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Sample records for hormone gh messenger

  1. Changes in growth hormone (GH) messenger RNA (GH mRNA) expression in the rat anterior pituitary after single interferon (IFN) alpha administration

    International Nuclear Information System (INIS)

    Romanowski, W.; Braczkowski, R.; Nowakowska-Zajdel, E.; Muc-Wierzgon, M.; Zubelewicz-Szkodzinska, B.; Kosiewicz, J.; Korzonek, I.

    2006-01-01

    Introduction: Interferon a (IFN-a) is a cytokine with pleiotropic effects which, via different pathways, influences the secretion of certain cytokines and hormones. Growth hormone (GH) secreted from the pituitary has physiological effects on various target tissues. The question is how IFN-a administered in various types of disease influences GH secretion. This study investigated the acute effect of IFN-a on GH mRNA expression in the rat anterior pituitary. Objective: The aim of the study was to measure the cellular expression of GH mRNA by in situ hybridisation in the anterior pituitary after a single administration of IFN-a. Material and methods: Rats were administered an intraperitoneal injection of IFN-a or saline. The rat pituitaries were taken 2 and 4 hours after IFN/saline administration and kept frozen until in situ hybridisation histochemistry. A 31 - base 35S -labelled oligonucleotide probe complementary to part of the exonic mRNA sequence coding for GH mRNA was used. All control and experimental sections were hybridised in the same hybridisation reaction. Results: Acute administration of interferon a increased GH mRNA expression in the anterior pituitary in the 4-hour group in comparison with the control group, and there was no difference between the control group and the 2-hour rats. Conclusion: A single IFN-a administration was found to exert an influence on anterior pituitary GH mRNA expression. These observations may pave the way for presenting a possible new action of IFN-a. (author) GH mRNA, anterior pituitary, interferon

  2. Growth Hormone (GH) and Cardiovascular System

    Science.gov (United States)

    Díaz, Oscar; Devesa, Pablo

    2018-01-01

    This review describes the positive effects of growth hormone (GH) on the cardiovascular system. We analyze why the vascular endothelium is a real internal secretion gland, whose inflammation is the first step for developing atherosclerosis, as well as the mechanisms by which GH acts on vessels improving oxidative stress imbalance and endothelial dysfunction. We also report how GH acts on coronary arterial disease and heart failure, and on peripheral arterial disease, inducing a neovascularization process that finally increases flow in ischemic tissues. We include some preliminary data from a trial in which GH or placebo is given to elderly people suffering from critical limb ischemia, showing some of the benefits of the hormone on plasma markers of inflammation, and the safety of GH administration during short periods of time, even in diabetic patients. We also analyze how Klotho is strongly related to GH, inducing, after being released from the damaged vascular endothelium, the pituitary secretion of GH, most likely to repair the injury in the ischemic tissues. We also show how GH can help during wound healing by increasing the blood flow and some neurotrophic and growth factors. In summary, we postulate that short-term GH administration could be useful to treat cardiovascular diseases. PMID:29346331

  3. Vitamin D across growth hormone (GH) disorders: From GH deficiency to GH excess.

    Science.gov (United States)

    Ciresi, A; Giordano, C

    2017-04-01

    The interplay between vitamin D and the growth hormone (GH)/insulin-like growth factor (IGF)-I system is very complex and to date it is not fully understood. GH directly regulates renal 1 alpha-hydroxylase activity, although the action of GH in modulating vitamin D metabolism may also be IGF-I mediated. On the other hand, vitamin D increases circulating IGF-I and the vitamin D deficiency should be normalized before measurement of IGF-I concentrations to obtain reliable and unbiased IGF-I values. Indeed, linear growth after treatment of nutritional vitamin D deficiency seems to be mediated through activation of the GH/IGF-I axis and it suggests an important role of vitamin D as a link between the proliferating cartilage cells of the growth plate and GH/IGF-I secretion. Vitamin D levels are commonly lower in patients with GH deficiency (GHD) than in controls, with a variable prevalence of insufficiency or deficiency, and this condition may worsen the already known cardiovascular and metabolic risk of GHD, although this finding is not common to all studies. In addition, data on the impact of GH treatment on vitamin D levels in GHD patients are quite conflicting. Conversely, in active acromegaly, a condition characterized by a chronic GH excess, both increased and decreased vitamin D levels have been highlighted, and the interplay between vitamin D and the GH/IGF-I axis becomes even more complicated when we consider the acromegaly treatment, both medical and surgical. The current review summarizes the available data on vitamin D in the main disorders of the GH/IGF-I axis, providing an overview of the current state of the art. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Growth hormone (GH)-releasing activity of chicken GH-releasing hormone (GHRH) in chickens.

    Science.gov (United States)

    Harvey, S; Gineste, C; Gaylinn, B D

    2014-08-01

    Two peptides with sequence similarities to growth hormone releasing hormone (GHRH) have been identified by analysis of the chicken genome. One of these peptides, chicken (c) GHRH-LP (like peptide) was previously found to poorly bind to chicken pituitary membranes or to cloned and expressed chicken GHRH receptors and had little, if any, growth hormone (GH)-releasing activity in vivo or in vitro. In contrast, a second more recently discovered peptide, cGHRH, does bind to cloned and expressed cGHRH receptors and increases cAMP activity in transfected cells. The possibility that this peptide may have in vivo GH-releasing activity was therefore assessed. The intravenous (i.v.) administration of cGHRH to immature chickens, at doses of 3-100 μg/kg, significantly increased circulating GH concentrations within 10 min of injection and the plasma GH levels remained elevated for at least 30 min after the injection of maximally effective doses. The plasma GH responses to cGHRH were comparable with those induced by human (h) or porcine (p) GHRH preparations and to that induced by thyrotropin releasing hormone (TRH). In marked contrast, the i.v. injection of cGHRH-LP had no significant effect on circulating GH concentrations in immature chicks. GH release was also increased from slaughterhouse chicken pituitary glands perifused for 5 min with cGHRH at doses of 0.1 μg/ml or 1.0 μg/ml, comparable with GH responses to hGHRH1-44. In contrast, the perifusion of chicken pituitary glands with cGHRH-LP had no significant effect on GH release. In summary, these results demonstrate that cGHRH has GH-releasing activity in chickens and support the possibility that it is the endogenous ligand of the cGHRH receptor. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Different growth hormone (GH) response to GH-releasing peptide and GH-releasing hormone in hyperthyroidism.

    Science.gov (United States)

    Ramos-Dias, J C; Pimentel-Filho, F; Reis, A F; Lengyel, A M

    1996-04-01

    Altered GH responses to several pharmacological stimuli, including GHRH, have been found in hyperthyroidism. The mechanisms underlying these disturbances have not been fully elucidated. GH-releasing peptide-6 (GHRP-6) is a synthetic hexapeptide that specifically stimulates GH release both in vitro and in vivo. The mechanism of action of GHRP-6 is unknown, but it probably acts by inhibiting the effects of somatostatin on GH release. The aim of this study was to evaluate the effects of GHRP-6 on GH secretion in patients with hyperthyroidism (n = 9) and in control subjects (n = 9). Each subject received GHRP-6 (1 microg/kg, iv), GHRH (100 microg, iv), and GHRP-6 plus GHRH on 3 separate days. GH peak values (mean +/- SE; micrograms per L) were significantly lower in hyperthyroid patients compared to those in control subjects after GHRH alone (9.0 +/- 1.3 vs. 27.0 +/- 5.2) and GHRP-6 plus GHRH (22.5 +/- 3.5 vs. 83.7 +/- 15.2); a lack of the normal synergistic effect of the association of both peptides was observed in thyrotoxicosis. However, a similar GH response was seen in both groups after isolated GHRP-6 injection (31.9 +/- 5.7 vs. 23.2 +/- 3.9). In summary, we have shown that hyperthyroid patients have a normal GH response to GHRP-6 together with a blunted GH responsiveness to GHRH. Our data suggest that thyroid hormones modulate GH release induced by these two peptides in a differential way.

  6. Growth hormone (GH) binding and effects of GH analogs in transgenic mice

    Energy Technology Data Exchange (ETDEWEB)

    Bartke, A.; Steger, R.W. [Southern Illinois Univ., Carbondale, IL (United States); Turyn, D. [UBA-CONICET, Buenos Aires (Argentina)] [and others

    1994-12-31

    Overexpression of human (h) or bovine (b) growth hormone (GH) in transgenic mice is associated with marked (2- to 12-fold) and significant increase in hepatic binding of GH and prolactin (PRL). This is due to an increase in the number of GH and PRL receptors (GHR, PRLR) per mg of microsomal protein without changes in binding affinity. Comparison of results obtained in transgenic animals expressing bGH with a mouse metallothionein (MT) or a rat phosphoenolpyruvate carboxykinase (PEPCK) promoter suggests that effects of bGH on hepatic GHR and PRLR do not require GH overexpression during fetal life and, within the dose range tested, the effects on PRLR are not dose dependent. The increase in hepatic GHR was accompanied by significant increases in plasma GH-binding protein (GHBP) and in mean residence time of injected GH. Thus life-long elevation of peripheral GH levels alters the availability of both free GH and GHR. Site-directed in vitro mutagenesis was used to produce hGH and bGH analogs mutated within one of the sites involved in binding to GHR and PRLR. Mutating hGH to produce amino acid identity with bGH at Position 11, 18 (within Helix 1), 57, or 60 (within the loop between Helix 1 and 2) did not affect binding to GHR in vitro, or somatotropic activity in transgenic mice in vivo but reduced lactogenic activity in Nb{sub 2} cells by 22%-45%. Mutations of bGH designed to produce amino acid identity with hGH at one to four of the corresponding positions in the bGH molecule did not interfere with binding to GHR or somatotropic activity in vivo, and failed to produce significant binding to PRLR but resulted in alterations in the effects on the hypothalamic and anterior pituitary function in transgenic mice. Apparently region(s) outside the domains examined are essential for lactogenic activity of hGH, and different portions of the GH molecule are responsible for its diverse actions in vivo. 35 refs.

  7. Effects of methimazole treatment on growth hormone (GH) response to GH-releasing hormone in patients with hyperthyroidism.

    Science.gov (United States)

    Giustina, A; Ferrari, C; Bodini, C; Buffoli, M G; Legati, F; Schettino, M; Zuccato, F; Wehrenberg, W B

    1990-12-01

    In vitro studies have demonstrated that thyroid hormones can enhance basal and stimulated growth hormone secretion by cultured pituitary cells. However, both in man and in the rat the effects of high thyroid hormone levels on GH secretion are unclear. The aim of our study was to test the GH response to human GHRH in hyperthyroid patients and to evaluate the effects on GH secretion of short- and long-term pharmacological decrease of circulating thyroid hormones. We examined 10 hyperthyroid patients with recent diagnosis of Graves' disease. Twelve healthy volunteers served as controls. All subjects received a bolus iv injection of GHRH(1-29)NH2, 100 micrograms. Hyperthyroid patients underwent a GHRH test one and three months after starting antithyroid therapy with methimazole, 10 mg/day po. GH levels at 15, 30, 45, 60 min and GH peak after stimulus were significantly lower in hyperthyroid patients than in normal subjects. The GH peak was also delayed in hyperthyroid patients. After one month of methimazole therapy, most of the hyperthyroid patients had thyroid hormone levels in the normal range, but they did not show significant changes in GH levels after GHRH, and the GH peak was again delayed. After three months of therapy with methimazole, the hyperthyroid patients did not show a further significant decrease in serum thyroid hormone levels. However, mean GH levels from 15 to 60 min were significantly increased compared with the control study. The GH peak after GHRH was also earlier than in the pre-treatment study.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Regulation of the growth hormone (GH) receptor and GH-binding protein mRNA

    Energy Technology Data Exchange (ETDEWEB)

    Kaji, Hidesuke; Ohashi, Shin-Ichirou; Abe, Hiromi; Chihara, Kazuo [Kobe Univ. School of Medicine, Kobe (Japan)

    1994-12-31

    In fasting rats, a transient increase in growth hormone-binding protein (GHBP) mRNA levels was observed after 1 day, in muscle, heart, and liver, but not in fat tissues. The liver GH receptor (GHR) mRNA level was significantly increased after 1 day (but not after 5 days) of bovine GH (bGH) treatment in fed rats. Both the liver GHR mRNA level and the net increment of plasma IGF-I markedly decreased after 5 days of bGH administration in fasting rats. These findings suggest that GHR and GHBP mRNAs in the liver are expressed in a different way and that the expression of GHBP mRNA is regulated differently between tissues, at least in rats. The results also suggest that refractoriness to GH in a sustained fasting state might be beneficial in preventing anabolic effects of GH. In humans, GHR mRNA in lymphocytes, from subjects with either GH-deficiency or acromegaly, could be detected by the reverse transcription-polymerase chain reaction method. In one patient with partial GH insensitivity, a heterozygous missense mutation (P561T) was identified in the cytoplasmic domain of GHR. 15 refs., 4 figs.

  9. Defective membrane expression of human growth hormone (GH) receptor causes Laron-type GH insensitivity syndrome.

    Science.gov (United States)

    Duquesnoy, P; Sobrier, M L; Amselem, S; Goossens, M

    1991-01-01

    Mutations in the growth hormone receptor (GHR) gene can cause growth hormone (GH) resistance. Given the sequence homology between the extracellular domain of the GHR and a soluble GH-binding protein (GH-BP), it is remarkable that GH-BP binding activity is absent from the serum of patients with Laron-type GH insensitivity, a hereditary form of severe dwarfism. We have previously identified a mutation within the extracellular domain of this receptor, replacing phenylalanine by serine at position 96 of the mature protein, in a patient with Laron syndrome. We have now investigated the effect of this Phe----Ser substitution on hormone binding activity by expressing the total human GHR cDNA and mutant form in eukaryotic cells. The wild-type protein expressed was able to bind GH but no plasma membrane binding was detectable on cells transfected with the mutant cDNA; this was also the case of cells transfected with a Phe96----Ala mutant cDNA, suggesting that the lack of binding activity is not due to a posttranslational modification of serine. Examination of the variant proteins in subcellular fractions revealed the presence of specific GH binding activity in the lysosomal fraction, whereas immunofluorescence studies located mutant proteins in the cytosol. Our findings suggest that these mutant GHRs fail to follow the correct intracellular transport pathway and underline the potential importance of this phenylalanine residue, which is conserved among the GH, prolactin, and erythropoietin receptors that belong to the same cytokine receptor superfamily. Images PMID:1719554

  10. Should we start and continue growth hormone (GH) replacement therapy in adults with GH deficiency?

    NARCIS (Netherlands)

    ter Maaten, JC

    2000-01-01

    During the last decade, growth hormone deficiency (GHD) in adults has been described as a clinical syndrome. Central features of this entity include increased fat mass, reduced muscle and bone mass, as well as impaired exercise capacity and quality of life. GH replacement therapy has been initiated

  11. Growth hormone (GH) and atherosclerosis: changes in morphology and function of major arteries during GH treatment.

    Science.gov (United States)

    Pfeifer, M; Verhovec, R; Zizek, B

    1999-04-01

    Patients with hypopituitarism have increased carotid artery intima-media thickness and reduced arterial distensibility. The effect of 2 years of growth hormone (GH) replacement therapy on these parameters was studied in 11 GH-deficient men (age range, 24-49 years) with hypopituitarism and compared with 12 healthy, age-matched men with no evidence of pituitary or vascular disease. Before treatment the intima-media of the common carotid arteries and the carotid bifurcations were significantly thicker in patients (P < 0.001) than in the control group. Treatment with GH normalized the intima-media thickness of the common carotid artery within 6 months and of the carotid bifurcation within 3 months. The changes in intima-media thickness of the carotid artery were negatively correlated with changes in serum levels of insulin-like growth factor I during treatment. There was a significant improvement in flow-mediated, endothelium-dependent dilation of the brachial artery at 3 months, which was sustained at 6, 18 and 24 months of GH treatment (P < 0.05). Thus, GH replacement therapy in GH-deficient men reverses early morphological and functional atherosclerotic changes in major arteries, and may reduce rates of vascular morbidity and mortality.

  12. Growth hormone (GH) activity is associated with increased serum oestradiol and reduced Anti-Müllerian Hormone in healthy male volunteers treated with GH and a GH antagonist

    DEFF Research Database (Denmark)

    Andreassen, M; Frystyk, Jan; Faber, J

    2013-01-01

    Growth hormone (GH) and insulin-like growth factor I (IGF-I) receptors are present on pituitary gonadotrophs and on testicular Leydig and Sertoli cells. Thus, the GH/IGF-I system may modulate the pituitary-gonadal axis in males. This is a randomized cross-over study. Eight healthy male volunteers...... (160-290) vs. 106 (97-157) μg/L, p = 0.001) and oestradiol (86 ± 28 vs. 79 ± 25 pm, p = 0.060) decreased. No significant changes or trends in the other reproductive hormones occurred during the two treatment regimens. GH/IGF-I activity was positively associated with serum oestradiol, suggesting that GH...

  13. Growth hormone (GH) secretion and pituitary size in children with short stature. Efficacy of GH therapy in GH-deficient children, depending on the pituitary size.

    Science.gov (United States)

    Hilczer, Maciej; Szalecki, Mieczysław; Smyczynska, Joanna; Stawerska, Renata; Kaniewska, Danuta; Lewinski, Andrzej

    2005-10-01

    Certain relationships between pituitary size and growth hormone (GH) secretion have previously been observed, however they are still a matter of controversy. Organic abnormalities of the hypothalamic-hypophyseal region are important for predicting growth response to GH therapy. Evaluation of relations between GH secretion and the pituitary size in short children and estimation of the efficacy of GH therapy in children with GH deficiency (GHD). The analysis comprised 216 short children (159 boys). Two GH stimulation tests, as well as magnetic resonance image (MRI) examination, were performed in each patient. All the patients with GHD were treated with GH for, at least, one year. Significant correlations were found between pituitary height and GH secretion (p < 0.05). Patients were classified into three (3) groups: 1) pituitary hypoplasia (HP) for height age; 2) HP for the chronological age but not for the height age; 3) normal pituitary size. Significant differences in GH secretion were observed among the groups (6.1+/-5.3 vs. 8.1+/-4.4 vs. 12.3+/-9.1 ng/mL, respectively). There was a negative correlation between GH peak and height gain during GH therapy (r = -0.34). The highest growth improvement was noticed in patients with HP for the height age. Pituitary hypoplasia for the height age is related to more severe GH deficiency and the best response to GH therapy.

  14. Evaluation of growth hormone (GH) action in mice: discovery of GH receptor antagonists and clinical indications.

    Science.gov (United States)

    Kopchick, John J; List, Edward O; Kelder, Bruce; Gosney, Elahu S; Berryman, Darlene E

    2014-04-05

    The discovery of a growth hormone receptor antagonist (GHA) was initially established via expression of mutated GH genes in transgenic mice. Following this discovery, development of the compound resulted in a drug termed pegvisomant, which has been approved for use in patients with acromegaly. Pegvisomant treatment in a dose dependent manner results in normalization of IGF-1 levels in most patients. Thus, it is a very efficacious and safe drug. Since the GH/IGF-1 axis has been implicated in the progression of several types of cancers, many have suggested the use of pegvisomant as an anti-cancer therapeutic. In this manuscript, we will review the use of mouse strains that possess elevated or depressed levels of GH action for unraveling many of GH actions. Additionally, we will describe experiments in which the GHA was discovered, review results of pegvisomant's preclinical and clinical trials, and provide data suggesting pegvisomant's therapeutic value in selected types of cancer. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  15. 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 (...

  16. The basic route of the nuclear translocation porcine growth hormone (GH)-growth hormone receptor (GHR) complex (pGH/GHR) in porcine hepatocytes.

    Science.gov (United States)

    Hainan, Lan; Huilin, Liu; Khan, Mahamad; Xin, Zheng; YuJiang, Yang; Hui, Zhang; Naiquan, Yao

    2018-06-08

    Traditional views suggest that growth hormone and the growth hormone receptor (GH/GHR complex) exert their functions only on the plasma membrane. This paradigm, however, has been challenged by recent new findings that the GH/GHR complex could translocate into cell nuclei where they could still exhibit important physiological functions. We also reported the nuclear localization of porcine GH/GHR and their potential functions in porcine hepatocytes. However, the basic path of pGH/GHR's nuclear translocation remains unclear. Combining previous research results and our current findings, we proposed two basic routes of pGH/GHR's nuclear transportation as follows: 1) after pGH binding to GHR, pGH/GHR enters into the cytoplasm though clathrin- or caveolin-mediated endocytosis, then the pGH/GHR complex enters into early endosomes (Rab5-positive), and the endosome carries the GH/GHR complex to the endoplasmic reticulum (ER). After endosome docking on the ER, the endosome starts fission, and the pGH/GHR complex enters into the ER lumen. Then the pGH/GHR complex transports into the cytoplasm, possibly by the ERAD pathway. Subsequently, the pGH/GHR complex interacts with IMPα/β, which, in turn, mediates GH/GHR nuclear localization; 2) pGH binds with the GHR on the cell membrane and, subsequently, pGH/GHR internalizes into the cell and enters into the endosome (this endosome may belong to a class of endosomes called envelope-associated endosomes (NAE)). Then, the endosome carries the pGH/GHR to the nuclear membrane. After docking on the nuclear membrane, the pGH/GHR complex fuses with the nuclear membrane and then enters into the cell nucleus. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Dominant dwarfism in transgenic rats by targeting human growth hormone (GH) expression to hypothalamic GH-releasing factor neurons.

    OpenAIRE

    Flavell, D M; Wells, T; Wells, S E; Carmignac, D F; Thomas, G B; Robinson, I C

    1996-01-01

    Expression of human growth hormone (hGH) was targeted to growth hormone-releasing (GRF) neurons in the hypothalamus of transgenic rats. This induced dominant dwarfism by local feedback inhibition of GRF. One line, bearing a single copy of a GRF-hGH transgene, has been characterized in detail, and has been termed Tgr (for Transgenic growth-retarded). hGH was detected by immunocytochemistry in the brain, restricted to the median eminence of the hypothalamus. Low levels were also detected in the...

  18. The growth hormone (GH) response to GH-releasing peptide (His-DTrp-Ala-Trp-DPhe-Lys-NH2), GH-releasing hormone, and thyrotropin-releasing hormone in acromegaly.

    Science.gov (United States)

    Alster, D K; Bowers, C Y; Jaffe, C A; Ho, P J; Barkan, A L

    1993-09-01

    In patients with acromegaly, GH-producing pituitary tumors release GH in response to specific stimuli such as GH-releasing hormone (GHRH) and are also responsive to a variety of nonspecific stimuli, such as TRH or GnRH, and may exhibit paradoxical responses to glucose and dopamine. In healthy humans, the synthetic peptide GH-releasing peptide (GHRP) (His-D-Trp-Ala-Trp-D-Phe-Lys-NH2) releases GH by a putative mechanism of action that is independent of GHRH. How these tumors respond to GHRP is not well characterized. We studied the GH responses to GHRH, GHRP, and TRH stimulation in 11 patients with active acromegaly. The peak GH responses to GHRP and GHRH were not correlated (r = 0.57; P = 0.066). In contrast, the peak GH responses to GHRP and TRH were highly correlated (r = 0.95; P < 0.001). In conclusion, in patients with acromegaly, the GH response to GHRP is qualitatively normal and does not appear to depend on GHRH.

