstitial cells and nerve fibres in the perivascular space; and 2, the presence of numerous gap junctions between the bulbous endings of cytoplasmic processes.

  16. Ultrastructure of interstitial cells of Cajal at the colonic submuscular border in patients with ulcerative colitis

    DEFF Research Database (Denmark)

    Rumessen, J J

    1996-01-01

    Submuscular interstitial cells of Cajal (ICC) are putative pacemaker cells of the colonic external muscle. Although motility disturbances and smooth muscle dysfunction are prevalent in patients with ulcerative colitis (UC), ICC have never been studied in this disease. The aim of this study...... was to examine the ultrastructure of submuscular ICC in UC....

  17. Superficial leiomyomas of the gastrointestinal tract with interstitial cells of Cajal

    OpenAIRE

    Janevska, Vesna; Qerimi, Adelina; Basheska, Neli; Stojkova, Elena; Janevski, Vlado; Jovanovic, Rubens; Zhivadinovik, Julija; Spasevska, Liljana

    2015-01-01

    Objective: Some authors suggest common origin of gastrointestinal stromal tumors from stem cells, which may show diverse differentiation. There are reports in which cells morphologically identical to the interstitial cells of Cajal are found in deep leiomyomas. The aim of this study was to demonstrate CD117 positive cells in superficial gastrointestinal (GI) leiomyomas and to find other cells that would suggest diverse differentiation in histologically typical leiomyoma. Materials and methods...

  18. Cloning and Expression of Luteinizing Hormone Subunits in Chinese Hamster Ovary Cell Line

    Directory of Open Access Journals (Sweden)

    Zeinab Soleimanifar

    2016-10-01

    Full Text Available Background: Luteinizing hormone (LH was secreted by the stimulating cells of the testes and ovaries in the anterior pituitary gland. The application of this hormone is in the treatment of men and women with infertility and amenorrhea respectively.Materials and Methods: In the present study the alpha and beta subunits of human LH gene were cloned into the pEGFP-N1 expression vector and produced the recombinant LH hormone in Chinese hamster ovary (CHO eukaryotic system.Results: Alpha and beta subunits of LH hormone were cloned between NheI and BamHI cut sites of pEGFP_N1 expression plasmid and confirmed by PCR.  Hormone expression was evaluated in CHO cell line by Western blotting using the specific antibody.Conclusion: Alpha and beta subunits of LH hormone were expressed in CHO cell line perfectly.

  19. 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....

  20. Intravascular Large B-Cell Lymphoma Presenting as Interstitial Lung Disease

    Directory of Open Access Journals (Sweden)

    Elham Vali Khojeini

    2014-01-01

    Full Text Available Intravascular large B-cell lymphoma (IVLBL is a rare subtype of diffuse large B-cell lymphoma that resides in the lumen of blood vessels. Patients typically present with nonspecific findings, particularly bizarre neurologic symptoms, fever, and skin lesions. A woman presented with shortness of breath and a chest CT scan showed diffuse interstitial thickening and ground glass opacities suggestive of an interstitial lung disease. On physical exam she was noted to have splenomegaly. The patient died and at autopsy was found to have an IVLBL in her lungs as well as nearly all her organs that were sampled. Although rare, IVLBL should be included in the differential diagnosis of interstitial lung disease and this case underscores the importance of the continuation of autopsies.

  1. Clinical role in biopsy after interstitial irradiation to squamous cell carcinoma of tongue

    International Nuclear Information System (INIS)

    Sato, Tomoichi

    1995-01-01

    The clinical role of biopsy after interstitial irradiation therapy was evaluated in 44 patients with squamous cell carcinoma of tongue on which biopsy was done in our hospital. More residual tumors were observed in the induration-positive groups compared to those of the induration-negative groups. No tumor was histologically observed in 71.4% of the induration-positive groups. On the adjacent and covering mucous membranes, epithelial dysplasia was detected in 15 patients, 1 of them was Grade III and 9 were Grade IV. Two patients had recurrence. In the initial stage of interstitial irradiation, reaction of stoma showed decrease of edema, inflammatory cell infiltration, regeneration and dilation of vessels after 6 weeks. The regeneration of collagen fiber increased within 3-14 weeks after irradiation, followed by decrease of its activity. After interstitial irradiation, 2 of 9 Grade IIb patients treated by surgery and 2 by re-interstitial irradiation survived. One of 3 Grade III patients manifested recurrence and was treated by surgery. All patients were alive. Fourteen of 17 Grade IV patients under careful observation were still alive. Eleven of 15 patients treated by total neck dissection after interstitial irradiation survived. Four Grade IV patients showed recurrence. Two-year primary lesion control rate was 91.2% and the survival rate for 5 year was 74.0%. (S.Y.). 54 refs

  2. Gene Profiling of Aortic Valve Interstitial Cells under Elevated Pressure Conditions: Modulation of Inflammatory Gene Networks

    Directory of Open Access Journals (Sweden)

    James N. Warnock

    2011-01-01

    Full Text Available The study aimed to identify mechanosensitive pathways and gene networks that are stimulated by elevated cyclic pressure in aortic valve interstitial cells (VICs and lead to detrimental tissue remodeling and/or pathogenesis. Porcine aortic valve leaflets were exposed to cyclic pressures of 80 or 120 mmHg, corresponding to diastolic transvalvular pressure in normal and hypertensive conditions, respectively. Linear, two-cycle amplification of total RNA, followed by microarray was performed for transcriptome analysis (with qRT-PCR validation. A combination of systems biology modeling and pathway analysis identified novel genes and molecular mechanisms underlying the biological response of VICs to elevated pressure. 56 gene transcripts related to inflammatory response mechanisms were differentially expressed. TNF-α, IL-1α, and IL-1β were key cytokines identified from the gene network model. Also of interest was the discovery that pentraxin 3 (PTX3 was significantly upregulated under elevated pressure conditions (41-fold change. In conclusion, a gene network model showing differentially expressed inflammatory genes and their interactions in VICs exposed to elevated pressure has been developed. This system overview has detected key molecules that could be targeted for pharmacotherapy of aortic stenosis in hypertensive patients.

  3. 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.

  4. 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.

  5. 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...

  6. Primary rat Sertoli and interstitial cells exhibit a differential response to cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Clough, S.R.; Welsh, M.J.; Payne, A.H.; Brown, C.D.; Brabec, M.J. (Eastern Michigan Univ., Ypsilanti (USA))

    1990-01-01

    Two cell types central to the support of spermatogenesis, the Sertoli cell and the interstitial (Leydig) cell, were isolated from the same cohort of young male rats and challenged with cadmium chloride to compare their susceptibility to the metal. Both cell types were cultured under similar conditions, and similar biochemical endpoints were chosen to minimize experimental variability. These endpoints include the uptake of 109Cd, reduction of the vital tetrazolium dye MTT, incorporation of 3H-leucine, change in heat-stable cadmium binding capacity, and production of lactate. Using these parameters, it was observed that the Sertoli cell cultures were adversely affected in a dose-and time-dependent manner, while the interstitial cell cultures, treated with identical concentrations of CdCl2, were less affected. The 72-hr LC50's for Sertoli cells and interstitial cells were 4.1 and 19.6 microM CdCl2, respectively. Thus, different cell populations within the same tissue may differ markedly in susceptibility to a toxicant. These in vitro data suggest that the Sertoli cell, in relation to the interstitium, is particularly sensitive to cadmium. Because the Sertoli cell provides functional support for the seminiferous epithelium, the differential sensitivity of this cell type may, in part, explain cadmium-induced testicular dysfunction, particularly at doses that leave the vascular epithelium intact.

  7. Pancreatic beta-cell lipotoxicity induced by overexpression of hormone-sensitive lipase

    DEFF Research Database (Denmark)

    Winzell, Maria Sörhede; Svensson, Håkan; Enerbäck, Sven

    2003-01-01

    Lipid perturbations associated with triglyceride overstorage in beta-cells impair insulin secretion, a process termed lipotoxicity. To assess the role of hormone-sensitive lipase, which is expressed and enzymatically active in beta-cells, in the development of lipotoxicity, we generated transgenic...... mice overexpressing hormone-sensitive lipase specifically in beta-cells. Transgenic mice developed glucose intolerance and severely blunted glucose-stimulated insulin secretion when challenged with a high-fat diet. As expected, both lipase activity and forskolin-stimulated lipolysis was increased...

  8. 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.

  9. Differential gene expression in the murine gastric fundus lacking interstitial cells of Cajal

    Directory of Open Access Journals (Sweden)

    Ward Sean M

    2003-06-01

    Full Text Available Abstract Background The muscle layers of murine gastric fundus have no interstitial cells of Cajal at the level of the myenteric plexus and only possess intramuscular interstitial cells and this tissue does not generate electric slow waves. The absence of intramuscular interstitial cells in W/WV mutants provides a unique opportunity to study the molecular changes that are associated with the loss of these intercalating cells. Method The gene expression profile of the gastric fundus of wild type and W/WV mice was assayed by murine microarray analysis displaying a total of 8734 elements. Queried genes from the microarray analysis were confirmed by semi-quantitative reverse transcription-polymerase chain reaction. Results Twenty-one genes were differentially expressed in wild type and W/WV mice. Eleven transcripts had 2.0–2.5 fold higher mRNA expression in W/WV gastric fundus when compared to wild type tissues. Ten transcripts had 2.1–3.9 fold lower expression in W/WV mutants in comparison with wild type animals. None of these genes have ever been implicated in any bowel motility function. Conclusions These data provides evidence that several important genes have significantly changed in the murine fundus of W/WV mutants that lack intramuscular interstitial cells of Cajal and have reduced enteric motor neurotransmission.

  10. 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.

  11. 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...

  12. 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...

  13. 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.

  14. Ultrastructure of Cajal-like interstitial cells in the human detrusor

    DEFF Research Database (Denmark)

    Rasmussen, Helle; Rumessen, Jüri J; Hansen, Alastair

    2009-01-01

    The aim of this ultrastructural study was to examine the human detrusor for interstitial cells of Cajal (ICC)-like cells (ICC-L) by conventional transmission electron microscopy (TEM) and immuno-transmission electron microscopy (I-TEM) with antibodies directed towards CD117 and CD34. Two main types...... of interstitial cells were identified by TEM: ICC-L and fibroblast-like cells (FLC). ICC-L were bipolar with slender (0.04 microm) flattened dendritic-like processes, frequently forming a branching labyrinth network. Caveolae and short membrane-associated dense bands were present. Mitochondria, rough endoplasmic...... reticulum and Golgi apparatus were observed in the cell somata and cytoplasmic processes. Intermediate filaments were abundant but no thick filaments were found. ICC-L were interconnected by close appositions, gap junctions and peg-and-socket junctions (PSJ) but no specialised contacts to smooth muscle...

  15. Ultrastructure of interstitial cells of Cajal associated with deep muscular plexus of human small intestine

    DEFF Research Database (Denmark)

    Rumessen, J J; Mikkelsen, H B; Thuneberg, L

    1992-01-01

    Evidence showing that interstitial cells of Cajal have important regulatory functions in the gut musculature is accumulating. In the current study, the ultrastructure of the deep muscular plexus and associated interstial cells of Cajal in human small intestine were studied to provide a reference...... for identification and further physiological or pathological studies. The deep muscular plexus was sandwiched between a thin inner layer of smooth muscle (one to five cells thick) and the bulk of the circular muscle. Interstitial cells of Cajal in this region very much resembled smooth muscle cells (with...... distinguished from fibroblasts or macrophages in the region. They ramified in the inner zone of the outer division of circular muscle, penetrated the inner-most circular layer, and were also found at the submucosal border. They were in close, synapselike contact with nerve terminals of the deep muscular plexus...

  16. Hormonal treatment may harm the germ cells in 1 to 3-year-old boys with cryptorchidism

    DEFF Research Database (Denmark)

    Cortes, D; Thorup, J; Visfeldt, J

    2000-01-01

    PURPOSE: Hormonal treatment with human chorionic gonadotropin (HCG) or gonadotropin releasing hormone may be given initially for cryptorchidism. We evaluated whether hormonal treatment is safe for the germ cells in boys with cryptorchidism 1 to 3 years old in whom follicle-stimulating hormone...... received HCG and 45 underwent orchiopexy without hormonal therapy. Groups were otherwise equal. RESULTS: Patients who underwent surgery only had a higher number of spermatogonia per tubule than those in whom hormonal treatment was unsuccessful (p... after surgery alone (p = 0.06). Gonadotropin releasing hormone and HCG influenced germ cells equally. CONCLUSIONS: In 1 to 3-year-old boys with cryptorchidism gonadotropin releasing hormone or HCG given for testicular descent may suppress the number of germ cells....

  17. Distribution and ultrastructure of interstitial cells of Cajal in the mouse colon, using antibodies to Kit and Kit(W-lacZ) mice

    DEFF Research Database (Denmark)

    Vanderwinden, J M; Rumessen, J J; Bernex, F

    2000-01-01

    The roles of the interstitial cells of Cajal in the stomach and intestine are becoming increasingly clear. Interstitial cells of Cajal in the colon are less well known, however. We studied the development and distribution of the interstitial cells of Cajal in the mouse colon, using the tyrosine k...

  18. Follicle-stimulating hormone receptor-mediated uptake of 45Ca2+ by cultured rat Sertoli cells does not require activation of cholera toxin- or pertussis toxin-sensitive guanine nucleotide binding proteins or adenylate cyclase

    International Nuclear Information System (INIS)

    Grasso, P.; Reichert, L.E. Jr.

    1990-01-01

    We have previously reported that FSH stimulates flux of 45Ca2+ into cultured Sertoli cells from immature rats via voltage-sensitive and voltage-independent calcium channels. In the present study, we show that this effect of FSH does not require cholera toxin (CT)- or pertussis toxin (PT)-sensitive guanine nucleotide binding (G) protein or activation of adenylate cyclase (AC). Significant stimulation of 45Ca2+ influx was observed within 1 min, and maximal response (3.2-fold over basal levels) was achieved within 2 min after exposure to FSH. FSH-stimulated elevations in cellular cAMP paralleled increases in 45Ca2+ uptake, suggesting a possible coupling of AC activation to 45Ca2+ influx. (Bu)2cAMP, however, was not able to enhance 45Ca2+ uptake over basal levels at a final concentration of 1000 microM, although a concentration-related increase in androstenedione conversion to estradiol was evident. Exposure of Sertoli cells to CT (10 ng/ml) consistently stimulated basal levels of androstenedione conversion to estradiol but had no effect on basal levels of 45Ca2+ uptake. Similarly, CT had no effect on FSH-induced 45Ca2+ uptake, but potentiated FSH-stimulated estradiol synthesis. PT (10 ng/ml) augmented basal and FSH-stimulated estradiol secretion without affecting 45Ca2+ influx. The adenosine analog N6-phenylisopropyladenosine, which binds to Gi-coupled adenosine receptors on Sertoli cells, inhibited FSH-stimulated androgen conversion to estradiol in a dose-related (1-1000 nM) manner, but FSH-stimulated 45Ca2+ influx remained unchanged. Our results show that in contrast to FSH-stimulated estradiol synthesis, the flux of 45Ca2+ into Sertoli cells in response to FSH is not mediated either directly or indirectly by CT- or PT-sensitive G protein, nor does it require activation of AC. Our data further suggest that the FSH receptor itself may function as a calcium channel

  19. Follicle-stimulating hormone receptor-mediated uptake of sup 45 Ca sup 2+ by cultured rat Sertoli cells does not require activation of cholera toxin- or pertussis toxin-sensitive guanine nucleotide binding proteins or adenylate cyclase

    Energy Technology Data Exchange (ETDEWEB)

    Grasso, P.; Reichert, L.E. Jr. (Albany Medical College, NY (USA))

    1990-08-01

    We have previously reported that FSH stimulates flux of 45Ca2+ into cultured Sertoli cells from immature rats via voltage-sensitive and voltage-independent calcium channels. In the present study, we show that this effect of FSH does not require cholera toxin (CT)- or pertussis toxin (PT)-sensitive guanine nucleotide binding (G) protein or activation of adenylate cyclase (AC). Significant stimulation of 45Ca2+ influx was observed within 1 min, and maximal response (3.2-fold over basal levels) was achieved within 2 min after exposure to FSH. FSH-stimulated elevations in cellular cAMP paralleled increases in 45Ca2+ uptake, suggesting a possible coupling of AC activation to 45Ca2+ influx. (Bu)2cAMP, however, was not able to enhance 45Ca2+ uptake over basal levels at a final concentration of 1000 microM, although a concentration-related increase in androstenedione conversion to estradiol was evident. Exposure of Sertoli cells to CT (10 ng/ml) consistently stimulated basal levels of androstenedione conversion to estradiol but had no effect on basal levels of 45Ca2+ uptake. Similarly, CT had no effect on FSH-induced 45Ca2+ uptake, but potentiated FSH-stimulated estradiol synthesis. PT (10 ng/ml) augmented basal and FSH-stimulated estradiol secretion without affecting 45Ca2+ influx. The adenosine analog N6-phenylisopropyladenosine, which binds to Gi-coupled adenosine receptors on Sertoli cells, inhibited FSH-stimulated androgen conversion to estradiol in a dose-related (1-1000 nM) manner, but FSH-stimulated 45Ca2+ influx remained unchanged. Our results show that in contrast to FSH-stimulated estradiol synthesis, the flux of 45Ca2+ into Sertoli cells in response to FSH is not mediated either directly or indirectly by CT- or PT-sensitive G protein, nor does it require activation of AC. Our data further suggest that the FSH receptor itself may function as a calcium channel.

  20. 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

  1. Interstitial mononuclear cell infiltrates in chronic rejection of the kidney and correlation with peripheral blood.

    OpenAIRE

    Jeong, H. J.; Hong, S. W.; Kim, Y. S.; Kim, M. S.; Choi, I. H.; Park, K.; Choi, I. J.

    1996-01-01

    To investigate the characteristics of interstitial inflammatory cells and possible involvement of nudelta T cells, 16 renal allograft biopsies showing chronic rejection were stained by immunohistochemical method and correlated with the data of peripheral blood evaluated by flow cytometry. For immunophenotyping, fresh frozen sections were stained with monoclonal antibodies against CD3, CD4, CD8, CD68, CD56, TCRdelta1 and HLA DR. Paraffin embedded tissue was stained with CD45RO, CD20-Cy and CD6...

  2. The Potential for Gut Organoid Derived Interstitial Cells of Cajal in Replacement Therapy

    OpenAIRE

    Jerry Zhou; Michael D. O’Connor; Vincent Ho

    2017-01-01

    Effective digestion requires propagation of food along the entire length of the gastrointestinal tract. This process involves coordinated waves of peristalsis produced by enteric neural cell types, including different categories of interstitial cells of Cajal (ICC). Impaired food transport along the gastrointestinal tract, either too fast or too slow, causes a range of gut motility disorders that affect millions of people worldwide. Notably, loss of ICC has been shown to affect gut motility. ...

  3. Generation of breast cancer stem cells by steroid hormones in irradiated human mammary cell lines.

    Directory of Open Access Journals (Sweden)

    Guillaume Vares

    Full Text Available Exposure to ionizing radiation was shown to result in an increased risk of breast cancer. There is strong evidence that steroid hormones influence radiosensitivity and breast cancer risk. Tumors may be initiated by a small subpopulation of cancer stem cells (CSCs. In order to assess whether the modulation of radiation-induced breast cancer risk by steroid hormones could involve CSCs, we measured by flow cytometry the proportion of CSCs in irradiated breast cancer cell lines after progesterone and estrogen treatment. Progesterone stimulated the expansion of the CSC compartment both in progesterone receptor (PR-positive breast cancer cells and in PR-negative normal cells. In MCF10A normal epithelial PR-negative cells, progesterone-treatment and irradiation triggered cancer and stemness-associated microRNA regulations (such as the downregulation of miR-22 and miR-29c expression, which resulted in increased proportions of radiation-resistant tumor-initiating CSCs.

  4. Inositol metabolism in WRK-1 cells. Relationship of hormone-sensitive to -insensitive pools of phosphoinositides

    International Nuclear Information System (INIS)

    Monaco, M.E.

    1987-01-01

    Previous studies have indicated the existence of two separate pools of phosphoinositides in WRK-1 cells; one is labile and hormone-sensitive with respect to turnover, while the other is stable. Hormonal stimulation results in a rapid increase in 32 Pi incorporation into the sensitive pool, while in the absence of hormone, incorporation of 32 Pi into this pool is slow. Results are quite different when [ 3 H]inositol is the precursor utilized. Incorporation of [ 3 H]inositol into hormone-sensitive phosphoinositides is not stimulated in the presence of hormone, suggesting entry of this exogenous precursor into the cycle by a route other than the resynthetic phase of the cycle. Furthermore, failure of hormone to induce loss of [ 3 H]phosphoinositide in pulse-chase experiments in the absence of lithium suggests reutilization of the [ 3 H]inositol moiety generated by phosphodiesteratic cleavage of hormone-sensitive phosphoinositide. Time course studies indicate that the relative rates of incorporation of [ 3 H]inositol into sensitive and insensitive phosphoinositide remain constant from 2 to 24 h. Several factors are capable of increasing [ 3 H]inositol incorporation into hormone-insensitive phosphoinositide including vasopressin, calcium ionophores, and manganese. On the other hand, vasopressin treatment appears to decrease incorporation of [ 3 H]inositol into the hormone-sensitive pool, probably by shifting the equilibrium between phosphoinositides and inositol phosphates, since the decrease in radioactivity observed in the phosphoinositides is equaled by the increase observed in that in the inositol phosphates

  5. 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.

  6. Interstitial cells in the musculature of the gastrointestinal tract: Cajal and beyond

    DEFF Research Database (Denmark)

    Rumessen, Jüri J; Vanderwinden, Jean-Marie

    2003-01-01

    , the ultrastructure and light microscopic morphology, as well as the functions and the development of ICC and of neighboring fibroblast-like cells (FLC), are critically reviewed. Directions for future research are considered and a unifying concept of mesenchymal cells, either KIT positive (the "ICC") or KIT negative...... "non-Cajal" (including the FLC and possibly also other cell types) cell types in the interstitium of the smooth musculature of the gastrointestinal tract, is proposed. Furthermore, evidence is accumulating to suggest that, as postulated by Santiago Ramon y Cajal, the concept of interstitial cells...

  7. 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...

  8. T Cell Interstitial Migration: Motility Cues from the Inflamed Tissue for Micro- and Macro-Positioning.

    Science.gov (United States)

    Gaylo, Alison; Schrock, Dillon C; Fernandes, Ninoshka R J; Fowell, Deborah J

    2016-01-01

    Effector T cells exit the inflamed vasculature into an environment shaped by tissue-specific structural configurations and inflammation-imposed extrinsic modifications. Once within interstitial spaces of non-lymphoid tissues, T cells migrate in an apparent random, non-directional, fashion. Efficient T cell scanning of the tissue environment is essential for successful location of infected target cells or encounter with antigen-presenting cells that activate the T cell's antimicrobial effector functions. The mechanisms of interstitial T cell motility and the environmental cues that may promote or hinder efficient tissue scanning are poorly understood. The extracellular matrix (ECM) appears to play an important scaffolding role in guidance of T cell migration and likely provides a platform for the display of chemotactic factors that may help to direct the positioning of T cells. Here, we discuss how intravital imaging has provided insight into the motility patterns and cellular machinery that facilitates T cell interstitial migration and the critical environmental factors that may optimize the efficiency of effector T cell scanning of the inflamed tissue. Specifically, we highlight the local micro-positioning cues T cells encounter as they migrate within inflamed tissues, from surrounding ECM and signaling molecules, as well as a requirement for appropriate long-range macro-positioning within distinct tissue compartments or at discrete foci of infection or tissue damage. The central nervous system (CNS) responds to injury and infection by extensively remodeling the ECM and with the de novo generation of a fibroblastic reticular network that likely influences T cell motility. We examine how inflammation-induced changes to the CNS landscape may regulate T cell tissue exploration and modulate function.

  9. Ulcerative colitis: ultrastructure of interstitial cells in myenteric plexus

    DEFF Research Database (Denmark)

    Rumessen, Jüri Johs.; Vanderwinden, J-M; Horn, T

    2010-01-01

    degenerative changes, such as lipid droplets and irregular vacuoles. Nerve terminals often appeared swollen and empty. Glial cells, muscle cells, and fibroblast-like cells (FLC) showed no alterations. FLC enclosed macrophages (MLC), which were in close contact with naked axon terminals. The organization...

  10. High-Cholesterol Diet Disrupts the Levels of Hormones Derived from Anterior Pituitary Basophilic Cells.

    Science.gov (United States)

    Yang, J; Zhang, X; Liu, Z; Yuan, Z; Song, Y; Shao, S; Zhou, X; Yan, H; Guan, Q; Gao, L; Zhang, H; Zhao, J

    2016-03-01

    Emerging evidence shows that elevated cholesterol levels are detrimental to health. However, it is unclear whether there is an association between cholesterol and the pituitary. We investigated the effects of a high-cholesterol diet on pituitary hormones using in vivo animal studies and an epidemiological study. In the animal experiments, rats were fed a high-cholesterol or control diet for 28 weeks. In rats fed the high-cholesterol diet, serum levels of thyroid-stimulating hormone (TSH; also known as thyrotrophin), luteinising hormone (LH) and follicle-stimulating hormone (FSH) produced by the basophilic cells of the anterior pituitary were elevated in a time-dependent manner. Among these hormones, TSH was the first to undergo a significant change, whereas adrenocorticotrophic hormone (ACTH), another hormone produced by basophilic cells, was not changed significantly. As the duration of cholesterol feeding increased, cholesterol deposition increased gradually in the pituitary. Histologically, basophilic cells, and especially thyrotrophs and gonadotrophs, showed an obvious increase in cell area, as well as a potential increase in their proportion of total pituitary cells. Expression of the β-subunit of TSH, FSH and LH, which controls hormone specificity and activity, exhibited a corresponding increase. In the epidemiological study, we found a similar elevation of serum TSH, LH and FSH and a decrease in ACTH in patients with hypercholesterolaemia. Significant positive correlations existed between serum total cholesterol and TSH, FSH or LH, even after adjusting for confounding factors. Taken together, the results of the present study suggest that the high-cholesterol diet affected the levels of hormones derived from anterior pituitary basophilic cells. This phenomenon might contribute to the pituitary functional disturbances described in hypercholesterolaemia. © 2016 British Society for Neuroendocrinology.

  11. 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...

  12. 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.

  13. An Interstitial Network of Podoplanin-Expressing Cells in the Human Endolymphatic Duct

    Science.gov (United States)

    Mayerl, Christina; Rubin, Kristofer; Wick, Georg; Rask-Andersen, Helge

    2006-01-01

    The human endolymphatic duct (ED) with encompassing interstitial connective tissue (CT) is believed to be important for endolymph resorption and fluid pressure regulation of the inner ear. The periductal CT cells are interconnected via numerous cellular extensions, but do not form vessel structures. Here we report that the periductal CT is populated by two distinct cell phenotypes; one expressing podoplanin, a protein otherwise found on lymph endothelia and on epithelia involved in fluid fluxes, and a second expressing a fibroblast marker. A majority of the interstitial cells expressed podoplanin but not the lymphatic endothelial cell markers hyaluronan receptor (LYVE-1) or vascular endothelial growth factor receptor-3 (VEGFR-3). The fibroblast marker positive cells were found close to the ED epithelium. In the mid- and distal parts of the ED, these cells were enriched under folded epithelia. Furthermore, subepithelial CT cells were found to express activated platelet derived growth factor (PDGF)-β receptors. Cultured CT cells from human inner ear periductal and perisaccular explant tissues were identified as fibroblasts. These cells compacted a three-dimensional collagen lattice by a process that could be promoted by PDGF-BB, a factor involved in interstitial fluid pressure regulation. Our results are compatible with the notion that the periductal CT cells are involved in the regulation of inner ear fluid pressure. By active compaction of the periductal CT and by the formation of villous structures, the CT cells could modulate fluid fluxes over the ED epithelium as well as the longitudinal flow of endolymph in the ED. PMID:16408168

  14. Superficial leiomyomas of the gastrointestinal tract with interstitial cells of Cajal.

    Science.gov (United States)

    Janevska, Vesna; Qerimi, Adelina; Basheska, Neli; Stojkova, Elena; Janevski, Vlado; Jovanovic, Rubens; Zhivadinovik, Julija; Spasevska, Liljana

    2015-01-01

    Some authors suggest common origin of gastrointestinal stromal tumors from stem cells, which may show diverse differentiation. There are reports in which cells morphologically identical to the interstitial cells of Cajal are found in deep leiomyomas. The aim of this study was to demonstrate CD117 positive cells in superficial gastrointestinal (GI) leiomyomas and to find other cells that would suggest diverse differentiation in histologically typical leiomyoma. We analyzed 8 cases of superficial leiomyomas and one deep leiomyoma, received in our institutions as endoscopically or surgically obtained material. The tumor sections were immunohistochemicaly stained with CD117, CD34, NF, S100, αSMA, desmin, caldesmon and mast cell antigen. All leiomyomas showed diffuse positivity for αSMA, caldesmon and desmin. All of them had CD117 and CD34 positive cells morphologically identical to the interstitial cells of Cajal between smooth muscle fibers, 5 had S-100 and NF positive cells and 2 showed positivity for GFAP. The cells were found in different quantity; they were usually diffusely scattered through the tumors without predilection site, forming small groups in some areas. CD177, CD34, S-100 and NF positive cells are present in superficial leiomyomas and they may suggest common origin of GI stromal tumors.