  19. Growth hormone (GH)-independent dimerization of GH receptor by a leucine zipper results in constitutive activation

    DEFF Research Database (Denmark)

    Behncken, S N; Billestrup, Nils; Brown, R

    2000-01-01

    Growth hormone initiates signaling by inducing homodimerization of two GH receptors. Here, we have sought to determine whether constitutively active receptor can be created in the absence of the extracellular domain by substituting it with high affinity leucine zippers to create dimers of the gro......Growth hormone initiates signaling by inducing homodimerization of two GH receptors. Here, we have sought to determine whether constitutively active receptor can be created in the absence of the extracellular domain by substituting it with high affinity leucine zippers to create dimers...

  20. Pioglitazone treatment increases spontaneous growth hormone (GH) secretion and stimulated GH levels in polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Støving, René Klinkby; Hagen, Claus

    2005-01-01

    BACKGROUND: Low GH levels, probably due to insulin resistance and increased abdominal fat mass, are well described in polycystic ovary syndrome (PCOS). GH acts as an important ovarian cogonadotropin, and GH disturbances may be an additional pathogenic factor in PCOS. Decreased abdominal fat mass...

  1. Circulating growth hormone (GH)-binding protein complex: a major constituent of plasma GH in man

    International Nuclear Information System (INIS)

    Baumann, G.; Amburn, K.; Shaw, M.A.

    1988-01-01

    The recent discovery of a specific binding protein for human GH (hGH) in human plasma suggests that hGH circulates in part as a complex in association with the binding protein(s). However, the magnitude of the complexed fraction prevailing under physiological conditions is unknown because of 1) dissociation of the complex during analysis and 2) potential differences in the binding characteristics of radiolabeled and native hGH. We conducted experiments designed to minimize dissociation during analysis (gel filtration in prelabeled columns, frontal analysis, and batch molecular sieving) with both native and radioiodinated hGH. All three methods yielded similar estimates for the complexed fraction. In normal plasma the bound fraction for 22 K hGH averaged 50.1% (range, 39-59%), that for 20 K hGH averaged 28.5% (range, 26-31%). Above a hGH level of about 20 ng/ml the bound fraction declines in concentration-dependent manner due to saturation of the binding protein. We conclude that a substantial part of circulating hGH is complexed with carrier proteins. This concept has important implications for the metabolism, distribution, and biological activity of hGH

  2. Growth hormone replacement does not elevate albuminuria in GH-deficient adults

    NARCIS (Netherlands)

    Beentjes, JAM; Dullaart, RPF

    2002-01-01

    Minor elevations in urinary albumin excretion rate (Ualb.V) are likely to be associated with renal function loss and increased cardiovascular risk. Since urinary albumin excretion is affected by the growth hormone (GH)-insulin-like growth factor-1 (IGF-1) axis, we evaluated the effect of 6 months GH

  3. Induction of chronic growth hormone deficiency by anti-GH serum

    Science.gov (United States)

    Grindeland, R. E.; Smith, A. T.; Ellis, S.; Evans, E. S.

    1974-01-01

    The observations reported indicate that the growth rate of neonatal rats can be specifically inhibited for at least 78 days following the administration of antisera against growth hormone (GH) for only four days after birth. The inhibition can be correlated with a marked deficit of tibial growth promoting activity in the pituitary but not with the plasma concentrations of immuno-reactive GH.

  4. Development of additional pituitary hormone deficiencies in pediatric patients originally diagnosed with idiopathic isolated GH deficiency

    NARCIS (Netherlands)

    W.F. Blum (Werner); C.L. Deal (Cheri Lynn); A.G. Zimmermann (Alan); E.P. Shavrikova (Elena); C.J. Child (Christopher); C.A. Quigley (Charmian); S.L.S. Drop (Stenvert); G. Cutler (Gordon); R.G. Rosenfeld (Ron)

    2014-01-01

    textabstractObjective: We assessed the characteristics of children initially diagnosed with idiopathic isolated GH deficiency (IGHD) who later developed additional (multiple) pituitary hormone deficiencies (MPHD). Design: Data were analyzed for 5805 pediatric patients with idiopathic IGHD, who were

  5. Growth hormone (GH) treatment reverses early atherosclerotic changes in GH-deficient adults.

    Science.gov (United States)

    Pfeifer, M; Verhovec, R; Zizek, B; Prezelj, J; Poredos, P; Clayton, R N

    1999-02-01

    Hypopituitary patients have increased mortality from vascular disease, and in these patients, early markers of atherosclerosis [increased carotid artery intima-media thickness (IMT) and reduced distensibility] are more prevalent. As GH replacement can reverse some risk factors of atherosclerosis, the present study examined the effect of GH treatment on morphological and functional changes in the carotid and brachial arteries of GH-deficient (GHD) adults. Eleven GHD hypopituitary men (24-49 yr old) were treated with recombinant human GH (0.018 U/kg BW x day) for 18 months. IMT of the common carotid artery (CCA) and the carotid bifurcation (CB), and flow-mediated endothelium-dependent dilation (EDD) of the brachial artery were measured by B mode ultrasound before and at 3, 6, 12, and 18 months of treatment, and values were compared with those in 12 age-matched control men. Serum concentrations of lipids, lipoprotein(a), insulin-like growth factor I (IGF-I), and IGF-binding protein-3 (IGFBP-3) were also measured. In GHD men before treatment the IMTs of the CCA [mean(SD), 0.67(0.05) mm] and CB [0.75(0.04) mm] were significantly greater (P < 0.001) than those in control men [0.52(0.07) and 0.65(0.07) mm, respectively]. GH treatment normalized the IMT of the CCA by 6 months [0.53(0.04) mm] and that of the CB by 3 months [0.68(0.05) mm]. The IMT of the carotid artery (CCA and CB) was negatively correlated with serum IGF-I (r = -0.53; P < 0.0001). There was a significant improvement in flow-mediated EDD of the brachial artery at 3 months, which was sustained at 6 and 18 months of GH treatment (P < 0.05). GH treatment increased high density lipoprotein cholesterol at 3 and 6 months, but did not reduce total or low density lipoprotein cholesterol and was without effect on lipoprotein(a). There was no correlation between plasma lipids and changes in IMT or EDD of the arteries examined. In conclusion, GH treatment of hypopituitary GHD men reverses early morphological and

  6. Approach to testing growth hormone (GH) secretion in obese subjects.

    Science.gov (United States)

    Popovic, Vera

    2013-05-01

    Identification of adults with GH deficiency (GHD) is challenging because clinical features of adult GHD are not distinctive and because clinical suspicion must be confirmed by biochemical tests. Adults are selected for testing for adult GHD if they have a high pretest probability of GHD, ie, if they have hypothalamic-pituitary disease, if they have received cranial irradiation or central nervous system tumor treatment, or if they survived traumatic brain injury or subarachnoid hemorrhage. Testing should only be carried out if a decision has already been made that if deficiency is found it will be treated. There are many pharmacological GH stimulation tests for the diagnosis of GHD; however, none fulfill the requirements for an ideal test having high discriminatory power; being reproducible, safe, convenient, and economical; and not being dependent on confounding factors such as age, gender, nutritional status, and in particular obesity. In obesity, GH secretion is reduced, GH clearance is enhanced, and stimulated GH secretion is reduced, causing a false-positive result. This functional hyposomatotropism in obesity is fully reversed by weight loss. In conclusion, GH stimulation tests should be avoided in obese subjects with very low pretest probability.

  7. Expression and ontogeny of growth hormone (Gh) in the protogynous hermaphroditic ricefield eel (Monopterus albus).

    Science.gov (United States)

    Chen, Dong; Liu, Jiang; Chen, Wanping; Shi, Shuxia; Zhang, Weimin; Zhang, Lihong

    2015-12-01

    Growth hormone (GH) is a single-chain polypeptide hormone mainly secreted by somatotropes of the anterior pituitary gland and is an important regulator of somatic growth in vertebrates including teleosts. In this study, a polyclonal antiserum against ricefield eel Gh was generated and the expression of Gh at the mRNA and protein levels was analyzed. Both RT-PCR and western blot analysis showed that Gh was predominantly expressed in the pituitary glands of ricefield eels. The immunoreactive Gh signals were localized to the multicellular layers of the adenohypophysis adjacent to the neurohypophysis in ricefield eels. Ontogenetic analysis showed that immunoreactive Gh signals could be detected in the pituitary glands of ricefield eel embryos as early as 3 days post-fertilization. During the sex change from female to male, the levels of the immunoreactive Gh signals in the pituitary glands of the ricefield eels peaked at the intersexual stage. These results suggest that Gh in the pituitary glands may be associated with embryonic development before hatching, as well as with the sex change in the adult ricefield eels, possibly via the classical endocrine manner.

  8. STIMULASI PERTUMBUHAN JUVENIL ABALON, Haliotis squamata DENGAN PEMBERIAN HORMON REKOMBINAN IKAN rElGH

    Directory of Open Access Journals (Sweden)

    Fitriyah Husnul Khotimah

    2017-01-01

    Full Text Available Masalah yang paling utama dalam budidaya abalon tropis adalah pertumbuhan yang lambat. Penggunaan rElGH (recombinant giant grouper, Epinephelus lanceolatus growth hormone untuk menstimulasi pertumbuhan beberapa spesies ikan sudah dilakukan. Penelitian ini bertujuan untuk menguji akselerasi pertumbuhan juvenil abalon tropis, Haliotis squamata setelah diberi perlakuan perendaman hormon rekombinan ikan kerapu kertang, Epinephelus lanceolatus pada frekuensi yang berbeda. Ada empat perlakuan frekuensi perendaman rElGH yaitu 4, 9, 16 kali, dan tanpa perendaman (kontrol. Masing-masing perlakuan diulang tiga kali. Perendaman dilakukan selama tiga jam, dengan interval waktu empat hari. Kepadatan abalon tropis 100 ekor/L air laut yang mengandung 30 mg rElGH. Wadah untuk perendaman berupa beaker glass yang dilengkapi dengan aerasi. Penelitian dilakukan selama tujuh bulan. Hasil penelitian menunjukkan bahwa abalon tropis yang direndam rElGH dengan frekuensi empat kali menghasilkan pertumbuhan bobot tubuh dan panjang cangkang tertinggi dan berbeda nyata dengan perlakuan lainnya (P<0,05. Sintasan abalon tropis yang diberi perlakuan perendaman hormon rElGH lebih tinggi dibandingkan perlakuan kontrol. The most crucial problem in tropical abalone aquaculture is the slow growth of the species. Studies investigating the use of rElGH (recombinant giant grouper, Epinephelus lanceolatus growth hormone for promoting growth have been performed in various species. This research aimed to examine the growth acceleration of tropical abalone, Haliotis squamata juvenile after being treated in different immersion frequencies of recombinant giant grouper, Epinephelus lanceolatus growth hormone (rElGH. There were four treatments of rElGH immersion frequency: 4, 9, 16 times and without rElGH immersion (control. Each treatment was performed in triplicates. Immersion was performed for 3 hours, at 4-day intervals and a density of 100 tropical abalones in 1 L seawater containing 30

  9. Expression of Lymphocyte-derived Growth Hormone (GH) and GH-releasing Hormone Receptors in Aging Rats

    OpenAIRE

    Weigent, Douglas A.

    2013-01-01

    In the present study, we show that higher levels of lymphocyte GH are expressed in spleen cells from aging animals compared to young animals. Further, leukocytes from primary and secondary immune tissues and splenic T and B cells from aging rats all express higher levels of GHRH receptors compared to younger animals. Bone marrow and splenic T cells express the highest levels of GHRH receptor in aging animals. Spleen cells from aging animals showed no significant change in proliferation or GH ...

  10. Natural history of the classical form of primary growth hormone (GH) resistance (Laron syndrome).

    Science.gov (United States)

    Laron, Z

    1999-04-01

    A description of the clinical, biochemical and endocrinological features of the classical form of the syndrome of primary growth hormone (GH) resistance (Laron syndrome) is presented including the progressive changes during follow-up from infancy into adulthood. The main diagnostic features are: severe growth retardation, acromicria, small gonads and genitalia, and obesity. Serum GH levels are elevated and insulin-like growth factor-I (IGF-I) values are low and do not rise upon stimulation by exogenous hGH. The pathogenesis of this syndrome is due to various molecular defects from exon deletion to nonsense, frameshift, splice and missense mutations in the GH receptor (GH-R) gene or in its post-receptor pathways.

  11. Structural Basis for Prereceptor Modulation of Plant Hormones by GH3 Proteins

    Energy Technology Data Exchange (ETDEWEB)

    Westfall, Corey S.; Zubieta, Chloe; Herrmann, Jonathan; Kapp, Ulrike; Nanao, Max H.; Jez, Joseph M. (WU); (EMBL); (ESRF)

    2013-04-08

    Acyl acid amido synthetases of the GH3 family act as critical prereceptor modulators of plant hormone action; however, the molecular basis for their hormone selectivity is unclear. Here, we report the crystal structures of benzoate-specific Arabidopsis thaliana AtGH3.12/PBS3 and jasmonic acid-specific AtGH3.11/JAR1. These structures, combined with biochemical analysis, define features for the conjugation of amino acids to diverse acyl acid substrates and highlight the importance of conformational changes in the carboxyl-terminal domain for catalysis. We also identify residues forming the acyl acid binding site across the GH3 family and residues critical for amino acid recognition. Our results demonstrate how a highly adaptable three-dimensional scaffold is used for the evolution of promiscuous activity across an enzyme family for modulation of plant signaling molecules.

  12. New insights into the mechanism and actions of growth hormone (GH) in poultry.

    Science.gov (United States)

    Vasilatos-Younken, R; Wang, X H; Zhou, Y; Day, J R; McMurtry, J P; Rosebrough, R W; Decuypere, E; Buys, N; Darras, V; Beard, J L; Tomas, F

    1999-10-01

    Despite well documented anabolic effects of GH in mammals, a clear demonstration of such responses in domestic poultry is lacking. Recently, comprehensive dose-response studies of GH have been conducted in broilers during late post-hatch development (8 to 9 weeks of age). GH reduced feed intake (FI) and body weight gain in a dose-dependent manner, whereas birds pair-fed to the level of voluntary FI of GH-infused birds did not differ from controls. The reduction in voluntary FI may involve centrally mediated mechanisms, as hypothalamic neuropeptide Y protein and mRNA were reduced with GH, coincident with the maximal depression in FI. Growth of breast muscle was also reduced in a dose-dependent manner. Circulating IGF-I was not enhanced by GH, despite evidence that early events in the GH signaling pathway were intact. A GH dose-dependent increase in circulating 3,3',5-triiodothyronine(T3) paralleled decreases in hepatic 5D-III monodeiodinase activity, whereas 5'D-I activity was not altered. This confirms that a marked hyperthyroid response to GH occurs in late posthatch chickens, resulting from a decrease in the degradative pathway of T3 metabolism. This secondary hyperthyroidism would account for the decreased skeletal muscle mass (52) and lack of enhanced IGF-I (53) in GH-treated birds. Based upon these studies, it is now evident that GH does in fact have significant effects in poultry, but metabolic responses may confound the anabolic potential of the hormone.

  13. Gene expression of a truncated and the full-length growth hormone (GH) receptor in subcutaneous fat and skeletal muscle in GH-deficient adults

    DEFF Research Database (Denmark)

    Fisker, Sidse; Kristensen, K; Rosenfalck, A M

    2001-01-01

    the relationship of circulating GHBP and body composition to GHR and GHRtr gene expression. Eleven adult GH-deficient patients were studied before and after 4 months of GH substitution therapy. Abdominal fat obtained by liposuction and femoral muscle biopsies were taken at baseline and after 4 months. Gene...... expression of GHR and GHRtr in adipose tissue and skeletal muscle was determined and expressed relative to the expression of beta-actin. Gene expression of GHR in abdominal sc adipose tissue was not altered, whereas the expression of GHRtr increased significantly. In skeletal muscle inverse changes were seen...... in the expression of messenger ribonucleic acid (mRNA) levels for the two GH receptor forms: expression of GHR increased significantly, whereas mRNA levels for GHRtr decreased. As expected, body composition changed with reduction of body fat mass after 4 months of GH treatment. Levels of circulating GHBP decreased...

  14. The effect of growth hormone (GH) replacement on muscle strength in patients with GH-deficiency: a meta-analysis.

    LENUS (Irish Health Repository)

    Widdowson, W Matthew

    2012-02-01

    CONTEXT\\/OBJECTIVES: GH replacement increases muscle mass and reduces body fat in growth hormone deficiency (GHD) adults. A recent meta-analysis has demonstrated that this improvement in body composition is associated with improved exercise performance. The current meta-analysis was carried out to determine whether high-quality evidence exists to support a beneficial effect of GH replacement on strength. DESIGN\\/METHODS: An extensive Medline search\\/literature review identified eight studies with utilizable, robust data, involving 231 patients in nine cohorts. Previously unpublished data were sought from authors and obtained in two cases. All studies included were randomized, double-blind, placebo-controlled, of parallel or cross-over design and of an average 6.7 months duration. Information was retrieved in uniform format, with data pertaining to patient numbers, study-design, GH-dose, mean age, IGF-I levels and muscle strength measurements (isometric or isokinetic quadriceps strength) recorded. Data were analysed using a fixed-effects model, utilizing continuous data measured on different scales. A summary effect measure (d(s)) was derived for individual strength variables, whereas an overall summary effect was derived from the sum of all studies incorporating different variables; 95% CIs were calculated from the weighted variances of individual study effects. RESULTS: Analysis revealed no significant improvement, neither when all studies were combined (d(s) = +0.01 +\\/- 0.26) nor when measured individually (isometric quadriceps strength, d(s) = +0.02 +\\/- 0.32 and isokinetic quadriceps strength, d(s) = 0.00 +\\/- 0.45). CONCLUSIONS: Evidence from short-term controlled studies fails to support a benefit on muscle strength of GH replacement in GHD patients, which is likely to occur over a longer time-course, as seen in open-label studies.

  15. Evaluation of in vivo [corrected] biological activity of new agmatine analogs of growth hormone-releasing hormone (GH-RH)

    Science.gov (United States)

    Bokser, L; Zarandi, M; Schally, A V

    1990-01-01

    The effects of agmatine analogs of growth hormone releasing hormone (GH-RH) were compared to GH-RH(1-29)-NH2 after intravenous (iv) and subcutaneous (sc) administration to pentobarbital-anesthetized male rats. After the iv injection, the analogs [desNH2-Tyr1,Ala15,Nle27] GH-RH(1-28)Agm (MZ-2-51); [desNH2-Tyr1,D-Lys12,Ala15,Nle27] GH-RH(1-28)Agm (MZ-2-57); [desNH2-Tyr1,Ala15,D-Lys21,Nle27] GH-RH(1-28)Agm (MZ-2-75) and [desNH2-Tyr1, D-Lys12,21, Ala15, Nle27] GH-RH(1-28)Agm (MZ-2-87) showed a potency equivalent to 4.4, 1.9, 1.07 and 1.03 times that of GH-RH (1-29)-NH2, respectively, at 5 min and 5.6, 1.8, 1.9 and 1.8 times higher, respectively, at 15 min. After sc administration, analogs MZ-2-51, MZ-2-57 and MZ-2-75 showed to be 34.3, 14.3 and 10.5 times more potent than the parent hormone at 15 min and 179.1, 88.9 and 45.0 times more active, respectively, at 30 min. In addition, MZ-2-51 had prolonged GH-releasing activity as compared to the standard. We also compared the activity of MZ-2-51 and MZ-2-57 with their homologous L-Arg and D-Arg analogs [desNH2-Tyr1,Ala15,Nle27] GH-RH(1-29)-NH2 (MZ-2-117), [des-NH2Tyr1,D-Lys12, Ala15, Nle27] GH-RH(1-29)NH2 (MZ-2-123) and [desNH2-Tyr1,D-Lys12,Ala15, Nle27,D-Arg29] GH-RH(1-29)NH2 (MZ-2-135) after intramuscular (im) injection. MZ-2-51 induced a somewhat greater GH release than MZ-2-117 at 15 min, both responses being larger than the controls (p less than 0.01) at 15 and 30 min. MZ-2-57, MZ-2-123 and MZ-2-135 given i.m. were able to stimulate GH release only at 15 minutes (p less than 0.05). Animals injected i.m. with MZ-2-51, but not with MZ-2-117, showed GH levels significantly higher than the control group (p less than 0.05) at 60 min. GH-RH(1-29)NH2 had low activity intramuscularly when tested at a dose of 2.5 micrograms. No toxic effects were observed after the iv administration of 1 mg/kg of Agm GH-RH analogs. These results indicate that our Agm analogs are active iv, sc and im and that the substitutions made in these

  16. Effects of growth hormone (GH) treatment on body fluid distribution in patients undergoing elective abdominal surgery

    DEFF Research Database (Denmark)

    Møller, Jacob; Jensen, Martin Bach; Frandsen, E.

    1998-01-01

    OBJECTIVE: To investigate the possible beneficial effects of growth hormone (GH) in catabolic patients we examined the impact of GH on body fluid distribution in patients with ulcerative colitis undergoing elective abdominal surgery. DESIGN AND MEASUREMENTS: Twenty-four patients (14 female, 10 male...... at day -2 and at day 7, and body composition was estimated by dual X-ray absorptiometry and bioimpedance. Changes in body weight and fluid balance were recorded and hence intracellular volume was assessed. RESULTS: During placebo treatment body weight decreased 4.3 +/- 0.6 kg; during GH treatment body.......05). Plasma renin and aldosterone remained unchanged in both study groups. CONCLUSION: Body weight, plasma volume and intracellular volume is preserved during GH treatment in catabolic patients and ECV is increased. From a therapeutic point of view these effects may be desirable under conditions of surgical...

  17. Glucocorticoid control of rat growth hormone gene expression: Effect on cytoplasmic messenger ribonucleic acid production and degradation

    International Nuclear Information System (INIS)

    Gertz, B.J.; Gardner, D.G.; Baxter, J.D.