  15. 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.

  16. Proliferation of Interstitial Cells in the Cyclophosphamide-Induced Cystitis and the Preventive Effect of Imatinib

    OpenAIRE

    Sancho, Maria; Triguero, Domingo; Lafuente-Sanchis, Aranzazu; Garcia-Pascual, Angeles

    2017-01-01

    Cyclophosphamide- (CYP-) induced cystitis in the rat is a well-known model of bladder inflammation that leads to an overactive bladder, a process that appears to involve enhanced nitric oxide (NO) production. We investigated the changes in the number and distribution of interstitial cells (ICs) and in the expression of endothelial NO synthase (eNOS) in the bladder and urethra of rats subjected to either intermediate or chronic CYP treatment. Pronounced hyperplasia and hypertrophy of ICs were ...

  17. 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 ...

  18. 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...

  19. 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

  20. 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.

  1. Persistent activation of autophagy in kidney tubular cells promotes renal interstitial fibrosis during unilateral ureteral obstruction

    Science.gov (United States)

    Livingston, Man J.; Ding, Han-Fei; Huang, Shuang; Hill, Joseph A.; Yin, Xiao-Ming; Dong, Zheng

    2016-01-01

    ABSTRACT Renal fibrosis is the final, common pathway of end-stage renal disease. Whether and how autophagy contributes to renal fibrosis remains unclear. Here we first detected persistent autophagy in kidney proximal tubules in the renal fibrosis model of unilateral ureteral obstruction (UUO) in mice. UUO-associated fibrosis was suppressed by pharmacological inhibitors of autophagy and also by kidney proximal tubule-specific knockout of autophagy-related 7 (PT-Atg7 KO). Consistently, proliferation and activation of fibroblasts, as indicated by the expression of ACTA2/α-smooth muscle actin and VIM (vimentin), was inhibited in PT-Atg7 KO mice, so was the accumulation of extracellular matrix components including FN1 (fibronectin 1) and collagen fibrils. Tubular atrophy, apoptosis, nephron loss, and interstitial macrophage infiltration were all inhibited in these mice. Moreover, these mice showed a specific suppression of the expression of a profibrotic factor FGF2 (fibroblast growth factor 2). In vitro, TGFB1 (transforming growth factor β 1) induced autophagy, apoptosis, and FN1 accumulation in primary proximal tubular cells. Inhibition of autophagy suppressed FN1 accumulation and apoptosis, while enhancement of autophagy increased TGFB1-induced-cell death. These results suggest that persistent activation of autophagy in kidney proximal tubules promotes renal interstitial fibrosis during UUO. The profibrotic function of autophagy is related to the regulation on tubular cell death, interstitial inflammation, and the production of profibrotic factors. PMID:27123926

  2. 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.

  3. The replacement of serum by hormones in cell culture media.

    Science.gov (United States)

    Sato, G; Hayashi, I

    1976-12-01

    The replacement of serum by hormones in cell culture media. (Reemplazo del suero por hormonas en el medio de cultivo de células). Arch. Biol. Med. Exper. 10: 120-121, 1976. The serum used in cell culture media can be replaced by a mixture of hormones and some accesory blood factors. The pituitary cell line GH3 can be grown in a medium in which serum is replaced by triiodothyronine, transferrin, parathormone, tyrotrophin releasing hormone and somatomedins. Hela and BHK cell strains can also be grown in serum free medium supplemented with hormones. Each cell type appears to have different hormonal requirements yet it may found that some hormones are required for most cell types.

  4. Interstitial cells of Cajal as targets for pharmacological intervention in gastrointestinal motor disorders

    DEFF Research Database (Denmark)

    Huizinga, J D; Thuneberg, L; Vanderwinden, J M

    1997-01-01

    Interstitial cells of Cajal (ICCs) have recently been identified as the pacemaker cells for contractile activity of the gastrointestinal tract. These cells generate the electrical 'slow-wave' activity that determines the characteristic frequency of phasic contractions of the stomach, intestine...... through the gut organs. Here Jan Huizinga, Lars Thuneberg, Jean-Marie Vanderwinden and Jüri Rumessen, suggest that, as ICCs are unique to the gut, they might be ideal targets for pharmacological intervention in gastrointestinal motility disorders, which are very common and costly....

  5. Problems in early diagnosis of bladder cancer in a spinal cord injury patient: Report of a case of simultaneous production of granulocyte colony stimulating factor and parathyroid hormone-related protein by squamous cell carcinoma of urinary bladder

    Directory of Open Access Journals (Sweden)

    Singh Gurpreet

    2002-08-01

    Full Text Available Abstract Background Typical symptoms and signs of a clinical condition may be absent in spinal cord injury (SCI patients. Case presentation A male with paraplegia was passing urine through penile sheath for 35 years, when he developed urinary infections. There was no history of haematuria. Intravenous urography showed bilateral hydronephrosis. The significance of abnormal outline of bladder was not appreciated. As there was large residual urine, he was advised intermittent catheterisation. Serum urea: 3.5 mmol/L; creatinine: 77 umol/L. A year later, serum urea: 36.8 mmol/l; creatinine: 632 umol/l; white cell count: 22.2; neutrophils: 18.88. Ultrasound: bilateral hydronephrosis. Bilateral nephrostomy was performed. Subsequently, blood tests showed: Urea: 14.2 mmol/l; Creatinine: 251 umol/l; Adjusted Calcium: 3.28 mmol/l; Parathyroid hormone: A repeat ultrasound scan demonstrated a tumour arising from right lateral wall; biopsy revealed squamous cell carcinoma. In view of persistently high white cell count and high calcium level, immunohistochemistry for G-CSF and PTHrP was performed. Dense staining of tumour cells for G-CSF and faintly positive staining for C-terminal PTHrP were observed. This patient expired about five months later. Conclusion This case demonstrates how delay in diagnosis of bladder cancer could occur in a SCI patient due to absence of characteristic symptoms and signs.

  6. Interstitial interfaces show marked differences in regenerating tubules, matured tubules, and the renal stem/progenitor cell niche.

    Science.gov (United States)

    Minuth, Will W; Denk, Lucia

    2012-05-01

    Stem/progenitor cells are promising candidates for the regeneration of parenchyma in acute and chronic renal failure. After an implantation stem/progenitor cells must migrate through the interstitial space to concentrate at the site of damage. However, information is lacking to what extent the interstitial interface is influencing the development of stem/progenitor cells into nephron structures. In consequence, tubule regeneration within an artificial polyester interstitium was analyzed by electron microscopy in comparison with the interstitial interface of matured tubules and the interstitium within the renal stem/progenitor cell niche. The experiments demonstrate that fixation of specimens with glutaraldehyde (GA) is leading in all cases to inconspicuously looking interstitial interfaces. In contrast, fixation of regenerating tubules in GA containing ruthenium red and tannic acid shows a dense network of fibers lining along the basal lamina. In contrast, matured tubules reveal after ruthenium red label an extremely thickened basal lamina, while only a punctate pattern is obtained after tannic acid treatment. Finally, within the renal stem/progenitor cell niche ruthenium red and tannic acid label reveals large amounts of extracellular matrix spanning through the interstitium. Thus, fixation of tissue in GA containing ruthenium red and tannic acid exhibits an unexpectedly regional heterogeneity of the renal interstitial interface. This fact has to be considered for an optimal therapeutic repair of parenchyma, since contacts between stem/progenitor cells with the interstitial interface influence further development. Copyright © 2012 Wiley Periodicals, Inc.

  7. 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.

  8. Thyroid hormone induced oxygen consumption and glucose-uptake in human mononuclear cells

    DEFF Research Database (Denmark)

    Kvetny, J; Matzen, L E

    1989-01-01

    Cellular oxygen consumption and glucose metabolism were examined in human mononuclear blood cells. The cellular oxygen consumption and glucose uptake were dependent on the number of cells, the temperature and the duration of incubation. Stimulation of the cells by T4 and T3 led to a dose dependen...... thyroid hormones and insulin exerted an additive effect on glucose uptake. Our study indicates a direct intracellular effect of T4 independent of its conversion to T3 and a different mechanism for insulin dependent and thyroid hormone glucose uptake....

  9. 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.

  10. Interstitial cystitis antiproliferative factor (APF as a cell-cycle modulator

    Directory of Open Access Journals (Sweden)

    Zhang Chen-Ou

    2004-04-01

    Full Text Available Abstract Background Interstitial cystitis (IC is a chronic bladder disorder of unknown etiology. Antiproliferative factor (APF, a peptide found in the urine of IC patients, has previously been shown to decrease incorporation of thymidine by normal bladder epithelial cells. This study was performed to determine the effect of APF on the cell cycle of bladder epithelial cells so as to better understand its antiproliferative activity. Methods Explant cultures from normal bladder biopsy specimens were exposed to APF or mock control. DNA cytometry was performed using an automated image analysis system. Cell cycle phase fractions were calculated from the DNA frequency distributions and compared by two-way analysis of variance (ANOVA. Results APF exposure produced statistically significant increases in the proportion of tetraploid and hypertetraploid cells compared to mock control preparations, suggesting a G2 and/or M phase cell cycle block and the production of polyploidy. Conclusions APF has a specific effect on cell cycle distributions. The presence of a peptide with this activity may contribute to the pathogenesis of interstitial cystitis through disruption of normal urothelial proliferation and repair processes.

  11. Cell cycle control by the thyroid hormone in neuroblastoma cells

    International Nuclear Information System (INIS)

    Garcia-Silva, Susana; Perez-Juste, German; Aranda, Ana

    2002-01-01

    The thyroid hormone (T3) blocks proliferation and induces differentiation of neuroblastoma N2a-β cells that overexpress the β1 isoform of the T3 receptor. An element in the region responsible for premature termination of transcription mediates a rapid repression of c-myc gene expression by T3. The hormone also causes a decrease of cyclin D1 gene transcription, and is able to antagonize the activation of the cyclin D1 promoter by Ras. In addition, a strong and sustained increase of the levels of the cyclin kinase inhibitor (CKI) p27 Kip1 are found in T3-treated cells. The increased levels of p27 Kip1 lead to a marked inhibition of the kinase activity of the cyclin-CDK2 complexes. As a consequence of these changes, retinoblastoma proteins are hypophosphorylated in T3-treated N2a-β cells, and progression through the restriction point in the cell cycle is blocked

  12. HGF Expressing Stem Cells in Usual Interstitial Pneumonia Originate from the Bone Marrow and Are Antifibrotic.

    Directory of Open Access Journals (Sweden)

    Amiq Gazdhar

    Full Text Available Pulmonary fibrosis may result from abnormal alveolar wound repair after injury. Hepatocyte growth factor (HGF improves alveolar epithelial wound repair in the lung. Stem cells were shown to play a major role in lung injury, repair and fibrosis. We studied the presence, origin and antifibrotic properties of HGF-expressing stem cells in usual interstitial pneumonia.Immunohistochemistry was performed in lung tissue sections and primary alveolar epithelial cells obtained from patients with usual interstitial pneumonia (UIP, n = 7. Bone marrow derived stromal cells (BMSC from adult male rats were transfected with HGF, instilled intratracheally into bleomycin injured rat lungs and analyzed 7 and 14 days later.In UIP, HGF was expressed in specific cells mainly located in fibrotic areas close to the hyperplastic alveolar epithelium. HGF-positive cells showed strong co-staining for the mesenchymal stem cell markers CD44, CD29, CD105 and CD90, indicating stem cell origin. HGF-positive cells also co-stained for CXCR4 (HGF+/CXCR4+ indicating that they originate from the bone marrow. The stem cell characteristics were confirmed in HGF secreting cells isolated from UIP lung biopsies. In vivo experiments showed that HGF-expressing BMSC attenuated bleomycin induced pulmonary fibrosis in the rat, indicating a beneficial role of bone marrow derived, HGF secreting stem cells in lung fibrosis.HGF-positive stem cells are present in human fibrotic lung tissue (UIP and originate from the bone marrow. Since HGF-transfected BMSC reduce bleomycin induced lung fibrosis in the bleomycin lung injury and fibrosis model, we assume that HGF-expressing, bone-marrow derived stem cells in UIP have antifibrotic properties.

  13. Morphometry and morphology of nucleus of the Sertoli and interstitial cells of the tambaqui Colossoma macropomum (Cuvier, 1881) (Pisces: Characidae) during the reproductive cycle.

    Science.gov (United States)

    Nakaghi, L S O; Mitsuiki, D; Santos, H S L; Pacheco, M R; Ganeco, L N

    2003-02-01

    This study allowed the characterization of the tambaqui Colossoma macropomum testes structural organization, emphasizing Sertoli and interstitial cells and analyzing morphometrically the Sertoli cell nucleus diameter and the interstitial tissue area during the reproductive cycle. Fragments of tambaqui testes were collected in the following reproductive cycle stages: immature, resting, maturation I and II, mature, and regression, and were histologically processed. The Sertoli cells were found at the periphery of the cysts of germinative lineage cells and the nuclei were shown to be smaller as these cells developed. The interstitial cells were better observed between the seminiferous lobules next to vessels in the interstitial tissue of maturing testes.

  14. 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

  15. 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.

  16. 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)

  17. 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.

  18. 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.

  19. Identification of Interstitial Cajal-Like Cells in the Human Thoracic Duct

    DEFF Research Database (Denmark)

    Briggs Boedtkjer, Donna; Rumessen, Jüri; Baandrup, Ulrik

    2012-01-01

    were used to identify ICLCs in live tissue. Methylene blue stained cells with morphology suggestive of ICLCs in the TD. Immunoreactivity localized the ICLC protein markers c-kit, CD34 and vimentin to many cells and processes associated with smooth muscle cells (SMCs): coexpression of c...... spindle shapes. Confocal imaging with calcium-dependent fluorophores corroborated cell morphology and localization observed in fixed tissues. Lymphatic ICLCs thus constitute a significant cell type of the human TD and physically interact with lymphatic SMCs.......Interstitial Cajal-like cells (ICLCs) are speculated to be pacemakers in smooth muscle tissues. While the human thoracic duct (TD) is spontaneously active, the origin of this activity is unknown. We hypothesized that ICLCs could be present in the TD and using histological techniques...

  20. Introduction of exogenous growth hormone receptors augments growth hormone-responsive insulin biosynthesis in rat insulinoma cells

    International Nuclear Information System (INIS)

    Billestrup, N.; Moeldrup, A.; Serup, P.; Nielsen, J.H.; Mathews, L.S.; Norstedt, G.

    1990-01-01

    The stimulation of insulin biosynthesis in the pancreatic insulinoma cell line RIN5-AH by growth hormone (GH) is initiated by GH binding to specific receptors. To determine whether the recently cloned rat hepatic GH receptor is able to mediate the insulinotropic effect of GH, the authors have transfected a GH receptor cDNA under the transcriptional control of the human metallothionein promoter into RIN5-AH cells. The transfected cells were found to exhibit an increased expression of GH receptors and to contain a specific GH receptor mRNA that was not expressed in the parent cell line. The expression of GH receptors in one clone (1.24) selected for detailed analysis was increased 2.6-fold compared to untransfected cells. The increased GH receptor expression was accompanied by an increased responsiveness to GH. Thus, the maximal GH-stimulated increase of insulin biosynthesis was 4.1-fold in 1.24 cells compared to 1.9-fold in the nontransfected RIN5-AH cells. The expression of the transfected receptor was stimulated 1.6- and 2.3-fold when cells were cultured in the presence of 25 or 50 μM Zn 2+ was associated with an increased magnitude of GH-stimulated insulin biosynthesis. A close stoichiometric relationship between the level of receptor expression and the level of GH-stimulated insulin biosynthesis was observed. They conclude from these results that the hepatic GH receptor is able to mediate the effect of GH on insulin biosynthesis in RIN5-AH cells

  1. 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.

  2. Effects of growth hormone-releasing hormone on sleep and brain interstitial fluid amyloid-β in an APP transgenic mouse model

    OpenAIRE

    Liao, Fan; Zhang, Tony J.; Mahan, Thomas E.; Jiang, Hong; Holtzman, David M.

    2014-01-01

    Alzheimer’s Disease (AD) is a neurodegenerative disorder characterized by impairment of cognitive function, extracellular amyloid plaques, intracellular neurofibrillary tangles, and synaptic and neuronal loss. There is substantial evidence that the aggregation of amyloid β (Aβ) in the brain plays a key role in the pathogenesis of AD and that Aβ aggregation is a concentration dependent process. Recently, it was found that Aβ levels in the brain interstitial fluid (ISF) are regulated by the sle...

  3. Role of thyrotropin-releasing hormone in prolactin-producing cell models.

    Science.gov (United States)

    Kanasaki, Haruhiko; Oride, Aki; Mijiddorj, Tselmeg; Kyo, Satoru

    2015-12-01

    Thyrotropin-releasing hormone (TRH) is a hypothalamic hypophysiotropic neuropeptide that was named for its ability to stimulate the release of thyroid-stimulating hormone in mammals. It later became apparent that it exerts a number of species-dependent hypophysiotropic activities that regulate other pituitary hormones. TRH also regulates the synthesis and release of prolactin, although whether it is a physiological regulator of prolactin that remains unclear. Occupation of the Gq protein-coupled TRH receptor in the prolactin-producing lactotroph increases the turnover of inositol, which in turn activates the protein kinase C pathway and the release of Ca(2+) from storage sites. TRH-induced signaling events also include the activation of extracellular signal-regulated kinase (ERK) and induction of MAP kinase phosphatase, an inactivator of activated ERK. TRH stimulates prolactin synthesis through the activation of ERK, whereas prolactin release occurs via elevation of intracellular Ca(2+). We have been investigating the role of TRH in a pituitary prolactin-producing cell model. Rat pituitary somatolactotroph GH3 cells, which produce and release both prolactin and growth hormone (GH), are widely used as a model for the study of prolactin- and GH-secreting cells. In this review, we describe the general action of TRH as a hypophysiotropic factor in vertebrates and focus on the role of TRH in prolactin synthesis using GH3 cells. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. 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

  5. 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...

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. Identification of interstitial cells of Cajal. Significance for studies of human small intestine and colon

    DEFF Research Database (Denmark)

    Rumessen, J J

    1994-01-01

    Interstitial cells of Cajal (ICC) were described a century ago by Ramón y Cajal a.o. as primitive neurons in the intestines. In the period 1900-1960 a large number of light microscopical studies of ICC were published, in which ICC were identified by heir characteristic morphology. After 1960...... muscle. These studies strongly suggested that ICC were fundamental regulators of external muscle function. These hypotheses have since been supported by independent morphological and electrophysiological evidence, strongly suggesting a pacemaker role of some ICC populations as well as other regulatory...

  11. 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

  12. Eplerenone-Mediated Aldosterone Blockade Prevents Renal Fibrosis by Reducing Renal Inflammation, Interstitial Cell Proliferation and Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Hui Chen

    2013-11-01

    Full Text Available Background/Aims: Prolonged elevation of serum aldosterone leads to renal fibrosis. Inflammation also plays a role in the pathogenesis of renal disease. We used a rat model of interstitial renal fibrosis to test the hypothesis that eplerenone-mediated aldosterone blockade prevents renal fibrosis due to its anti-inflammatory and anti-proliferative effects. Methods: Eplerenone (a selective aldosterone blocker or vehicle (control, was given to male Wistar rats (50 mg/kg, twice daily for 7 days before unilateral ureteral obstruction (UUO and for an additional 28 days after surgery. Body weight, blood pressure, renal histo-morphology, immune-staining for macrophages, monocyte chemotactic protein-1, proliferating cell nuclear antigen, α-smooth muscle actin, and serum and urine markers of renal function and oxidative stress were determined for both groups on 7, 14, and 28 days after surgery. Results: Epleronone had no effect on body weight or blood pressure. However, eplerenone inhibited the development of renal fibrosis, inflammation (macrophage and monocyte infiltration, interstitial cell proliferation, and activation of interstitial cells (α-SMA expression. Epleronone also reduced oxidative stress. Conclusion: The anti-fibrotic effect of eplerenone appears to be unrelated to its effect on blood pressure. Eplerenone inhibits renal inflammation, interstitial cell proliferation, phenotypic changes of interstitial cells, and reduces oxidative stress.

  13. T cells stimulate catabolic gene expression by the stromal cells from giant cell tumor of bone

    Energy Technology Data Exchange (ETDEWEB)

    Cowan, Robert W. [Department of Pathology and Molecular Medicine, McMaster University, 1280 Main St. W., Hamilton, ON, Canada L8S 4L8 (Canada); Juravinski Cancer Centre, 699 Concession St., Hamilton, ON, Canada L8V 5C2 (Canada); Ghert, Michelle [Juravinski Cancer Centre, 699 Concession St., Hamilton, ON, Canada L8V 5C2 (Canada); Department of Surgery, McMaster University, 1280 Main St. W., Hamilton, ON, Canada L8S 4L8 (Canada); Singh, Gurmit, E-mail: gurmit.singh@jcc.hhsc.ca [Department of Pathology and Molecular Medicine, McMaster University, 1280 Main St. W., Hamilton, ON, Canada L8S 4L8 (Canada); Juravinski Cancer Centre, 699 Concession St., Hamilton, ON, Canada L8V 5C2 (Canada)

    2012-03-23

    Highlights: Black-Right-Pointing-Pointer Two T cell lines stimulate PTHrP, RANKL, MMP13 gene expression in GCT cell cultures. Black-Right-Pointing-Pointer CD40 expressed by stromal cells; CD40L detected in whole tumor but not cultures. Black-Right-Pointing-Pointer Effect of CD40L treatment on GCT cells increased PTHrP and MMP13 gene expression. Black-Right-Pointing-Pointer PTHrP treatment increased MMP13 expression, while inhibition decreased expression. Black-Right-Pointing-Pointer T cells may stimulate GCT stromal cells and promote the osteolysis of the tumor. -- Abstract: The factors that promote the localized bone resorption by giant cell tumor of bone (GCT) are not fully understood. We investigated whether T cells could contribute to bone resorption by stimulating expression of genes for parathyroid hormone-related protein (PTHrP), matrix metalloproteinase (MMP)-13, and the receptor activator of nuclear-factor {kappa}B ligand (RANKL). Two cell lines, Jurkat clone E6-1 and D1.1, were co-cultured with isolated GCT stromal cells. Real-time PCR analyses demonstrated a significant increase of all three genes following 48 h incubation, and PTHrP and MMP-13 gene expression was also increased at 24 h. Further, we examined the expression of CD40 ligand (CD40L), a protein expressed by activated T cells, and its receptor, CD40, in GCT. Immunohistochemistry results revealed expression of the CD40 receptor in both the stromal cells and giant cells of the tumor. RNA collected from whole GCT tissues showed expression of CD40LG, which was absent in cultured stromal cells, and suggests that CD40L is expressed within GCT. Stimulation of GCT stromal cells with CD40L significantly increased expression of the PTHrP and MMP-13 genes. Moreover, we show that inhibition of PTHrP with neutralizing antibodies significantly decreased MMP13 expression by the stromal cells compared to IgG-matched controls, whereas stimulation with PTHrP (1-34) increased MMP-13 gene expression. These

  14. Hormonal protection of spermatogenic stem cells during irradiation

    International Nuclear Information System (INIS)

    Kroonenburgh, M.J.P.G. van.

    1986-01-01

    In this thesis it is examined if by hormonal suppression of spermatogenesis the disadvantageous side-effects of radiation therapy on the gonads can be reduced. Therefore a rat model was investigated, where hormonal suppression of spermatogenesis during irradiation was achieved and stem cell survival was measured. Attention was focussed on the stem cell, because this cell is primarily responsible for the late effects of radiation on fertility. Flow cytometrical and histological techniques were used as parameters for measuring stem cell survival. Serum concentrations of FSH, LH and testosterone were measured to evaluate the hormonal suppression. (Auth.)

  15. Increased CXCR3 Expression of Infiltrating Plasma Cells in Hunner Type Interstitial Cystitis

    Science.gov (United States)

    Akiyama, Yoshiyuki; Morikawa, Teppei; Maeda, Daichi; Shintani, Yukako; Niimi, Aya; Nomiya, Akira; Nakayama, Atsuhito; Igawa, Yasuhiko; Fukayama, Masashi; Homma, Yukio

    2016-01-01

    An up-regulated CXCR3 pathway and affluent plasma cell infiltration are characteristic features of Hunner type interstitial cystitis (HIC). We further examined these two features using bladder biopsy samples taken from 27 patients with HIC and 15 patients with non-IC cystitis as a control. The number of CD3-positive T lymphocytes, CD20-positive B lymphocytes, CD138-positive plasma cells, and CXCR3-positive cells was quantified by digital image analysis. Double-immunofluorescence for CXCR3 and CD138 was used to detect CXCR3 expression in plasma cells. Correlations between CXCR3 positivity and lymphocytic and plasma cell numbers and clinical parameters were explored. The density of CXCR3-positive cells showed no significant differences between HIC and non-IC cystitis specimens. However, distribution of CXCR3-positivity in plasma cells indicated co-localization of CXCR3 with CD138 in HIC specimens, but not in non-IC cystitis specimens. The number of CXCR3-positive cells correlated with plasma cells in HIC specimens alone. Infiltration of CXCR3-positive cells was unrelated to clinical parameters of patients with HIC. These results suggest that infiltration of CXCR3-positive plasma cells is a characteristic feature of HIC. The CXCR3 pathway and specific immune responses may be involved in accumulation/retention of plasma cells and pathophysiology of the HIC bladder. PMID:27339056

  16. Bone Marrow-Derived Stem Cell Populations Are Differentially Regulated by Thyroid or/and Ovarian Hormone Loss

    Directory of Open Access Journals (Sweden)

    Bassam F. Mogharbel

    2017-10-01

    Full Text Available Bone marrow-derived stem cells (BMDSCs play an essential role in organ repair and regeneration. The molecular mechanisms by which hormones control BMDSCs proliferation and differentiation are unclear. Our aim in this study was to investigate how a lack of ovarian or/and thyroid hormones affects stem cell number in bone marrow lineage. To examine the effect of thyroid or/and ovarian hormones on the proliferative activity of BMDSCs, we removed the thyroid or/and the ovaries of adult female rats. An absence of ovarian and thyroid hormones was confirmed by Pap staining and Thyroid Stimulating Hormone (TSH measurement, respectively. To obtain the stem cells from the bone marrow, we punctured the iliac crest, and aspirated and isolated cells by using a density gradient. Specific markers were used by cytometry to identify the different BMDSCs types: endothelial progenitor cells (EPCs, precursor B cells/pro-B cells, and mesenchymal stem cells (MSCs. Interestingly, our results showed that hypothyroidism caused a significant increase in the percentage of EPCs, whereas a lack of ovarian hormones significantly increased the precursor B cells/pro-B cells. Moreover, the removal of both glands led to increased MSCs. In conclusion, both ovarian and thyroid hormones appear to have key and diverse roles in regulating the proliferation of cells populations of the bone marrow.

  17. Modulation of Pacemaker Potentials by Pyungwi-San in Interstitial Cells of Cajal from Murine Small Intestine - Pyungwi-San and Interstitial Cells of Cajal -

    Directory of Open Access Journals (Sweden)

    Kim Jung Nam

    2013-03-01

    Full Text Available Objective: Pyungwi-san (PWS plays a role in a number of physiologic and pharmacologic functions in many organs. Interstitial cells of Cajal (ICCs are pacemaker cells that generate slow waves in the gastrointestinal (GI tract. We aimed to investigate the beneficial effects of PWS in mouse small-intestinal ICCs. Methods: Enzymatic digestion was used to dissociate ICCs from the small intestine of a mouse. The wholecell patch-clamp configuration was used to record membrane potentials from the cultured ICCs. Results: ICCs generated pacemaker potentials in the GI tract. PWS produced membrane depolarization in the current clamp mode. Pretreatment with a Ca2+-free solution and a thapsigargin, a Ca2+-ATPase, inhibitor in the endoplasmic reticulum, eliminated the generation of pacemaker potentials. However, only when the thapsigargin was applied in a bath solution, the membrane depolarization was not produced by PWS. Furthermore, the membrane depolarizations due to PWS were inhibited not by U-73122, an active phospholipase C inhibitor, but by chelerythrine and calphostin C, protein kinase C inhibitors. Conclusions: These results suggest that PWS might affect GI motility by modulating the pacemaker activity in the ICCs.