    1987-01-01

    The effect of the glucocorticoid dexamethasone on the production and degradation of rat GH (rGH) cytoplasmic mRNA was studied in cultured rat pituitary tumor (GC) cells. The incorporation of [3H]uridine into both rGH cytoplasmic mRNA and the pyrimidine nucleotide precursor pool was determined in hormone-treated and control cells. From these measurements glucocorticoid effects on absolute production rates of rGH cytoplasmic mRNA were determined and compared to effects on rGH mRNA accumulation. Rat GH mRNA half-life was then calculated based on a first-order decay model. Rat GH mRNA half-life was also directly assayed by: (1) pulse-chase studies and (2) measuring the kinetics of decay of rGH mRNA in cells after transfer from serum-containing to hormone-deficient media. From these independent analyses rGH mRNA half-life estimates ranged from 28-55 h in different experiments. Within individual experiments there was little variability of rGH mRNA decay rates; glucocorticoids were found not to alter the stability of rGH cytoplasmic mRNA. Glucocorticoid induction of rGH cytoplasmic mRNA accumulation was accounted for solely on the basis of increased mRNA production

  18. Growth Hormone Research Society perspective on biomarkers of GH action in children and adults.

    Science.gov (United States)

    Johannsson, Gudmundur; Bidlingmaier, Martin; Biller, Beverly M K; Boguszewski, Margaret; Casanueva, Felipe F; Chanson, Philippe; Clayton, Peter E; Choong, Catherine S; Clemmons, David; Dattani, Mehul; Frystyk, Jan; Ho, Ken; Hoffman, Andrew R; Horikawa, Reiko; Juul, Anders; Kopchick, John J; Luo, Xiaoping; Neggers, Sebastian; Netchine, Irene; Olsson, Daniel S; Radovick, Sally; Rosenfeld, Ron; Ross, Richard J; Schilbach, Katharina; Solberg, Paulo; Strasburger, Christian; Trainer, Peter; Yuen, Kevin C J; Wickstrom, Kerstin; Jorgensen, Jens O L

    2018-03-01

    The Growth Hormone Research Society (GRS) convened a Workshop in 2017 to evaluate clinical endpoints, surrogate endpoints and biomarkers during GH treatment of children and adults and in patients with acromegaly. GRS invited 34 international experts including clinicians, basic scientists, a regulatory scientist and physicians from the pharmaceutical industry. Current literature was reviewed and expert opinion was utilized to establish the state of the art and identify current gaps and unmet needs. Following plenary presentations, breakout groups discussed questions framed by the planning committee. The attendees re-convened after each breakout session to share the group reports. A writing team compiled the breakout session reports into a document that was subsequently discussed and revised by participants. This was edited further and circulated for final review after the meeting. Participants from pharmaceutical companies were not part of the writing process. The clinical endpoint in paediatric GH treatment is adult height with height velocity as a surrogate endpoint. Increased life expectancy is the ideal but unfeasible clinical endpoint of GH treatment in adult GH-deficient patients (GHDA) and in patients with acromegaly. The pragmatic clinical endpoints in GHDA include normalization of body composition and quality of life, whereas symptom relief and reversal of comorbidities are used in acromegaly. Serum IGF-I is widely used as a biomarker, even though it correlates weakly with clinical endpoints in GH treatment, whereas in acromegaly, normalization of IGF-I may be related to improvement in mortality. There is an unmet need for novel biomarkers that capture the pleiotropic actions of GH in relation to GH treatment and in patients with acromegaly. © 2018 Growth Hormone Research Society.

  19. Effects of up to 15 years of recombinant human GH (rhGH) replacement on bone metabolism in adults with growth hormone deficiency (GHD): the Leiden Cohort Study.

    Science.gov (United States)

    Appelman-Dijkstra, Natasha M; Claessen, Kim M J A; Hamdy, Neveen A T; Pereira, Alberto M; Biermasz, Nienke R

    2014-11-01

    Growth hormone deficiency (GHD) in adulthood may be associated with a decreased bone mineral density (BMD), a decreased bone mineral content (BMC) and an increased fracture risk. Recombinant human GH (rhGH) replacement induces a progressive increase in BMD for up to 5-7 years of treatment. Data on longer follow-up are, however, scarce. Two hundred and thirty-adult GHD patients (mean age 47·1 years, 52·6% female), of whom 88% patients had adult-onset (AO) GHD, receiving rhGH replacement for ≥5 years were included in the study. Most patients had multiple pituitary hormone deficiencies. Bone turnover markers, BMC and BMD and T-scores at the lumbar spine and femoral neck were evaluated at baseline, and after 5, 10 and 15 years of rhGH replacement. In addition, clinical fracture incidence was assessed. Mean lumbar spine BMD, lumbar spine BMC and T-scores gradually increased during the first 10 years of rhGH replacement and remained stable thereafter. Largest effects of rhGH supplementation were found in men. In the small subset of patients using bisphosphonates, use of bisphosphonates did not impact additional beneficial effects in the long term. Low baseline BMD positively affected the change in BMD and BMC over time, but there was a negative effect of high GH dose at 1 year on the change in BMD and BMC over time. Clinical fracture incidence during long-term rhGH replacement was 20.1/1000 py. Fifteen years of rhGH replacement in GHD adults resulted in a sustained increase in BMD values at the lumbar spine, particularly in men, and stabilization of BMD values at the femoral neck. Clinical fracture incidence was suggested not to be increased during long-term rhGH replacement. © 2014 John Wiley & Sons Ltd.

  20. Hypophysectomy eliminates and growth hormone (GH) maintains the midpregnancy elevation in GH receptor and serum binding protein in the mouse

    International Nuclear Information System (INIS)

    Sanchez-Jimenez, F.; Fielder, P.J.; Martinez, R.R.; Smith, W.C.; Talamantes, F.

    1990-01-01

    [ 125 I]Iodomouse GH [( 125 I]iodo-mGH) binding to samples of serum and hepatic microsomal membranes was measured in hypophysectomized pregnant, sham-operated pregnant, intact pregnant, and intact adult virgin mice. Surgeries were carried out on day 11 of pregnancy, and the animals were killed on day 14. The binding of mGH to both serum and hepatic microsomal membranes of intact virgin mice was much lower than to those of intact pregnant mice. In hypophysectomized mice, the mGH-binding capacity of both serum and hepatic microsomes decreased to values similar to those of nonpregnant mice. No significant differences were observed between intact and sham-operated pregnant animals in the maternal serum mGH concentration, the serum GH-binding protein concentration, or the hepatic GH receptor concentration. GH receptor and binding protein-encoding mRNAs were also higher in intact and sham-operated pregnant mice than in virgin and hypophysectomized mice. Hypophysectomized mice were treated with 200 micrograms/day bovine GH, administered by osmotic minipump; after 3 days of treatment, a significant elevation of hepatic GH receptor and serum GH-binding protein levels was observed. These results demonstrate an up-regulation of hepatic GH receptors and serum GH-binding protein by GH during pregnancy in the mouse

  1. Growth hormone (GH) treatment increases serum insulin-like growth factor binding protein-3, bone isoenzyme alkaline phosphatase and forearm bone mineral content in young adults with GH deficiency of childhood onset

    DEFF Research Database (Denmark)

    Juul, A; Pedersen, S A; Sørensen, S

    1994-01-01

    Recent studies have demonstrated that growth hormone (GH)-deficient adults have a markedly decreased bone mineral content compared to healthy adults. However, there are conflicting results regarding the effects of GH treatment on bone mineral content in GH-deficient adults. Therefore, we evaluated...... the effect of GH treatment on a marker of bone formation (bone alkaline phosphatase), hepatic excretory function and distal forearm bone mineral content in GH-deficient adults. Growth hormone was administered subcutaneously in 21 adults (13 males and 8 females) with GH deficiency of childhood onset for 4...

  2. Continuous infusion versus daily injections of growth hormone (GH) for 4 weeks in GH-deficient patients

    DEFF Research Database (Denmark)

    Laursen, Torben; Jørgensen, Jens Otto Lunde; Jakobsen, Grethe

    1995-01-01

    effects with constant and pulsatile GH delivery. This study was carried out to compare the metabolic effects of longer term continuous infusion vs. daily injections of GH. Thirteen GH-deficient patients were studied in a cross-over design. The patients were randomized to receive GH as a continuous sc...... infusion by means of a portable pump for 1 month and as daily sc injections (at 1900 h) for another month. An average daily GH dosage (+/- SEM) of 3.15 +/- 0.27 IU was administered during both periods. Steady state 24-h profiles of GH, IGF-I, IGF-binding proteins (IGFBPs), insulin, glucose, lipid.......35 (infusion); P infusion induced higher nighttime than daytime GH levels (P = 0.01), indicating a diurnal variation in the absorption or clearance of GH. Serum IGF-I levels (micrograms per L) were slightly higher (P infusion [312...

  3. Hormonal causes of male sexual dysfunctions and their management (hyperprolactinemia, thyroid disorders, GH disorders, and DHEA).

    Science.gov (United States)

    Maggi, Mario; Buvat, Jaques; Corona, Giovanni; Guay, André; Torres, Luiz Otavio

    2013-03-01

    Besides hypogonadism, other endocrine disorders have been associated with male sexual dysfunction (MSD). To review the role of the pituitary hormone prolactin (PRL), growth hormone (GH), thyroid hormones, and adrenal androgens in MSD. A systematic search of published evidence was performed using Medline (1969 to September 2011). Oxford Centre for Evidence-Based Medicine-Levels of Evidence (March 2009) was applied when possible. The most important evidence regarding the role played by PRL, GH, thyroid, and adrenal hormone was reviewed and discussed. Only severe hyperprolactinemia (>35 ng/mL or 735 mU/L), often related to a pituitary tumor, has a negative impact on sexual function, impairing sexual desire, testosterone production, and, through the latter, erectile function due to a dual effect: mass effect and PRL-induced suppression on gonadotropin secretion. The latter is PRL-level dependent. Emerging evidence indicates that hyperthyroidism is associated with an increased risk of premature ejaculation and might also be associated with erectile dysfunction (ED), whereas hypothyroidism mainly affects sexual desire and impairs the ejaculatory reflex. However, the real incidence of thyroid dysfunction in subjects with sexual problems needs to be evaluated. Prevalence of ED and decreased libido increase in acromegalic patients; however, it is still a matter of debate whether GH excess (acromegaly) may create effects due to a direct overproduction of GH/insulin-like growth factor 1 or because of the pituitary mass effects on gonadotropic cells, resulting in hypogonadism. Finally, although dehydroepiandrosterone (DHEA) and its sulfate have been implicated in a broad range of biological derangements, controlled trials have shown that DHEA administration is not useful for improving male sexual function. While the association between hyperprolactinemia and hypoactive sexual desire is well defined, more studies are needed to completely understand the role of other hormones in

  4. Long-term effects of growth hormone (GH) replacement in men with childhood-onset GH deficiency

    NARCIS (Netherlands)

    ter Maaten, JC; De Boer, H; Kamp, O; Stuurman, L; Van der Veen, EA

    Short term GH replacement therapy has been shown to improve body composition and exercise capacity. It is not yet known whether GH replacement remains beneficial over the long term. We assessed the effects of long term GH replacement on body composition, bone mineral density, and cardiac function.

  5. Growth hormone (GH) differentially regulates NF-kB activity in preadipocytes and macrophages: implications for GH's role in adipose tissue homeostasis in obesity.

    Science.gov (United States)

    Kumar, P Anil; Chitra, P Swathi; Lu, Chunxia; Sobhanaditya, J; Menon, Ram

    2014-06-01

    Adipose tissue remodeling in obesity involves macrophage infiltration and chronic inflammation. NF-kB-mediated chronic inflammation of the adipose tissue is directly implicated in obesity-associated insulin resistance. We have investigated the effect of growth hormone (GH) on NF-kB activity in preadipocytes (3T3-F442A) and macrophages (J774A.1). Our studies indicate that whereas GH increases NF-kB activity in preadipocytes, it decreases NF-kB activity in macrophages. This differential response of NF-kB activity to GH correlates with the GH-dependent expression of a cadre of NF-kB-activated cytokines in these two cell types. Activation of NF-kB by GH in preadipocytes heightens inflammatory response by stimulating production of multiple cytokines including TNF-α, IL-6, and MCP-1, the mediators of both local and systemic insulin resistance and chemokines that recruit macrophages. Our studies also suggest differential regulation of miR132 and SIRT1 expression as a mechanism underlying the observed variance in GH-dependent NF-kB activity and altered cytokine profile in preadipocytes and macrophages. These findings further our understanding of the complex actions of GH on adipocytes and insulin sensitivity.

  6. Inhibition of rat pituitary growth hormone (GH) release by subclinical levels of lead

    International Nuclear Information System (INIS)

    Camoratto, A.M.; White, L.M.; Lau, Y.S.; Moriarty, C.M.

    1990-01-01

    Lead toxicity has been associated with short stature in children. Since growth hormone is a major regulator of growth, the effects of chronic exposure to subclinical lead levels on pituitary function were assessed. Timed pregnant rats were given 125 ppm lead (as lead nitrate) in their drinking water beginning on day 5 of gestation. After weaning, pups were continued on lead until sacrifice at 7 weeks of age. The average blood lead level at this time was 18.9 ug/dl (range 13.7-27.8). On the day of sacrifice the pituitary was removed, hemisected and incubated with vehicle or 40 nM hGRH (human growth hormone releasing hormone). Pituitaries from chronically lead-treated pups were 64% less responsive to GRH than controls. In contrast, no difference in responsiveness was observed in pituitaries from the dams. The specific binding of GRH was also examined. Control animals showed a dose-dependent displacement of 125I-GRH by unlabeled ligand (10-1000 nM). In the pituitaries of lead-treated pups binding of labeled ligand was markedly reduced by unlabeled GRH (less than 100 nM). Chronic exposure to lead had no effect on serum GH or prolactin levels or on pituitary content of GH. These data suggest that one mechanism by which lead can affect growth is by inhibition of GH release

  7. Effects of a 7-day continuous infusion of octreotide on circulating levels of growth factors and binding proteins in growth hormone (GH)-treated GH-deficient patients

    DEFF Research Database (Denmark)

    Laursen, Torben; Møller, Jens; Fisker, Sanne

    1999-01-01

    Abstract In patients with acromegaly, clinical improvement has been reported after octreotide (OCT) treatment, even in cases of only a moderate suppression of growth hormone (GH) levels. In rats, OCT suppresses IGF-I mRNA expression and generation of serum and tissue IGF-I levels. A direct effect...

  8. A novel variant of growth hormone (GH) insufficiency following low dose cranial irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Crowne, E.C.; Moore, C.; Wallace, W.H.B.; Ogilvy-Stuart, A.L.; Addison, G.M.; Morris-Jones, P.H.; Shalet, S.M. (Christie Hospital, Manchester (United Kingdom) Royal Manchester Children' s Hospital (United Kingdom))

    1992-01-01

    We aimed to investigate the effect of low dose (1800 cGy) prophylactic cranial irradiation on physiological growth hormone secretion. Forty-four children were studied, of whom 21 were long-term survivors of acute lymphoblastic leukaemia and 23 were normal children. In the normal children, there was a significant increase in the median (range) area under the curve (AUC) of the GH profile between the prepubertal and pubertal groups. There was also a change in the spectral analysis through puberty. The dominant frequencies were spread widely in the prepubertal and post-pubertal groups but sharply focused in the pubertal group. In the cranially irradiated children there was no significant increase in AUC between the prepubertal and pubertal groups. The wide range of dominant frequencies persisted in the pubertal cranially irradiated group due to the presence of additional high frequency pulses. The impression of a disturbance of the periodicity of GH secretion in the cranially irradiated pubertal group was further supported by the finding that the autocorrelation function in this group alone was not significantly different from that which would arise from random data. A novel form of GH insufficiency has been observed after low dose irradiation in childhood in which an abnormality of periodicity and a quantitative reduction in GH secretion appears restricted to puberty. (author).

  9. Editorial Foreword: Comments on "Growth hormone (GH-releasing hormone and GH secretagogues in normal aging" || FREE PAPER ||

    Directory of Open Access Journals (Sweden)

    Richard F Walker

    2008-03-01

    Full Text Available Richard F WalkerInternational Society for Applied Research in Aging (SARAThis issue of Clinical Interventions in Aging contains a quite interesting and informative article about a topic that is popular and also controversial among practitioners of age-management medicine. Appropriate to that controversy, Drs Hersch and Merriam (2008 have asked the question in the title of their paper, does the use of growth hormone secretagogues in age management medicine hold the promise of a fountain of youth, or that of a pool of Tantalus? While there is universal understanding of the fountain imagery, the meaning of the pool is perhaps less obvious. It derives, of course, from the Greek myth of Tantalus, who had both a hidden, divine sire and a mortal one. As the son of Zeus, he was uniquely favored among mortals and was invited to share the food of the gods. However, driven by pride, he shared the divine ambrosia with other mortals, and thus aroused the ire of the gods. As punishment, he was made to stand chin-deep in water with a variety of sweet-smelling and delicious fruit dangling just over his head. However, whenever he tried to drink or eat, the water would magically recede or the fruit would miraculously be lifted just out of his reach. Thus, it is that torment, through which something seems to be offered only to be withdrawn again, that has been called “tantalizing” in memory of its best known victim.

  10. Growth hormone (GH) treatment increases serum insulin-like growth factor binding protein-3, bone isoenzyme alkaline phosphatase and forearm bone mineral content in young adults with GH deficiency of childhood onset

    DEFF Research Database (Denmark)

    Juul, A; Pedersen, S A; Sørensen, S

    1994-01-01

    Recent studies have demonstrated that growth hormone (GH)-deficient adults have a markedly decreased bone mineral content compared to healthy adults. However, there are conflicting results regarding the effects of GH treatment on bone mineral content in GH-deficient adults. Therefore, we evaluated...... the effect of GH treatment on a marker of bone formation (bone alkaline phosphatase), hepatic excretory function and distal forearm bone mineral content in GH-deficient adults. Growth hormone was administered subcutaneously in 21 adults (13 males and 8 females) with GH deficiency of childhood onset for 4...... months in a double-blind, placebo-controlled GH trial, while 13 of the patients then received further GH for an additional 14 months. Serum insulin-like growth factor I (IGF-I) increased significantly from 100 to 279 micrograms/l and IGF binding protein-3 (IGFBP-3) from 1930 to 3355 micrograms/l after 4...

  11. Mutation of the SHP-2 binding site in growth hormone (GH) receptor prolongs GH-promoted tyrosyl phosphorylation of GH receptor, JAK2, and STAT5B

    DEFF Research Database (Denmark)

    Stofega, M R; Herrington, J; Billestrup, Nils

    2000-01-01

    phosphorylation. Consistent with the effects on STAT5B phosphorylation, tyrosine-to-phenylalanine mutation of tyrosine 595 prolongs the duration of tyrosyl phosphorylation of GHR and JAK2. These data suggest that tyrosine 595 is a major site of interaction of GHR with SHP-2, and that GHR-bound SHP-2 negatively......Binding of GH to GH receptor (GHR) rapidly and transiently activates multiple signal transduction pathways that contribute to the growth-promoting and metabolic effects of GH. While the events that initiate GH signal transduction, such as activation of the Janus tyrosine kinase JAK2, are beginning...

  12. GH Responsiveness to Combined GH-Releasing Hormone and Arginine Administration in Obese Patients with Fibromyalgia Syndrome.

    Science.gov (United States)

    Rigamonti, Antonello E; Grugni, Graziano; Arreghini, Marco; Capodaglio, Paolo; De Col, Alessandra; Agosti, Fiorenza; Sartorio, Alessandro

    2017-01-01

    Reportedly, fibromyalgia (FM) is frequently associated with reduced IGF-1 levels and GH hyporesponsiveness to different GH stimulation tests. Since there is a high prevalence of obesity in FM, and obesity itself is characterized by hyposomatotropism, the aim of this study was to assess IGF-1 levels and GH responsiveness in sixteen severely obese women suffering from FM, who, subdivided into two subgroups on the basis of their age-dependent IGF-1 values (> or BMI than that with normal IGF-1 SDS. GH peak and area under the curve were not correlated with CRP, ESR, or tender point score, while significant correlations were found with fat-free mass and fat mass. In conclusion, this study shows the existence of a high prevalence of GH-IGF-1 dysfunction in patients with both FM and obesity, presumably as a consequence of the obese rather than fibromyalgic condition.

  13. A single amino acid substitution in the exoplasmic domain of the human growth hormone (GH) receptor confers familial GH resistance (Laron syndrome) with positive GH-binding activity by abolishing receptor homodimerization.

    Science.gov (United States)

    Duquesnoy, P; Sobrier, M L; Duriez, B; Dastot, F; Buchanan, C R; Savage, M O; Preece, M A; Craescu, C T; Blouquit, Y; Goossens, M

    1994-01-01

    Growth hormone (GH) elicits a variety of biological activities mainly mediated by the GH receptor (GHR), a transmembrane protein that, based on in vitro studies, seemed to function as a homodimer. To test this hypothesis directly, we investigated patients displaying the classic features of Laron syndrome (familial GH resistance characterized by severe dwarfism and metabolic dysfunction), except for the presence of normal binding activity of the plasma GH-binding protein, a molecule that derives from the exoplasmic-coding domain of the GHR gene. In two unrelated families, the same GHR mutation was identified, resulting in the substitution of a highly conserved aspartate residue by histidine at position 152 (D152H) of the exoplasmic domain, within the postulated interface sequence involved in homodimerization. The recombinant mutated receptor protein was correctly expressed at the plasma membrane. It displayed subnormal GH-binding activity, a finding in agreement with the X-ray crystal structure data inferring this aspartate residue outside the GH-binding domain. However, mAb-based studies suggested the critical role of aspartate 152 in the proper folding of the interface area. We show that a recombinant soluble form of the mutant receptor is unable to dimerize, the D152H substitution also preventing the formation of heterodimers of wild-type and mutant molecules. These results provide in vivo evidence that monomeric receptors are inactive and that receptor dimerization is involved in the primary signalling of the GH-associated growth-promoting and metabolic actions. Images PMID:8137822

  14. GH Responsiveness to Combined GH-Releasing Hormone and Arginine Administration in Obese Patients with Fibromyalgia Syndrome

    Directory of Open Access Journals (Sweden)

    Antonello E. Rigamonti

    2017-01-01

    Full Text Available Reportedly, fibromyalgia (FM is frequently associated with reduced IGF-1 levels and GH hyporesponsiveness to different GH stimulation tests. Since there is a high prevalence of obesity in FM, and obesity itself is characterized by hyposomatotropism, the aim of this study was to assess IGF-1 levels and GH responsiveness in sixteen severely obese women suffering from FM, who, subdivided into two subgroups on the basis of their age-dependent IGF-1 values (> or <−2 SDS, underwent the combined GHRH plus arginine test. Four out of 16 obese women with FM (25% had low IGF-1 SDS values, 2 cases of this subgroup (12.5% failing also to normally respond to the test. Among patients with normal GH responses, 4 showed a delayed GH peak. The subgroup with low IGF-1 SDS values had higher BMI than that with normal IGF-1 SDS. GH peak and area under the curve were not correlated with CRP, ESR, or tender point score, while significant correlations were found with fat-free mass and fat mass. In conclusion, this study shows the existence of a high prevalence of GH-IGF-1 dysfunction in patients with both FM and obesity, presumably as a consequence of the obese rather than fibromyalgic condition.