  18. Parathyroid hormone resistance and B cell lymphopenia in propionic acidemia.

    Science.gov (United States)

    Griffin, T A; Hostoffer, R W; Tserng, K Y; Lebovitz, D J; Hoppel, C L; Mosser, J L; Kaplan, D; Kerr, D S

    1996-07-01

    The mechanisms of hypocalcemia, recurrent infections and hypogammaglobulinemia associated with metabolic decompensation of propionic acidemia due to propionyl-CoA carboxylase deficiency have not been defined. A 7-week-old infant with this disorder presented with severe hypocalcemia and B cell lymphopenia during an episode of metabolic acidosis and hyperammonemia. Hypocalcemia (1.1 mmol l-1) was associated with elevated serum intact parathyroid hormone (122 ng l-1), hyperphosphatemia, hypophosphaturia and hypercalcuria, indicating parathyroid hormone resistance. B cell lymphopenia (20 cells microliters-1) was associated with transient neutropenia, anemia and subsequent hypogamma-globulinemia (IgG < 294 mg dl-1, IgM < 8 mg dl-1, IgA < 8 mg dl-1), while T cells were normal. Parathyroid hormone resistance and B cell lymphopenia resolved following treatment with hemodialysis, diet and carnitine. These complications may be due to interference with parathyroid hormone renal tubular action and B cell maturation/proliferation by accumulated organic acids.

  19. 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

  20. 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...

  1. 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

  2. Cdc42-dependent leading edge coordination is essential for interstitial dendritic cell migration

    DEFF Research Database (Denmark)

    Lammermann, Tim; Renkawitz, Jorg; Wu, Xunwei

    2009-01-01

    proteolysis. Instead, the protrusive flow of the actin cytoskeleton directly drives a basal mode of locomotion that is occasionally supported by actomyosin contractions at the trailing edge to propel the cell's rigid nucleus. We here delete the small GTPase Cdc42 in DCs and find that actin flow and actomyosin......Mature dendritic cells (DCs) moving from the skin to the lymph node are a prototypic example of rapidly migrating amoeboid leukocytes. Interstitial DC migration is directionally guided by chemokines, but independent of specific adhesive interactions with the tissue as well as pericellular...... contraction are still initiated in response to chemotactic cues. Accordingly, the cells are able to polarize and form protrusions. However, in the absence of Cdc42 the protrusions are temporally and spatially dysregulated which leads to impaired leading edge coordination. While this defect still allows...

  3. Image-guided Interstitial Photodynamic Therapy for Squamous Cell Carcinomas: Preclinical investigation

    Science.gov (United States)

    Sajisevi, Mirabelle; Rigual, Nestor R; Bellnier, David A.; Seshadri, Mukund

    2014-01-01

    Objective Photodynamic therapy (PDT) is a clinically approved minimally invasive treatment for cancer. In this preclinical study, using an imaging-guided approach, we examined the potential utility of PDT in the management of bulky squamous cell carcinomas (SCCs). Methods To mimic bulky oropharyngeal cancers seen in the clinical setting, intramuscular SCCs were established in six-to-eight week old female C3H mice. Animals were injected with the photosensitizer, 2-[hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH; 0.4 μmol/kg, i.v.) and tumors were illuminated 24 hours post injection with 665 nm light. PDT as a single treatment modality was administered by surface illumination or by interstitial placement of fibers (iPDT). Magnetic resonance imaging was used to guide treatment and assess tumor response to PDT along with correlative histopathologic assessment. Results Interstitial HPPH-PDT resulted in a marked change on T2 maps 24 hours post treatment compared to untreated controls or transcutaneous illumination. Corresponding apparent diffusion coefficient maps also showed hyperintense areas in tumors following iPDT suggestive of effective photodynamic cell kill. Histologic sections (H&E) confirmed presence of extensive tumor necrosis following iPDT. Conclusions These results highlight the potential utility of PDT in the treatment of bulky oropharyngeal cancers. The findings of our study also demonstrate the utility of MRI as a non-invasive tool for mapping of early tissue response to PDT. PMID:25750858

  4. Acute pergolide exposure stiffens engineered valve interstitial cell tissues and reduces contractility in vitro.

    Science.gov (United States)

    Capulli, Andrew K; MacQueen, Luke A; O'Connor, Blakely B; Dauth, Stephanie; Parker, Kevin Kit

    2016-01-01

    Medications based on ergoline-derived dopamine and serotonin agonists are associated with off-target toxicities that include valvular heart disease (VHD). Reports of drug-induced VHD resulted in the withdrawal of appetite suppressants containing fenfluramine and phentermine from the US market in 1997 and pergolide, a Parkinson's disease medication, in 2007. Recent evidence suggests that serotonin receptor activity affected by these medications modulates cardiac valve interstitial cell activation and subsequent valvular remodeling, which can lead to cardiac valve fibrosis and dysfunction similar to that seen in carcinoid heart disease. Failure to identify these risks prior to market and continued use of similar drugs reaffirm the need to improve preclinical evaluation of drug-induced VHD. Here, we present two complimentary assays to measure stiffness and contractile stresses generated by engineered valvular tissues in vitro. As a case study, we measured the effects of acute (24 h) pergolide exposure to engineered porcine aortic valve interstitial cell (AVIC) tissues. Pergolide exposure led to increased tissue stiffness, but it decreased both basal and active contractile tone stresses generated by AVIC tissues. Pergolide exposure also disrupted AVIC tissue organization (i.e., tissue anisotropy), suggesting that the mechanical properties and contractile functionality of these tissues are governed by their ability to maintain their structure. We expect further use of these assays to identify off-target drug effects that alter the phenotypic balance of AVICs, disrupt their ability to maintain mechanical homeostasis, and lead to VHD. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Acute Pergolide Exposure Stiffens Engineered Valve Interstitial Cell Tissues and Reduces Contractility In Vitro

    Science.gov (United States)

    Capulli, Andrew K.; MacQueen, Luke A.; O’Connor, Blakely B.; Dauth, Stephanie; Parker, Kevin Kit

    2016-01-01

    Medications based on ergoline-derived dopamine and serotonin agonists are associated with off-target toxicities that include valvular heart disease (VHD). Reports of drug-induced VHD resulted in the withdrawal of appetite suppressants containing fenfluramine and phentermine from the U.S. market in 1997 and pergolide, a Parkinson’s disease medication, in 2007. Recent evidence suggests that serotonin receptor activity affected by these medications modulates cardiac valve interstitial cell activation and subsequent valvular remodeling, which can lead to cardiac valve fibrosis and dysfunction similar to that seen in carcinoid heart disease. Failure to identify these risks prior to market, and continued use of similar drugs, reaffirms the need to improve preclinical evaluation of drug-induced VHD. Here, we present two complimentary assays to measure stiffness and contractile stresses generated by engineered valvular tissues in vitro. As a case study, we measured the effects of acute (24 hr) pergolide exposure to engineered porcine aortic valve interstitial cell (AVIC) tissues. Pergolide exposure led to increased tissue stiffness but it decreased both basal and active contractile tone stresses generated by AVIC tissues. Pergolide exposure also disrupted AVIC tissue organization (i.e., tissue anisotropy), suggesting that the mechanical properties and contractile functionality of these tissues are governed by their ability to maintain their structure. We expect further use of these assays to identify off-target drug effects that alter the phenotypic balance of AVICs, disrupt their ability to maintain mechanical homeostasis, and lead to VHD. PMID:27174867

  6. 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.

  7. 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

  8. 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.

  9. The human trigeminal ganglion: c-kit positive neurons and interstitial cells.

    Science.gov (United States)

    Rusu, M C; Pop, F; Hostiuc, S; Dermengiu, D; Lală, A I; Ion, D A; Mănoiu, V S; Mirancea, N

    2011-10-20

    The presence of c-kit positive neurons in sensory ganglia has been verified in various species but not in humans. Our aim has been to identify whether human primary trigeminal neurons label with c-kit/CD117 and thus, whether data gathered in animal studies can be extrapolated to humans. We also intended to establish whether, and which non-neuronal cells also label with c-kit in the trigeminal ganglion. Human adult trigeminal ganglia from eight cadavers were processed for immunohistochemistry on paraffin embedded samples using monoclonal antibodies for CD117/c-kit, and three additional trigeminal ganglia were used for transmission electron microscopy (TEM). To evaluate which neuronal type (A or B) was labeled with c-kit, we evaluated the same neurons on adjacent sections labeled with antibodies for neurofilaments (NF). c-kit has labeled trigeminal neurons (TNs), mast cells and interstitial cells (ICs) within the trigeminal ganglion. c-kit+TNs were NF-and thus were strongly presumed to be nociceptive, as such neurons are known to be NF-poor. c-kit+ICs with long and moniliform processes intermingled with the satellite glial cells (SGCs) of the neuronal envelopes. TEM evaluations confirmed this mixed composition of the neuronal envelopes and demonstrated that the perineuronal ICs are in fact interstitial Cajal-like cells (ICLCs) and/or telocytes. c-kit+TNs were objectified in humans and strongly presumed to be nociceptive. TNs envelopes mostly consist of SGCs, but are also combined with ICLCs/telocytes. Copyright © 2011 Elsevier GmbH. All rights reserved.

  10. Differential cell reaction upon Toll-like receptor 4 and 9 activation in human alveolar and lung interstitial macrophages

    Directory of Open Access Journals (Sweden)

    Meyerhans Andreas

    2010-09-01

    Full Text Available Abstract Background Investigations on pulmonary macrophages (MΦ mostly focus on alveolar MΦ (AM as a well-defined cell population. Characteristics of MΦ in the interstitium, referred to as lung interstitial MΦ (IM, are rather ill-defined. In this study we therefore aimed to elucidate differences between AM and IM obtained from human lung tissue. Methods Human AM and IM were isolated from human non-tumor lung tissue from patients undergoing lung resection. Cell morphology was visualized using either light, electron or confocal microscopy. Phagocytic activity was analyzed by flow cytometry as well as confocal microscopy. Surface marker expression was measured by flow cytometry. Toll-like receptor (TLR expression patterns as well as cytokine expression upon TLR4 or TLR9 stimulation were assessed by real time RT-PCR and cytokine protein production was measured using a fluorescent bead-based immunoassay. Results IM were found to be smaller and morphologically more heterogeneous than AM, whereas phagocytic activity was similar in both cell types. HLA-DR expression was markedly higher in IM compared to AM. Although analysis of TLR expression profiles revealed no differences between the two cell populations, AM and IM clearly varied in cell reaction upon activation. Both MΦ populations were markedly activated by LPS as well as DNA isolated from attenuated mycobacterial strains (M. bovis H37Ra and BCG. Whereas AM expressed higher amounts of inflammatory cytokines upon activation, IM were more efficient in producing immunoregulatory cytokines, such as IL10, IL1ra, and IL6. Conclusion AM appear to be more effective as a non-specific first line of defence against inhaled pathogens, whereas IM show a more pronounced regulatory function. These dissimilarities should be taken into consideration in future studies on the role of human lung MΦ in the inflammatory response.

  11. Transplantation of Allogeneic PW1pos/Pax7neg Interstitial Cells Enhance Endogenous Repair of Injured Porcine Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Fiona C. Lewis, BSc, PhD

    2017-12-01

    Full Text Available Skeletal muscle-derived PW1pos/Pax7neg interstitial cells (PICs express and secrete a multitude of proregenerative growth factors and cytokines. Utilizing a porcine preclinical skeletal muscle injury model, delivery of allogeneic porcine PICs (pPICs significantly improved and accelerated myofiber regeneration and neocapillarization, compared with saline vehicle control-treated muscles. Allogeneic pPICs did not contribute to new myofibers or capillaries and were eliminated by the host immune system. In conclusion, allogeneic pPIC transplantation stimulated the endogenous stem cell pool to bring about enhanced autologous skeletal muscle repair and regeneration. This allogeneic cell approach is considered a cost-effective, easy to apply, and readily available regenerative therapeutic strategy.

  12. 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

  13. 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.

  14. 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.

  15. Probing the mystery of Chinese medicine meridian channels with special emphasis on the connective tissue interstitial fluid system, mechanotransduction, cells durotaxis and mast cell degranulation

    Directory of Open Access Journals (Sweden)

    Fung Peter

    2009-05-01

    Full Text Available Abstract This article hypothesizes that the Chinese medicine meridian system is a special channel network comprising of skin with abundant nerves and nociceptive receptors of various types, and deeper connective tissues inside the body with the flowing interstitial fluid system. These meridian channels provide efficient migratory tracks mainly due to durotaxis (also including chemotaxis for mast cells, fibroblasts and other cells to migrate and carry out a number of physiological functions. Acupuncture acting on meridian channel causes cytoskeletal remodeling through mechanotransduction, leading to regulation of gene expression and the subsequent production of related proteins. Also, stimulation on cell surface can trigger Ca2+ activities, resulting in a cascade of intra- and inter-cellular signaling. Moreover, nerve endings in the meridian channels interact with mast cells and induce the degranulation of these cells, leading to the release of many specific biomolecules needed for homeostasis, immune surveillance, wound healing and tissue repair. Acupoint along a meridian channel is a functional site to trigger the above functions with specificity and high efficiency.

  16. 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.

  17. CD34+ cells in human intestine are fibroblasts adjacent to, but distinct from, interstitial cells of Cajal

    DEFF Research Database (Denmark)

    Vanderwinden, J M; Rumessen, J J; De Laet, M H

    1999-01-01

    Interstitial cells of Cajal (ICC) generate the pacemaker component of the gut and play important roles in the control of gut motility. The tyrosine kinase receptor Kit is an established marker for ICC. Recently, it has been reported that immunoreactivity for the sialomucin CD34 may be present...... and confocal microscopy. CD34 immunoreactivity identified previously unrecognized cells closely adjacent to, but distinct from, the Kit immunoreactive ICC. These CD34 immunoreactive cells expressed the fibroblast marker prolyl 4-hydroxylase-whereas ICC did not-and were also distinct from smooth muscle cells......, glial cells, and macrophages. In the human gut, CD34 immunoreactivity is not expressed by ICC but by a population of fibroblasts, likely corresponding to the "fibroblast-like cells" described in previous ultrastructural studies. Our findings also challenge the hypothesis that stromal tumors originate...

  18. 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

  19. A technique for in vitro culture of canine valvular interstitial cells.

    Science.gov (United States)

    Heaney, Allison M; Bulmer, Barret J; Ross, Christopher R; Schermerhorn, Thomas

    2009-06-01

    To develop a method for in vitro culture of canine valvular interstitial cells (VICs). Canine VICs were isolated from the distal third of the anterior mitral valve leaflet using an explant technique and maintained in cell culture. Molecular phenotyping of the cultured cells was performed using reverse transcription polymerase chain reaction and immunocytochemistry. Cells resembling fibroblasts migrated from canine mitral valve explants and were maintained in culture for up to eight passages. Establishment of the valve explant required collagen but once established, subsequent passages grew on non-coated plastic plates. At confluence the cultured cells exhibited the characteristic whorled pattern of fibroblasts in culture. The isolated valve cells expressed vimentin but not platelet endothelial cell adhesion molecule or von Willebrand's factor, consistent with the molecular phenotype of VICs. VICs can be readily isolated from canine mitral valve leaflets and successfully maintained in culture using standard culture techniques. The described techniques permit the study of bioactive VICs in a controlled environment and may be a useful in vitro model for investigation of cellular and molecular alterations associated with canine chronic degenerative valve disease.

  20. Progesterone stimulates pancreatic cell proliferation in vivo

    NARCIS (Netherlands)

    Nieuwenhuizen, AG; Schuiling, GA; Liem, SMS; Moes, H; Koiter, TR; Uilenbroek, JTJ

    Treatment of cyclic and pregnant rats with progesterone stimulates cell proliferation within the islets of Langerhans. It was investigated whether this effect of progesterone depends on sex and/or the presence of the gonads or the presence of oestradiol, For this purpose, Silastic tubes containing

  1. 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)

  2. Characterization of epicardial-derived cardiac interstitial cells: differentiation and mobilization of heart fibroblast progenitors.

    Directory of Open Access Journals (Sweden)

    Adrián Ruiz-Villalba

    Full Text Available The non-muscular cells that populate the space found between cardiomyocyte fibers are known as 'cardiac interstitial cells' (CICs. CICs are heterogeneous in nature and include different cardiac progenitor/stem cells, cardiac fibroblasts and other cell types. Upon heart damage CICs soon respond by initiating a reparative response that transforms with time into extensive fibrosis and heart failure. Despite the biomedical relevance of CICs, controversy remains on the ontogenetic relationship existing between the different cell kinds homing at the cardiac interstitium, as well as on the molecular signals that regulate their differentiation, maturation, mutual interaction and role in adult cardiac homeostasis and disease. Our work focuses on the analysis of epicardial-derived cells, the first cell type that colonizes the cardiac interstitium. We present here a characterization and an experimental analysis of the differentiation potential and mobilization properties of a new cell line derived from mouse embryonic epicardium (EPIC. Our results indicate that these cells express some markers associated with cardiovascular stemness and retain part of the multipotent properties of embryonic epicardial derivatives, spontaneously differentiating into smooth muscle, and fibroblast/myofibroblast-like cells. Epicardium-derived cells are also shown to initiate a characteristic response to different growth factors, to display a characteristic proteolytic expression profile and to degrade biological matrices in 3D in vitro assays. Taken together, these data indicate that EPICs are relevant to the analysis of epicardial-derived CICs, and are a god model for the research on cardiac fibroblasts and the role these cells play in ventricular remodeling in both ischemic or non/ischemic myocardial disease.

  3. 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.

  4. Posttranscriptional stimulation of endothelial cell matrix metalloproteinases 2 and 1 by endothelioma cells.

    Science.gov (United States)

    Taraboletti, G; Sonzogni, L; Vergani, V; Hosseini, G; Ceruti, R; Ghilardi, C; Bastone, A; Toschi, E; Borsotti, P; Scanziani, E; Giavazzi, R; Pepper, M S; Stetler-Stevenson, W G; Bani, M R

    2000-08-01

    Matrix metalloproteinases (MMPs) play a critical role in the development of hemangioma-like vascular tumors in mice injected with murine eEnd.1 endothelioma cells. The current study was designed to (a) characterize the presence of MMPs in the vascular tumor, (b) define whether these MMPs originate from the transformed cells or from the recruited stromal cells and (c) study the stimulatory effect of eEnd.1 cells on the production of MMPs by endothelial cells. Several gelatinases were present in the eEnd.1 tumor extract, including latent and activated MMP-2 (72-kDa gelatinase A, EC 3.4.24. 24) and MMP-9 (92-kDa gelatinase B, EC 3.4.24.35). Immunohistochemical analysis of the tumor revealed focal reactivity for MMP-2. No gelatinase was produced by cultured eEnd.1 cells, or by six of nine related endothelioma cell lines, suggesting that stroma cells, particularly endothelial cells recruited by the tumor cells, rather than eEnd.1 cells themselves, are the source of the gelatinases observed in the tumors in vivo. The conditioned medium of eEnd.1 cells stimulated the release of MMP-2 and MMP-1 (interstitial collagenase, EC 3.4.24.7) by endothelial cells, but not of the inhibitor TIMP-2. The increased production of MMP-2 and MMP-1, observed at the protein level (zymogram and Western blot analysis), occurred through a posttranscriptional mechanism, since no increase in mRNA was observed and the stimulation was not prevented by inhibitors of protein synthesis. The inhibitory effects of monensin and brefeldin A, inhibitors of protein secretion, and the decrease in cell-associated MMP-2 in stimulated endothelial cells indicated that regulation occurred mostly at the level of protease secretion. MMPs are known to be regulated at different levels; this study indicates that, in endothelial cells, the stimulation of MMPs can also occur at the level of secretion, a mechanism that provides a rapid mobilization of these crucial enzymes in the early phases of angiogenesis. Copyright

  5. 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.

  6. Biochemical and morphological changes in endothelial cells in response to hypoxic interstitial edema

    Directory of Open Access Journals (Sweden)

    Miserocchi Giuseppe

    2006-01-01

    Full Text Available Abstract Background A correlation between interstial pulmonary matrix disorganization and lung cellular response was recently documented in cardiogenic interstitial edema as changes in the signal-cellular transduction platforms (lipid microdomains: caveoale and lipid rafts. These findings led to hypothesize a specific "sensing" function by lung cells resulting from a perturbation in cell-matrix interaction. We reason that the cell-matrix interaction may differ between the cardiogenic and the hypoxic type of lung edema due to the observed difference in the sequential degradation of matrix proteoglycans (PGs family. In cardiogenic edema a major fragmentation of high molecular weight PGs of the interfibrillar matrix was found, while in hypoxia the fragmentation process mostly involved the PGs of the basement membrane controlling microvascular permeability. Based on these considerations, we aim to describe potential differences in the lung cellular response to the two types of edema. Methods We analysed the composition of plasma membrane and of lipid microdomains in lung tissue samples from anesthetized rabbits exposed to mild hypoxia (12 % O2 for 3–5 h causing interstitial lung edema. Lipid analysis was performed by chromatographic techniques, while protein analysis by electrophoresis and Western blotting. Lipid peroxidation was assessed on total plasma membranes by a colorimetric assay (Bioxytech LPO-586, OxisResearch. Plasma membrane fluidity was also assessed by fluorescence. Lipid microdomains were isolated by discontinuous sucrose gradient. We also performed a morphometric analysis on lung cell shape on TEM images from lung tissue specimen. Results After hypoxia, phospholipids content in plasma membranes remained unchanged while the cholesterol/phospholipids ratio increased significantly by about 9% causing a decrease in membrane fluidity. No significant increase in lipid peroxidation was detected. Analysis of lipid microdomains showed a

  7. Leukocyte compartments in the mouse lung: distinguishing between marginated, interstitial, and alveolar cells in response to injury.

    Science.gov (United States)

    Barletta, Kathryn E; Cagnina, R Elaine; Wallace, Kori L; Ramos, Susan I; Mehrad, Borna; Linden, Joel

    2012-01-31

    We developed a flow cytometry-based assay to simultaneously quantify multiple leukocyte populations in the marginated vascular, interstitial, and alveolar compartments of the mouse lung. An intravenous injection of a fluorescently labeled anti-CD45 antibody was used to label circulating and marginated vascular leukocytes. Following vascular flushing to remove non-adherent cells and collection of broncho-alveolar lavage (BAL) fluid, lungs were digested and a second fluorescent anti-CD45 antibody was added ex vivo to identify cells not located in the vascular space. In the naïve mouse lung, we found about 11 million CD45+ leukocytes, of which 87% (9.5 million) were in the vascular marginated compartment, consisting of 17% NK cells, 17% neutrophils, 57% mononuclear myeloid cells (monocytes, macrophage precursors and dendritic cells), and 10% T cells (CD4+, CD8+, and invariant NKT cells). Non-vascular compartments including the interstitial compartment contained 7.7×10(5)cells, consisting of 49% NK cells, 25% dendritic cells, and 16% other mononuclear myeloid cells. The alveolar compartment was overwhelmingly populated by macrophages (5.63×10(5)cells, or 93%). We next studied leukocyte margination and extravasation into the lung following acid injury, a model of gastric aspiration. At 1 h after injury, neutrophils were markedly elevated in the blood while all other circulating leukocytes declined by an average of 79%. At 4 h after injury, there was a peak in the numbers of marginated neutrophils, NK cells, CD4+ and CD8+ T cells and a peak in the number of alveolar NK cells. Most interstitial cells consisted of DCs, neutrophils, and CD4+ T cells, and most alveolar compartment cells consisted of macrophages, neutrophils, and NK cells. At 24 h after injury, there was a decline in the number of all marginated and interstitial leukocytes and a peak in alveolar neutrophils. In sum, we have developed a novel assay to study leukocyte margination and trafficking following

  8. Sunitinib-Induced Acute Interstitial Nephritis in a Thrombocytopenic Renal Cell Cancer Patient

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    Ibrahim Azar

    2017-01-01

    Full Text Available Sunitinib, a multitargeted tyrosine Kkinase inhibitor (TKI, is currently the standard of care for patients with metastatic renal cell carcinoma. Renal adverse events associated with sunitinib include proteinuria, renal insufficiency secondary to focal segmental glomerulosclerosis (FSGS, and thrombotic microangiopathy. We describe the second reported instance of biopsy-proven sunitinib-induced acute interstitial nephritis (AIN, in a challenging case complicated by thrombocytopenia. The case illustrates the importance of early diagnosis and intervention in ensuring long-term recovery from renal complications. Four other cases of AIN reported along with inhibition of the vascular endothelial growth factor (VEGF by either TKI (sunitinib and sorafenib or antibodies (bevacizumab suggest a possible class effect. Given our experience, we recommend monitoring renal function with VEGF inhibition, and in the case of renal failure in the setting of an unclear diagnosis, we recommend prompt biopsy.

  9. Sunitinib-Induced Acute Interstitial Nephritis in a Thrombocytopenic Renal Cell Cancer Patient.

    Science.gov (United States)

    Azar, Ibrahim; Esfandiarifard, Saghi; Sinai, Pedram; Wazir, Ali; Foulke, Llewellyn; Mehdi, Syed

    2017-01-01

    Sunitinib, a multitargeted tyrosine kinase inhibitor (TKI), is currently the standard of care for patients with metastatic renal cell carcinoma. Renal adverse events associated with sunitinib include proteinuria, renal insufficiency secondary to focal segmental glomerulosclerosis (FSGS), and thrombotic microangiopathy. We describe the second reported instance of biopsy-proven sunitinib-induced acute interstitial nephritis (AIN), in a challenging case complicated by thrombocytopenia. The case illustrates the importance of early diagnosis and intervention in ensuring long-term recovery from renal complications. Four other cases of AIN reported along with inhibition of the vascular endothelial growth factor (VEGF) by either TKI (sunitinib and sorafenib) or antibodies (bevacizumab) suggest a possible class effect. Given our experience, we recommend monitoring renal function with VEGF inhibition, and in the case of renal failure in the setting of an unclear diagnosis, we recommend prompt biopsy.

  10. Conditioned medium derived from mesenchymal stem cells culture as a intravesical therapy for cystitis interstitials.

    Science.gov (United States)

    Adamowicz, Jan; Pokrywczyńska, Marta; Drewa, Tomasz

    2014-06-01

    The treatment of Interstinal Cystitisis (IC) is still challenge for urologist. Available therapies do not result in long-term control of symptoms and do not provide pain relive to patients. Unique abilities of mesenchymal stem cells (MSC) could be used to develop new treatment approaches for Interstitial Cystitis. Conditioned Medium (CM) derived from MSC culture is rich in plenty of growth factors, cytokines and trophic agents which were widely reported to enhance regeneration of urinary bladder in different conditions. This ready mixture of growth factors could be used to develop intravesical therapy for patients with IC. MSC-CM has anti-apoptotic, anti-inflammatory, supportive, angiogenic, immunosuppressive and immunomodulative properties and seems to be ideal substance to prevent IC recurrence and to create favorable environment for regeneration of damaged bladder wall. Copyright © 2014. Published by Elsevier Ltd.

  11. Nestin expression is upregulated in the fibrotic rat heart and is localized in collagen-expressing mesenchymal cells and interstitial CD31(+- cells.

    Directory of Open Access Journals (Sweden)

    Vanessa Hertig

    Full Text Available Renal and lung fibrosis was characterized by the accumulation of collagen-immunoreactive mesenchymal cells expressing the intermediate filament protein nestin. The present study tested the hypothesis that nestin expression was increased in the hypertrophied/fibrotic left ventricle of suprarenal abdominal aorta constricted adult male Sprague-Dawley rats and induced in ventricular fibroblasts by pro-fibrotic peptide growth factors. Nestin protein levels were upregulated in the pressure-overloaded left ventricle and expression positively correlated with the rise of mean arterial pressure. In sham and pressure-overloaded hearts, nestin immunoreactivity was detected in collagen type I(+-and CD31(+-cells identified in the interstitium and perivascular region whereas staining was absent in smooth muscle α-actin(+-cells. A significantly greater number of collagen type I(+-cells co-expressing nestin was identified in the left ventricle of pressure-overloaded rats. Moreover, an accumulation of nestin(+-cells lacking collagen, CD31 and smooth muscle α-actin staining was selectively observed at the adventitial region of predominantly large calibre blood vessels in the hypertrophied/fibrotic left ventricle. Angiotensin II and TGF-β1 stimulation of ventricular fibroblasts increased nestin protein levels via phosphatidylinositol 3-kinase- and protein kinase C/SMAD3-dependent pathways, respectively. CD31/eNOS(+-rat cardiac microvascular endothelial cells synthesized/secreted collagen type I, expressed prolyl 4-hydroxylase and TGF-β1 induced nestin expression. The selective accumulation of adventitial nestin(+-cells highlighted a novel feature of large vessel remodelling in the pressure-overloaded heart and increased appearance of collagen type I/nestin(+-cells may reflect an activated phenotype of ventricular fibroblasts. CD31/collagen/nestin(+-interstitial cells could represent displaced endothelial cells displaying an unmasked mesenchymal phenotype

  12. 20 kDa human growth hormone (20K hGH) stimulates insulin-like growth factor-I (IGF-I) gene expression at lower concentrations than 22K hGH in hGH receptor-expressing Ba/F3 cells.