  15. Effects of growth hormone (GH) administration on homocyst(e)ine levels in men with GH deficiency: a randomized controlled trial.

    Science.gov (United States)

    Sesmilo, G; Biller, B M; Llevadot, J; Hayden, D; Hanson, G; Rifai, N; Klibanski, A

    2001-04-01

    GH deficiency is associated with increased cardiovascular mortality and early manifestations of atherosclerosis. Elevated serum homocyst(e)ine levels have been found to be associated with increased cardiovascular risk. The effect of GH replacement on homocyst(e)ine has not been investigated to date. We evaluated the effect of GH replacement on fasting homocyst(e)inemia in a group of men with adult-onset GH deficiency in a randomized, single blind, placebo-controlled trial. Forty men with adult-onset GH deficiency were randomized to GH or placebo for 18 months, with dose adjustments made according to serum insulin-like growth factor I (IGF-I) levels. Fasting serum homocyst(e)ine, folate, vitamin B12, and total T(3) levels were determined at baseline and 6 and 18 months. Anthropometry, IGF-I levels, insulin, and glucose were measured at 1, 3, 6, 12, and 18 months. Nutritional assessment, body composition, total T(4), thyroid hormone binding index, and free T(4) index were assessed every 6 months. Homocyst(e)ine decreased in the GH-treated group compared with that in the placebo group (net difference, -1.2 +/- 0.6 micromol/L; confidence interval, -2.4, -0.02 micromol/L; P = 0.047). Homocyst(e)ine at baseline was negatively correlated with plasma levels of folate (r = -0.41; P = 0.0087). Total T(3) increased in the GH-treated group vs. that in the placebo group (net difference, 0.17 +/- 0.046 ng/dL; confidence interval, 0.071, 0.26 nmol/L; P = 0.0012). Folate and vitamin B12 levels did not significantly change between groups. Changes in homocyst(e)ine were negatively correlated with changes in IGF-I. For each 1 nmol/L increase in IGF-I, homocyst(e)ine decreased by 0.04 +/- 0.02 micromol/L (P = 0.029). In contrast, changes in homocyst(e)ine did not correlate with changes in folate, vitamin B12, total T(3), C-reactive protein, interleukin-6, or insulin levels. This study shows that GH replacement decreases fasting homocyst(e)ine levels compared with placebo. This may be

  16. Early growth hormone (GH) treatment promotes relevant motor functional improvement after severe frontal cortex lesion in adult rats.

    Science.gov (United States)

    Heredia, Margarita; Fuente, A; Criado, J; Yajeya, J; Devesa, J; Riolobos, A S

    2013-06-15

    A number of studies, in animals and humans, describe the positive effects of the growth hormone (GH) treatment combined with rehabilitation on brain reparation after brain injury. We examined the effect of GH treatment and rehabilitation in adult rats with severe frontal motor cortex ablation. Thirty-five male rats were trained in the paw-reaching-for-food task and the preferred forelimb was recorded. Under anesthesia, the motor cortex contralateral to the preferred forelimb was aspirated or sham-operated. Animals were then treated with GH (0.15 mg/kg/day, s.c) or vehicle during 5 days, commencing immediately or 6 days post-lesion. Rehabilitation was applied at short- and long-term after GH treatment. Behavioral data were analized by ANOVA following Bonferroni post hoc test. After sacrifice, immunohistochemical detection of glial fibrillary acid protein (GFAP) and nestin were undertaken in the brain of all groups. Animal group treated with GH immediately after the lesion, but not any other group, showed a significant improvement of the motor impairment induced by the motor lesion, and their performances in the motor test were no different from sham-operated controls. GFAP immunolabeling and nestin immunoreactivity were observed in the perilesional area in all injured animals; nestin immunoreactivity was higher in GH-treated injured rats (mainly in animals GH-treated 6 days post-lesion). GFAP immunoreactivity was similar among injured rats. Interestingly, nestin re-expression was detected in the contralateral undamaged motor cortex only in GH-treated injured rats, being higher in animals GH-treated immediately after the lesion than in animals GH-treated 6 days post-lesion. Early GH treatment induces significant recovery of the motor impairment produced by frontal cortical ablation. GH effects include increased neurogenesis for reparation (perilesional area) and for increased brain plasticity (contralateral motor area). Copyright © 2013 Elsevier B.V. All rights

  17. Second messenger production in avian medullary nephron segments in response to peptide hormones.

    Science.gov (United States)

    Goldstein, D L; Reddy, V; Plaga, K

    1999-03-01

    We examined the sites of peptide hormone activation within medullary nephron segments of the house sparrow (Passer domesticus) kidney by measuring rates of hormone-induced generation of cyclic nucleotide second messenger. Thin descending limbs, thick ascending limbs, and collecting ducts had baseline activity of adenylyl cyclase that resulted in cAMP accumulation of 207 +/- 56, 147 +/- 31, and 151 +/- 41 fmol. mm-1. 30 min-1, respectively. In all segments, this activity increased 10- to 20-fold in response to forskolin. Activity of adenylyl cyclase in the thin descending limb was stimulated approximately twofold by parathyroid hormone (PTH) but not by any of the other hormones tested [arginine vasotocin (AVT), glucagon, atrial natriuretic peptide (ANP), or isoproterenol, each at 10(-6) M]. Thick ascending limb was stimulated two- to threefold by both AVT and PTH; however, glucagon and isoproterenol had no effect, and ANP stimulated neither cAMP nor cGMP accumulation. Adenylyl cyclase activity in the collecting duct was stimulated fourfold by AVT but not by the other hormones; likewise, ANP did not stimulate cGMP accumulation in this segment. These data support a tubular action of AVT and PTH in the avian renal medulla.

  18. Single nucleotide polymorphism of the growth hormone (GH encoding gene in inbred and outbred domestic rabbits

    Directory of Open Access Journals (Sweden)

    Deyana Gencheva Hristova

    2018-03-01

    Full Text Available Taking into consideration that the growth hormone (GH gene in rabbits is a candidate for meat production, understanding the genetic diversity and variation in this locus is of particular relevance. The present study comprised 86 rabbits (Oryctolagus cuniculus divided into 3 groups: New Zealand White (NZW outbred rabbits; first-generation inbred rabbits (F1 and second-generation inbred rabbits (F2. They were analysed by polymerase chain reaction-based restriction fragment length polymorphism method. A 231 bp fragment of the polymorphic site of the GH gene was digested with Bsh1236 restriction enzyme. Single nucleotide polymorphisms for the studied GH locus corresponding to 3 genotypes were detected in the studied rabbit populations: CC, CT and TT. In the synthetic inbred F1 and F2 populations, the frequency of the heterozygous genotype CT was 0.696 and 0.609, respectively, while for the homozygous CC genotype the frequency was lower (0.043 and 0.000, and respective values for the homozygous TT genotype were 0.261 and 0.391. This presumed a preponderance of the T allele (0.609 and 0.696 over the C allele (0.391 and 0.304 in these groups. In outbred rabbits, the allele frequencies were 0.613 (allele C and 0.387 (allele Т; consequently, the frequency of the homozygous CC genotype was higher than that of the homozygous TT genotype (0.300 vs. 0.075. Observed heterozygosity for the GH gene was higher than expected, and the result was therefore a negative inbreeding coefficient (Fis=–0.317 for outbred NZW rabbits; –0.460 for inbred F1 and –0.438 for inbred F2, indicating a sufficient number of heterozygous forms in all studied groups of rabbits. The application of narrow inbreeding by breeding full sibs in the synthetic population did not cause a rapid increase in homozygosity.

  19. Type I and III procollagen propeptides in growth hormone-deficient patients: effects of increasing doses of GH

    DEFF Research Database (Denmark)

    Jensen, L T; Jørgensen, J O; Risteli, J

    1991-01-01

    The effect of increasing doses of growth hormone on collagen synthesis in GH-treated GH-deficient patients was determined in a short-term study. The synthesis of type I and III collagen was estimated by measurements of the carboxyterminal propeptide of type I procollagen and the aminoterminal...... procollagen propeptide increased twice as much as type I procollagen propeptide, by 47 vs 25%, at a GH dose of 6 IU/day compared with 2 IU/day. The differences between the effects on type I and type III collagen may reflect differences in secretion or turn-over rate of collagen in bone and loose connective...

  20. Parentally-adjusted deficit of height as a prognostic factor of the effectiveness of growth hormone (GH) therapy in children with GH deficiency.

    Science.gov (United States)

    Hilczer, Maciej; Smyczyńska, Joanna; Lewiński, Andrzej

    2006-01-01

    Parental height is the most important identifiable factor influencing final height (FH) of children with growth hormone (GH) deficiency (GHD), treated with GH. Assessment of FH of patients with GHD--classified into familial short stature (FSS) and non-familial short stature (non-FSS) according to parentally adjusted deficit of height. The analysis comprised 101 patients (76 boys) with childhood-onset GHD. Final height was compared with patients' height before GH therapy, predicted adult height (PAH) and target height (TH). Both GH peak in stimulating tests and height standard deviation score (SDS) before the therapy were significantly lower in non-FSS than in FSS. Target height was significantly lower in FSS than in non-FSS. Parentally-adjusted deficit of height was significantly more profound in non-FSS than in FSS. The prognosis of adult height was very similar in both groups of patients, being significantly worse in non-FSS than in FSS while corrected by TH. The absolute FH was similar in FSS and non-FSS, being, however, significantly lower in non-FSS than in FSS while corrected by TH. Improvement of height was significantly better in non-FSS than in FSS. In both groups, FH SDS was significantly better than height SDS before the therapy (H0SDS). In FSS group, PAH was similar to TH, moreover, FH corresponded to both PAH and TH. In non-FSS group FH was significantly higher than PAH, but both FH and PAH were significantly lower than TH. 1) Growth hormone therapy was more effective in the patients with non-FSS than in those with FSS. 2) Parentally-adjusted deficit of height is an important prognostic factor of GH therapy effectiveness.

  1. Bioavailability and bioactivity of three different doses of nasal growth hormone (GH) administered to GH-deficient patients

    DEFF Research Database (Denmark)

    Laursen, Torben; Grandjean, Birgitte; Jørgensen, Jens Otto Lunde

    1996-01-01

    different occasions. On three occasions GH was administered intranasally in doses of 0.05, 0.10 and 0.20 IU/kg, using didecanoyl-L-alpha-phosphatidylcholine as an enhancer. On the other two occasions the patients received an sc injection (0.10 IU/kg) and an i.v. injection (0.015 IU/kg) of GH, respectively....... The absolute bioavailability of GH following s.c. relative to i.v. administration was 49.5%. The bioavailabilities of the nasal doses were: 7.8% (0.05 IU). 8.9% (0.10 IU) and 3.8% (0.20 IU). Serum insulin-like growth factor I (IGF-I) levels increased significantly after s.c. administration only. Mean levels...... of the i.v. (p insulin and blood glucose (p

  2. Changes in bone mineral density, body composition, and lipid metabolism during growth hormone (GH) treatment in children with GH deficiency

    NARCIS (Netherlands)

    A.M. Boot (Annemieke); M.A. Engels (Melanie); G.J.M. Boerma (Geert); E.P. Krenning (Eric); S.M.P.F. de Muinck Keizer-Schrama (Sabine)

    1997-01-01

    textabstractAdults with childhood onset GH deficiency (GHD) have reduced bone mass, increased fat mass, and disorders of lipid metabolism. The aim of the present study was to evaluate bone mineral density (BMD), bone metabolism, body composition, and lipid metabolism in

  3. The growth hormone (GH)-insulin-like growth factor axis during testosterone replacement therapy in GH-treated hypopituitary males

    DEFF Research Database (Denmark)

    Fisker, Sidse; Nørrelund, Helene; Juul, A

    2001-01-01

    in relation to two testosterone injections. Mean baseline IGF-I levels were 352 +/- 135 microg/L, and they remained unaltered during the study period (analysis of variance (ANOVA), P = 0.88). Free IGF-I levels did not change either (ANOVA, P = 0.35). Serum IGF binding protein-3 (IGFBP-3) and acid......-labile subunit decreased (ANOVA, P = 0.04 and P = 0.02 respectively) but post hoc analysis did not reveal a particular difference between days. IGFBP-1 increased following testosterone administration (ANOVA, P = 0.05), whereas GH binding protein levels tended to decrease following testosterone administration...... (ANOVA, P = 0.08). Prostate-specific antigen tended slightly to increase after each testosterone injection (ANOVA, P = 0.08, post hoc, NS). We conclude that major changes in total IGF-I are not induced during conventional intramuscular testosterone replacement in GH-treated hypopituitary males...

  4. A study on the serum growth hormone (GH) and insulin levels in patients with coronary heart disease

    International Nuclear Information System (INIS)

    Zhang Zhiwei; Ji Naijun; Mei Yibin; Chen Donghai; Tong Lijun; Fan Bifu; Wang Chengyao; Li Fuyuan

    2005-01-01

    Objective: To explore the clinical significance of the changes of serum growth hormone (GH) and insulin (IS) levels in patients with coronary heart disease (CHD). Methods: Serum GH and IS levels were determined with RIA in 120 patients with CHD and 50 controls. Results: The serum levels of GH in patients with CHD (127.16 ± 37.9 pmol/L) were significantly lower than those in controls (152.0 ± 41.2 pmol/L) (t=3.819, P 0.05). In patients complicated with heart failure, the serum GH levels were significantly lower than those in patients without heart failure (P 0.05). The serum IS levels were significantly higher in patients developing myocardial infarction than those in patients without this complication (P 0.05). In the patients succumbed in the hospital, both serum GH and IS levels were significantly lower than those in the patients finally recovered (P<0.05). Conclusion: In this study, serum GH levels were much lower in CHD patients. Whatever explanation of this finding is at best speculative and further study is mandatory. (authors)

  5. Growth hormone dose regimens in adult GH deficiency: effects on biochemical growth markers and metabolic parameters

    DEFF Research Database (Denmark)

    Møller, Jens; Jørgensen, Jens Otto Lunde; Laursen, Torben

    1993-01-01

    Abstract OBJECTIVE: We examined the effects of different doses of GH on insulin-like growth factor I (IGF-I), IGF binding protein 3 (IGFBP-3), body composition, energy expenditure, and various metabolites in GH deficient adults, in order to approach a metabolically appropriate GH dosage in young GH......-I in an age and sex matched control group was 248 +/- 25 micrograms/l. Corresponding serum IGFBP-3 levels also increased from 1860 +/- 239 to 3261 +/- 379, 3762 +/- 434 and 4384 +/- 652 micrograms/l (P = 0.01) respectively. Significant increases in diurnal serum insulin levels after 4 IU/m2 were recorded......, whereas plasma glucose levels remained unchanged. Lipid intermediates increased dose independently during GH administration. GH caused a significant increase in resting energy expenditure, whereas the respiratory exchange ratio was unaltered. Fat mass was increased without GH therapy and decreased during...

  6. Urinary growth hormone (U-GH) excretion and serum insulin-like growth factor 1 (IGF-1) in patients with alcoholic cirrhosis

    DEFF Research Database (Denmark)

    Møller, S; Grønbaek, M; Main, K

    1993-01-01

    was significantly higher in patients than in the healthy controls (p liver function assessed by modified Child-Turcotte score (p encephalopathy (p ...Basal serum growth hormone (GH) levels are elevated and insulin-like growth factor 1 (IGF-1) concentrations in serum are suppressed in patients with chronic liver disease. The aim of this study was to measure the urinary GH (U-GH) excretion and IGF-1 concentrations in patients with cirrhosis...... and correlated with liver function (p

  7. Excessive growth hormone expression in male GH transgenic mice adversely alters bone architecture and mechanical strength.

    Science.gov (United States)

    Lim, S V; Marenzana, M; Hopkinson, M; List, E O; Kopchick, J J; Pereira, M; Javaheri, B; Roux, J P; Chavassieux, P; Korbonits, M; Chenu, C

    2015-04-01

    Patients with acromegaly have a higher prevalence of vertebral fractures despite normal bone mineral density (BMD), suggesting that GH overexpression has adverse effects on skeletal architecture and strength. We used giant bovine GH (bGH) transgenic mice to analyze the effects of high serum GH levels on BMD, architecture, and mechanical strength. Five-month-old hemizygous male bGH mice were compared with age- and sex-matched nontransgenic littermates controls (NT; n=16/group). Bone architecture and BMD were analyzed in tibia and lumbar vertebrae using microcomputed tomography. Femora were tested to failure using three-point bending and bone cellular activity determined by bone histomorphometry. bGH transgenic mice displayed significant increases in body weight and bone lengths. bGH tibia showed decreases in trabecular bone volume fraction, thickness, and number compared with NT ones, whereas trabecular pattern factor and structure model index were significantly increased, indicating deterioration in bone structure. Although cortical tissue perimeter was increased in transgenic mice, cortical thickness was reduced. bGH mice showed similar trabecular BMD but reduced trabecular thickness in lumbar vertebra relative to controls. Cortical BMD and thickness were significantly reduced in bGH lumbar vertebra. Mechanical testing of femora confirmed that bGH femora have decreased intrinsic mechanical properties compared with NT ones. Bone turnover is increased in favor of bone resorption in bGH tibia and vertebra compared with controls, and serum PTH levels is also enhanced in bGH mice. These data collectively suggest that high serum GH levels negatively affect bone architecture and quality at multiple skeletal sites.

  8. 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, ...

  9. Reduction of free fatty acids by acipimox enhances the growth hormone (GH) responses to GH-releasing peptide 2 in elderly men

    NARCIS (Netherlands)

    Smid, HEC; de Vries, WR; Niesink, M; Bolscher, E; Waasdorp, EJ; Dieguez, C; Casanueva, FF; Koppeschaar, HPF

    2000-01-01

    GH release is increased by reducing circulating free fatty acids (FFAs). Aging is associated with decreased plasma GH concentrations. We evaluated GH releasing capacity in nine healthy elderly men after administration of GH-releasing peptide 2 (GHRP-2), with or without pretreatment with the

  10. The dwarf phenotype in GH240B mice, haploinsufficient for the autism candidate gene Neurobeachin, is caused by ectopic expression of recombinant human growth hormone.

    Science.gov (United States)

    Nuytens, Kim; Tuand, Krizia; Fu, Quili; Stijnen, Pieter; Pruniau, Vincent; Meulemans, Sandra; Vankelecom, Hugo; Creemers, John W M

    2014-01-01

    Two knockout mouse models for the autism candidate gene Neurobeachin (Nbea) have been generated independently. Although both models have similar phenotypes, one striking difference is the dwarf phenotype observed in the heterozygous configuration of the GH240B model that is generated by the serendipitous insertion of a promoterless human growth hormone (hGH) genomic fragment in the Nbea gene. In order to elucidate this discrepancy, the dwarfism present in this Nbea mouse model was investigated in detail. The growth deficiency in Nbea+/- mice coincided with an increased percentage of fat mass and a decrease in bone mineral density. Low but detectable levels of hGH were detected in the pituitary and hypothalamus of Nbea+/- mice but not in liver, hippocampus nor in serum. As a consequence, several members of the mouse growth hormone (mGH) signaling cascade showed altered mRNA levels, including a reduction in growth hormone-releasing hormone mRNA in the hypothalamus. Moreover, somatotrope cells were less numerous in the pituitary of Nbea+/- mice and both contained and secreted significantly less mGH resulting in reduced levels of circulating insulin-like growth factor 1. These findings demonstrate that the random integration of the hGH transgene in this mouse model has not only inactivated Nbea but has also resulted in the tissue-specific expression of hGH causing a negative feedback loop, mGH hyposecretion and dwarfism.

  11. The dwarf phenotype in GH240B mice, haploinsufficient for the autism candidate gene Neurobeachin, is caused by ectopic expression of recombinant human growth hormone.

    Directory of Open Access Journals (Sweden)

    Kim Nuytens

    Full Text Available Two knockout mouse models for the autism candidate gene Neurobeachin (Nbea have been generated independently. Although both models have similar phenotypes, one striking difference is the dwarf phenotype observed in the heterozygous configuration of the GH240B model that is generated by the serendipitous insertion of a promoterless human growth hormone (hGH genomic fragment in the Nbea gene. In order to elucidate this discrepancy, the dwarfism present in this Nbea mouse model was investigated in detail. The growth deficiency in Nbea+/- mice coincided with an increased percentage of fat mass and a decrease in bone mineral density. Low but detectable levels of hGH were detected in the pituitary and hypothalamus of Nbea+/- mice but not in liver, hippocampus nor in serum. As a consequence, several members of the mouse growth hormone (mGH signaling cascade showed altered mRNA levels, including a reduction in growth hormone-releasing hormone mRNA in the hypothalamus. Moreover, somatotrope cells were less numerous in the pituitary of Nbea+/- mice and both contained and secreted significantly less mGH resulting in reduced levels of circulating insulin-like growth factor 1. These findings demonstrate that the random integration of the hGH transgene in this mouse model has not only inactivated Nbea but has also resulted in the tissue-specific expression of hGH causing a negative feedback loop, mGH hyposecretion and dwarfism.

  12. Human metastatic melanoma cell lines express high levels of growth hormone receptor and respond to GH treatment

    Energy Technology Data Exchange (ETDEWEB)

    Sustarsic, Elahu G. [Edison Biotechnology Institute, 1 Watertower Drive, Athens, OH (United States); Department of Biological Sciences, Ohio University, Athens, OH (United States); Junnila, Riia K. [Edison Biotechnology Institute, 1 Watertower Drive, Athens, OH (United States); Kopchick, John J., E-mail: kopchick@ohio.edu [Edison Biotechnology Institute, 1 Watertower Drive, Athens, OH (United States); Department of Biological Sciences, Ohio University, Athens, OH (United States); Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH (United States)

    2013-11-08

    Highlights: •Most cancer types of the NCI60 have sub-sets of cell lines with high GHR expression. •GHR is highly expressed in melanoma cell lines. •GHR is elevated in advanced stage IV metastatic tumors vs. stage III. •GH treatment of metastatic melanoma cell lines alters growth and cell signaling. -- Abstract: Accumulating evidence implicates the growth hormone receptor (GHR) in carcinogenesis. While multiple studies show evidence for expression of growth hormone (GH) and GHR mRNA in human cancer tissue, there is a lack of quantification and only a few cancer types have been investigated. The National Cancer Institute’s NCI60 panel includes 60 cancer cell lines from nine types of human cancer: breast, CNS, colon, leukemia, melanoma, non-small cell lung, ovarian, prostate and renal. We utilized this panel to quantify expression of GHR, GH, prolactin receptor (PRLR) and prolactin (PRL) mRNA with real-time RT qPCR. Both GHR and PRLR show a broad range of expression within and among most cancer types. Strikingly, GHR expression is nearly 50-fold higher in melanoma than in the panel as a whole. Analysis of human metastatic melanoma biopsies confirmed GHR gene expression in melanoma tissue. In these human biopsies, the level of GHR mRNA is elevated in advanced stage IV tumor samples compared to stage III. Due to the novel finding of high GHR in melanoma, we examined the effect of GH treatment on three NCI60 melanoma lines (MDA-MB-435, UACC-62 and SK-MEL-5). GH increased proliferation in two out of three cell lines tested. Further analysis revealed GH-induced activation of STAT5 and mTOR in a cell line dependent manner. In conclusion, we have identified cell lines and cancer types that are ideal to study the role of GH and PRL in cancer, yet have been largely overlooked. Furthermore, we found that human metastatic melanoma tumors express GHR and cell lines possess active GHRs that can modulate multiple signaling pathways and alter cell proliferation. Based on

  13. Synthesis and in vitro and in vivo activity of analogs of growth hormone-releasing hormone (GH-RH) with C-terminal agmatine.