    Science.gov (United States)

    Yoshizato, H; Tanaka, M; Fujikawa, T; Higashimoto, Y; Shimizu, A; Nakashima, K

    2000-03-01

    Growth hormone (GH) secreted from the pituitary is essential for postnatal growth in animals. GH exerts its actions by a direct effect on target organs and by stimulating insulin-like growth factor I (IGF-I) production. In the human pituitary, there is a naturally occurring variant protein which has a molecular mass of 20 kDa (20K hGH) besides the major 22 kDa hGH (22K hGH), but the physiological actions of 20K hGH are still poorly understood. In this study we have examined its effects on the IGF-I mRNA expression in the pro B-cell line Ba/F3 cells stably expressing hGH receptor (Ba/F3-hGHR). Ba/F3-hGHR cells were incubated for 2 h with a series of various concentrations (10 pM to approximately 10 nM) of 20K or 22K hGH. The IGF-I mRNA expression in the Ba/F3-hGHR cells was detected by the RT-PCR method. IGF-I gene expression was increased by 20K and 22K hGH stimulation, but not by PRL or IL-3 in the Ba/F3-hGHR. And this effect was not observed in parental Ba/F3 cells. Lower concentrations of 20K hGH more strongly induced IGF-I gene expression than 22K-hGH. These results suggest that 20K and 22K hGH stimulate the IGF-I gene expression in the Ba/F3-hGHR through hGH receptors, and that the stronger effect of 20K hGH than that of 22K hGH in enhancing the IGF-I gene expression may be correlated with a 20K hGH specific receptor dimerization mechanism.

  13. Serum B cell-activating factor (BAFF) level in connective tissue disease associated interstitial lung disease.

    Science.gov (United States)

    Hamada, Tsutomu; Samukawa, Takuya; Kumamoto, Tomohiro; Hatanaka, Kazuhito; Tsukuya, Go; Yamamoto, Masuki; Machida, Kentaro; Watanabe, Masaki; Mizuno, Keiko; Higashimoto, Ikkou; Inoue, Yoshikazu; Inoue, Hiromasa

    2015-09-30

    Interstitial lung diseases (ILDs) are common in patients with connective tissue diseases (CTDs). Although the diagnosis of an underlying CTD in ILD (CTD-ILD) affects both prognosis and treatment, it is sometimes difficult to distinguish CTD-ILD from chronic fibrosing interstitial pneumonia (CFIP). B cell-activating factor belonging to the tumour necrosis factor family (BAFF) plays a crucial role in B cell development, survival, and antibody production. We examined serum levels of BAFF, surfactant protein D (SP-D), and Krebs von den Lungen-6 (KL-6) in 33 patients with CTD-ILD, 16 patients with undifferentiated CTD-ILD, 19 patients with CFIP, and 26 healthy volunteers. And we analysed the relationship between serum BAFF levels and pulmonary function, as well as the expression of BAFF in the lung tissue of patients with CTD-ILD. Serum levels of BAFF were significantly higher in CTD-ILD patients compared to healthy subjects and CFIP patients. However, there were no significant differences in serum levels of SP-D and KL-6. Furthermore, serum BAFF levels in CTD-ILD patients were inversely correlated with pulmonary function. BAFF was strongly expressed in the lungs of CTD-ILD patients, but weakly in normal lungs. This is the first study to demonstrate that serum BAFF levels were significantly higher in CTD-ILD patients compared to healthy subjects and CFIP patients. Furthermore, serum BAFF levels were correlated with pulmonary function. We consider that serum BAFF levels in patients with CTD-ILD reflect the presence of ILDs disease activity and severity. These finding suggest that BAFF may be a useful marker for distinguishing CTD-ILD from CFIP.

  14. Arabidopsis and Tobacco superman regulate hormone signalling and mediate cell proliferation and differentiation.

    Science.gov (United States)

    Nibau, Candida; Di Stilio, Verónica S; Wu, Hen-Ming; Cheung, Alice Y

    2011-01-01

    Arabidopsis thaliana superman (SUP) plays an important role during flower development by maintaining the boundary between stamens and carpels in the inner two whorls. It was proposed that SUP maintains this boundary by regulating cell proliferation in both whorls, as loss-of-function superman mutants produce more stamens at the expense of carpels. However, the cellular mechanism that underlies SUP function remains unknown. Here Arabidopsis or tobacco (Nicotiana tabacum) SUP was overexpressed in tobacco plants to substantiate SUP's role as a regulator of cell proliferation and boundary definition and provide evidence that its biological role may be mediated via hormonal changes. It was found that moderate levels of SUP stimulated cell growth and proliferation, whereas high levels were inhibitory. SUP stimulated auxin- and cytokinin-regulated processes, and cells overexpressing SUP displayed reduced hormone dependency for proliferation and regeneration into plants. SUP also induced proliferation of female traits in the second and third flower whorls and promoted differentiation of petaloid properties in sepals, further supporting a role for SUP as a boundary regulator. Moreover, cytokinin suppressed stamen development and promoted differentiation of carpeloid tissues, suggesting that SUP may regulate male and female development via its effect on cytokinin signalling. Taken together, these observations suggest a model whereby the effect of SUP on cell growth and proliferation involves the modulation of auxin- and cytokinin-regulated processes. Furthermore, differential SUP expression or different sensitivities of different cell types to SUP may determine whether SUP stimulates or suppresses their proliferation.

  15. 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...

  16. Effects of Raloxifene on the Proliferation and Apoptosis of Human Aortic Valve Interstitial Cells

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    Zhimin Fu

    2016-01-01

    Full Text Available We aimed to explore the effects of raloxifene (RAL on the proliferation and apoptosis of human aortic valve interstitial cells (AVICs. Different concentrations of RAL were used to act on AVICs. MTS kit is used to test the effects of different concentrations of RAL on the proliferation of AVICs. Cell cycle and apoptosis test used flow cytometry after seven-day treatment. The relative expression levels of caspase-3 and caspase-8 are tested with RT-qPCR and Western blot. The results of MTS testing revealed that the absorbance value (OD value of the cells in the concentration groups of 10 and 100 nmol/L RAL at a wavelength of 490 nm at five, seven, and nine days significantly decreased compared with that in the control group. Meanwhile, the results of flow cytometry of the cells collected after seven days showed that the ratio of the S stage and the cell apoptosis rate of AVICs can be significantly reduced by RAL in the concentration groups of 10 and 100 nmol/L. The mRNA and protein expressions of caspase-3 and caspase-8 were significantly decreased compared with those in the control group. This study laid the foundation for further treatment of aortic valve disease by using RAL.

  17. 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.

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

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    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

  19. Impact of environmental chemicals on the thyroid hormone function in pituitary rat GH3 cells

    DEFF Research Database (Denmark)

    Ghisari, Mandana; Bonefeld-Jørgensen, Eva

    2005-01-01

    Endocrine disrupting chemicals (EDCs) are widespread in the environment and suspected to interfere with the function of thyroid hormones (THs). We investigated the TH disrupting activity of different classes of EDCs including plasticizers (bisphenol A, bisphenol A dimethacrylate), alkylphenols (4-n...... line. All tested chemicals significantly interfered with the cell proliferation alone or upon co-treatment with T3. The growth of GH3 cells was stimulated by all tested chemicals, but 4-n-nonylphenol, 4-octylphenol, prochloraz and iprodion elicited an inhibitory effect on cell growth. In conclusion...

  20. Recruitment of Bone Marrow-Derived Valve Interstitial Cells is a Normal Homeostatic Process

    Science.gov (United States)

    Hajdu, Zoltan; Romeo, Stephen J.; Fleming, Paul A.; Markwald, Roger R.; Visconti, Richard P.; Drake, Christopher J.

    2011-01-01

    Advances in understanding of the maintenance of the cardiac valves during normal cardiac function and response to injury have lead to several novel findings, including that there is contribution of extra-cardiac cells to the major cellular population of the valve: the valve interstitial cell (VIC). While suggested to occur in human heart studies, we have been able to experimentally demonstrate, using a mouse model, that cells of bone marrow hematopoietic stem cell origin engraft into the valves and synthesize collagen type I. Based on these initial findings, we sought to further characterize this cell population in terms of its similarity to VICs and begin to elucidate its contribution to valve homeostasis. To accomplish this, chimeric mice whose bone marrow was repopulated with enhanced green fluorescent protein (EGFP) expressing total nucleated bone marrow cells were used to establish a profile of EGFP+ valve cells in terms of their expression of hematopoietic antigens, progenitor markers, fibroblast- and myofibroblast-related molecules, as well as their distribution within the valves. Using this profile, we show that normal (non-irradiated, non-transplanted) mice have BM-derived cell populations that exhibit identical morphology and phenotype to those observed in transplanted mice. Collectively, our findings establish that the engraftment of bone marrow-derived cells occurs as part of normal valve homeostasis. Further, our efforts demonstrate that the use of myeloablative irradiation, which is commonly employed in studies involving bone marrow transplantation, does not elicit changes in the bone marrow-derived VIC phenotype in recipient mice. PMID:21871458

  1. The Potential for Gut Organoid Derived Interstitial Cells of Cajal in Replacement Therapy.

    Science.gov (United States)

    Zhou, Jerry; O'Connor, Michael D; Ho, Vincent

    2017-09-26

    Effective digestion requires propagation of food along the entire length of the gastrointestinal tract. This process involves coordinated waves of peristalsis produced by enteric neural cell types, including different categories of interstitial cells of Cajal (ICC). Impaired food transport along the gastrointestinal tract, either too fast or too slow, causes a range of gut motility disorders that affect millions of people worldwide. Notably, loss of ICC has been shown to affect gut motility. Patients that suffer from gut motility disorders regularly experience diarrhoea and/or constipation, insomnia, anxiety, attention lapses, irritability, dizziness, and headaches that greatly affect both physical and mental health. Limited treatment options are available for these patients, due to the scarcity of human gut tissue for research and transplantation. Recent advances in stem cell technology suggest that large amounts of rudimentary, yet functional, human gut tissue can be generated in vitro for research applications. Intriguingly, these stem cell-derived gut organoids appear to contain functional ICC, although their frequency and functional properties are yet to be fully characterised. By reviewing methods of gut organoid generation, together with what is known of the molecular and functional characteristics of ICC, this article highlights short- and long-term goals that need to be overcome in order to develop ICC-based therapies for gut motility disorders.

  2. The Potential for Gut Organoid Derived Interstitial Cells of Cajal in Replacement Therapy

    Directory of Open Access Journals (Sweden)

    Jerry Zhou

    2017-09-01

    Full Text Available Effective digestion requires propagation of food along the entire length of the gastrointestinal tract. This process involves coordinated waves of peristalsis produced by enteric neural cell types, including different categories of interstitial cells of Cajal (ICC. Impaired food transport along the gastrointestinal tract, either too fast or too slow, causes a range of gut motility disorders that affect millions of people worldwide. Notably, loss of ICC has been shown to affect gut motility. Patients that suffer from gut motility disorders regularly experience diarrhoea and/or constipation, insomnia, anxiety, attention lapses, irritability, dizziness, and headaches that greatly affect both physical and mental health. Limited treatment options are available for these patients, due to the scarcity of human gut tissue for research and transplantation. Recent advances in stem cell technology suggest that large amounts of rudimentary, yet functional, human gut tissue can be generated in vitro for research applications. Intriguingly, these stem cell-derived gut organoids appear to contain functional ICC, although their frequency and functional properties are yet to be fully characterised. By reviewing methods of gut organoid generation, together with what is known of the molecular and functional characteristics of ICC, this article highlights short- and long-term goals that need to be overcome in order to develop ICC-based therapies for gut motility disorders.

  3. 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.

  4. 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.

  5. Hormonal regulation of Na+-K+-ATPase in cultured epithelial cells

    International Nuclear Information System (INIS)

    Johnson, J.P.; Jones, D.; Wiesmann, W.P.

    1986-01-01

    Aldosterone and insulin stimulate Na + transport through mechanisms involving protein synthesis. Na + -K + -ATPase has been implicated in the action of both hormones. The authors examined the effect of aldosterone and insulin on Na + -K + -ATPase in epithelial cells in culture derived from toad urinary bladder (TB6C) and toad kidney (A6). Aldosterone, but not insulin, increases short-circuit current (I/sub sc/) in TB6C cells. Aldosterone increases Na + -K + -[ 32 P]ATPase activity after 18 h of incubation, but no effect can be seen at 3 and 6 h. Amiloride, which inhibits aldosterone-induced increases in I/sub sc/, has no effect on either basal or aldosterone stimulated enzyme activity. Both aldosterone and insulin increase I/sub sc/ in A6 cells and when added together are synergistic. Aldosterone stimulates enzyme activity in A6 cells, but insulin alone has no effect. However, aldosterone and insulin together stimulate enzyme activity more than aldosterone alone. It appears that stimulation of Na + -K + -ATPase activity is involved in aldosterone action in both cell lines but does not appear to be due to increased Na + entry, since enhanced enzyme activity is not inhibited by amiloride. In contrast, insulin alone has no direct effect on Na + -K + -ATPase, although the increased enzyme activity following both agents in combination may explain their synergism on I/sub sc/

  6. Dynamic Heterogeneity of the Heart Valve Interstitial Cell Population in Mitral Valve Health and Disease

    Directory of Open Access Journals (Sweden)

    Tori E. Horne

    2015-08-01

    Full Text Available The heart valve interstitial cell (VIC population is dynamic and thought to mediate lay down and maintenance of the tri-laminar extracellular matrix (ECM structure within the developing and mature valve throughout life. Disturbances in the contribution and distribution of valve ECM components are detrimental to biomechanical function and associated with disease. This pathological process is associated with activation of resident VICs that in the absence of disease reside as quiescent cells. While these paradigms have been long standing, characterization of this abundant and ever-changing valve cell population is incomplete. Here we examine the expression pattern of Smooth muscle α-actin, Periostin, Twist1 and Vimentin in cultured VICs, heart valves from healthy embryonic, postnatal and adult mice, as well as mature valves from human patients and established mouse models of disease. We show that the VIC population is highly heterogeneous and phenotypes are dependent on age, species, location, and disease state. Furthermore, we identify phenotypic diversity across common models of mitral valve disease. These studies significantly contribute to characterizing the VIC population in health and disease and provide insights into the cellular dynamics that maintain valve structure in healthy adults and mediate pathologic remodeling in disease states.

  7. Proliferative potential of malignant glioma cells before and after interstitial brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Kunishiro, Katsuzo; Matsumoto, Kengo; Higashi, Hisato; Adachi, Hisashi; Tamiya, Takashi; Furuta, Tomohisa; Ohtomo, Takashi [Okayama Univ. (Japan). School of Medicine

    1999-05-01

    The viability of tumor cells in radionecrotic tissue after interstitial brachytherapy (BRTX) was evaluated using immunohistochemical markers of proliferative potential in primary and recurrent tumors. Tumor specimens from 30 patients with malignant gliomas (14 anaplastic astrocytomas, 16 glioblastomas) taken before and after BRTX were examined using MIB-1 monoclonal antibody. Histological examinations of specimens obtained by craniotomy or stereotactic biopsy after BRTX revealed tumor recurrence in 18 patients and radionecrosis in 12 patients including two with pure radionecrosis and 10 with a mixture of both tumor and radionecrosis. The MIB-1 index of the tumors with radionecrosis was 7.6{+-}5.5%, and that of the primary tumors was 17.0{+-}11.2%, showing a significant difference (p<0.05). There was no significant difference between the MIB-1 index of the primary tumors with local recurrence after BRTX and the primary tumors which underwent radionecrosis. Although morphologically viable tumor cells were found in the radionecrotic tissue, BRTX causes a reduction in the proliferative potential of these tumor cells. (author)

  8. Parathyroid hormone dependent T cell proliferation in uremic rats

    DEFF Research Database (Denmark)

    Lewin, E; Ladefoged, Jens; Brandi, L

    1993-01-01

    Chronic renal failure (CRF) is combined with an impairment of the immune system. The T cell may be a target for the action of parathyroid hormone (PTH). Rats with CRF have high blood levels of PTH. Therefore, the present investigation examined some aspects of the T cell function in both normal...

  9. Exogenous serotonin regulates proliferation of interstitial cells of Cajal in mouse jejunum through 5-HT2B receptors

    OpenAIRE

    Wouters, Mira; Gibbons, Simon J; Roeder, Jaime L; Distad, Marne; Ou, Yijun; Strege, Peter R; Szurszewski, Joseph H; Farrugia, Gianrico

    2007-01-01

    BACKGROUND & AIMS: Interstitial cells of Cajal (ICC) are required for normal gastrointestinal motility. Loss of ICC is associated with several motility disorders. The mechanisms modulating ICC survival and proliferation are poorly understood. This study aimed to establish whether 5-hydroxytryptamine (5-HT) plays a role in regulating ICC proliferation. METHODS: Expression of 5-HT receptor mRNA was investigated in muscle strips, in purified populations of ICC, and in identified single cells. Th...

  10. 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.

  11. 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.

  12. Peripheral-type benzodiazepine receptors in bronchoalveolar lavage cells of patients with interstitial lung disease

    International Nuclear Information System (INIS)

    Branley, Howard M.; Bois, Roland M. du; Wells, Athol U.; Jones, Hazel A.

    2007-01-01

    Introduction: PK11195 is a ligand with high affinity for peripheral benzodiazepine receptors (PBRs), which are present in large numbers in macrophages. PBRs play a role in antioxidant pathways and apoptosis, key factors in control of lung health. Intrapulmonary PBRs, assessed in vivo by positron emission tomography (PET), are decreased in interstitial lung disease (ILD) despite increased macrophage numbers. We wished to ascertain whether the observed decrease in in vivo expression of PBRs in the PET scans could be accounted for by a reduction in PBRs per cell by saturation-binding assays of R-PK11195 in cells obtained by bronchoalveolar lavage (BAL). Methods: We performed receptor saturation-binding assays with [ 3 H]-R-PK11195 on a mixed population of cells recovered by BAL to quantify the number of R-PK11195 binding sites per macrophage in 10 subjects with ILD and 10 normal subjects. Results: Receptor affinity [dissociation constant (Kd)] was similar in ILD patients and controls. However, R-PK11195 binding sites per cell [(maximal binding sites available (B max )] were decreased in macrophages obtained by BAL from subjects with ILD compared to normal (P<.0005). Microautoradiography confirmed localization of R-PK11195 to macrophages in a mixed inflammatory cell population obtained by BAL. Conclusion: These results demonstrate that in vitro PBR expression per cell on macrophages obtained by BAL is reduced in patients with ILD indicating a potentially functionally different macrophage phenotype. As PBRs are involved in the orchestration of lung inflammatory responses, this finding offers further insight into the role of macrophages in the pathogenesis of ILDs and offers a potential avenue for pharmacological strategy

  13. 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.

  14. Incidence of interstitial pneumonia after hyperfractionated total body irradiation before autologous bone marrow/stem cell transplantation

    International Nuclear Information System (INIS)

    Lohr, F.; Schraube, P.; Wenz, F.; Flentje, M.; Kalle, K. von; Haas, R.; Hunstein, W.; Wannenmacher, M.

    1995-01-01

    Purpose/Objectives Interstitial pneumonia (IP) is a severe complication after allogenic bone marrow transplantation (BMT) with incidence rates between 10 % and 40 % in different series. It is a polyetiologic disease that occurs depending on age, graft vs. host disease (GvHD), CMV-status, total body irradiation (TBI) and immunosuppressive therapy after BMT. The effects of fractionation and dose rate are not entirely clear. This study evaluates the incidence of lethal IP after hyperfractionated TBI for autologous BMT or stem cell transplantation. Materials and Methods Between 1982 and 1992, 182 patients (60 % male, 40 % female) were treated with hyperfractionated total body irradiation (TBI) before autologous bone marrow transplantation. Main indications were leukemias and lymphomas (53 % AML, 21 % ALL, 22 % NHL, 4 % others) Median age was 30 ys (15 - 55 ys). A total dose of 14.4 Gy was applied using lung blocks (12 fractions of 1.2 Gy in 4 days, dose rate 7-18 cGy/min, lung dose 9 - 9.5 Gy). TBI was followed by cyclophosphamide (200 mg/kg). 72 % were treated with bone marrow transplantation, 28 % were treated with stem cell transplantation. Interstitial pneumonia was diagnosed clinically, radiologically and by autopsy. Results 4 patients died most likely of interstitial pneumonia. For another 12 patients interstitial pneumonia was not the most likely cause of death but could not be excluded. Thus, the incidence of lethal IP was at least 2.2 % but certainly below 8.8 %. Conclusion Lethal interstitial pneumonia is a rare complication after total body irradiation before autologous bone marrow transplantation in this large, homogeously treated series. In the autologous setting, total doses of 14.4 Gy can be applied with a low risk for developing interstitial pneumonia if hyperfractionation and lung blocks are used. This falls in line with data from series with identical twins or t-cell depleted marrow and smaller, less homogeneous autologous transplant studies. Thus

  15. Response of the ABCG2 promoter in T47D cells and BeWo cells to sex hormone treatment.

    Science.gov (United States)

    Yasuda, Satoru; Kobayashi, Masaki; Itagaki, Shirou; Hirano, Takeshi; Iseki, Ken

    2009-09-01

    The aim of this study was to elucidate the effects of sex hormones on activity of the ABCG2 promoter in different cell lines. T47D cells and BeWo cells were used as models for ABCG2-expressing cell lines, and luciferase assays using ABCG2 promoter-luciferase constructs were performed. It was shown that progesterone increased the response of the ABCG2 promoter in T47D cells but not in BeWo cells. On the other hand, estradiol had no effect on response of the ABCG2 promoter in either cell line. However, response of the ABCG2 promoter was enhanced by overexpression of ERalpha in both T47D cells and BeWo cells. T47D cells had higher sensitivity to ERalpha than did BeWo cells. Furthermore, it was shown that the inductive effect of progesterone on the ABCG2 promoter was inhibited by addition of RU486 or mithramycin A. Therefore, it was thought that the ABCG2 promoter responded to stimulation of the progesterone receptor (PR)-Sp1 pathway in T47D cells. Furthermore, progesterone suppressed the response of the ABCG2 promoter by changing the expression levels of PR-A and PR-B in BeWo cells. These findings suggested that there are differences between cell lines in the regulation mechanism of ABCG2 expression by sex hormone treatment.

  16. The Role of Interstitial Cells of Cajal in Acute Cholecystitis in Guinea Pig Gallbladder.

    Science.gov (United States)

    Huang, Zhen-Peng; Qiu, Hu; Yang, Yan; Zhang, Li; Yang, Bin; Lin, Meng-Juan; Yu, Bao-Ping

    2016-01-01

    Acute cholecystitis is common in gallbladder motility disorder. Interstitial cells of Cajal (ICCs) in the gallbladder are involved in the regulation of gallbladder motility. The aim of this study was to explore the change of gallbladder ICCs in acute cholecystitis. Thirty adult guinea pigs were randomly divided into 3 groups: a sham-operated group (healthy controls) and 2 study groups. The animals in the study group were subjected to bile duct ligation and then to laparotomy and cholecystectomy at 24 and 48 hours after surgery. Immunohistochemistry, immunohistofluorescence, and laser confocal microscopy were performed to observe the shape, size, morphology, and density of gallbladder ICCs. Western blot and real-time PCR were performed to detect stem cell factor and c-kit protein and mRNA expression, respectively. There were no differences in the shape, size, and morphology of the gallbladder ICCs in the control and the two acute cholecystitis groups. Density of gallbladder ICCs, SCF level, and c-kit protein and mRNA expression all decreased in the acute cholecystitis groups. Further, SCF level and c-kit protein and mRNA expression decreased with progress of acute cholecystitis (all P cholecystitis can decrease ICCs through repression of SCF and c-kit expression and that ICCs loss play a role in acute cholecystitis. © 2016 The Author(s) Published by S. Karger AG, Basel.

  17. Differentiation of interstitial cells of Cajal in the human distal colon.

    Science.gov (United States)

    Radenkovic, Goran; Abramovic, Mirjana

    2012-01-01

    At the end of the embryonic period of human development, interstitial cells of Cajal (ICC) are present in the esophagus, stomach, and proximal duodenum, around the inception of the myenteric plexus (MP) ganglia. In the small and large bowel, ICC appear later. The object of the present study was to determine the timing of appearance and pattern of distribution of ICC in the human embryonic and fetal distal colon. Human distal colon specimens were obtained from 8 embryos and 14 fetuses without gastrointestinal disorders. The specimens were 7-16 weeks of gestational age. The specimens were exposed to anti-c-kit antibodies to investigate ICC differentiation. Enteric plexuses were immunohistochemically examined using anti-neuron-specific enolase, and the differentiation of smooth muscle cells was studied with anti-desmin antibodies. In the distal colon, ICC emerged at weeks 10-11 of the fetal period in the form of two parallel belts of densely packed cells extending at the submucous plexus (SMP) and the MP level. These cells correspond to ICC of the SMP (ICC-SMP) and ICC of the MP (ICC-MP). The simultaneous appearance of ICC at the SMP and MP level in the distal colon can be explained by the fact that there are differences in the migration of neural crest cells in particular portions of the digestive tube. In conclusion, in humans, there was a difference in the patterns of development of ICC in the distal colon compared to the rest of the gut. Copyright © 2012 S. Karger AG, Basel.

  18. 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....

  19. [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.

  20. 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.

  1. 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.

  2. 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.

  3. 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)

  4. 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

  5. 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

  6. 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.

  7. Thyroid hormone-like and estrogenic activity of hydroxylated PCBs in cell culture

    International Nuclear Information System (INIS)

    Kitamura, Shigeyuki; Jinno, Norimasa; Suzuki, Tomoharu; Sugihara, Kazumi; Ohta, Shigeru; Kuroki, Hiroaki; Fujimoto, Nariaki

    2005-01-01

    The thyroid hormone-disrupting activity of hydroxylated PCBs was examined. 4-Hydroxy-2,2',3,4',5,5'-hexachlorobiphenyl (4-OH-2,2',3,4',5,5'-HxCB), 4-hydroxy-3,3',4',5-tetrachlorobiphenyl (4-OH-3,3',4',5-TCB) and 4,4'-dihydroxy-3,3',5,5'-tetrachlorobiphenyl (4,4'-diOH-3,3',5,5'-TCB), which have been detected as metabolites of PCBs in animals and humans, and six other 4-hydroxylated PCBs markedly inhibited the binding of triiodothyronine (1 x 10 -10 M) to thyroid hormone receptor (TR) in the concentration range of 1 x 10 -6 to 1 x 10 -4 M. However, 4-hydroxy-2',4',6'-trichlorobiphenyl (4-OH-2',4',6'-TCB), 3-hydroxy-2,2',5,5'-tetrachlorobiphenyl, 4-hydroxy-2,2',5,5'-tetrachlorobiphenyl, 4-hydroxy-2,3,3',4'-tetrachlorobiphenyl, 2,3',5,5'-tetrachlorobiphenyl and 2,3',4',5,5'-pentachlorodiphenyl did not show affinity for TR. The thyroid hormonal activity of PCBs was also examined using rat pituitary cell line GH3 cells, which grow and release growth hormone in a thyroid hormone-dependent manner. 4-OH-2,2',3,4',5,5'-HxCB, 4,4'-diOH-3,3',5,5'-TCB and 4-OH-3,3',4',5-TCB enhanced the proliferation of GH3 cells and stimulated their production of growth hormone in the concentration range of 1 x 10 -7 to 1 x 10 -4 M, while PCBs which had no affinity for thyroid hormone receptor were inactive. In contrast, only 4-OH-2',4',6'-TCB exhibited a significant estrogenic activity using estrogen-responsive reporter assay in MCF-7 cells. However, the 3,5-dichloro substitution of 4-hydroxylated PCBs markedly decreased the estrogenic activity. These results suggest that, at least for the 17 PCB congeners and hydroxylated metabolites tested, a 4-hydroxyl group in PCBs is essential for thyroid hormonal and estrogenic activities, and that 3,5-dichloro substitution favors thyroid hormonal activity, but not estrogenic activity

  8. 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.

  9. Progesterone-specific stimulation of triglyceride biosynthesis in a breast cancer cell line (T-47D)

    International Nuclear Information System (INIS)

    Judge, S.M.; Chatterton, R.T. Jr.

    1983-01-01

    The purpose of this study was to examine the lactogenic response of human mammary cancer cell lines to hormones in vitro. Progesterone was found to stimulate the incorporation of 14C from [14C]acetate into triglycerides (TG) and to promote accumulation of TG with a fatty acid composition similar to that of human milk fat in T-47D cells. Lipid droplets were observed in larger numbers without concomitant accumulation of casein granules in cells incubated with progesterone, but secretion of lipid into the medium did not occur. An effect of progesterone on TG accumulation was detectable after 12 hr and was maximal at 72 hr. Increasing doses of progesterone (10(-9) to 10(-5) M) caused a progressive increase in TG accumulation. The presence of cortisol and/or prolactin did not alter TG formation nor the dose response of the cells to progesterone. The growth rate of T-47D cells was not altered by the presence of progesterone in the medium. Neither of the human mammary cancer cell lines, MCF-7 and HBL-100, nor the human fibroblast cell lines, 28 and 857, responded to progesterone. The data indicate that, while the normally lactogenic hormones do not stimulate milk product biosynthesis in the cell lines tested, progesterone specifically stimulated synthesis and accumulation of TG in the T-47D cells

  10. Interstitial cell tumor in a black-and-white ruffed lemur (Varecia variegatus variegatus).

    Science.gov (United States)

    Neiffer, D L; Klein, E C

    2001-06-01

    A 14.5-yr-old, male black-and-white ruffed lemur (Varecia variegatus variegatus) presented for acute enlargement of the left testicle and hemiscrotum. Physical examination also revealed poor pelage quality with short guard hairs, sparse undercoat, and areas of alopecia. Increased aggression was also reported. A unilateral, open orchiectomy was performed, with the left testicle, epidydymis, associated vaginal tunic, and attached spermatic cord removed. Microscopic evaluation was consistent with an interstitial cell tumor, with many morphologic features similar to this neoplasm in people. No overt histopathologic criteria of malignancy were present. Following orchiectomy, gradual improvement in pelage quality was noted and was considered almost normal by 5 mo postoperative. In contrast with the aggressive preoperative behavior, the lemur was extremely submissive for 3 mo following the surgery. Gradual return to normal behavior and social status occurred over the next 2 mo. Multiple follow-up examinations and radiographs revealed no evidence of metastasis, and biopsy of the remaining testicle 4 mo later revealed no evidence of neoplasia. Serial measurements of testosterone and estradiol revealed levels within the range of those for other ruffed lemurs, as were repeated measurements taken of the remaining testicle. At 19 mo postoperative, the lemur had a coat quality considered nearly normal and maintained its historical social position in the lemur group without abnormal aggressive behavior.

  11. Biophysically-based modelling of the interstitial cells of Cajal: Current status and future perspectives

    Directory of Open Access Journals (Sweden)

    Rachel eLees-Green

    2011-07-01

    Full Text Available Gastrointestinal motility research is progressing rapidly, leading to significant advances in the last 15 years in understanding the cellular mechanisms underlying motility, following the discovery of the central role played by the interstitial cells of Cajal (ICC. As experimental knowledge of ICC physiology has expanded, biophysically-based modelling has become a valuable tool for integrating experimental data, for testing hypotheses on ICC pacemaker mechanisms, and for applications in in silico studies including in multiscale models. This review is focused on the cellular electrophysiology of ICC. Recent evidence from both experimental and modelling domains have called aspects of the existing pacemaker theories into question. Therefore, current experimental knowledge of ICC pacemaker mechanisms is examined in depth, and current theories of ICC pacemaking are evaluated and further developed. Existing biophysically-based ICC models and their physiological foundations are then critiqued in light of the recent advances in experimental knowledge, and opportunities to improve these models are identified. The review concludes by examining several potential clinical applications of biophysically-based ICC modelling from the subcellular through to the organ level, including ion channelopathies and ICC network degradation.

  12. Proliferation of Interstitial Cells in the Cyclophosphamide-Induced Cystitis and the Preventive Effect of Imatinib

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    Maria Sancho

    2017-01-01

    Full Text Available Cyclophosphamide- (CYP- induced cystitis in the rat is a well-known model of bladder inflammation that leads to an overactive bladder, a process that appears to involve enhanced nitric oxide (NO production. We investigated the changes in the number and distribution of interstitial cells (ICs and in the expression of endothelial NO synthase (eNOS in the bladder and urethra of rats subjected to either intermediate or chronic CYP treatment. Pronounced hyperplasia and hypertrophy of ICs were evident within the lamina propria and in the muscle layer. IC immunolabeling with CD34, PDGFRα, and vimentin was enhanced, as reflected by higher colocalization indexes of the distinct pairs of markers. Moreover, de novo expression of eNOS was evident in vimentin and CD34 positive ICs. Pretreatment with the receptor tyrosine kinase inhibitor Imatinib prevented eNOS expression and ICs proliferation, as well as the increased voiding frequency and urinary tract weight provoked by CYP. As similar results were obtained in the urethra, urethritis may contribute to the uropathology of CYP-induced cystitis.

  13. Squamous Cell Carcinoma of the Bladder Mimicking Interstitial Cystitis and Voiding Dysfunction

    Directory of Open Access Journals (Sweden)

    Colton Prudnick

    2013-01-01

    Full Text Available Squamous cell carcinoma (SCC of the bladder is a relatively uncommon cause of bladder cancer accounting for <5% of bladder tumors in the western countries. SCC has a slight male predominance and tends to occur in the seventh decade of life. The main presenting symptom of SCC is hematuria, and development of this tumor in the western world is associated most closely with chronic indwelling catheters and spinal cord injuries. A 39-year-old Caucasian female presented with bladder and lower abdominal pain, urinary frequency, and nocturia which was originally believed to be interstitial cystitis (IC but was later diagnosed as SCC of the bladder. Presentation of SCC without hematuria is an uncommon presentation, but the absence of this symptom should not lead a practitioner to exclude the diagnosis of SCC. This case is being reported in an attempt to explain the delay and difficulty of diagnosis. Background on the risk factors for SCC of the bladder and the typical presenting symptoms of bladder SCC and IC are also reviewed.

  14. Transcriptome of interstitial cells of Cajal reveals unique and selective gene signatures.

    Directory of Open Access Journals (Sweden)

    Moon Young Lee

    Full Text Available Transcriptome-scale data can reveal essential clues into understanding the underlying molecular mechanisms behind specific cellular functions and biological processes. Transcriptomics is a continually growing field of research utilized in biomarker discovery. The transcriptomic profile of interstitial cells of Cajal (ICC, which serve as slow-wave electrical pacemakers for gastrointestinal (GI smooth muscle, has yet to be uncovered. Using copGFP-labeled ICC mice and flow cytometry, we isolated ICC populations from the murine small intestine and colon and obtained their transcriptomes. In analyzing the transcriptome, we identified a unique set of ICC-restricted markers including transcription factors, epigenetic enzymes/regulators, growth factors, receptors, protein kinases/phosphatases, and ion channels/transporters. This analysis provides new and unique insights into the cellular and biological functions of ICC in GI physiology. Additionally, we constructed an interactive ICC genome browser (http://med.unr.edu/physio/transcriptome based on the UCSC genome database. To our knowledge, this is the first online resource that provides a comprehensive library of all known genetic transcripts expressed in primary ICC. Our genome browser offers a new perspective into the alternative expression of genes in ICC and provides a valuable reference for future functional studies.

  15. Distribution of Interstitial Cells of Cajal in the Esophagus of Fetal Rats with Esophageal Atresia

    Directory of Open Access Journals (Sweden)

    Caner Isbir

    2016-04-01

    Full Text Available Aim: Scarcity of the interstitial cells of Cajal (ICC is related to motility disorders. In the study, we aimed to evaluate the number and density of ICCs in the fetal rat esophagus in the adriamycin - esophageal atresia (EA model. Material and Method: Rat fetuses were divided into three groups as a control, adriamycin group without EA and adriamycin group with EA. Four doses of adriamycin, 2 mg/kg each, were injected intraperitoneally to the adriamycin group rats between on 6 and 9 days of gestation. The presence of ICCs in the esophagus of the rat fetuses was determined by using an immunohistochemistry technique (c-kit, CD117. The average numbers of ICCs were calculated with microscopic evaluation by using a visual scoring system (range1 to 3. Results: Seven fetuses were included in each group. The ICCs score 3 distributions of fetuses were 5 (72% fetuses in the control group, 3 (43% fetuses in the adriamycin group without EA, 1 (14% fetus in the adriamycin group with EA. It have been found that there was a marked reduction of ICCs distribution in the adriamycin group with EA compared to control group (p 0.05. Discussion: ICCs density was significantly decreased in the rat fetuses with EA compared to the fetuses without EA. These findings support the idea that ICCs density may be congenitally abnormal in EA. This may be led to dismotility seen in the operated esophagus due to EA.

  16. Immunohistochemical studies of the enteric nervous system and interstitial cells of Cajal in the canine stomach

    Directory of Open Access Journals (Sweden)

    Colin Musara

    2013-03-01

    Full Text Available The distribution of interstitial cells of Cajal (ICC, the probable pacemakers in gastrointestinal motility, was investigated using an antigenic marker of gastric ICC known as C-Kit. Antiserum raised against the general neuronal marker protein gene peptide 9.5 (PGP as well as the nitrergic neuronal marker neuronal nitric oxide synthase (nNOS were used to investigate the distribution of gastric nerves. Polyclonal goat anti-human C-Kit was reliable in labelling ICC in the stomach. Two classes of ICC were identified according to their distribution: ICC-MY distributed around the periphery of myenteric ganglia and ICC-IM in the circular and longitudinal muscle layers. The neuronal marker PGP was reliably consistent in revealing the density and distribution of the enteric nervous system. Density of nerve fibres was higher in circular smooth muscle than in longitudinal smooth muscle. From nNOS immunohistochemistry, it is evident that inhibitory (nitrergic nerves constitute a substantial fraction of the enteric nervous system.

  17. 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...

  18. 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...

  19. 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

  20. 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.

  1. PTH [parathyroid hormone] elevates inositol polyphosphates and diacylglycerol in a rat osteoblast-like cell line

    International Nuclear Information System (INIS)

    Civitelli, R.; Reid, I.R.; Westbrook, S.; Avioli, L.V.; Hruska, K.A.

    1988-01-01

    Parathyroid hormone (PTH)-stimulated signal transduction through mechanisms alternate to adenosine 3',5'-cyclic monophosphate (cAMP) production were studied in UMR 106-01 cells, a cell line with an osteoblastic phenotype. PTH produced transient, dose-related increases in cytosolic calcium ([Ca 2+ ] i ), inositol trisphosphates, and diacylglycerol (DAG). Both inositol 1,4,5-trisphosphate (Ins-1,4,5P 3 ) and inositol 1,3,4-trisphosphate (Ins-1,3,4P 3 ) production were rapidly stimulated by PTH. Consistent with the production of Ins-1,3,4P 3 , rapid stimulation of late eluting inositol tetrakisphosphate was observed. The effects on the inositol phosphates were induced rapidly, consistent with roles as signals for changes in [Ca 2+ ] i . In saponin-permeabilized UMR 106-01 cells, Ins-1,4,5P 3 stimulated 45 Ca release from a nonmitochondrial intracellular pool. Thus the hypothesis that PTH-stimulated Ins-1,4,5P 3 production initiates Ca 2+ release and contributes to transient elevations of [Ca 2+ ] i is supported. These data suggest that stimulation of cAMP production during PTH stimulation may negatively affect production of rises in [Ca 2+ ] i during PTH stimulation. The inactivation of the inhibitory G protein of adenylate cyclase by pertussis toxin could explain its action similar to cAMP analogues. Cyclci nucleotides diminish the effects of PTH on [Ca 2+ ] i , probably interacting on a biochemical step subsequent to or independent of Ins-1,4,5P 3 release

  2. 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.

  3. Cress oil modulates radiation-induced hormonal, histological, genetic disorders and sperm head abnormalities in albino rat

    International Nuclear Information System (INIS)

    Said, U.Z.; Azab, KH.SH.; Soliman, S.M.

    2005-01-01

    Watercress (Nasturtium officinale) is an aquatic perennial herb of mustard family. The plant is rich in glucosinolates, specially gluconasturtin, which can be hydrolyzed to 2- phenylethyl isothiocyanate (PEITC) and known to activate detoxification enzymes. Cress oil (0.1 ml/kg/day) was given to rats, receiving a standard diet, by gavage for 2 weeks before whole body gamma irradiation at 7 Gy (single dose) and treatment was continued one week after irradiation. The results obtained showed that cress oil treatment significantly diminished the radiation-induced alterations in levels of testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin in serum and also blunted the increased levels of thiobarbituric acid reactive substances (TBARS) in serum and testes. Histopathological examination of testicular tissue showed that radiation exposure leads to atrophic testis with marked loss of germ cells, remaining tall pink Sertoli cells, peri tubular fibrosis and interstitial fibrosis. Cress oil treatments ameliorated the intensity of these changes where signs of partial recovery were observed in the histological configuration of leydig cells, seminiferous tubules, spermatocytes and in the structure of interstitial cells. Moreover, administration of cress oil significantly reduced the score of sperm head abnormalities and chromosomal aberration frequencies. It could be concluded that watercress may have a bio protective effect on radiation-induced oxidative stress where phytochemicals present in watercress could protect against hormone-dependent disease

  4. The Role of Cytotoxic T-lymphocyte-associated Protein 4 (CTLA-4) Gene, Thyroid Stimulating Hormone Receptor (TSHR) Gene and Regulatory T-cells as Risk Factors for Relapse in Patients with Graves Disease.

    Science.gov (United States)

    Eliana, Fatimah; Suwondo, Pradana; Asmarinah, Asmarinah; Harahap, Alida; Djauzi, Samsuridjal; Prihartono, Joedo; Pemayun, Tjokorda Gde Dalem

    2017-07-01

    graves' disease (GD) is the most common condition of thyrotoxicosis. The management of GD is initiated with the administration of antithyroid drugs; however, it requires a long time to achieve remission. In reality more than 50% of patients who had remission may be at risk for relapse after the drug is stopped. This study aimed to evaluate the role of clinical factors such as smoking habit, degree of ophtalmopathy, degree of thyroid enlargement; genetic factors such as CTLA-4 gene on nucleotide 49 at codon 17 of exon 1, CTLA-4 gene of promotor -318, TSHR gene polymorphism rs2268458 of intron 1; and immunological factors such as regulatory T cells (Treg) and thyroid receptor antibody (TRAb); that affecting the relapse of patients with Graves' disease in Indonesia. this was a case-control study, that compared 72 subjects who had relapse and 72 subjects without relapse at 12 months after cessation of antithyroid treatment, who met the inclusion criteria. Genetic polymorphism examination was performed using PCR-RFLP. The number of regulatory T cells was counted using flow cytometry analysis and ELISA was used to measure TRAb. The logistic regression was used since the dependent variables were categorical variables. the analysis of this study demonstrated that there was a correlation between relapse of disease and family factors (p=0.008), age at diagnosis (p=0.021), 2nd degree of Graves' ophthalmopathy (p=0.001), enlarged thyroid gland, which exceeded the lateral edge of the sternocleidomastoid muscles (p=0.040), duration of remission period (p=0.029), GG genotype of CTLA-4 gene on the nucleotide 49 at codon 17 of exon 1 (p=0.016), CC genotype of TSHR gene on the rs2268458 of intron 1 (p=0.003), the number of regulatory T cells (p=0.001) and TRAb levels (p=0.002). genetic polymorphisms of CTLA-4 gene on the nucleotide 49 at codon 17 of exon 1, TSHR gene SNP rs2268458 of intron 1, number of regulatory T cells and TRAb levels play a role as risk factors for relapse in

  5. Caffeine inhibits nonselective cationic currents in interstitial cells of Cajal from the murine jejunum.

    Science.gov (United States)

    Jin, Nan Ge; Koh, Sang Don; Sanders, Kenton M

    2009-10-01

    Interstitial cells of Cajal (ICC) discharge unitary potentials in gastrointestinal muscles that constitute the basis for pacemaker activity. Caffeine has been used to block unitary potentials, but the ionic conductance responsible for unitary potentials is controversial. We investigated currents in cultured ICC from murine jejunum that may underlie unitary potentials and studied the effects of caffeine. Networks of ICC generated slow wave events under current clamp, and these events were blocked by caffeine in a concentration-dependent manner. Single ICC generated spontaneous transient inward currents (STICs) under voltage clamp at -60 mV and noisy voltage fluctuations in current clamp. STICs were unaffected when the equilibrium potential for Cl- (ECl) was set to -60 mV (excluding Cl- currents) and reversed at 0 mV, demonstrating that a nonselective cationic conductance, and not a Cl- conductance, is responsible for STICs in ICC. Caffeine inhibited STICs in a concentration-dependent manner. Reduced intracellular Ca2+ and calmidazolium (CMZ; 1 microM) activated persistent inward, nonselective cation currents in ICC. Currents activated by CMZ and by dialysis of cells with 10 mM BAPTA were also inhibited by caffeine. Excised inside-out patches contained channels that exhibited spontaneous openings, and resulting currents reversed at 0 mV. Channel openings were increased by reducing Ca2+ concentration from 10(-6) M to 10(-8) M. CMZ (1 microM) also increased openings of nonselective cation channels. Spontaneous currents and channels activated by CMZ were inhibited by caffeine (5 mM). The findings demonstrate that the Ca2+-inhibited nonselective cation channels that generate STICs in ICC are blocked directly by caffeine. STICs are responsible for unitary potentials in intact muscles, and the block of these events by caffeine is consistent with the idea that a nonselective cation conductance underlies unitary potentials in ICC.

  6. Mesenchymal Stem Cell Therapy Alleviates Interstitial Cystitis by Activating Wnt Signaling Pathway

    Science.gov (United States)

    Song, Miho; Lim, Jisun; Yu, Hwan Yeul; Park, Junsoo; Chun, Ji-Youn; Jeong, Jaeho; Heo, Jinbeom; Kang, Hyunsook; Kim, YongHwan; Cho, Yong Mee; Kim, Seong Who; Oh, Wonil; Choi, Soo Jin; Jang, Sung-Wuk; Park, Sanghyeok

    2015-01-01

    Interstitial cystitis (IC) is a syndrome characterized by urinary urgency, frequency, pelvic pain, and nocturia in the absence of bacterial infection or identifiable pathology. IC is a devastating disease that certainly decreases quality of life. However, the causes of IC remain unknown and no effective treatments or cures have been developed. This study evaluated the therapeutic potency of using human umbilical cord-blood-derived mesenchymal stem cells (UCB-MSCs) to treat IC in a rat model and to investigate its responsible molecular mechanism. IC was induced in 10-week-old female Sprague–Dawley rats via the instillation of 0.1 M HCl or phosphate-buffered saline (PBS; sham). After 1 week, human UCB-MSC (IC+MSC) or PBS (IC) was directly injected into the submucosal layer of the bladder. A single injection of human UCB-MSCs significantly attenuated the irregular and decreased voiding interval in the IC group. Accordingly, denudation of the epithelium and increased inflammatory responses, mast cell infiltration, neurofilament production, and angiogenesis observed in the IC bladders were prevented in the IC+MSC group. The injected UCB-MSCs successfully engrafted to the stromal and epithelial tissues and activated Wnt signaling cascade. Interference with Wnt and epidermal growth factor receptor activity by small molecules abrogated the benefits of MSC therapy. This is the first report that provides an experimental evidence of the therapeutic effects and molecular mechanisms of MSC therapy to IC using an orthodox rat animal model. Our findings not only provide the basis for clinical trials of MSC therapy to IC but also advance our understanding of IC pathophysiology. PMID:25745847

  7. Comparative immunohistochemical characterization of interstitial cells in the urinary bladder of human, guinea pig and pig.

    Science.gov (United States)

    Steiner, Clara; Gevaert, Thomas; Ganzer, Roman; De Ridder, Dirk; Neuhaus, Jochen

    2018-02-20

    Interstitial cells (ICs) are thought to play a functional role in urinary bladder. Animal models are commonly used to elucidate bladder physiology and pathophysiology. However, inter-species comparative studies on ICs are rare. We therefore analyzed ICs and their distribution in the upper lamina propria (ULP), the deeper lamina propria (DLP) and the detrusor muscular layer (DET) of human, guinea pig (GP) and pig. Paraffin slices were examined by immunohistochemistry and 3D confocal immunofluorescence of the mesenchymal intermediate filament vimentin (VIM), alpha-smooth muscle actin (αSMA), platelet-derived growth factor receptor alpha (PDGFRα) and transient receptor potential cation channel A1 (TRPA1). Image stacks were processed for analysis using Huygens software; quantitative analysis was performed with Fiji macros. ICs were identified by immunoreactivity for VIM (excluding blood vessels). In all species ≥ 75% of ULP ICs were VIM + /PDGFRα + and ≥ 90% were VIM + /TRPA1 + . In human and pig ≥ 74% of ULP ICs were VIM + /αSMA + , while in GP the percentage differed significantly with only 37% VIM + /αSMA + ICs. Additionally, over 90% of αSMA + ICs were also TRPA1 + and PDGFRα + in human, GP and pig. In all three species, TRPA1 + and PDGFRα + ICs point to an active role for these cells in bladder physiology, regarding afferent signaling processes and signal modification. We hypothesize that decline in αSMA-positivity in GP reflects adaptation of bladder histology to smaller bladder size. In our experiments, pig bladder proved to be highly comparable to human urinary bladder and seems to provide safer interpretation of experimental findings than GP.

  8. Hydrogen Passivation of Interstitial Zn Defects in Heteroepitaxial InP Cell Structures and Influence on Device Characteristics

    Science.gov (United States)

    Ringel, S. A.; Chatterjee, B.

    2004-01-01

    Hydrogen passivation of heteroepitaxial InP solar cells is of recent interest for deactivation of dislocations and other defects caused by the cell/substrate lattice mismatch that currently limit the photovoltaic performance of these devices. In this paper we present strong evidence that, in addition to direct hydrogen-dislocation interactions, hydrogen forms complexes with the high concentration of interstitial Zn defects present within the p(+) Zn-doped emitter of MOCVD-grown heteroepitaxial InP devices, resulting in a dramatic increase of the forward bias turn-on voltage by as much as 280 mV, from 680 mV to 960 mV. This shift is reproducible and thermally reversible and no such effect is observed for either n(+)p structures or homoepitaxial p(+)n structures grown under identical conditions. A combination of photoluminescence (PL), electrochemical C-V dopant profiling, SIMS and I-V measurements were performed on a set of samples having undergone a matrix of hydrogenation and post-hydrogenation annealing conditions to investigate the source of this voltage enhancement and confirm the expected role of interstitial Zn and hydrogen. A precise correlation between all measurements is demonstrated which indicates that Zn interstitials within the p(+) emitter and their interaction with hydrogen are indeed responsible for this device behavior.

  9. 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.

  10. 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/.

  11. 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.

  12. 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

  13. 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.

  14. Beryllium-stimulated apoptosis in macrophage cell lines.

    Science.gov (United States)

    Sawyer, R T; Fadok, V A; Kittle, L A; Maier, L A; Newman, L S

    2000-08-21

    In vitro stimulation of bronchoalveolar lavage cells from patients with chronic beryllium disease (CBD) induces the production of TNF-alpha. We tested the hypothesis that beryllium (Be)-stimulated TNF-alpha might induce apoptosis in mouse and human macrophage cell lines. These cell lines were selected because they produce a range of Be-stimulated TNF-alpha. The mouse macrophage cell line H36.12j produces high levels of Be-stimulated TNF-alpha. The mouse macrophage cell line P388D.1 produces low, constitutive, levels of TNF-alpha and does not up-regulate Be-stimulated TNF-alpha production. The DEOHS-1 human CBD macrophage cell line does not produce constitutive or Be-stimulated TNF-alpha. Apoptosis was determined by microscopic observation of propidium iodide stained fragmented nuclei in unstimulated and BeSO(4)-stimulated macrophage cell lines. BeSO(4) induced apoptosis in all macrophage cell lines tested. Beryllium-stimulated apoptosis was dose-responsive and maximal after 24 h of exposure to 100 microM BeSO(4). In contrast, unstimulated and Al(2)(SO(4))(3)-stimulated macrophage cell lines did not undergo apoptosis. The general caspase inhibitor BD-fmk inhibited Be-stimulated macrophage cell line apoptosis at concentrations above 50 microM. Our data show that Be-stimulated macrophage cell line apoptosis was caspase-dependent and not solely dependent on Be-stimulated TNF-alpha levels. We speculate that the release of Be-antigen from apoptotic macrophages may serve to re-introduce Be material back into the lung microenvironment, make it available for uptake by new macrophages, and thereby amplify Be-stimulated cytokine production, promoting ongoing inflammation and granuloma maintenance in CBD.

  15. 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.

  16. 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

  17. Interstitial Cystitis

    Science.gov (United States)

    ... bathroom at scheduled times and using relaxation techniques. Physical therapy. People who have interstitial cystitis may have painful spasms of pelvic floor muscles. If you have muscle spasms, you can ...

  18. Interstitial nephritis

    Science.gov (United States)

    ... Allergic reaction to a drug (acute interstitial allergic nephritis). Autoimmune disorders, such as antitubular basement membrane disease, Kawasaki disease, Sjögren syndrome, systemic lupus erythematosus, or Wegener granulomatosis. Infections. Long-term use ...

  19. Molecular mechanisms of regulation of growth hormone gene expression in cultured rat pituitary cells by thyroid and glucocorticoid hormones

    International Nuclear Information System (INIS)

    Yaffe, B.M.

    1989-01-01

    In cultured GC cells, a rat pituitary tumor cell line, growth hormone [GH] is induced in a synergistic fashion by physiologic concentrations of thyroid and glucocorticoid hormones. Abundant evidence indicates that these hormones mediate this response via their specific receptors. The purpose of this thesis is to explore the mechanisms by which these hormones affect GH production. When poly (A) + RNA was isolated from cells grown both with and without hormones and translated in a cell-free wheat germ system, the preGH translation products were shown to be proportional to immunoassayable GH production under all combinations of hormonal milieux, indicating that changes in GH production is modulated at a pretranslational level. A cDNA library was constructed from poly (A) + RNA and one clone containing GH cDNA sequences was isolated. This was used to confirm the above results by Northern dot blot analysis. This probe was also used to assess hormonal effects on GH mRNA half-life and synthetic rates as well as GH gene transcription rates in isolated nuclei. Using a pulse-chase protocol in which cellular RNA was labeled in vivo with [ 3 H]uridine, and quantitating [ 3 H]GHmRNA directly by hybridization to GH cDNA bound to nitrocellulose filters, GHmRNA was found to have a half-life of approximately 50 hours, and was not significantly altered by the presence of inducing hormones

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

    Directory of Open Access Journals (Sweden)

    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.

  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. Granulosa cell tumor associated with secondary amenorrhea and serum luteinizing hormone elevation.

    Science.gov (United States)

    Nasu, Kaei; Fukuda, Junichiro; Yoshimatsu, Jun; Takai, Noriyuki; Kashima, Kenji; Narahara, Hisashi

    2007-06-01

    Adult granulosa cell tumors (GCTs) are the most common type of ovarian sex cord tumors. Menstrual irregularity, menorrhagia, or even secondary amenorrhea is frequently observed in premenopausal women bearing GCTs with hormonal activity. We report herein a case of GCT in a patient presenting with secondary amenorrhea and serum luteinizing hormone elevation. A 28-year-old primigravid Japanese woman was admitted complaining of secondary amenorrhea of 2 years' duration. Pelvic examination, transvaginal ultrasonography, and magnetic resonance imaging demonstrated a left ovarian tumor 4 cm in diameter. Serum hormone assays revealed a follicle-stimulating hormone level of 4.8 mIU/ml, luteinizing hormone (LH) of 35.8 mIU/ml, estradiol of 24 pg/ml, progesterone of 1.6 ng/ml, and testosterone of 40 ng/dl. A left salpingo-oophorectomy was performed. The tumor was diagnosed as an adult-type GCT stage IIb (FIGO [International Federation of Obstetricians and Gynecologists], 1988). Spontaneous menstruation occurred soon after the surgery. Serum levels of LH also decreased to normal levels and showed cyclic changes during the menstrual cycle. Subsequently, the patient conceived and delivered a healthy female baby. The tumor recurred in the pelvis 50 months after the initial conservative surgery, with elevated serum LH levels of 36.0 mIU/ml and amenorrhea. The patient was treated by hysterectomy, right salpingo-oophorectomy, omentectomy, paraaortic and pelvic lymphadenectomy, and low anterior resection of the recto-sigmoid colon. Her hormone levels progressed to the postmenopausal state after this surgery. Although LH elevation in patients with GCT is rare and its mechanism is unknown, monitoring of serum LH may provide an additional tumor marker after conservative surgery in such patients.