    Science.gov (United States)

    Zarandi, M; Csernus, V; Bokser, L; Bajusz, S; Groot, K; Schally, A V

    1990-12-01

    In the search for more active analogs of human growth hormone-releasing hormone (GH-RH), 37 new compounds were synthesized by solid phase methodology, purified, and tested biologically. Most of the analogs contained a sequence of 27 amino acids and N-terminal desaminotyrosine (Dat) and C-terminal agmatine (Agm), which are not amino acids. In addition to Dat in position 1 and Agm in position 29, the majority of the analogs had Ala15 and Nle27 substitutions and one or more additional L- or D-amino acid modifications. [Dat1, Ala15, Nle27]GH-RH(1-28)Agm (MZ-2-51) was the most active analog. Its in vitro GH-releasing potency was 10.5 times higher than that of GH-RH(1-29)NH2 and in the i.v. in vivo assay, MZ-2-51 was 4-5 times more active than the standard. After s.c. administration to rats. MZ-2-51 showed an activity 34 times higher at 15 min and 179 times greater at 30 min than GH-RH(1-29)NH2 and also displayed a prolonged activity. D-Tyr10, D-Lys12, and D-Lys21 homologs of MZ-2-51 also showed enhanced activities. Thus, [Dat1, D-Tyr10, Ala15, Nle27]GH-RH(1-28)Agm (MZ-2-159), [Dat1, D-Lys12, Ala15, Nle27]GH-RH(1-28)AGM (MZ-2-57), and [Dat1, Ala15, D-Lys21, Nle27]GH-RH(1-28)Agm (MZ-2-75) were 4-6 times more active in vitro than GH-RH(1-29)NH2. In vivo, after i.v. administration, analog MZ-2-75 was equipotent and analogs MZ-2-159 and MZ-2-57 about twice as potent as the standard.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Isolated growth hormone deficiency in two siblings because of paternal mosaicism for a mutation in the GH1 gene.

    Science.gov (United States)

    Tsubahara, Mayuko; Hayashi, Yoshitaka; Niijima, Shin-ichi; Yamamoto, Michiyo; Kamijo, Takashi; Murata, Yoshiharu; Haruna, Hidenori; Okumura, Akihisa; Shimizu, Toshiaki

    2012-03-01

      Mutations in the GH1 gene have been identified in patients with isolated growth hormone deficiency (IGHD). Mutations causing aberrant splicing of exon 3 of GH1 that have been identified in IGHD are inherited in an autosomal dominant manner, whereas other mutations in GH1 that have been identified in IGHD are inherited in an autosomal recessive manner.   Two siblings born from nonconsanguineous healthy parents exhibited IGHD. To elucidate the cause, GH1 in all family members was analysed.   Two novel mutations in GH1, a point mutation in intron 3 and a 16-bp deletion in exon 3, were identified by sequence analyses. The intronic mutation was present in both siblings and was predicted to cause aberrant splicing. The deletion was present in one of the siblings as well as the mother with normal stature and was predicted to cause rapid degradation of mRNA through nonsense-mediated mRNA decay. The point mutation was not identified in the parents' peripheral blood DNA; however, it was detected in the DNA extracted from the father's sperms. As a trace of the mutant allele was detected in the peripheral blood of the father using PCR-RFLP, the mutation is likely to have occurred de novo at an early developmental stage before differentiation of somatic cells and germline cells.   This is the first report of mosaicism for a mutation in GH1 in a family with IGHD. It is clear that the intronic mutation plays a dominant role in the pathogenesis of IGHD in this family, as one of the siblings who had only the point mutation was affected. On the other hand, the other sibling was a compound heterozygote for the point mutation and the 16-bp deletion and it may be arguable whether IGHD in this patient should be regarded as autosomal dominant or recessive. © 2012 Blackwell Publishing Ltd.

  15. Bioavailability and bioactivity of intravenous vs subcutaneous infusion of growth hormone in GH-deficient patients

    DEFF Research Database (Denmark)

    Laursen, Torben; Møller, Jens; Ørskov, Hans

    1996-01-01

    Abstract OBJECTIVE: The bioavailability of GH immunoreactive serum concentrations is reduced following subcutaneous (s.c.) as compared with intravenous (i.v.) administration. Whether this difference also translates into a different biological activity remains to be investigated. The aim of the pr......Abstract OBJECTIVE: The bioavailability of GH immunoreactive serum concentrations is reduced following subcutaneous (s.c.) as compared with intravenous (i.v.) administration. Whether this difference also translates into a different biological activity remains to be investigated. The aim...... = 0.09) were observed on the two occasions. CONCLUSIONS: A reduced bioavailability of s.c. as compared with i.v. administered GH has been recorded with two independent GH assays, and this was also accompanied by a significant, albeit modest, reduction in biological activity....

  16. Adherence in children with growth hormone deficiency treated with r-hGH and the easypod™ device.

    Science.gov (United States)

    Loche, S; Salerno, M; Garofalo, P; Cardinale, G M; Licenziati, M R; Citro, G; Caruso Nicoletti, M; Cappa, M; Longobardi, S; Maghnie, M; Perrone, R

    2016-12-01

    Poor adherence to recombinant human growth hormone (r-hGH) therapy is associated with reduced growth velocity in children with growth hormone deficiency (GHD). This twelve-month observational study was to assess adherence in r-hGH patients treated with the easypod ™ , an electronic, fully automated injection device designed to track the time, date and dose administered. Ninety-seven prepubertal patients receiving r-hGH therapy were included in the study from ten Italian clinical sites and 88 completed the study. To avoid possible confounding effects, only GHD patients (79/88; 89.7 % of the overall study population) were considered in the final analysis. The primary endpoint-adherence to treatment-was calculated as the proportion of injections correctly administered during the observational period out of the expected total number of injections. The relevant information, tracked by the easypod ™ , was collected at months 6 (V1) and 12 (V2) after baseline (V0). At study termination, adherence data were partially available from 16 patients and fully available from 53 patients. As secondary endpoints, serum IGF-1 levels, fasting serum glucose and insulin levels and key anthropometric characteristics (height, waist circumference and BMI) were also determined. The easypod ™ data showed that 56.7 % of the patients were considered to be fully (≥92 %) adherent to their treatment throughout the period V0-V2. Treatment improved stature, significantly increased IGF-1 and produced a non-significant increase in blood glucose and insulin levels. The injection-recording system and other characteristics of easypod ™ could enhance the ability of physicians to monitor adherence to r-hGH treatment.

  17. Is further evaluation for growth hormone (GH) deficiency necessary in fibromyalgia patients with low serum insulin-like growth factor (IGF)-I levels?

    Science.gov (United States)

    Yuen, Kevin C J; Bennett, Robert M; Hryciw, Cheryl A; Cook, Marie B; Rhoads, Sharon A; Cook, David M

    2007-02-01

    Fibromyalgia (FM) is characterized by diffuse pain, fatigue, and sleep disturbances; symptoms that resemble the adult growth hormone (GH) deficiency syndrome. Many FM patients have low serum GH levels, with a hypothesized aetiology of dysregulated GH/insulin-like growth factor (IGF)-I axis. The aim of this study was to assess the GH reserve in FM patients with low serum IGF-I levels using the GH-releasing hormone (GHRH)-arginine test. We retrospectively reviewed the GHRH-arginine data of 77 FM patients with low serum IGF-I levels referred to our tertiary unit over a 4-year period. Of the 77 FM patients, 13 patients (17%) failed the GHRH-arginine test. Further evaluation with pituitary imaging revealed normal pituitary glands (n=7), coincident microadenomas (n=4), empty sella (n=1) and pituitary cyst (n=1), and relevant medical histories such as previous head injury (n=4), Sheehan's syndrome (n=1), and whiplash injury (n=1). In contrast, the remaining 64 patients (83%) that responded to the GHRH-arginine test demonstrated higher peak GH levels compared to age and BMI-matched controls (n=24). Our data shows that a subpopulation of FM patients with low serum IGF-I levels will fail the GHRH-arginine test. We, thus, recommend that the GH reserve of these patients should be evaluated further, as GH replacement may potentially improve the symptomatology of those with true GH deficiency. Additionally, the increased GH response rates to GHRH-arginine stimulation in the majority of FM patients with low serum IGF-I levels further supports the hypothesis of a dysregulated GH/IGF-I axis in the pathophysiology of FM.

  18. Transcription elongation factors are involved in programming hormone production in pituitary neuroendocrine GH4C1 cells.

    Science.gov (United States)

    Fujita, Toshitsugu; Piuz, Isabelle; Schlegel, Werner

    2010-05-05

    Transcription elongation of many eukaryotic genes is regulated. Two negative transcription elongation factors, 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) sensitivity-inducing factor (DSIF) and negative elongation factor (NELF) are known to stall collaboratively RNA polymerase II promoter proximally. We discovered that DSIF and NELF are linked to hormone expression in rat pituitary GH4C1 cells. When NELF-E, a subunit of NELF or Spt5, a subunit of DSIF was stably knocked-down, prolactin (PRL) expression was increased both at the mRNA and protein levels. In contrast, stable knock-down of only Spt5 abolished growth hormone (GH) expression. Transient NELF-E knock-down increased coincidentally PRL expression and enhanced transcription of a PRL-promoter reporter gene. However, no direct interaction of NELF with the PRL gene could be demonstrated by chromatin immuno-precipitation. Thus, NELF suppressed PRL promoter activity indirectly. In conclusion, transcription regulation by NELF and DSIF is continuously involved in the control of hormone production and may contribute to neuroendocrine cell differentiation. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  19. The Dwarfs of Sindh: severe growth hormone (GH) deficiency caused by a mutation in the GH-releasing hormone receptor gene.

    Science.gov (United States)

    Baumann, G; Maheshwari, H

    1997-11-01

    We report the discovery of a cluster of severe familial dwarfism in two villages in the Province of Sindh in Pakistan. Dwarfism is proportionate and occurs in members of a kindred with a high degree of consanguinity. Only the last generation is affected, with the oldest dwarf being 28 years old. The mode of inheritance is autosomal recessive. Phenotype analysis and endocrine testing revealed isolated growth hormone deficiency (GHD) as the reason for growth failure. Linkage analysis for the loci of several candidate genes yielded a high lod score for the growth hormone-releasing hormone receptor (GHRH-R) locus on chromosome 7. Amplification and sequencing of the GHRH-R gene in affected subjects demonstrated an amber nonsense mutation (GAG-->TAG; Glu50-->Stop) in exon 3. The mutation, in its homozygous form, segregated 100% with the dwarf phenotype. It predicts a truncation of the GHRH-R in its extracellular domain, which is likely to result in a severely disabled or non-existent receptor protein. Subjects who are heterozygous for the mutation show mild biochemical abnormalities in the growth hormone-releasing hormone (GHRH)--growth hormone--insulin-like growth factor axis, but have only minimal or no growth retardation. The occurrence of an offspring of two dwarfed parents indicates that the GHRH-R is not necessary for fertility in either sex. We conclude that Sindh dwarfism is caused by an inactivating mutation in the GHRH-R gene, resulting in the inability to transmit a GHRH signal and consequent severe isolated GHD.

  20. Do IGF-I concentrations better reflect growth hormone (GH action in children with short stature than the results of GH stimulating tests? Evidence from the simultaneous assessment of thyroid function

    Directory of Open Access Journals (Sweden)

    Smyczyńska Joanna

    2011-01-01

    Full Text Available Abstract Background The diagnosis of growth hormone (GH deficiency (GHD in short children seems unquestionable when both GH peak in stimulating tests (GHST and IGF-I concentration are decreased. However, the discrepancies between the results of GHST and IGF-I secretion are observed. It seems purposeful to determine the significance of GHST and IGF-I assessment in diagnosing GHD. The relationship between GH secretion and thyroid function, as well as GH influence on the peripheral thyroxine (T4 to triiodothyronine (T3 deiodination, mediated by IGF-I, were identified. Thus, clear differences in thyroid function between GH-deficient and non-GH-deficient subjects should exist. Methods Analysis comprised 800 children (541 boys, age 11.6 ± 3.1 years (mean ± SD, with short stature, in whom two (2 standard GHST (with clonidine and with glucagon were performed and IGF-I, free T4 (FT4, free T3 (FT3 and TSH serum concentrations were assessed. The patients were qualified to the following groups: GHD - decreased GH peak in GHST and IGF-I SDS (n = 81, ISS - normal GH peak and IGF-I SDS (n = 347, low GH - normal IGF-I SDS, and decreased GH peak (n = 212, low IGF - decreased IGF-I SDS, and normal GH peak (n = 160. The relationships among the results of particular tests were evaluated. Results In the groups with decreased IGF-I concentrations (GHD Group and low IGF Group, the more severe deficit of height was observed, together with higher TSH and FT4 but lower FT3 levels than in groups with normal IGF-I concentrations (ISS Group and low GH Group, independently of the results of GHST. TSH, FT4 and FT3 concentrations were - respectively - similar in two groups with decreased IGF-I secretion, as well as in two groups with normal IGF-I levels. Significant correlations were found between patients' height SDS and IGF-I SDS, between FT3 and IGF-I SDS (positive, and between FT4 and IGF-I SDS (negative, with no correlation between GH peak and any of the parameters

  1. Effects of short-term glucocorticoid deprivation on growth hormone (GH) response to GH-releasing peptide-6: Studies in normal men and in patients with adrenal insufficiency

    OpenAIRE

    Pinto, Ana Claudia de Assis Rocha [UNIFESP; Dias-da-Silva, Magnus Régios [UNIFESP; Martins, Manoel R. [UNIFESP; Brunner, Elisa [UNIFESP; Lengyel, Ana Maria Judith [UNIFESP

    2000-01-01

    There are no data in the literature about the effects of glucocorticoid deprivation on GH-releasing peptide-g (GHRP-6)-induced GH release. the aims of this study were to evaluate GH responsiveness to GHRP-6 1) after metyrapone administration in normal men, and 2) in patients with chronic hypocortisolism after glucocorticoid withdrawal for 72 h. in normal subjects, metyrapone ingestion did not alter significantly GH responsiveness to GHRP-6 [n = 8; peak, 39.3 +/- 7.1 mu g/L; area under the cur...

  2. The Long Intron 1 of Growth Hormone Gene from Reeves’ Turtle (Chinemys reevesii Correlates with Negatively Regulated GH Expression in Four Cell Lines

    Directory of Open Access Journals (Sweden)

    Wen-Sheng Liu

    2016-04-01

    Full Text Available Turtles grow slowly and have a long lifespan. Ultrastructural studies of the pituitary gland in Reeves’ turtle (Chinemys reevesii have revealed that the species possesses a higher nucleoplasmic ratio and fewer secretory granules in growth hormone (GH cells than other animal species in summer and winter. C. reevesii GH gene was cloned and species-specific similarities and differences were investigated. The full GH gene sequence in C. reevesii contains 8517 base pairs (bp, comprising five exons and four introns. Intron 1 was found to be much longer in C. reevesii than in other species. The coding sequence (CDS of the turtle’s GH gene, with and without the inclusion of intron 1, was transfected into four cell lines, including DF-1 chicken embryo fibroblasts, Chinese hamster ovary (CHO cells, human embryonic kidney 293FT cells, and GH4C1 rat pituitary cells; the turtle growth hormone (tGH gene mRNA and protein expression levels decreased significantly in the intron-containing CDS in these cell lines, compared with that of the corresponding intronless CDS. Thus, the long intron 1 of GH gene in Reeves’ turtle might correlate with downregulated gene expression.

  3. 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

    -nonylphenol, 4-octylphenol), pesticides (prochloraz, iprodion, chlorpyrifos), PCB metabolites (OH-PCB 106, OH-PCB 121, OH-PCB 69) and brominated flame-retardants (tetrabromobisphenol A). The ED potential of a chemical was determined by its effect on the cell proliferation of TH-dependent rat pituitary GH3 cell...

  4. Keragaman Genetik Gen Hormon Pertumbuhan (GH|MboII pada Itik Sikumbang Janti Menggunakan Penciri PCR-RFLP

    Directory of Open Access Journals (Sweden)

    T.D. Nova

    2016-02-01

    Full Text Available Penelitian ini bertujuan untuk mengetahui keragaman gen hormon pertumbuhan (GH dengan enzim MboII pada itik Sikumbang Janti dengan menggunakan penciri PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism. Penelitian ini menggunakan sebanyak 50 sampel darah itik Sikumbang Janti. Sampel darah itik Sikumbang Janti diambil melalui vena achilaris sebanyak ± 1 ml. DNA sampel darah diisolasi menggunakan protocol Genomik DNA Purification Kit (Promega. DNA total diamplifikasi menggunakan sepasang primer F : 5’-CTG GAG CAG GCA GGA AAA TT-3’ dan R: 5’-TCC AGG GAC AGT GAC TCA AC-3’ yang menghasilkan fragmen exon 1 gen GH dengan panjang 801 bp. Produk amplifikasi direstriksi dengan menggunakan MboII yang mengenali situs pemotongan GAAGA (N/8↓ . Dari 46 sampel hasil restriksi diperoleh dua posisi. Pada posisi 618 bp dengan genotip yaitu genotip heterozigot (+/- yang terdiri dari 3 pita (266 bp, 535 bp dan 801 bp, genotip homozigot (+/+ yang terdiri dari 3 pita (109 bp, 266 bp, 426 bp dan genotip homozigot (-/- yang terdiri dari 1 pita ( 801 dan terdapat dua tipe alel, yaitu alel (+ dan all (-, all (+ sebesar 0,79 dan alel (- sebesar 0,21. Sedangkan pada posisi 727 bp memiliki genotip yaitu genotip heterozigot (+/- yang terdiri dari 3 pita (109 bp, 266 bp, 426 bp, dan genotip homozigot (-/- yang terdiri dari 3 pita dan terdapat dua tipe alel, yaitu frekuensi alel (+ sebesar 0,61 dan frekuensi alel (- sebesar 0,39. Dari hasil penelitian ini dapat disimpulkan bahwa gen GH-MboII memiliki keragamanan yang tinggi serta menunjukkan adanya keseimbangan atau tidak menyimpang dari keseimbangan Hardy Weinberg pada posisi keragaman 618 bp dan pada posisi 727 dalam ketidakseimbangan Hardy Weinberg.

  5. 64 kDa protein is a candidate for a thyrotropin-releasing hormone receptor in prolactin-producing rat pituitary tumor cells (GH4C1 cells)

    International Nuclear Information System (INIS)

    Wright, M.; Hogset, A.; Alestrom, P.; Gautvik, K.M.

    1988-01-01

    A thyrotropin-releasing hormone (TRH) binding protein of 64 kDa has been identified by covalently crosslinking [ 3 H]TRH to GH4C1 cells by ultraviolet illumination. The crosslinkage of [ 3 H]TRH is UV-dose dependent and is inhibited by an excess of unlabeled TRH. A 64 kDa protein is also detected on immunoblots using an antiserum raised against GH4C1 cell surface epitopes. In a closely related cell line (GH12C1) which does not bind [ 3 H]TRH, the 64 kDa protein cannot be demonstrated by [ 3 H]TRH crosslinking nor by immunoblotting. These findings indicate that the 64 kDa protein is a candidate for a TRH-receptor protein in GH4C1 cells

  6. The effects of GH and hormone replacement therapy on serum concentrations of mannan-binding lectin, surfactant protein D and vitamin D binding protein in Turner syndrome

    DEFF Research Database (Denmark)

    Gravholt, Claus Højbjerg; Leth-Larsen, Rikke; Lauridsen, Anna Lis

    2004-01-01

    function. In the present study we examined whether GH or hormone replacement therapy (HRT) in Turner syndrome (TS) influence the serum concentrations of MBL and two other proteins partaking in the innate immune defence, surfactant protein D (SP-D) and vitamin D binding protein (DBP). DESIGN: Study 1...

  7. Impact of recombinant human growth hormone (rh-GH treatment on psychiatric, neuropsychological and clinical profiles of GH deficient adults: a placebo - controlled trial Impacto do tratamento com hormônio de crescimento recombinante (rh-GH sobre as características psiquiátricas, neuropsicológicas e clínicas de adultos com deficiência de GH: ensaio clínico duplo-cego controlado com placebo

    Directory of Open Access Journals (Sweden)

    CLÁUDIO DE NOVAES SOARES

    1999-06-01

    Full Text Available BACKGROUND: Untreated GH-deficient adults have a diversity of dysfunctions (e.g. reduced muscle strength, emotional instability during stress, depressive symptoms that may cause deleterious effects on quality of life, and may be positively influenced by recombinant human growth hormone (rh-GH therapy. AIM: To evaluate the impact of a clinical intervention with rh-GH therapy on GH - deficient adults. METHOD: The physical, psychiatric and neuropsychological status of 9 GH-deficient adults was determined before and after the administration of rh-GH (0.250 IU/Kg/week in a double blind placebo-controlled trial for six months. Patients then received rh-GH for a further period of 6 months and their status was re-evaluated. RESULTS: Rh-GH was significant better than placebo at 6th month (pINTRODUÇÃO: Pacientes com deficiência de hormônio de crescimento (GH apresentam diversas alterações clínicas (ex: redução de massa muscular e de função cardíaca e psíquicas (ex: quadros fóbicos, sintomas depressivos, déficits cognitivos. OBJETIVO: Avaliar o impacto da terapêutica com rh-GH em adultos com deficiência de GH. MÉTODO: Nove pacientes foram diagnosticados com deficiência de GH e então submetidos a ensaio clínico, duplo-cego, controlado, recebendo rh-GH (0,250UI/Kg/semana ou placebo, por período de 6 meses. RESULTADOS: Houve melhora significativa (p<0,05 em parâmetros clínicos ( aumento de massa muscular, redução do índice de massa corpórea (BMI, aumento de gasto energético, psiquiátricos (sintomas depressivos avaliados pelas escalas de Beck e Hamilton (p= 0,043 e neuropsicológicos (testes de atenção (p= 0,035, fluência verbal (FAS: p= 0,02, além da melhora de eficiência cognitiva (testes do WAIS-R: vocabulário (p= 0,027 , Arranjo de Figuras (p= 0,017, Compreensão (p= 0,01 . CONCLUSÃO: Prejuízos clínicos, psíquicos e neuropsicológicos causados pela deficiência de GH em adultos podem ser reduzidos pela terap

  8. Carbohydrate metabolism during long-term growth hormone (GH) treatment and after discontinuation of GH treatment in girls with Turner syndrome participating in a randomized dose-response study. Dutch Advisory Group on Growth Hormone

    NARCIS (Netherlands)

    T.C.J. Sas (Theo); S.M.P.F. de Muinck Keizer-Schrama (Sabine); Th. Stijnen (Theo); H-J. Aanstoot (Henk-Jan); S.L.S. Drop (Stenvert)

    2000-01-01

    textabstractTo assess possible side-effects of GH treatment with supraphysiological doses on carbohydrate (CH) metabolism in girls with Turner syndrome (TS) during long term GH treatment and after discontinuation of GH treatment, the results of oral glucose tolerance

  9. Continuous 24-hour intravenous infusion of recombinant human growth hormone (GH)-releasing hormone-(1-44)-amide augments pulsatile, entropic, and daily rhythmic GH secretion in postmenopausal women equally in the estrogen-withdrawn and estrogen-supplemented states.