  4. EVALUATION OF STEROID HORMONES AND THEIR RECEPTORS IN DEVELOPMENT AND PROGRESSION OF RENAL CELL CARCINOMA

    Directory of Open Access Journals (Sweden)

    Nigel Bennett

    2014-06-01

    Full Text Available Steroid hormones and their receptors have important roles in normal kidney biology, and alterations in their expression and function help explain the differences in development of kidney diseases, such as nephrotic syndrome and chronic kidney disease. The distinct gender difference in incidence of renal cell carcinoma (RCC, with males having almost twice the incidence as females globally, also suggests a role for sex hormones or their receptors in RCC development and progression. There was a peak in interest in evaluating the roles of androgen and estrogen receptors in RCC pathogenesis in the late 20th century, with some positive outcomes for RCC therapy that targeted estrogen receptors, especially for metastatic disease. Since that time, however, there have been few studies that look at use of steroid hormone modulators for RCC, especially in the light of new therapies such as the tyrosine kinase inhibitors and new immune therapies, which are having some success for treatment of metastatic RCC. This review summarises past and current literature and attempts to stimulate renewed interest in research into the steroid hormones and their receptors, which might be used to effect, for example, in combination with the other newer targeted therapies for RCC.

  5. The safety and efficacy of carboplatin plus nanoparticle albumin-bound paclitaxel in the treatment of non-small cell lung cancer patients with interstitial lung disease.

    Science.gov (United States)

    Yasuda, Yuichiro; Hattori, Yoshihiro; Tohnai, Rie; Ito, Shoichi; Kawa, Yoshitaka; Kono, Yuko; Urata, Yoshiko; Nogami, Munenobu; Takenaka, Daisuke; Negoro, Shunichi; Satouchi, Miyako

    2018-01-01

    The optimal chemotherapy regimen for non-small cell lung cancer patients with interstitial lung disease is unclear. We therefore investigated the safety and efficacy of carboplatin plus nab-paclitaxel as a first-line regimen for non-small cell lung cancer in patients with interstitial lung disease. We retrospectively reviewed advanced non-small cell lung cancer patients with interstitial lung disease who received carboplatin plus nab-paclitaxel as a first-line chemotherapy regimen at Hyogo Cancer Center between February 2013 and August 2016. interstitial lung disease was diagnosed according to the findings of pretreatment chest high-resolution computed tomography. Twelve patients were included (male, n = 11; female, n = 1). The overall response rate was 67% and the disease control rate was 100%. The median progression free survival was 5.1 months (95% CI: 2.9-8.3 months) and the median overall survival was 14.9 months (95% CI: 4.8-not reached). A chemotherapy-related acute exacerbation of interstitial lung disease was observed in one patient; the extent of this event was Grade 2. There were no treatment-related deaths. Carboplatin plus nab-paclitaxel, as a first-line chemotherapy regimen for non-small cell lung cancer, showed favorable efficacy and safety in patients with preexisting interstitial lung disease. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

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

    Directory of Open Access Journals (Sweden)

    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.

  7. 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...

  8. 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.

  9. 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.

  10. 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)

  11. 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.

  12. 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.

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

    Science.gov (United States)

    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.

  14. 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)

  15. 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

  16. 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

  17. Loss of nitric oxide-mediated inhibition of purine neurotransmitter release in the colon in the absence of interstitial cells of Cajal.

    Science.gov (United States)

    Durnin, Leonie; Lees, Andrea; Manzoor, Sheerien; Sasse, Kent C; Sanders, Kenton M; Mutafova-Yambolieva, Violeta N

    2017-11-01

    Regulation of colonic motility depends on the integrity of enteric inhibitory neurotransmission mediated by nitric oxide (NO), purine neurotransmitters, and neuropeptides. Intramuscular interstitial cells of Cajal (ICC-IM) and platelet-derived growth factor receptor-α-positive (PDGFRα + ) cells are involved in generating responses to NO and purine neurotransmitters, respectively. Previous studies have suggested a decreased nitrergic and increased purinergic neurotransmission in Kit W /Kit W-v ( W/W v ) mice that display lesions in ICC-IM along the gastrointestinal tract. However, contributions of NO to these phenotypes have not been evaluated. We used small-chamber superfusion assays and HPLC to measure the spontaneous and electrical field stimulation (EFS)-evoked release of nicotinamide adenine dinucleotide (NAD + )/ADP-ribose, uridine adenosine tetraphosphate (Up4A), adenosine 5'-triphosphate (ATP), and metabolites from the tunica muscularis of human, monkey, and murine colons and circular muscle of monkey colon, and we tested drugs that modulate NO levels or blocked NO receptors. NO inhibited EFS-evoked release of purines in the colon via presynaptic neuromodulation. Colons from W/W v , Nos1 -/- , and Prkg1 -/- mice displayed augmented neural release of purines that was likely due to altered nitrergic neuromodulation. Colons from W/W v mice demonstrated decreased nitrergic and increased purinergic relaxations in response to nerve stimulation. W/W v mouse colons demonstrated reduced Nos1 expression and reduced NO release. Our results suggest that enhanced purinergic neurotransmission may compensate for the loss of nitrergic neurotransmission in muscles with partial loss of ICC. The interactions between nitrergic and purinergic neurotransmission in the colon provide novel insight into the role of neurotransmitters and effector cells in the neural regulation of gastrointestinal motility. NEW & NOTEWORTHY This is the first study investigating the role of nitric

  18. Growth hormone action in rat insulinoma cells expressing truncated growth hormone receptors

    DEFF Research Database (Denmark)

    Møldrup, Annette; Allevato, G; Dyrberg, Thomas

    1991-01-01

    Transfection of the insulin-producing rat islet tumor cell line RIN-5AH with a full length cDNA of the rat hepatic growth hormone (GH) receptor (GH-R1-638) augments the GH-responsive insulin synthesis in these cells. Using this functional system we analyzed the effect of COOH-terminal truncation...... of the GH receptor. Two mutated cDNAs encoding truncated GH receptors, GH-R1-294 and GH-R1-454, respectively, were generated by site-directed mutagenesis and transfected into the RIN cells. Both receptor mutants were expressed on the cell surface and displayed normal GH binding affinity. Whereas GH-R1......-638 had a molecular mass of about 110 kDa, GH-R1-294 and GH-R1-454 showed molecular masses of 49 and 80 kDa, respectively. Cells expressing GH-R1-454 internalized GH to a similar extent as cells transfected with the full length receptor and the parent cell line, but GH-R1-294-expressing cells showed...

  19. YKL-40 and mast cells are associated with detrusor fibrosis in patients diagnosed with bladder pain syndrome/interstitial cystitis according to the 2008 criteria of the European Society for the Study of Interstitial Cystitis

    DEFF Research Database (Denmark)

    Richter, Benedikte; Roslind, A.; Hesse, U.

    2010-01-01

    Aims: Bladder pain syndrome/interstitial cystitis (BPS/IC), diagnosed according to the new 2008 criteria of the European Society for the Study of Interstitial Cystitis (ESSIC), may lead to detrusor fibrosis. In some inflammatory diseases, fibrosis is related to YKL-40. The aims were to examine YKL......-40 antigenic expression in bladder tissue and levels in serum and urine in BPS/IC and to evaluate whether YKL-40 could be a non-invasive, prognostic biomarker for bladder fibrogenesis and treatment intensity. Methods and results: Immunohistochemistry, immunoelectron microscopy and enzyme...... of detrusor fibrosis with YKL-40-positive cells (P = 0.001), mast cells (P = 0.014) and urine YKL-40 (P = 0.009). Bladder capacity correlated inversely with YKL-40-positive cells (P Treatment intensity was not associated with YKL-40. Conclusion: Serum and urine levels...

  20. Transepithelial resistance and claudin expression in trout RTgill-W1 cell line: effects of osmoregulatory hormones.

    Science.gov (United States)

    Trubitt, Rebecca T; Rabeneck, D Brett; Bujak, Joanna K; Bossus, Maryline C; Madsen, Steffen S; Tipsmark, Christian K

    2015-04-01

    In the present study, we examined the trout gill cell line RTgill-W1 as a possible tool for in vitro investigation of epithelial gill function in fish. After seeding in transwells, transepithelial resistance (TER) increased until reaching a plateau after 1-2 days (20-80Ω⋅cm(2)), which was then maintained for more than 6 days. Tetrabromocinnamic acid, a known stimulator of TER via casein kinase II inhibition, elevated TER in the cell line to 125% of control values after 2 and 6h. Treatment with ethylenediaminetetraacetic acid induced a decrease in TER to hormone (Gh). The effects of three osmoregulatory hormones, Gh, prolactin, and cortisol, on the mRNA expression of three tight junction proteins were examined: claudin-10e (Cldn-10e), Cldn-30, and zonula occludens-1 (Zo-1). The expression of cldn-10e was stimulated by all three hormones but with the strongest effect of Gh (50-fold). cldn-30 expression was stimulated especially by cortisol (20-fold) and also by Gh (4-fold). Finally, zo-1 was unresponsive to hormone treatment. Western blot analysis detected Cldn-10e and Cldn-30 immunoreactive proteins of expected molecular weight in samples from rainbow trout gills but not from RTgill-W1 cultures, possibly due to low expression levels. Collectively, these results show that the RTgill-W1 cell layers have tight junctions between cells, are sensitive to hormone treatments, and may provide a useful model for in vitro study of some in vivo gill phenomena. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. 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.

  2. Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells.

    Science.gov (United States)

    D'Amour, Kevin A; Bang, Anne G; Eliazer, Susan; Kelly, Olivia G; Agulnick, Alan D; Smart, Nora G; Moorman, Mark A; Kroon, Evert; Carpenter, Melissa K; Baetge, Emmanuel E

    2006-11-01

    Of paramount importance for the development of cell therapies to treat diabetes is the production of sufficient numbers of pancreatic endocrine cells that function similarly to primary islets. We have developed a differentiation process that converts human embryonic stem (hES) cells to endocrine cells capable of synthesizing the pancreatic hormones insulin, glucagon, somatostatin, pancreatic polypeptide and ghrelin. This process mimics in vivo pancreatic organogenesis by directing cells through stages resembling definitive endoderm, gut-tube endoderm, pancreatic endoderm and endocrine precursor--en route to cells that express endocrine hormones. The hES cell-derived insulin-expressing cells have an insulin content approaching that of adult islets. Similar to fetal beta-cells, they release C-peptide in response to multiple secretory stimuli, but only minimally to glucose. Production of these hES cell-derived endocrine cells may represent a critical step in the development of a renewable source of cells for diabetes cell therapy.

  3. Mucus secretion-stimulating activity in human lymphoblastoid cells.

    Science.gov (United States)

    Kulemann-Kloene, H; Krag, S S; Bang, F B

    1982-08-20

    Two fractions isolated from cultured lymphoblastoid cells stimulated mucus secretion from the urn cell complex of the marine invertebrate Sipunculus nudus. The activity detected in the nuclear fraction was trypsin-sensitive, and it increased in response to specific nucleotides.

  4. Stimulation of adult oligodendrogenesis by myelin-specific T cells

    DEFF Research Database (Denmark)

    Hvilsted Nielsen, Helle; Toft-Hansen, Henrik; Lambertsen, Kate Lykke

    2011-01-01

    investigated the effect of myelin-specific T cells on oligodendrocyte formation at sites of axonal damage in the mouse hippocampal dentate gyrus. Infiltrating T cells specific for myelin proteolipid protein stimulated proliferation of chondroitin sulfate NG2-expressing oligodendrocyte precursor cells early...... of calretinergic associational/commissural fibers within the dentate gyrus. These results have implications for the perception of MS pathogenesis because they show that infiltrating myelin-specific T cells can stimulate oligodendrogenesis in the adult central nervous system....

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

    Directory of Open Access Journals (Sweden)

    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.

  6. 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.

  7. 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.

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

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    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.

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

    Directory of Open Access Journals (Sweden)

    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. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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)

  15. 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.

  16. Thyroid Hormone and P-Glycoprotein in Tumor Cells

    Directory of Open Access Journals (Sweden)

    Paul J. Davis

    2015-01-01

    Full Text Available P-glycoprotein (P-gp; multidrug resistance pump 1, MDR1; ABCB1 is a plasma membrane efflux pump that when activated in cancer cells exports chemotherapeutic agents. Transcription of the P-gp gene (MDR1 and activity of the P-gp protein are known to be affected by thyroid hormone. A cell surface receptor for thyroid hormone on integrin αvβ3 also binds tetraiodothyroacetic acid (tetrac, a derivative of L-thyroxine (T4 that blocks nongenomic actions of T4 and of 3,5,3′-triiodo-L-thyronine (T3 at αvβ3. Covalently bound to a nanoparticle, tetrac as nanotetrac acts at the integrin to increase intracellular residence time of chemotherapeutic agents such as doxorubicin and etoposide that are substrates of P-gp. This action chemosensitizes cancer cells. In this review, we examine possible molecular mechanisms for the inhibitory effect of nanotetrac on P-gp activity. Mechanisms for consideration include cancer cell acidification via action of tetrac/nanotetrac on the Na+/H+ exchanger (NHE1 and hormone analogue effects on calmodulin-dependent processes and on interactions of P-gp with epidermal growth factor (EGF and osteopontin (OPN, apparently via αvβ3. Intracellular acidification and decreased H+ efflux induced by tetrac/nanotetrac via NHE1 is the most attractive explanation for the actions on P-gp and consequent increase in cancer cell retention of chemotherapeutic agent-ligands of MDR1 protein.

  17. Foetal immune programming: hormones, cytokines, microbes and regulatory T cells.

    Science.gov (United States)

    Hsu, Peter; Nanan, Ralph

    2014-10-01

    In addition to genetic factors, environmental cues play important roles in shaping the immune system. The first environment that the developing foetal immune system encounters is the uterus. Although physically the mother and the foetus are separated by the placental membranes, various factors such as hormones and cytokines may provide "environmental cues" to the foetal immune system. Additionally, increasing evidence suggests that prenatal maternal environmental factors, particularly microbial exposure, might significantly influence the foetal immune system, affecting long-term outcomes, a concept termed foetal immune programming. Here we discuss the potential mediators of foetal immune programming, focusing on the role of pregnancy-related hormones, cytokines and regulatory T cells, which play a critical role in immune tolerance. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. Parathyroid hormone dependent T cell proliferation in uremic rats

    DEFF Research Database (Denmark)

    Lewin, E; Ladefoged, Jens; Brandi, L

    1993-01-01

    was normalized. Rat PTH 1-84 stimulated in vitro the PHA-induced proliferation of T cells in a dose dependent manner. This effect was significant in CRF rat lymphocytes, but not in lymphocytes obtained from normal rats. Based upon the present results it is suggested that the secondary hyperparathyroidism...

  19. Desensitization of parathyroid hormone receptors on cultured bone cells

    International Nuclear Information System (INIS)

    Pun, K.K.; Ho, P.W.; Nissenson, R.A.; Arnaud, C.D.

    1990-01-01

    Administration of excessive amounts of parathyroid hormone (PTH) in the treatment of osteoporosis can reverse the beneficial effects of a low-dose, intermittent regime. To investigate the direct actions and the possible cellular mechanisms of PTH in inducing desensitization of PTH receptors, we studied the effects of desensitization on rat osteoblastic UMR-106 cells. When the osteoblasts were preincubated with bPTH-(1-34), complete refractoriness to a subsequent challenge with the hormone developed within 1 h and at hormone concentrations as low as 5 nM. When osteoblasts thus desensitized were incubated in hormone-free medium, recovery of the cAMP responses began within 2 h and reached maximum after 16 h. Cycloheximide did not affect the process of desensitization. [Nle8,Nle18,Tyr34]bPTH-(3-34)amide significantly impaired the desensitization process by PTH-(1-34) but did not have stimulatory effect on cAMP responses. No significant heterologous desensitization was obvious after preincubation with isoprenaline (50 microM), prostaglandin E1 (50 microM), or prostaglandin E2 (50 microM) for 2 h. Binding experiments with [125I]PLP-(1-36)amide after desensitization revealed that there was an approximate twofold decrease in receptor affinities as analyzed by Scatchard analysis, showing that the decrease in affinity was prominent in the process of desensitization. When the cells were treated with monensin during desensitization, PTH challenge after desensitization produced significantly lower cyclic AMP responses. Recovery after desensitization occurred over a period of 16 h. Inclusion of monensin, but not cycloheximide, impaired the recovery. The results show that homologous desensitization of rat osteoblasts to PTH is brought about by the occupancy of receptors by PTH-(1-34) but not by cAMP generation itself

  20. Desensitization of parathyroid hormone receptors on cultured bone cells

    Energy Technology Data Exchange (ETDEWEB)

    Pun, K.K.; Ho, P.W.; Nissenson, R.A.; Arnaud, C.D. (Univ. of Hong Kong (Hong Kong))

    1990-12-01

    Administration of excessive amounts of parathyroid hormone (PTH) in the treatment of osteoporosis can reverse the beneficial effects of a low-dose, intermittent regime. To investigate the direct actions and the possible cellular mechanisms of PTH in inducing desensitization of PTH receptors, we studied the effects of desensitization on rat osteoblastic UMR-106 cells. When the osteoblasts were preincubated with bPTH-(1-34), complete refractoriness to a subsequent challenge with the hormone developed within 1 h and at hormone concentrations as low as 5 nM. When osteoblasts thus desensitized were incubated in hormone-free medium, recovery of the cAMP responses began within 2 h and reached maximum after 16 h. Cycloheximide did not affect the process of desensitization. (Nle8,Nle18,Tyr34)bPTH-(3-34)amide significantly impaired the desensitization process by PTH-(1-34) but did not have stimulatory effect on cAMP responses. No significant heterologous desensitization was obvious after preincubation with isoprenaline (50 microM), prostaglandin E1 (50 microM), or prostaglandin E2 (50 microM) for 2 h. Binding experiments with (125I)PLP-(1-36)amide after desensitization revealed that there was an approximate twofold decrease in receptor affinities as analyzed by Scatchard analysis, showing that the decrease in affinity was prominent in the process of desensitization. When the cells were treated with monensin during desensitization, PTH challenge after desensitization produced significantly lower cyclic AMP responses. Recovery after desensitization occurred over a period of 16 h. Inclusion of monensin, but not cycloheximide, impaired the recovery. The results show that homologous desensitization of rat osteoblasts to PTH is brought about by the occupancy of receptors by PTH-(1-34) but not by cAMP generation itself.

  1. 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- ...

  2. 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.

  3. Tumor interstitial fluid

    DEFF Research Database (Denmark)

    Gromov, Pavel; Gromova, Irina; Olsen, Charlotta J.

    2013-01-01

    Tumor interstitial fluid (TIF) is a proximal fluid that, in addition to the set of blood soluble phase-borne proteins, holds a subset of aberrantly externalized components, mainly proteins, released by tumor cells and tumor microenvironment through various mechanisms, which include classical secr...

  4. 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...

  5. 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...

  6. Extracellular matrix and hormones transcriptionally regulate bovine. beta. -casein 5 prime sequences in stably transfected mouse mammary cells

    Energy Technology Data Exchange (ETDEWEB)

    Schmidhauser, C. Bissell, M.J. (Univ. of California, Berkeley (United States)); Myers, C.A.; Casperson, G.F. (Monsanto Corporate Research, St. Louis, MO (United States))

    1990-12-01

    Milk protein regulation involves synergistic action of lactogenic hormones and extracellular matrix (ECM). It is well established that substratum has a dramatic effect on morphology and function of mammary cells. The molecular mechanisms that regulate the ECM- and hormone-dependent gene expression, however, have not been resolved. To address this question, a subpopulation (designated CID 9) of the mouse mammary epithelial cell strain COMMA-2D has been developed in which more than 35% of the cells express {beta}-casein, form alveoli-like structures when plated onto a reconstituted basement membrane, and secrete {beta}-casein undirectionally into a lumen. These cells were stably transfected with a series of chloramphenicol acetyltransferase (CAT) fusion genes to study transcriptional regulation of the bovine {beta}-casein gene. The expression of CAT in these lines demonstrated a striking matrix and hormone dependency. This regulation occurered primarily at the transcriptional level and was dependent on the length of the 5{prime} flanking region of the {beta}-casein promotor. Both matrix and hormonal control of transcription occurred within at least the first 1790 base pairs upstream and/or 42 base pairs downstream of the transcriptional initiation site. The ECM effect was independent of glucocorticoid stimulation. However, prolactin was essential and hydrocortisone further increased CAT expression. Endogenous {beta}-casein expression in these lines was similar to that of the parent CID 9 cells. Our data indicate the existence of matrix-dependent elements that regulate transcription.

  7. Effect of hormone replacement therapy on sex hormones and tumor markers in cervical squamous cell carcinoma postoperative patients

    Directory of Open Access Journals (Sweden)

    Hong-Yan Ding

    2016-12-01

    Full Text Available Objective: To investigate the effect of hormone replacement therapy on sex hormones and tumor markers in cervical squamous cell carcinoma postoperative patients. Methods: A total of 100 cases of cervical squamous cell carcinoma from January 2012 to December 2014 in our hospital were selected as research objects, and the observation group (58 cases were willing to receive hormone replacement therapy, while the control group (42 cases were not willing to receive hormone replacement therapy, with routine treatment. Before and after treatment, the serum levels of neutral hormone and tumor markers were detected in two groups of patients. Results: Before treatment, there were no significant differences in serum E2, FSH and LH levels between the two groups (all P>0.05; after treatment, in the observation group compared with before treatment, the level of serum E2 increased significantly (P0.05. Before and after treatment, the levels of serum SCC-Ag, VEGF-C, M MP-2 and MMP-9 showed no significant differences between the two groups (all P>0.05. Conclusions: The use of hormone replacement therapy in cervical squamous cell carcinoma patients can significantly improve the adverse symptoms caused by low estrogen, improve the quality of life of patients, and not affect the prognosis of patients in the short term.

  8. Growth hormone (GH) and GH-releasing hormone (GHRH): Co-localization and action in the chicken testis.

    Science.gov (United States)

    Martínez-Moreno, Carlos G; López-Marín, Luz M; Carranza, Martha; Giterman, Daniel; Harvey, Steve; Arámburo, Carlos; Luna, Maricela

    2014-04-01

    Growth hormone (GH) gene expression is not confined to the pituitary gland and occurs in many extrapituitary tissues, including the chicken testis. The regulation and function of GH in extrapituitary tissues is, however, largely unknown. The possibility that chicken testicular GH might be regulated by GH-releasing hormone (GHRH), as in the avian pituitary gland, was investigated in the present study. GHRH co-localized with GH in the germinal epithelium and in interstitial zones within the chicken testes, particularly in the spermatogonia and spermatocytes. In testicular cell cultures, exogenous human GHRH1-44 induced (at 1, 10 and 100nM) a dose-related increase in GH release. Western blot analysis showed a heterogeneous pattern in the GH moieties released during GHRH stimulation. 26kDa monomer GH was the most abundant moiety under basal conditions, but 15 and 17kDa isoforms were more abundant after GHRH stimulation. GHRH treatment also increased the abundance of PCNA (proliferating cell nuclear antigen) immunoreactivity in the testes. This may have been GH-mediated, since exogenous GH similarly increased the incorporation of ((3)H)-thymidine into cultured testicular cells and increased their metabolic activity, as determined by increased MTT reduction. Furthermore, GH and GHRH immunoneutralization blocked GHRH-stimulated proliferative activity. In summary, these results indicate that GHRH stimulates testicular GH secretion in an autocrine or paracrine manner. Data also demonstrate proliferative actions of GHRH on testicular cell number and suggest that this action is mediated by local GH production. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  10. 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

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

    Science.gov (United States)

    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

  12. Localization of calcium changes in stimulated rat mast cells.

    Science.gov (United States)

    Horoyan, M; Soler, M; Benoliel, A M; Fraterno, M; Passerel, M; Subra, H; Martin, J M; Bongrand, P; Foa, C

    1992-01-01

    We studied intracellular free, bound, and sequestered calcium in rat mast cells after various stimulations. The use of a fluorescent probe combined with digitized imaging on individual living cells demonstrated transient increases of free Ca2+ in the micromolar range. The use of histochemical techniques (K pyroantimonate and anhydrous fixation), together with X-ray microanalysis, energy electron-loss spectroscopy, and electron spectroscopic imaging, revealed large amounts of stored calcium within the cells (in the millimolar range). Chelation experiments and stimulations enabled us to identify at least two pools of bound calcium which exhibited different dynamic behaviors. Stimulation in the presence of EGTA did not modify calcium from granules, granule membranes, and heterochromatin, whereas it decreased calcium from other cell compartments. Stimulation triggered variations in the amount of bound calcium but they did not parallel free calcium movements. Hence, whereas free calcium is implicated in exocytosis, bound calcium may be involved in altogether different cell functions.

  13. Changes in the interstitial cells of Cajal and neuronal nitric oxide synthase positive neuronal cells with aging in the esophagus of F344 rats.

    Science.gov (United States)

    Kim, Hee Jin; Kim, Nayoung; Kim, Yong Sung; Nam, Ryoung Hee; Lee, Sun Min; Park, Ji Hyun; Choi, Daeun; Hwang, Young-Jae; Lee, Jongchan; Lee, Hye Seung; Kim, Min-Seob; Lee, Moon Young; Lee, Dong Ho

    2017-01-01

    The aging-associated cellular and molecular changes in esophagus have not been established, yet. Thus we evaluated histological structure, interstitial cells of Cajal (ICCs), neuronal nitric oxide synthase (nNOS)-positive cells, and contractility in the esophagus of Fischer 344 rat at different ages (6-, 31-, 74-weeks, and 2-years). The lamina propria thickness and endomysial area were calculated. The immunoreactivity of c-Kit, nNOS and protein gene product (PGP) 9.5 was counted after immunohistochemistry. Expression of c-Kit, stem cell factor (SCF), nNOS and PGP 9.5 mRNA was measured by real-time PCR, and expression of c-Kit and nNOS protein was detected by Western blot. Isovolumetric contractile force measurement and electrical field stimulation (EFS) were conducted. The lamina propria thickness increased (6 week vs 2 year, P = 0.005) and the endomysial area of longitudinal muscle decreased with aging (6 week vs 2 year, Paging (6 week vs 2 year; Pchange of PGP 9.5-immunopositiviy. The expressions of nNOS, c-Kit and SCF mRNA also reduced with aging (6 week vs 2 year; P = 0.006, P = 0.001 and P = 0.006, respectively), while the change of PGP 9.5 mRNA expression was not significant. Western blot showed the significant decreases of nNOS and c-Kit protein expression with aging (6 week vs 2 year; P = 0.008 and P = 0.012, respectively). The EFS-induced esophageal contractions significantly decreased in 2-yr-old rat compared with 6-wk-old rats, however, L-NG-Nitroarginine methylester did not significantly increase the spontaneous and EFS-induced contractions in the 6-wk- and 2-yr-old rat esophagus. In conclusion, an increase of lamina propria thickness, a decrease of endomysial area, c-Kit, SCF and NOS expression with preserved total enteric neurons, and contractility in aged rat esophagus may explain the aging-associated esophageal dysmotility.

  14. 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 (...

  15. Effects of sex and pregnancy hormones on growth hormone and prolactin receptor gene expression in insulin-producing cells

    DEFF Research Database (Denmark)

    Møldrup, Annette; Petersen, Elisabeth D.; Nielsen, Jens Høiriis

    1993-01-01

    During pregnancy, marked hyperplasia of the pancreatic islet cells has been observed. This effect may be mediated by the pregnancy-associated peptide hormones, placental lactogen, PRL, and GH, which were previously shown to be mitogenic to beta-cells in vitro. To study whether the responsiveness ...

  16. Mesenchymal stromal stem cell therapy in advanced interstitial lung disease - Anaphylaxis and short-term follow-up

    Directory of Open Access Journals (Sweden)

    Balamugesh Thangakunam

    2015-01-01

    Full Text Available There are limited treatment options for advanced interstitial lung disease (ILD. We describe a patient of ILD treated with mesenchymal stromal stem cell infusion. The index patient had end-stage ILD due to a combination of insults including treatment with radiotherapy and a tyrosine kinase inhibitor Erlotinib. He was oxygen-dependent and this was hampering his quality of life. He tolerated the first infusion stem cells without any problem. During the second infusion he developed anaphylactic shock, which was appropriately managed. At 6-months follow-up he had no improvement in oxygenation, pulmonary function or CT scan parameters. In view of anaphylaxis, further infusions of MSC were withheld. A longer follow-up may reveal long-term benefits or side effects, if any. However the occurrence of anaphylaxis is of concern suggesting that further trials should be conducted with intensive monitoring.

  17. 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...

  18. 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

  19. The protective effects of total phenols in magnolia officinalix rehd. et wils on gastrointestinal tract dysmotility is mainly based on its influence on interstitial cells of cajal

    Science.gov (United States)

    Tian, Hui; Huang, Dazhi; Li, Tao; Huang, Lihua; Zheng, Xingguang; Tang, Danxia; Zhang, Lu; Wang, Jian

    2015-01-01

    Magnolia officinalix Rehd. et Wils is a kind of herb which is widely used for gastrointestinal tract mobility disorder in Asian countries. In this study, we investigated whether the total phenols of Magnolia officinalix Rehd. et Wils (TPM) treatment improves gastrointestinal tract dysmobility induced by intraperitoneal injection of atropine (5 mg/kg) in rats. Rats were randomly grouped into three units: TPM-pretreated/atropine-treated group, atropinetreated group and control group. TPM were administrated for 7 days. Gastric residual rate and intestinal transit were measured 20 min after atropine injected, and gastrointestinal hormones (including: gastrin (GAS), motilin (MTL), somatostatin (SS) and p substance (PS) levels in serum were also measured by ELISA kits. The number and distribution of interstitial cells of Cajal (ICCs) in stomach were detected by immunohistochemistry analysis, while c-kit and stem cell factor (SCF) expressions in stomach were also measured by western blotting. We found that TPM pretreatment significantly improved atropine-induced gastric residual rate increase, while had no significantly effects on intestinal transit; it also significantly normalized GAS, MTL and PS serum levels. Atropine-induced ICCs numbers decreased in both sinuses ventriculi and body of stomach, which is improved by TPM pretreatment. Western blotting results showed the expressions of c-kit and SCF were down-regulated after atropine injection, which can be reversed with TPM pretreatment. These results above indicates that TPM treatment can significantly protected atropine-induced gastric dysmoblility, which may owed to its regulation on c-kit/SCF signing pathway. PMID:26884941

  20. Passivation of interstitial and vacancy mediated trap-states for efficient and stable triple-cation perovskite solar cells

    Science.gov (United States)

    Mahmud, Md Arafat; Elumalai, Naveen Kumar; Upama, Mushfika Baishakhi; Wang, Dian; Gonçales, Vinicius R.; Wright, Matthew; Xu, Cheng; Haque, Faiazul; Uddin, Ashraf

    2018-04-01

    The current work reports the concurrent passivation of interstitial and oxygen vacancy mediated defect states in low temperature processed ZnO electron transport layer (ETL) via Ultraviolet-Ozone (UVO) treatment for fabricating highly efficient (maximum efficiency: 16.70%), triple cation based MA0.57FA0.38Rb0.05PbI3 (MA: methyl ammonium, FA: formamidinium, Rb: rubidium) perovskite solar cell (PSC). Under UV exposure, ozone decomposes to free atomic oxygen and intercalates into the interstitial and oxygen vacancy induced defect sites in the ZnO lattice matrix, which contributes to suppressed trap-assisted recombination phenomena in perovskite device. UVO treatment also reduces the content of functional hydroxyl group on ZnO surface, that increases the inter-particle connectivity and grain size of perovskite film on UVO treated ZnO ETL. Owing to this, the perovskite film atop UVO treated ZnO film exhibits reduced micro-strain and dislocation density values, which contribute to the enhanced photovoltaic performance of PSC with modified ZnO ETL. The modified PSCs exhibit higher recombination resistance (RRec) ∼40% compared to pristine ZnO ETL based control devices. Adding to the merit, the UVO treated ZnO PSC also demonstrates superior device stability, retaining about 88% of its initial PCE in the course of a month-long, systematic degradation study.

  1. Hormone action. Part I. Peptide hormones

    International Nuclear Information System (INIS)

    Birnbaumer, L.; O'Malley, B.W.

    1985-01-01

    The major sections of this book on the hormonal action of peptide hormones cover receptor assays, identification of receptor proteins, methods for identification of internalized hormones and hormone receptors, preparation of hormonally responsive cells and cell hybrids, purification of membrane receptors and related techniques, assays of hormonal effects and related functions, and antibodies in hormone action

  2. Transfection of Sertoli cells with androgen receptor alters gene expression without androgen stimulation.

    Science.gov (United States)

    Fietz, D; Markmann, M; Lang, D; Konrad, L; Geyer, J; Kliesch, S; Chakraborty, T; Hossain, H; Bergmann, M

    2015-12-29

    Androgens play an important role for the development of male fertility and gained interest as growth and survival factors for certain types of cancer. Androgens act via the androgen receptor (AR/Ar), which is involved in various cell biological processes such as sex differentiation. To study the functional mechanisms of androgen action, cell culture systems and AR-transfected cell lines are needed. Transfection of AR into cell lines and subsequent gene expression analysis after androgen treatment is well established to investigate the molecular biology of target cells. However, it remains unclear how the transfection with AR itself can modulate the gene expression even without androgen stimulation. Therefore, we transfected Ar-deficient rat Sertoli cells 93RS2 by electroporation using a full length human AR. Transfection success was confirmed by Western Blotting, immunofluorescence and RT-PCR. AR transfection-related gene expression alterations were detected with microarray-based genome-wide expression profiling of transfected and non-transfected 93RS2 cells without androgen stimulation. Microarray analysis revealed 672 differentially regulated genes with 200 up- and 472 down-regulated genes. These genes could be assigned to four major biological categories (development, hormone response, immune response and metabolism). Microarray results were confirmed by quantitative RT-PCR analysis for 22 candidate genes. We conclude from our data, that the transfection of Ar-deficient Sertoli cells with AR has a measurable effect on gene expression even without androgen stimulation and cause Sertoli cell damage. Studies using AR-transfected cells, subsequently stimulated, should consider alterations in AR-dependent gene expression as off-target effects of the AR transfection itself.

  3. 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.

  4. Follicle-stimulating hormone (FSH activates extracellular signal-regulated kinase phosphorylation independently of beta-arrestin- and dynamin-mediated FSH receptor internalization

    Directory of Open Access Journals (Sweden)

    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.

  5. 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.

  6. 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.

  7. Cholera toxin stimulation of human mammary epithelial cells in culture

    Energy Technology Data Exchange (ETDEWEB)

    Stampfer, M.R.

    1982-06-01

    Addition of cholera toxin to human mammary epithelial cultures derived from reduction mammoplasties and primary carcinomas greatly stimulated cell growth and increased the number of times the cells could be successfully subcultured. Other agents known to increase intracellular cAMP levels were also growth stimulatory. The increased growth potential conferred by cholera toxin enhances the usefulness of this cell culture system.

  8. 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.

  9. Feasibility of pig and human-derived aortic valve interstitial cells seeding on fixative-free decellularized animal pericardium.

    Science.gov (United States)

    Santoro, Rosaria; Consolo, Filippo; Spiccia, Marco; Piola, Marco; Kassem, Samer; Prandi, Francesca; Vinci, Maria Cristina; Forti, Elisa; Polvani, Gianluca; Fiore, Gianfranco Beniamino; Soncini, Monica; Pesce, Maurizio

    2016-02-01

    Glutaraldehyde-fixed pericardium of animal origin is the elective material for the fabrication of bio-prosthetic valves for surgical replacement of insufficient/stenotic cardiac valves. However, the pericardial tissue employed to this aim undergoes severe calcification due to chronic inflammation resulting from a non-complete immunological compatibility of the animal-derived pericardial tissue resulting from failure to remove animal-derived xeno-antigens. In the mid/long-term, this leads to structural deterioration, mechanical failure, and prosthesis leaflets rupture, with consequent need for re-intervention. In the search for novel procedures to maximize biological compatibility of the pericardial tissue into immunocompetent background, we have recently devised a procedure to decellularize the human pericardium as an alternative to fixation with aldehydes. In the present contribution, we used this procedure to derive sheets of decellularized pig pericardium. The decellularized tissue was first tested for the presence of 1,3 α-galactose (αGal), one of the main xenoantigens involved in prosthetic valve rejection, as well as for mechanical tensile behavior and distensibility, and finally seeded with pig- and human-derived aortic valve interstitial cells. We demonstrate that the decellularization procedure removed the αGAL antigen, maintained the mechanical characteristics of the native pig pericardium, and ensured an efficient surface colonization of the tissue by animal- and human-derived aortic valve interstitial cells. This establishes, for the first time, the feasibility of fixative-free pericardial tissue seeding with valve competent cells for derivation of tissue engineered heart valve leaflets. © 2015 Wiley Periodicals, Inc.

  10. 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.

  11. Holographically generated structured illumination for cell stimulation in optogenetics

    Science.gov (United States)

    Schmieder, Felix; Büttner, Lars; Czarske, Jürgen; Torres, Maria Leilani; Heisterkamp, Alexander; Klapper, Simon; Busskamp, Volker

    2017-06-01

    In Optogenetics, cells, e.g. neurons or cardiac cells, are genetically altered to produce for example the lightsensitive protein Channelrhodopsin-2. Illuminating these cells induces action potentials or contractions and therefore allows to control electrical activity. Thus, light-induced cell stimulation can be used to gain insight to various biological processes. Many optogenetics studies, however, use only full field illumination and thus gain no local information about their specimen. But using modern spatial light modulators (SLM) in conjunction with computer-generated holograms (CGH), cells may be stimulated locally, thus enabling the research of the foundations of cell networks and cell communications. In our contribution, we present a digital holographic system for the patterned, spatially resolved stimulation of cell networks. We employ a fast ferroelectric liquid crystal on silicon SLM to display CGH at up to 1.7 kHz. With an effective working distance of 33 mm, we achieve a focus of 10 μm at a positioning accuracy of the individual foci of about 8 μm. We utilized our setup for the optogenetic stimulation of clusters of cardiac cells derived from induced pluripotent stem cells and were able to observe contractions correlated to both temporal frequency and spatial power distribution of the light incident on the cell clusters.

  12. 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.

  13. 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.

  14. 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.

  15. Action potential generation in the small intestine of W mutant mice that lack interstitial cells of Cajal

    DEFF Research Database (Denmark)

    Malysz, J; Thuneberg, L; Mikkelsen, Hanne Birte

    1996-01-01

    The small intestine of W/Wv mice lacks both the network of interstitial cells of Cajal (ICC), associated with Auerbach's plexus, and pacemaker activity, i.e., it does not generate slow-wave-type action potentials. The W/Wv muscle preparations showed a wide variety of electrical activities, ranging...... from total quiescence to generation of action potentials at regular or irregular frequency with or without periods of quiescence. The action potentials consisted of a slow component with superimposed spikes, preceded by a slowly developing depolarization and followed by a transient hyperpolarization....... The action potentials were completely abolished by L-type Ca2+ channel blockers. W/Wv mice responded to K+ channel blockade (0.5 mM Ba2+ or 10 mM tetraethylammonium chloride) with effects on amplitude, frequency, rate of rise, and duration of the action potentials. In quiescent tissues from W/Wv mice, K...

  16. Abnormal distribution of the interstitial cells of cajal in an adult patient with pseudo-obstruction and megaduodenum

    DEFF Research Database (Denmark)

    Boeckxstaens, Guy E; Rumessen, Jüri J; de Wit, Laurens

    2002-01-01

    Interstitial cells of Cajal (ICC) are fundamental regulators of GI motility. Here, we report the manometrical abnormalities and abnormalities of ICC distribution and ultrastructure encountered in a 30-yr-old patient with megaduodenum and pseudo-obstruction. Full thickness biopsies taken during...... laparoscopic placement of a jejunostomy showed vacuolated myocytes and fibrosis predominantly in the outer third of the circular muscle layer of the duodenum, suggestive for visceral myopathy. The distribution of ICC was also strikingly abnormal: by light microscopy, ICC surrounding the myenteric plexus were...... lacking in the megaduodenum, whereas ICC were normally present in the duodenal circular muscle and in the jejunum. By electron microscopy, very few ICC were identified around the duodenal myenteric plexus. These findings suggest that abnormalities in ICC may contribute to the disturbed motility in some...

  17. Adult neural stem cell fate is determined by thyroid hormone activation of mitochondrial metabolism.

    Science.gov (United States)

    Gothié, J D; Sébillot, A; Luongo, C; Legendre, M; Nguyen Van, C; Le Blay, K; Perret-Jeanneret, M; Remaud, S; Demeneix, B A

    2017-11-01

    In the adult brain, neural stem cells (NSCs) located in the subventricular zone (SVZ) produce both neuronal and glial cells. Thyroid hormones (THs) regulate adult NSC differentiation towards a neuronal phenotype, but also have major roles in mitochondrial metabolism. As NSC metabolism relies mainly on glycolysis, whereas mature cells preferentially use oxidative phosphorylation, we studied how THs and mitochondrial metabolism interact on NSC fate determination. We used a mitochondrial membrane potential marker in vivo to analyze mitochondrial activity in the different cell types in the SVZ of euthyroid and hypothyroid mice. Using primary adult NSC cultures, we analyzed ROS production, SIRT1 expression, and phosphorylation of DRP1 (a mitochondrial fission mediator) as a function of TH availability. We observed significantly higher mitochondrial activity in cells adopting a neuronal phenotype in vivo in euthyroid mice. However, prolonged hypothyroidism reduced not only neuroblast numbers but also their mitochondrial activity. In vitro studies showed that TH availability favored a neuronal phenotype and that blocking mitochondrial respiration abrogated TH-induced neuronal fate determination. DRP1 phosphorylation was preferentially activated in cells within the neuronal lineage and was stimulated by TH availability. These results indicate that THs favor NSC fate choice towards a neuronal phenotype in the adult mouse SVZ through effects on mitochondrial metabolism. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

  18. Role of mitochondria in modulation of spontaneous Ca2+ waves in freshly dispersed interstitial cells of Cajal from the rabbit urethra.

    Science.gov (United States)

    Sergeant, Gerard P; Bradley, Eamonn; Thornbury, Keith D; McHale, Noel G; Hollywood, Mark A

    2008-10-01

    Interstitial cells of Cajal (ICC) isolated from the rabbit urethra exhibit pacemaker activity that results from spontaneous Ca(2+) waves. The purpose of this study was to investigate if this activity was influenced by Ca(2+) uptake into mitochondria. Spontaneous Ca(2+) waves were recorded using a Nipkow spinning disk confocal microscope and spontaneous transient inward currents (STICs) were recorded using the whole-cell patch clamp technique. Disruption of the mitochondrial membrane potential with the electron transport chain inhibitors rotenone (10 microm) and antimycin A (5 microm) abolished Ca(2+) waves and increased basal Ca(2+) levels. Similar results were achieved when mitochondria membrane potential was collapsed using the protonophores FCCP (0.2 microm) and CCCP (1 microm). Spontaneous Ca(2+) waves were not inhibited by the ATP synthase inhibitor oligomycin (1 microm), suggesting that these effects were not attributable to an effect on ATP levels. STICs recorded under voltage clamp at -60 mV were also inhibited by CCCP and antimycin A. Dialysis of cells with the mitochondrial uniporter inhibitor RU360 (10 microm) also inhibited STICS. Stimulation of Ca(2+) uptake into mitochondria using the plant flavonoid kaempferol (10 microm) induced a series of propagating Ca(2+) waves. The kaempferol-induced activity was inhibited by application of caffeine (10 mm) or removal of extracellular Ca(2+), but was not significantly affected by the IP(3) receptor blocker 2-APB (100 microm). These data suggest that spontaneous Ca(2+) waves in urethral ICC are regulated by buffering of cytoplasmic Ca(2+) by mitochondria.

  19. Role of mitochondria in modulation of spontaneous Ca2+ waves in freshly dispersed interstitial cells of Cajal from the rabbit urethra

    Science.gov (United States)

    Sergeant, Gerard P; Bradley, Eamonn; Thornbury, Keith D; McHale, Noel G; Hollywood, Mark A

    2008-01-01

    Interstitial cells of Cajal (ICC) isolated from the rabbit urethra exhibit pacemaker activity that results from spontaneous Ca2+ waves. The purpose of this study was to investigate if this activity was influenced by Ca2+ uptake into mitochondria. Spontaneous Ca2+ waves were recorded using a Nipkow spinning disk confocal microscope and spontaneous transient inward currents (STICs) were recorded using the whole-cell patch clamp technique. Disruption of the mitochondrial membrane potential with the electron transport chain inhibitors rotenone (10 μm) and antimycin A (5 μm) abolished Ca2+ waves and increased basal Ca2+ levels. Similar results were achieved when mitochondria membrane potential was collapsed using the protonophores FCCP (0.2 μm) and CCCP (1 μm). Spontaneous Ca2+ waves were not inhibited by the ATP synthase inhibitor oligomycin (1 μm), suggesting that these effects were not attributable to an effect on ATP levels. STICs recorded under voltage clamp at −60 mV were also inhibited by CCCP and antimycin A. Dialysis of cells with the mitochondrial uniporter inhibitor RU360 (10 μm) also inhibited STICS. Stimulation of Ca2+ uptake into mitochondria using the plant flavonoid kaempferol (10 μm) induced a series of propagating Ca2+ waves. The kaempferol-induced activity was inhibited by application of caffeine (10 mm) or removal of extracellular Ca2+, but was not significantly affected by the IP3 receptor blocker 2-APB (100 μm). These data suggest that spontaneous Ca2+ waves in urethral ICC are regulated by buffering of cytoplasmic Ca2+ by mitochondria. PMID:18703577

  20. KCl stimulation increases norepinephrine transporter function in PC12 cells.

    Science.gov (United States)

    Mandela, Prashant; Ordway, Gregory A

    2006-09-01

    The norepinephrine transporter (NET) plays a pivotal role in terminating noradrenergic signaling and conserving norepinephrine (NE) through the process of re-uptake. Recent evidence suggests a close association between NE release and regulation of NET function. The present study evaluated the relationship between release and uptake, and the cellular mechanisms that govern these processes. KCl stimulation of PC12 cells robustly increased [3H]NE uptake via the NET and simultaneously increased [3H]NE release. KCl-stimulated increases in uptake and release were dependent on Ca2+. Treatment of cells with phorbol-12-myristate-13-acetate (PMA) or okadaic acid decreased [3H]NE uptake but did not block KCl-stimulated increases in [3H]NE uptake. In contrast, PMA increased [3H]NE release and augmented KCl-stimulated release, while okadaic acid had no effects on release. Inhibition of Ca2+-activated signaling cascades with KN93 (a Ca2+ calmodulin-dependent kinase inhibitor), or ML7 and ML9 (myosin light chain kinase inhibitors), reduced [3H]NE uptake and blocked KCl-stimulated increases in uptake. In contrast, KN93, ML7 and ML9 had no effect on KCl-stimulated [3H]NE release. KCl-stimulated increases in [3H]NE uptake were independent of transporter trafficking to the plasma membrane. While increases in both NE release and uptake mediated by KCl stimulation require Ca2+, different intracellular mechanisms mediate these two events.

  1. Therapeutic effect of urine-derived stem cells for protamine/lipopolysaccharide-induced interstitial cystitis in a rat model.

    Science.gov (United States)

    Li, Jia; Luo, Hui; Dong, Xingyou; Liu, Qian; Wu, Chao; Zhang, Teng; Hu, Xiaoyan; Zhang, Yuanyuan; Song, Bo; Li, Longkun

    2017-05-08

    Interstitial cystitis (IC) is a chronic inflammation disorder mainly within the submucosal and muscular layers of the bladder. As the cause of IC remains unknown, no effective treatments are currently available. Administration of stem cell provides a potential for treatment of IC. This study was conducted using urine-derived stem cells (USCs) for protamine/lipopolysaccharide (PS/LPS)-induced interstitial cystitis in a rodent model. In total, 60 female Sprague-Dawley rats were randomized into three experimental groups (n = 5/group): sham controls; IC model alone; and IC animals intravenously treated with USCs (1.2 × 10 6 suspended in 0.2 ml phosphate-buffered saline (PBS). Our data showed that the bladder micturition function was significantly improved in IC animals intravenously treated with USCs compared to those in the IC model alone group. The amount of antioxidants and antiapoptotic protein biomarkers heme oxygenase (HO)-1, NAD(P)H quinine oxidoreductase (NQO)-1, and Bcl-2 within the bladder tissues were significantly higher in IC animals intravenously treated with USCs and lower in the sham controls group as assessed by Western blot and immunofluorescent staining. In addition, the expression of autophagy-related protein LC3A was significantly higher in the IC model alone group than that in IC animals intravenously treated with USCs. Inflammatory biomarkers and apoptotic biomarkers (interleukin (IL)-6, tumor necrosis factor (TNF)α, nuclear factor (NF)-κB, caspase 3, and Bax) and the downstream inflammatory and oxidative stress biomarkers (endoplasmic reticulum stress and autophagy-related protein (GRP78, LC3, Beclin1)) in the bladder tissue revealed statistically different results between groups. USCs restored the bladder function and histological construction via suppressing oxidative stress, inflammatory reaction, and apoptotic processes in a PS/LPS-induced IC rodent model, which provides potential for treatment of patients with IC.

  2. Skeletal unloading causes resistance of osteoprogenitor cells to parathyroid hormone and to insulin-like growth factor-I

    Science.gov (United States)

    Kostenuik, P. J.; Harris, J.; Halloran, B. P.; Turner, R. T.; Morey-Holton, E. R.; Bikle, D. D.

    1999-01-01

    Skeletal unloading decreases bone formation and osteoblast number in vivo and decreases the number and proliferation of bone marrow osteoprogenitor (BMOp) cells in vitro. We tested the ability of parathyroid hormone (PTH) to stimulate BMOp cells in vivo by treating Sprague Dawley rats (n = 32) with intermittent PTH(1-34) (1 h/day at 8 microg/100 g of body weight), or with vehicle via osmotic minipumps during 7 days of normal weight bearing or hind limb unloading. Marrow cells were flushed from the femur and cultured at the same initial density for up to 21 days. PTH treatment of normally loaded rats caused a 2.5-fold increase in the number of BMOp cells, with similar increases in alkaline phosphatase (ALP) activity and mineralization, compared with cultures from vehicle-treated rats. PTH treatment of hind limb unloaded rats failed to stimulate BMOp cell number, ALP activity, or mineralization. Hind limb unloading had no significant effect on PTH receptor mRNA or protein levels in the tibia. Direct in vitro PTH challenge of BMOp cells isolated from normally loaded bone failed to stimulate their proliferation and inhibited their differentiation, suggesting that the in vivo anabolic effect of intermittent PTH on BMOp cells was mediated indirectly by a PTH-induced factor. We hypothesize that this factor is insulin-like growth factor-I (IGF-I), which stimulated the in vitro proliferation and differentiation of BMOp cells isolated from normally loaded bone, but not from unloaded bone. These results suggest that IGF-I mediates the ability of PTH to stimulate BMOp cell proliferation in normally loaded bone, and that BMOp cells in unloaded bone are resistant to the anabolic effect of intermittent PTH therapy due to their resistance to IGF-I.

  3. 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)

  4. The preparation and application of N-terminal 57 amino acid protein of the follicle-stimulating hormone receptor as a candidate male contraceptive vaccine

    Directory of Open Access Journals (Sweden)

    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.

  5. 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

  6. 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...

  7. 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

  8. Interstitial flow promotes vascular fibroblast, myofibroblast, and smooth muscle cell motility in 3-D collagen I via upregulation of MMP-1

    Science.gov (United States)

    Shi, Zhong-Dong; Ji, Xin-Ying; Qazi, Henry

    2009-01-01

    Neointima formation often occurs in regions where the endothelium has been damaged and the transmural interstitial flow is elevated. Vascular smooth muscle cells (SMCs) and fibroblasts/myofibroblasts (FBs/MFBs) contribute to intimal thickening by migrating from the media and adventitia into the site of injury. In this study, for the first time, the direct effects of interstitial flow on SMC and FB/MFB migration were investigated in an in vitro three-dimensional system. Collagen I gels were used to mimic three-dimensional extracellular matrix (ECM) for rat aortic SMCs and FBs/MFBs. Exposure to interstitial flow induced by 1 cmH2O pressure differential (shear stress, ∼0.05 dyn/cm2; flow velocity, ∼0.5 μm/s; and Darcy permeability, ∼10−11 cm2) substantially enhanced cell motility. Matrix metalloproteinase (MMP) inhibitor (GM-6001) abolished flow-induced migration augmentation, which suggested that the enhanced motility was MMP dependent. The upregulation of MMP-1 played a critical role for the flow-enhanced motility, which was further confirmed by silencing MMP-1 gene expression. Longer exposures to higher flows suppressed the number of migrated cells, although MMP-1 gene expression remained high. This suppression was a result of both flow-induced tissue inhibitor of metalloproteinase-1 upregulation and increased apoptotic and necrotic cell death. Interstitial flow did not affect MMP-2 gene expression or activity in the collagen I gel for any cell type. Our findings shed light on the mechanism by which vascular SMCs and FBs/MFBs contribute to intimal thickening in regions of vascular injury where interstitial flow is elevated. PMID:19465549

  9. 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

  10. One year growth hormone replacement therapy does not alter colonic epithelial cell proliferation in growth hormone deficient adults

    NARCIS (Netherlands)

    Beentjes, JAM; van Gorkom, BAP; Sluiter, WJ; de Vries, Emma; Kleibeuker, JH; Dullaart, RPF

    OBJECTIVE Increased colonic epithelial cell proliferation has been found in various conditions associated with increased risk of colorectal cancer including acromegaly. In a placebo-controlled study we determined the effect of growth hormone (GH) replacement therapy in GH deficient adults on the

  11. Interstitial Cystitis Association

    Science.gov (United States)

    ... frequency? You may have IC. Get The Facts Interstitial Cystitis Association The Interstitial Cystitis Association (ICA) is the ... news and events. Please leave this field empty Interstitial Cystitis Association 7918 Jones Branch Drive, Suite 300 McLean, ...

  12. 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.

  13. 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....

  14. Mechanical stimulation of bone cells using fluid flow

    NARCIS (Netherlands)

    Huesa, C.; Bakker, A.D.

    2012-01-01

    This chapter describes several methods suitable for mechanically stimulating monolayers of bone cells by fluid shear stress (FSS) in vitro. Fluid flow is generated by pumping culture medium through two parallel plates, one of which contains a monolayer of cells. Methods for measuring nitric oxide

  15. Derivation of Diverse Hormone-Releasing Pituitary Cells from Human Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Bastian Zimmer

    2016-06-01

    Full Text Available Human pluripotent stem cells (hPSCs provide an unlimited cell source for regenerative medicine. Hormone-producing cells are particularly suitable for cell therapy, and hypopituitarism, a defect in pituitary gland function, represents a promising therapeutic target. Previous studies have derived pituitary lineages from mouse and human ESCs using 3D organoid cultures that mimic the complex events underlying pituitary gland development in vivo. Instead of relying on unknown cellular signals, we present a simple and efficient strategy to derive human pituitary lineages from hPSCs using monolayer culture conditions suitable for cell manufacturing. We demonstrate that purified placode cells can be directed into pituitary fates using defined signals. hPSC-derived pituitary cells show basal and stimulus-induced hormone release in vitro and engraftment and hormone release in vivo after transplantation into a murine model of hypopituitarism. This work lays the foundation for future cell therapy applications in patients with hypopituitarism.

  16. 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.

  17. Effects of new-generation TMEM16A inhibitors on calcium-activated chloride currents in rabbit urethral interstitial cells of Cajal.

    Science.gov (United States)

    Fedigan, Stephen; Bradley, Eamonn; Webb, Timothy; Large, Roddy J; Hollywood, Mark A; Thornbury, Keith D; McHale, Noel G; Sergeant, Gerard P

    2017-11-01

    Interstitial cells of Cajal (ICC) isolated from the rabbit urethra exhibit Ca 2+ -activated Cl - currents (I ClCa ) that are important for the development of urethral tone. Here, we examined if TMEM16A (ANO1) contributed to this activity by examining the effect of "new-generation" TMEM16A inhibitors, CACC inh -A01 and T16A inh -A01, on I ClCa recorded from freshly isolated rabbit urethral ICC (RUICC) and on contractions of intact strips of rabbit urethra smooth muscle. Real-time quantitative PCR experiments demonstrated that TMEM16A was highly expressed in rabbit urethra smooth muscle, in comparison to TMEM16B and TMEM16F. Single-cell RT-PCR experiments revealed that only TMEM16A was expressed in freshly isolated RUICC. Depolarization-evoked I ClCa in isolated RUICC, recorded using voltage clamp, were inhibited by CACC inh -A01 and T16A inh -A01 with IC 50 values of 1.2 and 3.4 μM, respectively. Similarly, spontaneous transient inward currents (STICs) recorded from RUICC voltage clamped at -60 mV and spontaneous transient depolarizations (STDs), recorded in current clamp, were also inhibited by CACC inh -A01 and T16A inh -A01. In contrast, spontaneous Ca 2+ waves in isolated RUICC were only partially reduced by CACC inh -A01 and T16A inh -A01. Finally, neurogenic contractions of strips of rabbit urethra smooth muscle (RUSM), evoked by electric field stimulation (EFS), were also significantly reduced by CACC inh -A01 and T16A inh -A01. These data are consistent with the idea that TMEM16A is involved with CACCs in RUICC and in contraction of rabbit urethral smooth muscle.