    Science.gov (United States)

    Evans, W S; Anderson, S M; Hull, L T; Azimi, P P; Bowers, C Y; Veldhuis, J D

    2001-02-01

    How estrogen amplifies GH secretion in the human is not known. The present study tests the clinical hypothesis that estradiol modulates the stimulatory actions of a primary GH feedforward signal, GHRH. To this end, we investigated the ability of short-term (7- to 12-day) supplementation with oral estradiol vs. placebo to modulate basal, pulsatile, entropic, and 24-h rhythmic GH secretion driven by a continuous iv infusion of recombinant human GHRH-(1--44)-amide vs. saline in nine healthy postmenopausal women. Volunteers underwent concurrent blood sampling every 10 min for 24 h on four occasions in a prospectively randomized, single blind, within-subject cross-over design (placebo/saline, placebo/GHRH, estradiol/saline, estradiol/GHRH). Intensively sampled serum GH concentrations were quantitated by ultrasensitive chemiluminescence assay. Basal, pulsatile, entropic (feedback-sensitive), and 24-h rhythmic modes of GH secretion were appraised by deconvolution analysis, the approximate entropy (ApEn) statistic, and cosine regression, respectively. ANOVA revealed that continuous iv infusion of GHRH in the estrogen-withdrawn (control) milieu 1) amplified individual basal (P = 0.00011) and pulsatile (P < 10(-13)) GH secretion rates by 12- and 11-fold, respectively; 2) augmented GH secretory burst mass and amplitude each by 10-fold (P < 10(-11)), without altering GH secretory burst frequency, duration, or half-life; 3) increased the disorderliness (ApEn) of GH release patterns (P = 0.0000002); 4) elevated the mesor (cosine mean) and amplitude of the 24-h rhythm in serum GH concentrations by nearly 30-fold (both P < 10(-12)); 5) induced a phase advance in the clocktime of the GH zenith (P = 0.021); and 6) evoked a new 24-h rhythm in GH secretory burst mass with a maximum at 0018 h GH (P < 10(-3)), while damping the mesor of the 24-h rhythm in GH interpulse intervals (P < 0.025). Estradiol supplementation alone 1) increased the 24-h mean and integrated serum GH concentration

  10. Histamine-induced paradoxical GH response to TRH/GnRH in men and women: dependence on gonadal steroid hormones

    DEFF Research Database (Denmark)

    Knigge, U; Thuesen, B; Dejgaard, A

    1990-01-01

    .025), but not during the early follicular phase of the cycle (GH peak: 1.7 +/- 0.5 vs 1.6 +/- 0.3 micrograms/l). In luteal-phase women the GH response to TRH/GnRH correlated with the serum estradiol-17 beta level (GH area/E2: r = 0.98; p less than 0.005) and the serum estrone level (GH area/E1: r = 0.81; p less than 0...

  11. Distinct cytoplasmic domains of the growth hormone receptor are required for glucocorticoid- and phorbol ester-induced decreases in growth hormone (GH) binding. These domains are different from that reported for GH-induced receptor internalization

    DEFF Research Database (Denmark)

    King, A P; Tseng, M J; Logsdon, C D

    1996-01-01

    Glucocorticoids inhibit growth in children and antagonize the growth-promoting action of GH in peripheral tissues. Recently, they have been shown to decrease GH binding. In this study we examine the molecular mechanisms by which the glucocorticoid dexamethasone (DEX) and the phorbol ester phorbol...... of GH binding are also observed in a Chinese hamster ovary (CHO) cell line stably transfected with a rat liver GHR cDNA, further arguing that DEX and PMA act post-translationally on GHR. Using mutant GHRs stably expressed in CHO cells, amino acids 455-506 and tyrosines 333 and/or 338 of GHR were shown...... to be required for maximal DEX-induced inhibition of GH binding. DEX decreased GH binding to a GHR mutant F346A, which is reported to be deficient in ligand-induced internalization, suggesting that DEX decreases GH binding by a mechanism distinct from that of ligand-induced GHR internalization. PMA reduced GH...

  12. Jointly Amplified Basal and Pulsatile Growth Hormone (GH) Secretion and Increased Process Irregularity in Women with Anorexia Nervosa

    DEFF Research Database (Denmark)

    Støving, R K; Veldhuis, J D; Flyvbjerg, A

    1999-01-01

    Anorexia nervosa (AN) is associated with multiple endocrine alterations. In the majority of AN patients, basal and GHRH-stimulated serum GH levels are increased. The metabolic effects of GH are known to be related to its pulsatile secretory pattern. The present study was performed to examine GH...

  13. Growth hormone (GH) effects on bone and collagen turnover in healthy adults and its potential as a marker of GH abuse in sports: a double blind, placebo-controlled study. The GH-2000 Study Group.

    Science.gov (United States)

    Longobardi, S; Keay, N; Ehrnborg, C; Cittadini, A; Rosén, T; Dall, R; Boroujerdi, M A; Bassett, E E; Healy, M L; Pentecost, C; Wallace, J D; Powrie, J; Jørgensen, J O; Saccà, L

    2000-04-01

    The effects of GH on bone remodeling in healthy adults have not been systematically investigated. An analysis of these effects might provide insights into GH physiology and might yield data useful for the detection of GH doping in sports. The aim of this study was to evaluate the effects of GH administration on biochemical markers of bone and collagen turnover in healthy volunteers. Ninety-nine healthy volunteers of both sexes were enrolled in a multicenter, randomized, double blind, placebo-controlled study and assigned to receive either placebo (40 subjects) or recombinant human GH (0.1 IU/kg day in 29 subjects and 0.2 IU/kg x day in 30 subjects). The treatment duration was 28 days, followed by a 56-day wash-out period. The biochemical markers evaluated were the bone formation markers osteocalcin and C-terminal propeptide of type I procollagen, the resorption marker type I collagen telopeptide, and the soft tissue marker procollagen type III. All variables increased on days 21 and 28 in the two active treatment groups vs. levels in both the baseline (P < 0.01) and placebo (P < 0.01) groups. The increment was more pronounced in the 0.2 IU/kg-day group and remained significant on day 84 for procollagen type III (from 0.53 +/- 0.13 to 0.61 +/- 0.14 kU/L; P < 0.02) and osteocalcin (from 12.2 + 2.9 to 14.6 +/- 3.6 UG/L; P < 0.02), whereas levels of C-terminal propeptide of type I procollagen and type I collagen telopeptide declined after day 42 and were no longer significantly above baseline on day 84 (from 3.9 +/- 1.2 to 5.1 +/-1.5 microg/L and from 174 +/- 60 to 173 +/- 53 microg/L, respectively). Gender-related differences were observed in the study; females were less responsive than males to GH administration with respect to procollagen type III and type I collagen telopeptide (P < 0.001). In conclusion, exogenous GH administration affects the biochemical parameters of bone and collagen turnover in a dose- and gender-dependent manner. As GH-induced modifications

  14. Examination of Growth Hormone (GH) Gene Polymorphism and its Association with Body Weight and Selected Body Dimensions in Ducks.

    Science.gov (United States)

    Mazurowski, Artur; Frieske, Anna; Kokoszynski, Dariusz; Mroczkowski, Sławomir; Bernacki, Zenon; Wilkanowska, Anna

    2015-01-01

    The main objective of the study was to assess the polymorphism in intron 2 of the GH gene and its association with some morphological traits (body weight--BW, length of trunk with neck--LTN, length of trunk--LT, chest girth--CG, length of breast bone--LBB, length of shank--LS). Polymorphism in intron 2 of the GH gene was evaluated for four duck populations (Pekin ducks AF51, Muscovy ducks from a CK and CRAMMLCFF mother and Mulard ducks). Genetic polymorphism was determined with the PCR-RFLP method using the BsmFI restriction enzyme. In the studied duck sample two alleles (GH(C) and GH(T)) and three genotypes (GH/TT, GH/CT, GH/CC) were found at locus GH/BsmFI. In both groups of Muscovies and in Mulards the dominant allele was GH(T). On the contrary in Pekin ducks AF51, the frequency of both alleles was found to be similar. The most frequent genotype in the examined ducks was GH/TT. In Pekin ducks AF51 three genotypes were observed, while in Mulard ducks and in male Muscovy ducks from a mother marked as CK, two genotypes (GH/TT and GH/CT) were identified. Muscovy duck females from a CK mother and all males and females of Muscovy duck from a CRAMMLCFF mother were monomorphic with only the GH/TTgenotype detected. The results showed that males of Pekin duck AF51 with the GH/TT genotype were characterized by higher (P ducks AF51, this same trend was observed; individuals with GH/TT genotype were superior (P ducks with the GH/TT genotype were distinguished by higher values of all evaluated traits compared to ducks with GH/CT and GH/CC genotypes, however most of the recorded differences were not significant. The only trait markedly impacted (P < 0.05) by the polymorphism of the GH gene intron 2 was the LS value in males.

  15. Effects of polybrominated diphenyl ethers (PBDEs) and their derivatives on protein disulfide isomerase activity and growth hormone release of GH3 cells.

    Science.gov (United States)

    Hashimoto, Shoko; Yoshimura, Hiromi; Okada, Kazushi; Uramaru, Naoto; Sugihara, Kazumi; Kitamura, Shigeyuki; Imaoka, Susumu

    2012-03-19

    Polybrominated diphenyl ethers (PBDEs) have been used in a variety of consumer products such as flame retardants and recently have been known to be widespread environmental pollutants, which probably affect biological functions of mammalian cells. However, the risk posed by PBDE metabolites has not been clarified. Our previous study suggested that bisphenol A (BPA), an endocrine-disrupting chemical, binds to protein disulfide isomerase (PDI) and inhibits its activity. PDI is an isomerase enzyme in the endoplasmic reticulum and facilitates the formation or cleavage of disulfide bonds. PDI consists of a, b, b', and a' domains and the c region, with the a and a' domains having isomerase active sites. In the present study, we tested the effects of 10 kinds of PBDE compounds and their metabolites on PDI. OH-PBDEs specifically inhibited the isomerase activity of PDI, with 4'-OH-PBDE more effective than 2' (or 2)-OH-PBDEs. 4'-OH-PBDE inhibited the isomerase activity of the b'a'c fragment but not that of ab and a'c, suggesting that the b' domain of PDI is essential for the inhibition by 4'-OH-PBDE. We also investigated the effects of these chemicals on the production of growth hormone (GH) in GH3 cells. In GH3 cells, levels of mRNA and protein of GH stimulated by T(3) were reduced by 4'-OH-PBDE and 4'-MeO-PBDE. The reduction in GH expression caused by these compounds was not changed by the overexpression or knockdown of PDI in GH3 cells, while these manipulations of PDI levels significantly suppressed the expression of GH. These results suggest that the biological effects of PBDEs differed depending on their brominated and hydroxylated positions. © 2011 American Chemical Society

  16. Growth and Growth hormone - Insulin Like Growth Factor -I (GH-IGF-I) Axis in Chronic Anemias.

    Science.gov (United States)

    Soliman, Ashraf T; De Sanctis, Vincenzo; Yassin, Mohamed; Adel, Ashraf

    2017-04-28

    Anaemia is a global public health problem affecting both developing and developed countries with major consequences for human health as well as social and economic development. It occurs at all stages of the life cycle, but is more prevalent in pregnant women and young children. Iron deficiency anaemia (IDA) was considered to be among the most important contributing factors to the global burden of disease. Prolonged and/or chronic anemia has a negative effect on linear growth especially during the rapid phases (infancy and puberty). Additionally infants with chronic IDA have delayed cognitive, motor, and affective development that may be long-lasting. In view of the significant impact of chronic anemias on growth, pediatricians endocrinologists and hematologists should advocate primary prevention and screening for growth disturbance in these forms of anemias. The extent of the negative effect of different forms of chronic anemias on linear growth and its possible reversibilty is addressed in this review. The possible mechanisms that may impair growth in the different forms of anemias are addressed with special attention to their effect on the growth hormone (GH) - insulin like growth factor -I (IGF-I).

  17. Chronic alcohol consumption, type 2 diabetes mellitus, insulin-like growth factor-I (IGF-I), and growth hormone (GH) in ethanol-treated diabetic rats.

    Science.gov (United States)

    Kim, Soo-Jeong; Ju, Anes; Lim, Seul-Gi; Kim, Dai-Jin

    2013-11-13

    Alcohol has deleterious influences on glucose metabolism which may contribute to the development of type 2 diabetes mellitus (T2DM). Insulin-like growth factor I (IGF-I) and growth hormone (GH), which interact with insulin to modulate metabolic control, have been shown to be related to impaired glucose tolerance. This study was conducted to assess the possibility that altered circulating IGF-I and GH levels contribute to the exacerbation of T2DM by alcohol use in type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats and non-diabetic Long-Evans Tokushima Otsuka (LETO) rats. OLETF rats were pair-fed a Lieber-DeCarli Regular Ethanol diet and LETO rats were pair-fed a control diet for 6 weeks. At 6 weeks, an Intraperitoneal Glucose Tolerance Test (IP-GTT) was performed and IGF-I and GH levels were evaluated. Prior to an IP-GTT, OLETF-Ethanol (O-E) group had significantly a decrease in the mean glucose levels compared to OLETF-Control (O-C) group. At 120 min post IP-GTT, the O-E group had significantly an increase in the mean glucose levels compared to O-C group. The serum IGF-I levels were significantly lower and the serum GH levels were significantly higher in the O-E group than in L-C group. These results suggest that IGF-I and GH are prominent in defining the risk and development of T2DM, and may be adversely affected by heavy alcohol use, possibly mediating its diabetogenic effects. Thus, the overall glucose intolerance in the setting of alcoholism may be attributable to inappropriate alteration of IGF-I and GH levels. © 2013. Published by Elsevier Inc. All rights reserved.

  18. Human metastatic melanoma cell lines express high levels of growth hormone receptor and respond to GH treatment

    DEFF Research Database (Denmark)

    Sustarsic, Elahu G; Junnila, Riia K; Kopchick, John J.

    2013-01-01

    cell lines tested. Further analysis revealed GH-induced activation of STAT5 and mTOR in a cell line dependent manner. In conclusion, we have identified cell lines and cancer types that are ideal to study the role of GH and PRL in cancer, yet have been largely overlooked. Furthermore, we found...

  19. Manipulation of the Growth Hormone-Insulin-Like Growth Factor (GH-IGF) Axis: A Treatment Strategy to Reverse the Effects of Early Life Developmental Programming.

    Science.gov (United States)

    Reynolds, Clare M; Perry, Jo K; Vickers, Mark H

    2017-08-08

    Evidence from human clinical, epidemiological, and experimental animal models has clearly highlighted a link between the early life environment and an increased risk for a range of cardiometabolic disorders in later life. In particular, altered maternal nutrition, including both undernutrition and overnutrition, spanning exposure windows that cover the period from preconception through to early infancy, clearly highlight an increased risk for a range of disorders in offspring in later life. This process, preferentially termed "developmental programming" as part of the developmental origins of health and disease (DOHaD) framework, leads to phenotypic outcomes in offspring that closely resemble those of individuals with untreated growth hormone (GH) deficiency, including increased adiposity and cardiovascular disorders. As such, the use of GH as a potential intervention strategy to mitigate the effects of developmental malprogramming has received some attention in the DOHaD field. In particular, experimental animal models have shown that early GH treatment in the setting of poor maternal nutrition can partially rescue the programmed phenotype, albeit in a sex-specific manner. Although the mechanisms remain poorly defined, they include changes to endothelial function, an altered inflammasome, changes in adipogenesis and cardiovascular function, neuroendocrine effects, and changes in the epigenetic regulation of gene expression. Similarly, GH treatment to adult offspring, where an adverse metabolic phenotype is already manifest, has shown efficacy in reversing some of the metabolic disorders arising from a poor early life environment. Components of the GH-insulin-like growth factor (IGF)-IGF binding protein (GH-IGF-IGFBP) system, including insulin-like growth factor 1 (IGF-1), have also shown promise in ameliorating programmed metabolic disorders, potentially acting via epigenetic processes including changes in miRNA profiles and altered DNA methylation. However, as

  20. Effects of growth hormone replacement therapy on IGF-related parameters and on the pituitary-gonadal axis in GH-deficient males. A double-blind, placebo-controlled crossover study

    DEFF Research Database (Denmark)

    Juul, A; Andersson, A M; Pedersen, S A

    1998-01-01

    It has been suggested that growth hormone (GH) may play a regulatory role in male reproductive function. To express full anabolic effect in immature boys testosterone apparently requires the presence of GH. In GH-deficient adults, GH replacement therapy exerts a variety of anabolic actions, some...... study in 13 young males with childhood-onset GH deficiency of which 6 had isolated GH deficiency. GH treatment significantly increased serum levels of total IGF-I from 98 (68) to 323 (126) microg/l, free IGF-I from 0.48 (0.47) to 2.24 (1.66) microg/l, IGFBP-3 from 1,874 (1,178) to 3,520 (778) microg...... in hypogonadal patients substituted with androgens, but GH had no effect on inhibin-B levels. In conclusion, GH replacement therapy in 13 GH-deficient young adult males resulted in significant increases in total and free IGF-I as well as in ALS levels in all patients, but had no significant effect on: (1...

  1. GH and IGF1: Roles in Energy Metabolism of Long-Living GH Mutant Mice

    OpenAIRE

    Brown-Borg, Holly M.; Bartke, Andrzej

    2012-01-01

    Of the multiple theories to explain exceptional longevity, the most robust of these has centered on the reduction of three anabolic protein hormones, growth hormone (GH), insulin-like growth factor, and insulin. GH mutant mice live 50% longer and exhibit significant differences in several aspects of energy metabolism as compared with wild-type mice. Mitochondrial metabolism is upregulated in the absence of GH, whereas in GH transgenic mice and dwarf mice treated with GH, multiple aspects of t...

  2. Significance of measurement of serum somatostatin (SS), growth hormone (GH), insulin-like growth factor-1 (IGF-1) and some related cytokines levels in patients with graves' disease

    International Nuclear Information System (INIS)

    Zhu Bao; Ma Yunbao; Zhang Xiaoyi

    2005-01-01

    Objective: To study the possible roles of the related hormones and cytokines in the pathogenesis of Graves' disease. Methods: Serum levels of SS, GH, IGF-1, IL-2, IL-4 and IL-6 were measured with RIA in 1) 36 patients with Graves' disease before any treatment 2) another 30 patients with Graves' disease after successful anti-thyroid drug therapy and 3) 35 controls. Results: In the untreated group, the serum levels of SS, GH, IGF-1, IL-4 and IL-6 were significantly higher but serum IL-2 levels were significantly lower than those in the controls (P<0.01). In the successfully treated group, the serum levels of SS, GH, IGF-1, IL-4 and IL-6 were significantly lower (P<0.05 or P<0.01), but serum IL-2 levels were significantly higher (P<0.01) than those in the untreated group. Conclusion: These parameters played significant roles in the pathogenesis of Graves' disease; however, the precise mechanism remained to be speculative and further studies required. (authors)

  3. Growth hormone (GH) provocative retesting of 108 young adults with childhood-onset GH deficiency and the diagnostic value of insulin-like growth factor I (IGF-I) and IGF-binding protein-3

    DEFF Research Database (Denmark)

    Juul, A; Kastrup, K W; Pedersen, S A

    1997-01-01

    .e. 45% of patients treated with GH during childhood because of isolated GHD had a normal GH response when retested in adulthood. Multiple regression analysis revealed that peak GH levels were dependent on the degree of hypopituitarism, body mass index, and duration of disease. IGF-I levels were below -2...

  4. Long-term effects of continuous subcutaneous infusion versus daily subcutaneous injections of growth hormone (GH) on the insulin-like growth factor system, insulin sensitivity, body composition, and bone and lipoprotein metabolism in GH-deficient adults

    DEFF Research Database (Denmark)

    Laursen, Torben; Gravholt, Claus Højbjerg; Heickendorff, Lene

    2001-01-01

    injections (inj) in the evening as usual, and 7 received a continuous infusion (inf) of GH by means of a portable pump. The GH dose was kept unchanged before and during the study. Serum levels of insulin-like growth factor I (IGF-I) tended to increase in the patients switched to constant infusion (from 175...... for 6 months are comparable with respect to the IGF-IGFBP axis, whereas intermittent exposure may be of importance for the lipolytic effect of GH. The data on insulin sensitivity and lipoproteins suggest that constant GH exposure is as safe as intermittent GH administration....

  5. Recombinant bovine growth hormone (rBGH) enhances somatic growth by regulating the GH-IGF axis in fingerlings of gilthead sea bream (Sparus aurata).