  18. 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.

  19. Beta-cell-tropin is associated with short-term stimulation of food intake in chicks.

    Science.gov (United States)

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

    2015-12-01

    Beta-cell-tropin, a peptide derived from adrenocorticotropic hormone, is an insulin secretagogue. When centrally injected, it increases food intake in rats, but its appetite-associated effects have not been reported in any other species. Thus, the present study was designed to evaluate the effects of central beta-cell-tropin on appetite-associated parameters in an alternative vertebrate model, the chick. Central injection of 2 or 4 nmol beta-cell-tropin increased food intake for 60 min. Whole hypothalamus was collected at 60 min post-injection, and real-time PCR performed to measure mRNA abundance of agouti-related peptide, corticotropin releasing factor, galanin, melanin concentrating hormone, neuropeptide Y, orexin, prohormone convertase 2, pro-opiomelanocortin, peroxisome proliferator-activated receptor γ, urotensin 2, and visfatin, not one of which were affected by beta-cell-tropin treatment. Results demonstrate that beta-cell-tropin is associated with short-term stimulation of food intake. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. 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

  1. Differential action of glycoprotein hormones: significance in cancer progression.

    Science.gov (United States)

    Govindaraj, Vijayakumar; Arya, Swathy V; Rao, A J

    2014-02-01

    Growth of multicellular organisms depends on maintenance of proper balance between proliferation and differentiation. Any disturbance in this balance in animal cells can lead to cancer. Experimental evidence is provided to conclude with special reference to the action of follicle-stimulating hormone (FSH) on Sertoli cells, and luteinizing hormone (LH) on Leydig cells that these hormones exert a differential action on their target cells, i.e., stimulate proliferation when the cells are in an undifferentiated state which is the situation with cancer cells and promote only functional parameters when the cell are fully differentiated. Hormones and growth factors play a key role in cell proliferation, differentiation, and apoptosis. There is a growing body of evidence that various tumors express some hormones at high levels as well as their cognate receptors indicating the possibility of a role in progression of cancer. Hormones such as LH, FSH, and thyroid-stimulating hormone have been reported to stimulate cell proliferation and act as tumor promoter in a variety of hormone-dependent cancers including gonads, lung, thyroid, uterus, breast, prostate, etc. This review summarizes evidence to conclude that these hormones are produced by some cancer tissues to promote their own growth. Also an attempt is made to explain the significance of the differential action of hormones in progression of cancer with special reference to prostate cancer.

  2. Plant hormones increase efficiency of reprogramming mouse somatic cells to induced pluripotent stem cells and reduce tumorigenicity.

    Science.gov (United States)

    Alvarez Palomo, Ana Belén; McLenachan, Samuel; Requena Osete, Jordi; Menchón, Cristina; Barrot, Carme; Chen, Fred; Munné-Bosch, Sergi; Edel, Michael J

    2014-03-15

    Reprogramming of somatic cells into induced pluripotent stem (iPS) cells by defined pluripotency and self-renewal factors has taken stem cell technology to the forefront of regenerative medicine. However, a number of challenges remain in the field including efficient protocols and the threat of cancer. Reprogramming of plant somatic cells to plant embryonic stem cells using a combination of two plant hormones was discovered in 1957 and has been a routine university laboratory practical for over 30 years. The plant hormones responsible for cell reprogramming to pluripotency, indole-3-acetic acid (IAA) and isopentenyl adenosine (IPA), are present in human cells, leading to the exciting possibility that plant hormones might reprogram mammalian cells without genetic factors. We found that plant hormones on their own could not reprogram mammalian cells but increase the efficiency of the early formation of iPS cells combined with three defined genetic factors during the first 3 weeks of reprogramming by accelerating the cell cycle and regulating pluripotency genes. Moreover, the cytokinin IPA, a known human anticancer agent, reduced the threat of cancer of iPS cell in vitro by regulating key cancer and stem cell-related genes, most notably c-Myc and Igf-1. In conclusion, the plant hormones, auxin and cytokinin, are new small chemicals useful for enhancing early reprogramming efficiency of mammalian cells and reducing the threat of cancer from iPS cells. These findings suggest a novel role for plant hormones in the biology of mammalian cell plasticity.

  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. Toward a Concept of Stretch Coupling in Smooth Muscle: A Thesis by Lars Thuneberg on Contractile Activity in Neonatal Interstitial Cells of Cajal

    DEFF Research Database (Denmark)

    Huizinga, Jan D; Lammers, Wim J E P; Mikkelsen, Hanne B

    2010-01-01

    The hypothesis was put forward by Thuneberg that rhythmically contracting interstitial cells of Cajal (ICC) were sensing stretch of the musculature and that this information was transmitted to smooth muscle cells via peg and socket contacts. The present study provides the evidence for the contrac...... amongst the physiological properties of the ICC networks of the gut musculature. Anat Rec, 2010. (c) 2010 Wiley-Liss, Inc....

  5. Local expression and distribution of growth hormone and growth hormone receptor in the chicken ovary: effects of GH on steroidogenesis in cultured follicular granulosa cells.

    Science.gov (United States)

    Ahumada-Solórzano, S Marisela; Carranza, Martha E; Pedernera, Enrique; Rodríguez-Méndez, Adriana J; Luna, Maricela; Arámburo, Carlos

    2012-01-15

    Preovulatory follicular development (PFD) is mainly regulated by gonadotropins (FSH, LH) and steroids, although other intraovarian factors are also involved. We analyzed the local expression of growth hormone (GH) in the hen ovary and the role that this hormone may play on the regulation of steroidogenesis in granulosa cells (GCs). Ovarian follicles from sexually mature hens were studied at different developmental stages. Both GH mRNA (by in situ hybridization) and protein (by immunohistochemistry) were expressed mainly in the GCs, and to a lesser extent in the theca cells of the follicular wall. Sequence of a GH cDNA 690-bp fragment obtained from the follicular wall was identical to that obtained from the pituitary. The growth hormone receptor (GHR) mRNA was also expressed in the follicles. Nine GH variants were observed by SDS-PAGE and Western blotting, but the main isoform showed a MW of 17 kDa, at all developmental stages. Addition of GH (0.1, 1, 10 nM) stimulated the synthesis of progesterone (P4) in primary GCs cultures in a dose-dependent manner (1.5, 2.9, 5.4 times, respectively). GH also stimulated the expression of cholesterol side-chain cleavage enzyme (cytochrome P450scc) mRNA, a rate-limiting enzyme during P4 synthesis (2.9, 4.6, 4.9 times, respectively), whereas the synthesis of 3β-hydroxysteroid dehydrogenase (3β-HSD) mRNA (a constitutive enzyme) was not changed. Both GH and GHR were co-expressed in GCs cultures. The locally expressed GH present in concentrated (4×, 6×, 8×) conditioned media obtained from ovarian GC cultures stimulated P4 production (1.2, 2.2, 4.4 times, respectively) in additional fresh cultured GCs, and this effect disappeared when the conditioned media were treated with antiserum against GH. These data suggest that locally produced GH may modulate follicular development through autocrine/paracrine effects in the chicken ovary. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. 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

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

    Directory of Open Access Journals (Sweden)

    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

  8. Mixed Primary Cultures of Murine Small Intestine Intended for the Study of Gut Hormone Secretion and Live Cell Imaging of Enteroendocrine Cells.

    Science.gov (United States)

    Psichas, Arianna; Tolhurst, Gwen; Brighton, Cheryl A; Gribble, Fiona M; Reimann, Frank

    2017-04-20

    The gut is the largest endocrine organ of the body, with hormone-secreting enteroendocrine cells located along the length of the gastrointestinal epithelium. Despite their physiological importance, enteroendocrine cells represent only a small fraction of the epithelial cell population and in the past, their characterization has presented a considerable challenge resulting in a reliance on cell line models. Here, we provide a detailed protocol for the isolation and culture of mixed murine small intestinal cells. These primary cultures have been used to identify the signaling pathways underlying the stimulation and inhibition of gut peptide secretion in response to a number of nutrients and neuropeptides as well as pharmacological agents. Furthermore, in combination with the use of transgenic fluorescent reporter mice, we have demonstrated that these primary cultures become a powerful tool for the examination of fluorescently-tagged enteroendocrine cells at the intracellular level, using methods such as patch clamping and single-cell calcium and cAMP-FRET imaging.

  9. Stimulation and support of haemopoietic stem cell proliferation by irradiated stroma cell colonies in bone marrow cell culture in vitro

    International Nuclear Information System (INIS)

    Mori, K.J.; Izumi, Hiroko; Seto, Akira

    1981-01-01

    A culture system was established in which haemopoietic stem cells can undergo a recovery proliferation after a depletion of the stem cells, completely in vitro. To elucidate the source of the stimulatory factors, normal bone marrow cells were overlayed on top of the irradiated adherent 'stromal' cell colonies in the bone marrow cell culture. This stimulated the proliferation of haemopoietic stem cells in the cultured cells in suspension. The present results indicate that the stromal cells produce factors which stimulate stem cell proliferation. Whether the stimulation is evoked by direct cell-cell interactions or by humoral factors is as yet to be studied. (author)

  10. Sex Hormone Binding Globulin Modifies Testosterone Action and Metabolism in Prostate Cancer Cells

    OpenAIRE

    Li, Huika; Pham, Thy; McWhinney, Brett C.; Ungerer, Jacobus P.; Pretorius, Carel J.; Richard, Derek J.; Mortimer, Robin H.; d'Emden, Michael C.; Richard, Kerry

    2016-01-01

    Sex Hormone Binding Globulin (SHBG) is the major serum carrier of sex hormones. However, growing evidence suggests that SHBG is internalised and plays a role in regulating intracellular hormone action. This study was to determine whether SHBG plays a role in testosterone uptake, metabolism, and action in the androgen sensitive LNCaP prostate cancer cell line. Internalisation of SHBG and testosterone, the effects of SHBG on testosterone uptake, metabolism, regulation of androgen responsive gen...

  11. 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...

  12. Leydig cell clustering and Reinke crystal distribution in relation to hormonal function in adult patients with testicular dysgenesis syndrome (TDS) including cryptorchidism

    DEFF Research Database (Denmark)

    Soerensen, Rikke R; Johannsen, Trine H; Skakkebaek, Niels E

    2016-01-01

    (micronodules) are frequently present. This study aimed to investigate possible associations of LC micronodules with the presence of Reinke crystals and hormonal function of LCs, the latter primarily reflected by serum concentrations of luteinising hormone (LH) and testosterone, in patients with TDS. DESIGN......: A retrospective study of 101 andrological patients with TDS (infertility with and without a history of cryptorchidism or presence of germ cell neoplasia in situ) and 20 controls with normal testis histology and LC-function. Archived testicular biopsies were re-evaluated for the presence of LC micronodules...... and Reinke crystals and the findings were correlated with testis size and serum concentrations of LH, follicle-stimulating hormone (FSH), testosterone, inhibin B, estradiol and sex hormone binding globulin (SHBG). RESULTS: TDS patients with bilateral LC micronodules had significantly lower concentrations...

  13. Hypothyroidism in utero stimulates pancreatic beta cell proliferation and hyperinsulinaemia in the ovine fetus during late gestation.

    Science.gov (United States)

    Harris, Shelley E; De Blasio, Miles J; Davis, Melissa A; Kelly, Amy C; Davenport, Hailey M; Wooding, F B Peter; Blache, Dominique; Meredith, David; Anderson, Miranda; Fowden, Abigail L; Limesand, Sean W; Forhead, Alison J

    2017-06-01

    Thyroid hormones are important regulators of growth and maturation before birth, although the extent to which their actions are mediated by insulin and the development of pancreatic beta cell mass is unknown. Hypothyroidism in fetal sheep induced by removal of the thyroid gland caused asymmetric organ growth, increased pancreatic beta cell mass and proliferation, and was associated with increased circulating concentrations of insulin and leptin. In isolated fetal sheep islets studied in vitro, thyroid hormones inhibited beta cell proliferation in a dose-dependent manner, while high concentrations of insulin and leptin stimulated proliferation. The developing pancreatic beta cell is therefore sensitive to thyroid hormone, insulin and leptin before birth, with possible consequences for pancreatic function in fetal and later life. The findings of this study highlight the importance of thyroid hormones during pregnancy for normal development of the fetal pancreas. Development of pancreatic beta cell mass before birth is essential for normal growth of the fetus and for long-term control of carbohydrate metabolism in postnatal life. Thyroid hormones are also important regulators of fetal growth, and the present study tested the hypotheses that thyroid hormones promote beta cell proliferation in the fetal ovine pancreatic islets, and that growth retardation in hypothyroid fetal sheep is associated with reductions in pancreatic beta cell mass and circulating insulin concentration in utero. Organ growth and pancreatic islet cell proliferation and mass were examined in sheep fetuses following removal of the thyroid gland in utero. The effects of triiodothyronine (T 3 ), insulin and leptin on beta cell proliferation rates were determined in isolated fetal ovine pancreatic islets in vitro. Hypothyroidism in the sheep fetus resulted in an asymmetric pattern of organ growth, pancreatic beta cell hyperplasia, and elevated plasma insulin and leptin concentrations. In pancreatic

  14. 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....

  15. A primary colonic crypt model enriched in enteroendocrine cells facilitates a peptidomic survey of regulated hormone secretion.

    Science.gov (United States)

    Nikoulina, Svetlana E; Andon, Nancy L; McCowen, Kevin M; Hendricks, Michelle D; Lowe, Carolyn; Taylor, Steven W

    2010-04-01

    To enable the first physiologically relevant peptidomic survey of gastrointestinal tissue, we have developed a primary mouse colonic crypt model enriched for enteroendocrine L-cells. The cells in this model were phenotypically profiled using PCR-based techniques and showed peptide hormone and secretory and processing marker expression at mRNA levels that were increased relative to the parent tissue. Co-localization of glucagon-like peptide-1 and peptide YY, a characteristic feature of L-cells, was demonstrated by double label immunocytochemistry. The L-cells displayed regulated hormone secretion in response to physiological and pharmacological stimuli as measured by immunoassay. Using a high resolution mass spectrometry-based platform, more than 50 endogenous peptides (<16 kDa), including all known major hormones, were identified a priori. The influence of culture conditions on peptide relative abundance and post-translational modification was characterized. The relative abundance of secreted peptides in the presence/absence of the stimulant forskolin was measured by label-free quantification. All peptides exhibiting a statistically significant increase in relative concentration in the culture media were derived from prohormones, consistent with a cAMP-coupled response. The only peptides that exhibited a statistically significant decrease in secretion on forskolin stimulation were derived from annexin A1 and calcyclin. Biophysical interactions between annexin A1 and calcyclin have been reported very recently and may have functional consequences. This work represents the first step in characterizing physiologically relevant peptidomic secretion of gastrointestinally derived primary cells and will aid in elucidating new endocrine function.

  16. 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.

  17. Histamine-enhanced contractile responses of gastric smooth muscle via interstitial cells of Cajal in the Syrian hamster.

    Science.gov (United States)

    Naganuma, S; Shiina, T; Yasuda, S; Suzuki, Y; Shimizu, Y

    2017-11-21

    Gastric motility is controlled by the autonomic and enteric nervous systems and by interstitial cells of Cajal (ICCs). Although histamine is known to be released from enterochromaffin-like cells in the gastric mucosa, its regulatory roles in gastric motility are still controversial. Therefore, we investigated the functional roles of histamine in gastric motility. Stomach preparations from hamsters were used because the stomach of hamsters can be easily separated into the forestomach and the glandular stomach. A whole preparation of the stomach was mounted in a Magnus tube, and mechanical responses were recorded using a force transducer. Exogenous application of histamine had little effect on contractile activity of the glandular stomach. In contrast, the monoamine evoked regular, periodic contractions in the forestomach. An H1 receptor agonist reproduced the contractile responses and an H1 receptor antagonist blocked histamine-evoked contractions. Atropine and tetrodotoxin did not affect the histamine-evoked contractions. Pretreatment with drugs that inhibit the activity of ICCs abolished the effects of histamine. The findings suggest that histamine regulates gastric motility by acting on ICCs via H1 receptors in the hamster. The remarkable ability of histamine to induce rhythmic contractions would be useful for treatment of gastric dysmotility. © 2017 John Wiley & Sons Ltd.

  18. 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....

  19. 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

  20. 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.

  1. Laser stimulation can activate autophagy in HeLa cells

    International Nuclear Information System (INIS)

    Wang, Yisen; Hu, Minglie; Wang, Chingyue; Lan, Bei; Cao, Youjia; He, Hao

    2014-01-01

    For decades, lasers have been a daily tool in most biological research for fluorescent excitation by confocal or multiphoton microscopy. More than 20 years ago, cell photodamage caused by intense laser stimulation was noticed by generating reactive oxygen species, which was then thought as the main damage effect by photons. In this study, we show that laser stimulation can induce autophagy, an important cell lysosomal pathway responding to immune stimulation and starvation, without any biochemical treatment. Two different types of laser stimulations are found to be capable of activating autophagy: continuous scanning by continuous-wave visible lasers and a short-time flash of femtosecond laser irradiation. The autophagy generation is independent from wavelength, power, and scanning duration of the visible lasers. In contrast, the power of femtosecond laser is very critical to autophagy because the multiphoton excited Ca 2+ dominates autophagy signaling. In general, we show here the different mechanisms of autophagy generation by such laser stimulation, which correspond to confocal microscopy and cell surgery, respectively. Those results can help further understanding of photodamage and autophagy signaling.

  2. Laser stimulation can activate autophagy in HeLa cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yisen; Hu, Minglie; Wang, Chingyue [Ultrafast Laser Laboratory, Key Laboratory of Optoelectronic Information Technology (Ministry of Education), College of Precision Instrument and Optoelectronics Engineering, Tianjin University, Tianjin (China); Lan, Bei; Cao, Youjia [Key Laboratory of Microbial Functional Genomics of Ministry of Education, College of Life Sciences, Nankai University, Tianjin (China); He, Hao, E-mail: haohe@tju.edu.cn [Ultrafast Laser Laboratory, Key Laboratory of Optoelectronic Information Technology (Ministry of Education), College of Precision Instrument and Optoelectronics Engineering, Tianjin University, Tianjin (China); Med-X Research Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai (China)

    2014-10-27

    For decades, lasers have been a daily tool in most biological research for fluorescent excitation by confocal or multiphoton microscopy. More than 20 years ago, cell photodamage caused by intense laser stimulation was noticed by generating reactive oxygen species, which was then thought as the main damage effect by photons. In this study, we show that laser stimulation can induce autophagy, an important cell lysosomal pathway responding to immune stimulation and starvation, without any biochemical treatment. Two different types of laser stimulations are found to be capable of activating autophagy: continuous scanning by continuous-wave visible lasers and a short-time flash of femtosecond laser irradiation. The autophagy generation is independent from wavelength, power, and scanning duration of the visible lasers. In contrast, the power of femtosecond laser is very critical to autophagy because the multiphoton excited Ca{sup 2+} dominates autophagy signaling. In general, we show here the different mechanisms of autophagy generation by such laser stimulation, which correspond to confocal microscopy and cell surgery, respectively. Those results can help further understanding of photodamage and autophagy signaling.

  3. Establishment of a protocol to extend the lifespan of human hormone-secreting pituitary adenoma cells.

    Science.gov (United States)

    Aiello, Aurora; Cassarino, Maria Francesca; Nanni, Simona; Sesta, Antonella; Ferraú, Francesco; Grassi, Claudio; Losa, Marco; Trimarchi, Francesco; Pontecorvi, Alfredo; Cannavò, Salvatore; Pecori Giraldi, Francesca; Farsetti, Antonella

    2018-01-01

    The aim of this study was to generate immortalized human anterior pituitary adenoma cells. Reliable cell models for the study of human pituitary adenomas are as yet lacking and studies performed so far used repeated passaging of freshly excised adenomas, with the attendant limitations due to limited survival in culture, early senescence, and poor reproducibility. We devised a technique based upon repeated co-transfections of two retroviral vectors, one carrying the catalytic subunit of human telomerase, hTERT, the other SV40 large T antigen. This approach extended the lifespan of cells derived from a human growth hormone-secreting adenoma up to 18 months while retaining morphology of primary cells, growth hormone synthesis and growth hormone secretion. Our attempt represents the first demonstration of successful lifespan extension of human growth hormone-secreting pituitary adenoma cells via co-transfection of hTERT and SV40T and paves the way to future attempts to obtain stable cell lines.

  4. FOXL2-induced follistatin attenuates activin A-stimulated cell proliferation in human granulosa cell tumors

    International Nuclear Information System (INIS)

    Cheng, Jung-Chien; Chang, Hsun-Ming; Qiu, Xin; Fang, Lanlan; Leung, Peter C.K.

    2014-01-01

    Highlights: •Activin A stimulates cell proliferation in KGN human granulosa cell tumor-derived cell line. •Cyclin D2 mediates activin A-induced KGN cell proliferation. •FOXL2 induces follistatin expression in KGN cells. •FOXL2-induced follistatin attenuates activin A-stimulated KGN cell proliferation. -- Abstract: Human granulosa cell tumors (GCTs) are rare, and their etiology remains largely unknown. Recently, the FOXL2 402C > G (C134W) mutation was found to be specifically expressed in human adult-type GCTs; however, its function in the development of human GCTs is not fully understood. Activins are members of the transforming growth factor-beta superfamily, which has been shown to stimulate normal granulosa cell proliferation; however, little is known regarding the function of activins in human GCTs. In this study, we examined the effect of activin A on cell proliferation in the human GCT-derived cell line KGN. We show that activin A treatment stimulates KGN cell proliferation. Treatment with the activin type I receptor inhibitor SB431542 blocks activin A-stimulated cell proliferation. In addition, our results show that cyclin D2 is induced by treatment with activin A and is involved in activin A-stimulated cell proliferation. Moreover, the activation of Smad signaling is required for activin A-induced cyclin D2 expression. Finally, we show that the overexpression of the wild-type FOXL2 but not the C134W mutant FOXL2 induced follistatin production. Treatment with exogenous follistatin blocks activin A-stimulated cell proliferation, and the overexpression of wild-type FOXL2 attenuates activin A-stimulated cell proliferation. These results suggest that FOXL2 may act as a tumor suppressor in human adult-type GCTs by inducing follistatin expression, which subsequently inhibits activin-stimulated cell proliferation

  5. 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.

  6. 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.

  7. Thyroid hormones and adult-type Leydig cell development

    NARCIS (Netherlands)

    Rijntjes, E.

    2008-01-01

    Alterations in thyroid hormone levels are well known to influence key functions in growth and development. Although in many countries the diet is fortified with iodide, essential for thyroid hormone synthesis, still not all humans have access to fortified diets, leaving a substantial part of the

  8. Smoking-related interstitial lung diseases

    International Nuclear Information System (INIS)

    Marten, K.

    2007-01-01

    The most important smoking-related interstitial lung diseases (ILD) are respiratory bronchiolitis, respiratory bronchiolitis-associated interstitial lung disease, desquamative interstitial pneumonia, and Langerhans' cell histiocytosis. Although traditionally considered to be discrete entities, smoking-related ILDs often coexist, thus accounting for the sometimes complex patterns encountered on high-resolution computed tomography (HRCT). Further studies are needed to elucidate the causative role of smoking in the development of pulmonary fibrosis

  9. Evaluation of testosterone serum levels in testicular interstitial fluid under thyroxine influence; Avaliacao da testosterona no fluido intersticial testicular sob influencia da tiroxina

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Isvania Maria S. da; Pereira, Simey de L.S.; Souza, Grace Mary L.; Carvalho, Elaine F.M.B.; Catanho, Maria Teresa J. de A. [Pernambuco Univ., Recife, PE (Brazil). Dept. de Biofisica e Radiobiologia; Silveira, Maria de Fatima G. da [Pernambuco Univ., Recife, PE (Brazil). Dept. de Anatomia; Lima Filho, Guilherme L. [Universidade de Pernambuco (UPE), Nazare da Mata, PE (Brazil). Faculdade de Formacao de Professores

    2000-07-01

    The thyroid hormones possibly exert a reciprocal action between testicular steroids and Sertoli's cells during the premature period. This work aims to evaluate thyroxine effect on testosterone serum levels and in the testicular interstitial fluid (TIF) in rats. Wistar males rats, 22 days old, 80g of body weight, were induced to hyperthyroidism with thyroxine (20{mu}g/kg) in periods of 5, 10, 15 and 20 consecutive days. After the treatment the animals were weighed and sacrificed for blood and testis collection. From the blood serum and from the TIF drained from the testis were performed testes in order to obtain testosterone attached to {sup 125} I with a specific activity of 36,86 MBq/ig. The results have shown a testosterone significant lineal increase in both - serum and TIF - in the group treated with thyroxine as a time function. In the control group, testosterone levels remained low in both serum and TIF dosages. As a result, we were able to verify that the testosterone levels could be modified by thyroxine in serum and TIF. And so, it could affect luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in hypophysis. (author)

  10. Gastrointestinal Hormone Cholecystokinin Increases P-Glycoprotein Membrane Localization and Transport Activity in Caco-2 Cells.

    Science.gov (United States)

    Yano, Kentaro; Shimizu, Saori; Tomono, Takumi; Ogihara, Takuo

    2017-09-01

    It was reported that stimulation of taste receptor type 2 member 38 by a bitter substance, phenylthiocarbamide (PTC), increased P-glycoprotein (P-gp) mRNA level and transport activity via release of the gastrointestinal hormone cholecystokinin-8 (CCK-8) at 9 h. Therefore, we hypothesized that CCK-8 and PTC might also regulate P-gp activity more rapidly via a different mechanism. As a result, we found that the pretreatment of human colon adenocarcinoma (Caco-2) cells with 10-mM PTC significantly decreased the intracellular accumulation of P-gp substrate rhodamine 123 (Rho123) compared with the control after 90-min incubation. Moreover, CCK-8 treatments significantly reduced the accumulation of Rho123 within 30 min, compared with the control. On the other hand, when Caco-2 cells were pretreated with PTC, the efflux ratio of Rho123 was significantly increased compared with control. The efflux ratio of Rho123 in CCK-8 treatment cells was also significantly increased compared with control. Furthermore, CCK-8 increased the phosphorylation of the scaffold proteins ezrin, radixin, and moesin, which regulate translocation of P-gp to the plasma membrane. Therefore, our results indicate that PTC induced release of CCK-8, which in turn induced the phosphorylation of ezrin, radixin, and moesin proteins, leading to upregulation of P-gp transport activity via increased membrane localization of P-gp. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  11. Immunotherapy of hormone-refractory prostate cancer with antigen-loaded dendritic cells.

    Science.gov (United States)

    Small, E J; Fratesi, P; Reese, D M; Strang, G; Laus, R; Peshwa, M V; Valone, F H

    2000-12-01

    Provenge (Dendreon Corp, Seattle, WA) is an immunotherapy product consisting of autologous dendritic cells loaded ex vivo with a recombinant fusion protein consisting of prostatic acid phosphatase (PAP) linked to granulocyte-macrophage colony-stimulating factor. Sequential phase I and phase II trials were performed to determine the safety and efficacy of Provenge and to assess its capacity to break immune tolerance to the normal tissue antigen PAP. All patients had hormone-refractory prostate cancer. Dendritic-cell precursors were harvested by leukapheresis in weeks 0, 4, 8, and 24, loaded ex vivo with antigen for 2 days, and then infused intravenously over 30 minutes. Phase I patients received increasing doses of Provenge, and phase II patients received all the Provenge that could be prepared from a leukapheresis product. Patients tolerated treatment well. Fever, the most common adverse event, occurred after 15 infusions (14.7%). All patients developed immune responses to the recombinant fusion protein used to prepare Provenge, and 38% developed immune responses to PAP. Three patients had a more than 50% decline in prostate-specific antigen (PSA) level, and another three patients had 25% to 49% decreases in PSA. The time to disease progression correlated with development of an immune response to PAP and with the dose of dendritic cells received. Provenge is a novel immunotherapy agent that is safe and breaks tolerance to the tissue antigen PAP. Preliminary evidence for clinical efficacy warrants further exploration.

  12. Thyroid hormone transport into liver cells: its (patho)physiological significance

    NARCIS (Netherlands)

    M. de Jong (Marion)

    1993-01-01

    textabstractIn the experiments described in this thesis transmembrane transport of thyroid hormones into liver cells is investigated, in particular the regulatory role of this transport process in the bioavailability of thyroid hormones in (patho )fysiological conditions. This first chapter is an

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