    Science.gov (United States)

    Vélez, Emilio J; Perelló, Miquel; Azizi, Sheida; Moya, Alberto; Lutfi, Esmail; Pérez-Sánchez, Jaume; Calduch-Giner, Josep A; Navarro, Isabel; Blasco, Josefina; Fernández-Borràs, Jaume; Capilla, Encarnación; Gutiérrez, Joaquim

    2018-02-01

    The growth hormone (GH)/insulin-like growth factors (IGFs) endocrine axis is the main growth-regulator system in vertebrates. Some authors have demonstrated the positive effects on growth of a sustained-release formulation of a recombinant bovine GH (rBGH) in different fish species. The aim of this work was to characterize the effects of a single injection of rBGH in fingerlings of gilthead sea bream on growth, GH-IGF axis, and both myogenic and osteogenic processes. Thus, body weight and specific growth rate were significantly increased in rBGH-treated fish respect to control fish at 6weeks post-injection, whereas the hepatosomatic index was decreased and the condition factor and mesenteric fat index were unchanged, altogether indicating enhanced somatic growth. Moreover, rBGH injection increased the plasma IGF-I levels in parallel with a rise of hepatic mRNA from total IGF-I, IGF-Ic and IGF-II, the binding proteins IGFBP-1a and IGFBP-2b, and also the receptors IGF-IRb, GHR-I and GHR-II. In skeletal muscle, the expression of IGF-Ib and GHR-I was significantly increased but that of IGF-IRb was reduced; the mRNA levels of myogenic regulatory factors, proliferation and differentiation markers (PCNA and MHC, respectively), or that of different molecules of the signaling pathway (TOR/AKT) were unaltered. Besides, the growth inhibitor myostatin (MSTN1 and MSTN2) and the hypertrophic marker (MLC2B) expression resulted significantly enhanced, suggesting altogether that the muscle is in a non-proliferative stage of development. Contrarily in bone, although the expression of most molecules of the GH/IGF axis was decreased, the mRNA levels of several osteogenic genes were increased. The histology analysis showed a GH induced lipolytic effect with a clear decrease in the subcutaneous fat layer. Overall, these results reveal that a better growth potential can be achieved on this species and supports the possibility to improve growth and quality through the optimization of its

  6. The GH/IGF axis in the mouse kidney

    NARCIS (Netherlands)

    V. Cingel-Ristic

    2004-01-01

    textabstractGrowth hormone (GH) is a protein hormone synthesized and secreted by somatotroph cells within the anterior pituitary predominantly under regulation of hypothalamic peptides, GH releasing hormone (GHRH) and somatostatin (SS) (1-3) (Figure 1). Further, production of GH is modulated by

  7. GH-replacement therapy in adults

    DEFF Research Database (Denmark)

    Christiansen, J S; Jørgensen, J O; Pedersen, S A

    1991-01-01

    Growth hormone (GH) deficiency in adults, whether GH deficient since childhood or patients rendered GH deficient in adult life, is associated with psychosocial maladjustment, reduced muscle strength and reduced exercise capacity. Body composition is significantly altered with increased fat and de...

  8. The effect of 30 months of low-dose replacement therapy with recombinant human growth hormone (rhGH) on insulin and C-peptide kinetics, insulin secretion, insulin sensitivity, glucose effectiveness, and body composition in GH-deficient adults

    DEFF Research Database (Denmark)

    Rosenfalck, A M; Maghsoudi, S; Fisker, S

    2000-01-01

    The aim of the present study was to evaluate the long-term (30 months) metabolic effects of recombinant human GH (rhGH) given in a mean dose of 6.7 microg/kg x day (= 1.6 IU/day), in 11 patients with adult GH deficiency. Glucose metabolism was evaluated by an oral glucose tolerance test and an iv...... (frequently sampled iv glucose tolerance test) glucose tolerance test, and body composition was estimated by dual-energy x-ray absorptiometry. Treatment with rhGH induced persistent favorable changes in body composition, with a 10% increase in lean body mass (P ... in glucose tolerance, beta-cell response was still inappropriate. Our conclusion is that long-term rhGH-replacement therapy in GH deficiency adults induced a significant deterioration in glucose tolerance, profound changes in kinetics of C-peptide, and insulin and prehepatic insulin secretion, despite...

  9. New diagnostic tests of GH reserve.

    Science.gov (United States)

    Martul, P; Pineda, J; Pombo, M; Peñalva, A; Bokser, L; Dieguez, C

    1993-01-01

    Pharmacological tests are essential for the diagnosis of growth hormone (GH) insufficiency. Obesity is a pathological state associated with blunted GH response to all the classical stimuli tested. In the present study, three new pharmacological stimuli for GH reserve were evaluated in three groups of subjects: Normal, GH-insufficient and normal growing obese children. Dexamethasone provokes a clear GH-response in normal children, whereas the response in the other 2 groups of patients is significantly diminished. Galanin-induced GH-secretion is significantly higher in normal than in obese children. GHRP-6 causes a potent GH release in normal children, higher than in GH-insufficiency or obesity. The overlap shown between GH-insufficient patients and normal children reduces the usefulness of the tests. Similar to the classical stimuli, the response to these new tests is also decreased in obesity.

  10. Genotype analysis of partial growth hormone gene (GH891│MspI in Pesisir cattle and Simmental-Pesisir crossbred cattle

    Directory of Open Access Journals (Sweden)

    T. Hartatik

    2018-03-01

    Full Text Available Growth hormone gene that controls metabolism and body size of animals and polymorphism of the gene is known related to performance of livestock. Identification of gene polymorphisms was important to get early information to determine genetic markers associated with economically desirable traits. Genetic mapping is one of important characterizations in the selection process. Pesisir cattle is one of local cattle in Indonesia that are reared in West Sumatera and have become adaptive to local environment. The present study aimed to identify the genotype of Growth Hormone gene (GH891│MspI of the Pesisir cattle and crossbred Simmental-Pesisir cattle (designated as SimPes and relationship between growth performance (body weight and body size. The present study was conducted to 30 blood samples consisted of 15 Pesisir cattle and 15 SimPes cattle. Body weight and body size were measured at 12-18 months of age. The Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP method was used in this research. The results showed that there exist three variant genotypes (MspI-/-, MspI+/-, MspI+/+ and that allele frequencies of MspI- and MspI+ were 53.3% and 46.7%, respectively. Non-significant effect has found between GH’s genotype and growth traits (Body measurement and body weight in both of breed cattle. In conclusion, three variant genotypes (GH891│MspI in Pesisir and SimPes (Simmental x Pesisir cattle population were found and no significant effect on growth trait performance.

  11. Adult height after long-term, continuous growth hormone (GH) treatment in short children born small for gestational age: results of a randomized, double-blind, dose-response GH trial

    NARCIS (Netherlands)

    Y. van Pareren; M. Houdijk; M. Jansen (Maarten); M. Reeser; P.G.H. Mulder (Paul); A.C.S. Hokken-Koelega (Anita)

    2003-01-01

    textabstractThe GH dose-response effect of long-term continuous GH treatment on adult height (AH) was evaluated in 54 short children born small for gestational age (SGA) who were participating in a randomized, double-blind, dose-response trial. Patients were randomly and blindly

  12. strong>A novel oral preparation of human growth hormone (hGH) is absorbed and increases serum IGF-I levels after 7 days administration to GH-deficient adultsstrong>

    DEFF Research Database (Denmark)

    Laursen, Torben; Mindeholm, Linda; Haemmerle, Sibylle

    2007-01-01

    ) as carrier has recently been developed. The aim of this study was to determine if this oral formulation of hGH could be absorbed and be bioactive. Eight GHD men (mean age 50 years) receiving sc hGH therapy were withdrawn from therapy for 7 days and then treated for 7 days orally with tablets of HGH191...

  13. High serum levels of growth hormone (GH) and insulin-like growth factor-I (IGF-I) during high-dose GH treatment in short children born small for gestational age

    NARCIS (Netherlands)

    M. van Dijk (Marije); P.G.H. Mulder (Paul); E.C.A.M. Houdijk (Mieke); J.C. Mulder (Jaap); K. Noordam (Kees); R.J.H. Odink (Roelof); C. Rongen-Westerlaken (Ciska); P.G. Voorhoeve (Paul); J.J.J. Waelkens (Johan); W.H. Stokvis-Brantsma; A.C.S. Hokken-Koelega (Anita)

    2006-01-01

    textabstractContext: Epidemiological studies have indicated that high serum levels of GH and IGF-I are associated with long-term risks. Objective: The objective of the study was to evaluate the changes in serum levels of GH during overnight profiles, IGF-I, and IGF binding protein 3 (IGFBP-3) in

  14. Improvement in insulin sensitivity without concomitant changes in body composition and cardiovascular risk markers following fixed administration of a very low growth hormone (GH) dose in adults with severe GH deficiency

    NARCIS (Netherlands)

    Yuen, Kevin C. J.; Frystyk, Jan; White, Deborah K.; Twickler, Th B.; Koppeschaar, Hans P. F.; Harris, Philip E.; Fryklund, Linda; Murgatroyd, Peter R.; Dunger, David B.

    2005-01-01

    OBJECTIVE: Untreated GH-deficient adults are predisposed to insulin resistance and excess cardiovascular mortality. We showed previously that short-term treatment with a very low GH dose (LGH) enhanced insulin sensitivity in young healthy adults. The present study was therefore designed to explore

  15. Mercury's Messenger

    Science.gov (United States)

    Chapman, Clark R.

    2004-01-01

    Forty years after Mariner 2, planetary exploration has still only just begun, and many more missions are on drawing boards, nearing the launch pad, or even en route across interplanetary space to their targets. One of the most challenging missions that will be conducted this decade is sending the MESSENGER spacecraft to orbit the planet Mercury.…

  16. Two siblings with isolated GH deficiency due to loss-of-function mutation in the GHRHR gene: successful treatment with growth hormone despite late admission and severe growth retardation.

    Science.gov (United States)

    Sıklar, Zeynep; Berberoğlu, Merih; Legendre, Maria; Amselem, Serge; Evliyaoğlu, Olcay; Hacıhamdioğlu, Bülent; Savaş Erdeve, Senay; Oçal, Gönül

    2010-01-01

    Patients with growth hormone releasing hormone receptor (GHRHR) mutations exhibit pronounced dwarfism and are phenotypically and biochemically indistinguishable from other forms of isolated growth hormone deficiency (IGHD). We presented here two siblings with clinical findings of IGHD due to a nonsense mutation in the GHRHR gene who reached their target height in spite of late GH treatment. Two female siblings were admitted to our clinic with severe short stature at the age of 13.8 (patient 1) and 14.8 years (patient 2). On admission, height in patient 1 was 107 cm (-8.6 SD) and 117 cm (-6.7 SD) in patient 2. Bone age was delayed in both patients (6 years and 9 years). Clinical and biochemical analyses revealed a diagnosis of complete IGHD (peak GH levels on stimulation test was 0.06 ng/mL in patient 1 and 0.16 ng/mL in patient 2). Patients were given recombinant human GH treatment. Genetic analysis of the GH and GHRHR genes revealed that both patientscarried the GHRHR gene mutation p.Glu72X (c.214 G>T) in exon 3 in homozygous (or hemizygous) state. After seven years of GH treatment, the patients reached a final height appropriate for their target height. Final height was 151 cm (-1.5 SD) in patient 1 and 153 cm (-1.2 SD) in patient 2. In conclusion, genetic analysis is indicated in IGHD patients with severe growth failure and a positive family history. In spite of the very late diagnosis in these two patients who presented with severe growth deficit due to homozygous loss-of-function mutations in GHRHR, their final heights reached the target height.

  17. Delayed release formulation of the somatostatin analog RC-160 inhibits the growth hormone (GH) response to GH-releasing factor-(1-29)NH2 and decreases elevated prolactin levels in rats.

    Science.gov (United States)

    Bokser, L; Schally, A V

    1988-10-01

    Recently, we have developed a long-acting delivery system for our somatostatin (SS) analog RC-160 based on injectable microcapsules in poly-(D,L-lactide-coglycolide). We studied the capacity of this formulation to repeatedly block the GH secretion induced by administration of GRF-(1-29)NH2 (GRF) on different days. Male rats anesthetized with pentobarbital were injected iv with 2.5 micrograms/kg BW GRF-(1-29)NH2 or saline. Five minutes later, blood samples were taken for GH measurement, and the animals were injected im with RC-160 microcapsules at a dose calculated to release 25 micrograms/day of the analog for 7 days or with the vehicle. The GRF stimuli were repeated 48 h, 96 h, and 8 days after administration of SS analog in microcapsules. GRF administration increased GH levels at the four times tested (P less than 0.01) in the control group injected with vehicle, while RC-160 microcapsules inhibited the GH response for more than 96 h (P less than 0.01). The GH levels augmented by pentobarbital were also decreased by the RC-160 microcapsules (P less than 0.01). Animals treated with microcapsules showed smaller increases in their body weight than untreated rats (P less than 0.05). We also investigated the effect of RC-160 microcapsules on hyperprolactinemic female rats implanted with pituitary glands under the kidney capsules. High PRL levels in rats bearing pituitary grafts showed a significant decrease when measured 4 days after the administration of RC-160 microcapsules. These results demonstrate the efficacy of the long-acting delivery system of the SS analog RC-160 and suggest the possible clinical usefulness of this formulation for lowering GH and PRL levels.

  18. Similar effects of long-term exogenous growth hormone (GH) on bone and muscle parameters: a pQCT study of GH-deficient and small-for-gestational-age (SGA) children.

    Science.gov (United States)

    Schweizer, Roland; Martin, David D; Haase, Martin; Roth, Johannes; Trebar, Branko; Binder, Gerhard; Schwarze, C Philipp; Ranke, Michael B

    2007-11-01

    Treatment with GH in short children has focused on height development. Little is known about the concomitant changes in muscle mass, bone structure and bone strength. Muscle area as well as parameters of bone architecture (bone mineral content, BMC; volumetric cortical density, total bone area, TBA; cortical area, cortical thickness, CT; and marrow area) were measured by means of pQCT (Stratec) at 65% of the proximal length of the forearm. The strength-strain index (SSI) was calculated as an indicator of bone strength. Prepubertal children with GHD (mean values: age; 7.2 years; height SDS=-2.9 SDS; GH dose: 30 microg/kg/d) were followed at 0, 6, 12 (n=74) and 24 (n=55) months. Prepubertal children with SGA (mean values: age: 7.1 years; height SDS=-3.4 SDS; GH dose: 55 mug/kg/d) were followed at 0, 6, 12 (n=47) and 24 (n=35) months. Both groups showed a similar increase in height. At GH start, muscle mass and bone characteristics were lower than normal but similar in SGA vs. GHD. Muscle area (mean values, SDS) increased from -3.0 to -1.5 in SGA and from -2.4 to -1.0 in GHD. Bone geometry changed in a biphasic mode, with an increase in total bone area and lowering of bone mineral content (BMC) during the first 12 months, followed by an increase of BMC and CT thereafter. SSI (mean values, mm(3)) improved from 78 to 114 in GHD and from 62 to 101 in SGA after 24 months on GH. The increment in terms of SDS did not reach significance in SGA. SSI correlated positively with muscle area before and during GH treatment. Bone strength and muscle mass are impaired in prepubertal children with GHD and SGA. Exogenous GH can indirectly improve bone structure and strength by inducing an increase in muscle mass. Our findings support the assumption that, in SGA, there is impaired tissue responsiveness to GH.

  19. Growth differentiation factor 3 is induced by bone morphogenetic protein 6 (BMP-6) and BMP-7 and increases luteinizing hormone receptor messenger RNA expression in human granulosa cells.

    Science.gov (United States)

    Shi, Jia; Yoshino, Osamu; Osuga, Yutaka; Akiyama, Ikumi; Harada, Miyuki; Koga, Kaori; Fujimoto, Akihisa; Yano, Tetsu; Taketani, Yuji

    2012-04-01

    To examine the relevance of growth differentiation factor 3 (GDF-3) and bone morphogenetic protein (BMP) cytokines in human ovary. Molecular studies. Research laboratory. Eight women undergoing salpingo-oophorectomy and 30 women undergoing ovarian stimulation for in vitro fertilization. Localizing GDF-3 protein in human ovaries; granulosa cells (GC) cultured with GDF-3, BMP-6, or BMP-7 followed by RNA extraction. The localization of GDF-3 protein in normal human ovaries via immunohistochemical analysis, GDF-3 messenger RNA (mRNA) expression evaluation via quantitative real-time reverse transcription and polymerase chain reaction (RT-PCR), and evaluation of the effect of GDF-3 on leuteinizing hormone (LH) receptor mRNA expression via quantitative real-time RT-PCR. In the ovary, BMP cytokines, of the transforming growth factor beta (TGF-β) superfamily, are known as a luteinization inhibitor by suppressing LH receptor expression in GC. Growth differentiation factor 3, a TGF-β superfamily cytokine, is recognized as an inhibitor of BMP cytokines in other cells. Immunohistochemical analysis showed that GDF-3 was strongly detected in the GC of antral follicles. An in vitro assay revealed that BMP-6 or BMP-7 induced GDF-3 mRNA in GC. Also, GDF-3 increased LH receptor mRNA expression and inhibited the effect of BMP-7, which suppressed the LH receptor mRNA expression in GC. GDF-3, induced with BMP-6 and BMP-7, might play a role in folliculogenesis by inhibiting the effect of BMP cytokines. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  20. Long-term effects of growth hormone (GH) treatment on body composition and bone mineral density in short children born small-for-gestational-age : six-year follow-up of a randomized controlled GH trial

    NARCIS (Netherlands)

    Willemsen, Ruben H.; Arends, Nicolette J. T.; Waarde, Willie M. Bakker-van; Jansen, Maarten; van Mil, Edgar G. A. H.; Mulder, Jaap; Odink, Roelof J.; Reeser, Maarten; Rongen-Westerlaken, Ciska; Stokvis-Brantsma, Wilhelmina H.; Waelkens, Johan J. J.; Hokken-Koelega, Anita C. S.

    2007-01-01

    Context Alterations in the GH-IGF-I axis in short small-for-gestational-age (SGA) children might be associated with abnormalities in bone mineral density (BMD) and body composition. In addition, birth weight has been inversely associated with diabetes and cardiovascular disease in adult life. Data

  1. Baseline characteristics and response to 2 years of growth hormone (GH) replacement of hypopituitary patients with GH deficiency due to adult-onset craniopharyngioma in comparison with patients with nonfunctioning pituitary adenoma: data from KIMS (Pfizer International Metabolic Database).

    Science.gov (United States)

    Verhelst, Johan; Kendall-Taylor, Pat; Erfurth, Eva Marie; Price, David Anthony; Geffner, Mitchell; Koltowska-Häggström, Maria; Jönsson, Peter J; Wilton, Patrick; Abs, Roger

    2005-08-01

    In epidemiological studies, hypopituitary adults show increased mortality compared with population controls. Patients with hypopituitarism caused by a craniopharyngioma (CP) and/or its treatment have a higher mortality than patients with other etiologies, such as a nonfunctioning pituitary adenoma (NFPA). To analyze this difference, we used the KIMS database (Pfizer International Metabolic Database) comparing CP and NFPA patients in terms of baseline characteristics and responses to GH replacement. Baseline characteristics were studied in 351 CP patients (189 men and 162 women; mean age, 42.5 yr) and compared with 370 NFPA patients, matched for age and sex (185 men and 185 women; mean age, 42.5 yr). The effects of 2 yr of GH replacement were analyzed in a subgroup of 183 CP and 209 NFPA patients. At baseline, both CP and NFPA patients had characteristic features of GH deficiency, with low serum IGF-I, increased body fat, dyslipidemia, and reduced quality of life. Male CP patients were significantly more obese (30.0 vs. 28.2 kg/m2; P = 0.0003) compared with NFPA patients, had a higher waist/hip ratio (P = 0.004), higher triglycerides (P = 0.003), and lower high-density lipoprotein cholesterol (P = 0.03). Similar, but much smaller, differences were seen in female CP compared with NFPA patients, only reaching significance for waist/hip ratio (P = 0.05) and triglycerides (P = 0.0004). CP patients had more often undergone surgery by the transcranial route (68.8% vs. 30.9%; P NFPA patients (58.7% vs. 19.8%; P NFPA patients. After 2 yr of GH replacement therapy, similar significant improvements were evident in both groups in fat-free mass, total and low-density lipoprotein cholesterol, and Quality-of-Life-Assessment in GH Deficient Adults score compared with baseline. In contrast to NFPA patients, CP patients had no significant decrease in body fat with GH therapy. In the KIMS database, patients with CP have more often undergone surgery by the transcranial route than

  2. Effect of long-term administration of an analog of growth hormone-releasing factor on the GH response in rats.

    Science.gov (United States)

    Karashima, T; Olsen, D; Schally, A V

    1987-06-22

    The effect of the repeated or continuous administration of an analog of GH releasing factor (GH-RF), D-Tyr-1, D-Ala-2, Nle-27, GH-RF(1-29)-NH2 (DBO-29), on the subsequent response to this peptide was investigated in pentobarbital-anesthetized male rats. A sc administration of this analog induced a greater and more prolonged GH release than doses 10 times larger of GH-RF(1-29). The GH increase after sc injection of 10 micrograms/kg bw of the analog was greater than that induced by iv administration of 2 micrograms/kg bw of GH-RF(1-44). Pretreatment with 10 micrograms/kg bw of the analog did not affect the pituitary response to a strong stimulus (20 micrograms/kg bw) of GH-RF(1-44), 24 h later. Pretreatment with the analog in doses of 10 micrograms/kg bw, sc twice a day, 5 days per week for 4 weeks, significantly diminished the GH release in response to a sc injection of the analog (10 micrograms/kg bw), as compared to vehicle-pretreated controls (P less than 0.01). On the other hand, a continuous sc administration of 0.4 micrograms/h of the analog to intact rats for 7 days did not result in a decrease in GH response to a sc injection of the analog (10 micrograms/kg bw). Since the rats injected repeatedly with the analog for 4 weeks still showed a marked, although somewhat reduced response, analogs of this type may be useful clinically.

  3. EXPRESSION OF GROWTH HORMONE (PhGH GENE AND ANALYSIS OF INSULINE-LIKE GROWTH FACTOR I (IGF-I PRODUCTION IN AFRICAN CATFISH (Clarias gariepinus TRANSGENIC F-1

    Directory of Open Access Journals (Sweden)

    Huria Marnis

    2013-12-01

    Full Text Available We have previously produced F-1 transgenic of African catfish from crosses between founder transgenic female and non transgenic male. The aim of this study was to evaluate distribution and expression PhGH growth hormone gene transgenic African catfish organs and to measure the concentration of IGF-I in plasma. Transgene was detected using the PCR method in various organs, namely pituitary, brain, liver, heart, spleen, kidney, intestine, stomach, muscle, gill, and eye. Transgene expression levels were analyzed using the method of quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR. Plasma samples were analyzed for Insuline-like Growth Factor (IGF-I using Enzyme Linked Immunosorbent Assay (ELISA method. The results showed that the PhGH was detected and expressed in all organs of the transgenic African catfish (F-1. Liver exhibited the highest level of PhGH mRNA (23 x 106 copies. The plasma IGF-I levels in transgenic individuals were not significant than non transgenic. The higher level of exogenous PhGH gene expression may not represent the production of IGF-1.

  4. Comparison of two dose regimens of growth hormone (GH) with different target IGF-1 levels on glucose metabolism, lipid profile, cardiovascular function and anthropometric parameters in gh-deficient adults.

    Science.gov (United States)

    Cenci, Maria Claudia Peixoto; Soares, Débora Vieira; Spina, Luciana Diniz Carneiro; Brasil, Rosane Resende de Lima Oliveira; Lobo, Priscila Marise; Michmacher, Eduardo; Vaisman, Mario; Boguszewski, Cesar Luiz; Conceição, Flávia Lúcia

    2012-01-01

    To compare the effects of two regimens of GH therapy with different target IGF-1 levels on anthropometric parameters, glucose metabolism, lipid profile and cardiac function in adults with GH deficiency (GHD). Retrospective analysis of 14 GHD adults from Clementino Fraga Filho University Hospital, Rio de Janeiro, Brazil, who were treated with a GH regimen aimed at maintaining serum IGF-1 levels between the median and upper reference limit (high dose group - HDGH) and 18 GHD adults from Federal University Hospital, Curitiba, Brazil, who received a fixed GH dose of 0.2mg/day in the first year of treatment, followed by titration to maintain serum IGF-1 levels between the median and lower reference limit (low dose group - LDGH). All patients were followed for 2 years with analysis of anthropometric parameters, serum levels of IGF-1, glucose, insulin, HOMA-IR, lipid profile, and transthoracic echocardiography. Changes on weight, BMI and waist circumference were similar between the two groups. Insulin levels increased and HOMA-IR worsened in the LDGH group at 1year and improved thereafter. Total cholesterol and triglycerides did not change with therapy. LDL cholesterol reduced in both groups, while HDL-cholesterol significantly increased only in the HDGH group (p=0.007 vs LDGH). No significant variations on echocardiographic parameters were observed. The HDGH and LDGH regimens resulted in similar changes on anthropometric, echocardiographic, glucose and lipid parameters in GHD adults, except for increase in HDL cholesterol that was only observed in the HDGH regimen. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. GH and IGF1: roles in energy metabolism of long-living GH mutant mice.

    Science.gov (United States)

    Brown-Borg, Holly M; Bartke, Andrzej

    2012-06-01

    Of the multiple theories to explain exceptional longevity, the most robust of these has centered on the reduction of three anabolic protein hormones, growth hormone (GH), insulin-like growth factor, and insulin. GH mutant mice live 50% longer and exhibit significant differences in several aspects of energy metabolism as compared with wild-type mice. Mitochondrial metabolism is upregulated in the absence of GH, whereas in GH transgenic mice and dwarf mice treated with GH, multiple aspects of these pathways are suppressed. Core body temperature is markedly lower in dwarf mice, yet whole-body metabolism, as measured by indirect calorimetry, is surprisingly higher in Ames dwarf and Ghr-/- mice compared with normal controls. Elevated adiponectin, a key antiinflammatory cytokine, is also very likely to contribute to longevity in these mice. Thus, several important components related to energy metabolism are altered in GH mutant mice, and these differences are likely critical in aging processes and life-span extension.

  6. Correlation between GH and IGF-1 during treatment for acromegaly.

    Science.gov (United States)

    Oldfield, Edward H; Jane, John A; Thorner, Michael O; Pledger, Carrie L; Sheehan, Jason P; Vance, Mary Lee

    2017-06-01

    OBJECTIVE The relationship between growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in patients with acromegaly as serial levels drop over time after treatment has not been examined previously. Knowledge of this relationship is important to correlate pretreatment levels that best predict response to treatment. To examine the correlation between GH and IGF-1 and IGF-1 z-scores over a wide range of GH levels, the authors examined serial GH and IGF-1 levels at intervals before and after surgery and radiosurgery for acromegaly. METHODS This retrospective analysis correlates 414 pairs of GH and IGF-1 values in 93 patients with acromegaly. RESULTS Absolute IGF-1 levels increase linearly with GH levels only up to a GH of 4 ng/ml, and with IGF-1 z-scores only to a GH level of 1 ng/ml. Between GH levels of 1 and 10 ng/ml, increases in IGF-1 z-scores relative to changes in GH diminish and then plateau at GH concentrations of about 10 ng/ml. From patient to patient there is a wide range of threshold GH levels beyond which IGF-1 increases are no longer linear, GH levels at which the IGF-1 response plateaus, IGF-1 levels at similar GH values after the IGF-1 response plateaus, and of IGF-1 levels at similar GH levels. CONCLUSIONS In acromegaly, although IGF-1 levels represent a combination of the integrated effects of GH secretion and GH action, the tumor produces GH, not IGF-1. Nonlinearity between GH and IGF-1 occurs at GH levels far below those previously recognized. To monitor tumor activity and tumor viability requires measurement of GH levels.

  7. 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.

  8. In Silico characterization of growth hormone from freshwater ...

    African Journals Online (AJOL)

    dimensional (3D) structure prediction and evolutionary profile of growth hormone (GH) from 14 ornamental freshwater fishes. The analyses were performed using the sequence data of growth hormone gene (gh) and its encoded GH protein.

  9. Beneficial effects of GH/IGF-1 on skeletal muscle atrophy and function in experimental heart failure.

    Science.gov (United States)

    Dalla Libera, Luciano; Ravara, Barbara; Volterrani, Maurizio; Gobbo, Valerio; Della Barbera, Mila; Angelini, Annalisa; Danieli Betto, Daniela; Germinario, Elena; Vescovo, Giorgio

    2004-01-01

    Muscle atrophy is a determinant of exercise capacity in heart failure (CHF). Myocyte apoptosis, triggered by tumor necrosis factor-alpha (TNF-alpha) or its second messenger sphingosine (SPH), is one of the causes of atrophy. Growth hormone (GH) improves hemodynamic and cardiac trophism in several experimental models of CHF, but its effect on skeletal muscle in CHF is not yet clear. We tested the hypothesis that GH can prevent skeletal muscle apoptosis in rats with CHF. CHF was induced by injecting monocrotaline. After 2 wk, 2 groups of rats were treated with GH (0.2 mg.kg(-1).day(-1) and 1.0 mg.kg(-1).day(-1)) subcutaneously. A third group of controls had saline. After 2 additional weeks, rats were killed. Tibialis anterior cross-sectional area, myosin heavy chain (MHC) composition, and a study on myocyte apoptosis and serum levels of TNF-alpha and SPH were carried out. The number of apoptotic nuclei, muscle atrophy, and serum levels of TNF-alpha and SPH were decreased with GH at high but not at low doses compared with CHF rats. Bcl-2 was increased, whereas activated caspases and bax were decreased. The MHC pattern in GH-treated animals was similar to that of controls. Monocrotaline slowed down both contraction and relaxation but did not affect specific tetanic force, whereas absolute force was decreased. GH treatment restored contraction and relaxation to control values and brought muscle mass and absolute twitch and tetanic tension to normal levels. These findings may provide an insight into the therapeutic strategy of GH given to patients with CHF to improve exercise capacity.

  10. Justified and unjustified use of growth hormone.

    NARCIS (Netherlands)

    A-J. van der Lely (Aart-Jan)

    2004-01-01

    textabstractGrowth hormone (GH) replacement therapy for children and adults with proven GH deficiency due to a pituitary disorder has become an accepted therapy with proven efficacy. GH is increasingly suggested, however, as a potential treatment for frailty, osteoporosis,

  11. Growth hormone administration stimulates energy expenditure and extrathyroidal conversion of thyroxine to triiodothyronine in a dose-dependent manner and suppresses circadian thyrotrophin levels: studies in GH-deficient adults

    DEFF Research Database (Denmark)

    Laursen, Torben; Jørgensen, Jens Otto Lunde; Møller, Jens

    1994-01-01

    . CONCLUSIONS: GH administration stimulated peripheral T4 to T3 conversion in a dose-dependent manner. Serum T3 levels were subnormal despite T4 substitution when the patients were off GH but normalized with GH therapy. Energy expenditure increased with GH and correlated with free T3 levels. GH caused......Abstract OBJECTIVE: The impact of exogenous GH on thyroid function remains controversial although most data add support to a stimulation of peripheral T4 to T3 conversion. For further elucidation we evaluated iodothyronine and circadian TSH levels in GH-deficient patients as part of a GH dose...... without GH, whereas GH therapy significantly suppressed the TSH levels and blunted the circadian rhythm (mean TSH levels (mU/l) 0.546 +/- 0.246 (no GH) vs 0.066 +/- 0.031 (2 IU GH) (P

  12. GH receptor signaling in skeletal muscle and adipose tissue in human subjects following exposure to an intravenous GH bolus

    DEFF Research Database (Denmark)

    Jørgensen, Jens O L; Jessen, Niels; Pedersen, Steen Bønløkke

    2006-01-01

    Growth hormone (GH) regulates muscle and fat metabolism, which impacts on body composition and insulin sensitivity, but the underlying GH signaling pathways have not been studied in vivo in humans. We investigated GH signaling in biopsies from muscle and abdominal fat obtained 30 (n = 3) or 60 (n...... was measured by in vitro phosphorylation of PI. STAT5 DNA binding activity was assessed with EMSA, and the expression of IGF-I and SOCS mRNA was measured by real-time RT-PCR. GH induced a 52% increase in circulating FFA levels with peak values after 155 min (P = 0.03). Tyrosine-phosphorylated STAT5...... tended to increase after GH in muscle and fat, respectively. We conclude that 1) STAT5 is acutely activated in human muscle and fat after a GH bolus, but additional downstream GH signaling was significant only in fat; 2) the direct GH effects in muscle need further characterization; and 3) this human...

  13. Expanding the spectrum of mutations in GH1 and GHRHR: genetic screening in a large cohort of patients with congenital isolated growth hormone deficiency

    DEFF Research Database (Denmark)

    Alatzoglou, Kyriaki S; Turton, James P; Kelberman, Daniel

    2009-01-01

    mutations in GH1 (C182X, G120V, R178H, IVS3+4nt, a>t) and GHRHR (W273S, R94L, R162W). Autosomal dominant, type II IGHD was the commonest form (52.4%), followed by type IB (42.8%) and type IA (4.8%). Patients with type II IGHD had highly variable phenotypes. There was no difference in the endocrinology...... or magnetic resonance imaging appearance between patients with and without mutations, although those with mutations presented with more significant growth failure (height, -4.7 +/- 1.6 SDS vs. -3.4 +/- 1.7 SDS) (P = 0.001). There was no apparent difference between patients with mutations in GH1 and GHRHR...

  14. Interaction of Mechanical Load with Growth Hormone (GH) and Insulin-Like Growth Factor I (IGF-I) on Slow-Twitch Skeletal Muscle and Bone

    Science.gov (United States)

    Linderman, Jon K.; Gosselink, Kristin L.; Wang, Tommy J.; Mukku, Venkat R.; Grindeland, Richard E.

    1994-01-01

    Exogenous humoral growth factors, combined with increased mechanical loading, reportedly induce hypertrophy of fast-, but not slow-twitch skeletal muscles, and have little effect in attenuating atrophy of slow-twitch muscle associated with exposure to microgravity in animals with intact neuroendocrine systems. These observations suggest that anabolic adjuvants and muscle tension do not interact to stimulate growth or maintenance of slow-twitch skeletal muscle. The purpose of the present study was to determine whether a chronic increase in mechanical loading (synergistic ablation) or hindlimb unweighting (hindlimb suspension) interact with exogenous GH and IGF-I (Genentech, So San Francisco, CA) in the slow-twitch soleus muscles of female rats (approx. 250 g). Bilateral ablation of the plantaris and gastrocnemius muscles induced 38% and 40% increases in the absolute (mg/pair) and relative (mg/100 g body weight) weights of the soleus, respectively (p less than or = 0.05), in ambulatory rats. GH and IGF-I interacted with chronic loading to increase absolute soleus mass an additional 20% (p less than or = 0.05), and mixed and myofibrillar protein contents an additional 12% and 7%, respectively (NS). In contrast, hindlimb suspension (HLS) resulted in 20% and 18% decreases in the absolute and relative weights of the soleus, respectively (p less than or = 0.05); GH and IGF-I did not spare loss of soleus mass or protein content in HLS rats. HLS decreased tibial plate thickness approx. 11% (p less than or = 0.05), but not weights of the tibia or femus. GH and IGF-I increased tibial plate thickness approx. 30% (p less than or = 0.05), in ambulatory and HLS rats, and increased femur and tibial weights 12% (p less than or = 0.05) and 8% (NS), respectively, in ambulatory rats, but had no effect in HLS rats. Results of the present investigation suggest that GH and IGF-I can stimulate hypertrophy of slow-twitch skeletal muscle when chronically overloaded, but can also stimulate

  15. Health Alert: Adrenal Crisis Causes Death in Some People Who Were Treated with hGH

    Science.gov (United States)

    ... Were Treated with hGH Health Alert: Adrenal Crisis Causes Death in Some People Who Were Treated with hGH ... Adrenal crisis is a serious condition that can cause death in people who lack the pituitary hormone ACTH. ...

  16. Growth hormone stimulation test - series (image)

    Science.gov (United States)

    The growth hormone (GH) is a protein hormone released from the anterior pituitary gland under the control of the hypothalamus. In children, GH has growth-promoting effects on the body. It stimulates the ...

  17. Hat das humane Wachtumshormon (hGH eine Relevanz in der Kontrolle der penilen Erektion?

    Directory of Open Access Journals (Sweden)

    Ückert St

    2003-01-01

    Full Text Available Allgemeines: Schon seit langem wird die Frage einer Beteiligung des Hypophysenhormons Human Growth Hormone (Wachstumshormon, hGH, GH an der Kontrolle der sexuellen Maturation und der Reproduktionsfunktion des Menschen diskutiert. Die Symptome eines GH-Defizits beim Mann sind u. a. allgemeine Antriebslosigkeit, Oligo- oder Azoospermie, eine Verminderung der Libido sowie eine Beeinträchtigung der normalen Erektionsfähigkeit. Es wird vermutet, daß die biologischen Effekte des GH eine durch das Somatomedin Insulin-like Growth Factor 1 (IGF-1 vermittelte Stimulation der Produktion von Stickoxid (NO durch die endotheliale und neuronale Form des Enzyms NO-Synthase einschließen. So konnte gezeigt werden, daß physiologische Konzentrationen von GH den adrenergen Tonus isolierter Streifenpräparate humaner Schwellkörpermuskulatur antagonisieren und den Gewebegehalt des Second Messengers cGMP erhöhen. Im Rahmen dieser Studie haben wir in einem Kollektiv gesunder Männer und in einer Gruppe von Patienten mit erektiler Dysfunktion (ED die systemischen und cavernösen Serumkonzentrationen von GH während verschiedener peniler Funktionszustände, d. h. verschiedener Stadien der sexuellen Erregung, untersucht. Methoden: 35 gesunden männlichen Probanden und 45 Patienten mit einer ED organogener oder psychogener Genese wurden während der penilen Flakzidität, Tumeszenz, Rigidität - dieses Stadium wurde nur von den Gesunden erreicht - und Detumeszenz zeitgleich Blutproben aus einer Cubitalvene und dem Corpus cavernosum penis entnommen. Tumeszenz und Rigidität wurden durch visuelle und taktile Stimulation ausgelöst. Die Quantifizierung von GH in Aliquots der Serumfraktionen erfolgte mit immunradiometrischen Methoden (IRMA. Ergebnisse: In der Gruppe der gesunden Männer stieg die mittlere systemische und cavernöse Serumkonzentration von GH während der Tumeszenz an, während in den Phasen der Rigidität und Detumeszenz eine Abnahme registriert wurde

  18. The interrelationships of thyroid and growth hormones: effect of growth hormone releasing hormone in hypo- and hyperthyroid male rats.

    Science.gov (United States)

    Root, A W; Shulman, D; Root, J; Diamond, F

    1986-01-01

    Growth hormone (GH) and the thyroid hormones interact in the hypothalamus, pituitary and peripheral tissues. Thyroid hormone exerts a permissive effect upon the anabolic and metabolic effects of GH, and increases pituitary synthesis of this protein hormone. GH depresses the secretion of thyrotropin and the thyroid hormones and increases the peripheral conversion of thyroxine to triiodothyronine. In the adult male rat experimental hypothyroidism produced by ingestion of propylthiouracil depresses the GH secretory response to GH-releasing hormone in vivo and in vitro, reflecting the lowered pituitary stores of GH in the hypothyroid state. Short term administration of large amounts of thyroxine with induction of the hyperthyroid state does not affect the in vivo GH secretory response to GH-releasing hormone in this animal.

  19. Plerocercoid growth factor (PGF), a human growth hormone (hGH) analogue produced by the tapeworm Spirometra mansonoides, has direct insulin-like action in adipose tissue of normal rats in vitro

    International Nuclear Information System (INIS)

    Salem, M.A.M.; Phares, C.K.

    1986-01-01

    The metabolic actions of GH can be divided into acute (insulin-like) and chronic (lipolytic/anti-insulin). The insulin-like actions of GH are most readily elicited in GH-deficient animals as GH induces resistance to its own insulin-like action. Like GH, PGF stimulates growth and cross-reacts with anti-hGH antibodies. Independent experiments were conducted comparing the direct actions of PGF to insulin or hGH in vitro. Insulin-like effects were determined by the ability of PGF, insulin or hGH to stimulate [U- 14 C]glucose metabolism in epidydimal fat pads from normal rats and by inhibition of epinephrine-stimulated lipolysis. Direct stimulation of lipolysis was used as anti-insulin activity. To determine if PGF competes for insulin or GH receptors, adipocytes (3 x 10 5 cells/ml) were incubated with either [ 125 I]insulin or [ 125 I]hGH +/- PGF, +/- insulin or +/- hGH. PGF stimulated glucose oxidation and 14 C-incorporation into lipids. Insulin, hGH and PGF inhibited lipolysis (33%, 29% and 34%, respectively). Adipose tissue was very sensitive to the lipolytic effect of hGH but PGF was neither lipolytic nor did it confer refractoriness to its insulin-like action. PGF bound to GH but not to insulin receptors. Therefore, PGF had direct insulin-like effects but did not stimulate lipolysis in tissue from normal rats in vitro

  20. Effect of cessation of GH treatment on cognition during transition phase in Prader-Willi syndrome: Results of a 2-year crossover GH trial

    NARCIS (Netherlands)

    R.J. Kuppens (Renske); Mahabier, E.F.; N.E. Bakker (Nienke); E.P.C. Siemensma (Elbrich); S.H. Donze (Stephanie); A.C.S. Hokken-Koelega (Anita)

    2016-01-01

    textabstractBackground: Patients with Prader-Willi syndrome (PWS) have a cognitive impairment. Growth hormone (GH) treatment during childhood improves cognitive functioning, while cognition deteriorates in GH-untreated children with PWS. Cessation of GH treatment at attainment of adult height (AH)

  1. Primary empty sella and GH deficiency: prevalence and clinical implications

    Directory of Open Access Journals (Sweden)

    Maurizio Poggi

    2012-01-01

    Full Text Available Primary empty sella (PES is a particular anatomical condition characterized by the herniation of liquor within the sella turcica. The pathogenesis of this alteration, frequently observed in general population, is not yet completely understood. Recently reports demonstrated, in these patients, that hormonal pituitary dysfunctions, specially growth hormone (GH/insulin-like growth factor (IGF-I axis ones, could be relevant. The aim of this paper is to evaluate GH/IGF-I axis in a group of adult patients affected by PES and to verify its clinical relevance. We studied a population of 28 patients with a diagnosis of PES. In each patient we performed a basal study of thyroid, adrenal and gonadal - pituitary axis and a dynamic evaluation of GH/IGF-I after GH-releasing hormone (GHRH plus arginine stimulation test. To evaluate the clinical significance of GH/IGF-I axis dysfunction we performed a metabolic and bone status evaluation in every patients. We found the presence of GH deficit in 11 patients (39.2 %. The group that displayed a GH/IGF-I axis dysfunction showed an impairment in metabolic profile and bone densitometry. This study confirms the necessity to screen the pituitary function in patients affected by PES and above all GH/IGF-I axis. Moreover the presence of GH deficiency could be clinically significant.

  2. Head circumference in untreated and IGF-I treated patients with Laron syndrome: comparison with untreated and hGH-treated children with isolated growth hormone deficiency.

    Science.gov (United States)

    Laron, Zvi; Iluz, Moshe; Kauli, Rivka

    2012-04-01

    Head circumference (HC) is a simple and practical measure of brain size, development and longitudinal measurements of the HC in childhood are an index of brain growth. To determine the effects of long IGF-I deficiency and treatment on HC in patients with Laron syndrome (LS). 20 untreated adult LS patients, aged 48.4±11.2 years and 13 LS patients treated between ages of 5.6±4 to 11.3±3 years were studied. 15 patients with congenital IGHD treated between age 6.1±4 and 13±4 by hGH served as controls. HC was expressed as standard deviation (SD) and Ht as SDS. HC was measured and plotted on Nellhaus charts. Linear height (Ht) was measured by a Harpenden Stadiometer. The mean HC deficit of the adult untreated LS males was -2.9±0.6 SD compared to a Ht deficit of -7.0±1.7 SDS. The HC of the LS adult females was -3.6±1 SD compared to a Ht SDS of -6.9±1.5 (pdeficit decreased only by 1.5 SDS. hGH treatment of cIGHD children increased the HC from -2.0±1.8 to 0.3±1.2 SD and the Ht SDS from -4.8±1.6 to 1.6±1.0. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Growth hormone stimulation test

    Science.gov (United States)

    ... this 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 ...

  4. Production and characterisation of glycoside hydrolases from GH3, GH5, GH10, GH11 and GH61 for chemo-enzymatic synthesis of xylo- and mannooligosaccharides

    DEFF Research Database (Denmark)

    Dilokpimol, Adiphol

    Produktion og karakterisering af glykosid hydrolaser fro GH3, GH5, GH10, GH11 og GH61 til chemo-enzymatisk syntese af xylo- og mannooligosakkarider Biprodukter fra hydrolyse af plantecellevægge er kilder til oligosakkarider, som potentielt kan fungere som prebiotika ved at stimulere væksten af...... omfatter karakterisering af de producerede enzymer samt cDNA kloning af formodet GH61 endo Produktion og karakterisering af glykosid hydrolaser fro GH3, GH5, GH10, GH11 og GH61 til chemo-enzymatisk syntese af xylo- og mannooligosakkarider Biprodukter fra hydrolyse af plantecellevægge er kilder til...

  5. Influence of gender on the correlation between plasma growth hormone profiles and urinary growth hormone excretion

    DEFF Research Database (Denmark)

    Main, K M; Jansson, C; Skakkebak, N

    1997-01-01

    A lot of interest has been directed towards the measurement of urinary growth hormone (GH) excretion instead of plasma GH profiles or provocation tests. We investigated the factors influencing the relationship between 24- and 3-hour plasma GH profiles and urinary GH excretion in a cohort of 113...... than spontaneous GH peaks. The difference in cross-reactivities of molecular GH forms in polyclonal assays may have an impact on the correlation between plasma and urinary GH. Thus, the diagnostic value of urinary GH measurement as compared to serum GH profiles needs to be further evaluated....

  6. [A case of GH and TSH secreting pituitary macroadenoma].

    Science.gov (United States)

    Gołkowski, Filip; Buziak-Bereza, Monika; Stefańska, Agnieszka; Trofimiuk, Małgorzata; Pantofliński, Jacek; Huszno, Bohdan; Czepko, Ryszard; Adamek, Dariusz

    2006-01-01

    A case of GH and TSH secreting pituitary macroadenoma is reported. A 45-year-old female presented clinical features of acromegaly (the abnormal growth of the hands and feet, with lower jaw protrusion), diabetes mellitus, hypertension, nodular goiter and hyperthyroidism of unclear origin. NMR pituitary imaging revealed intra and extrasellar tumor. The laboratory examinations showed very high plasma levels of GH and IGF-1 and normal level of TSH coexisting with high plasma levels of free thyroid hormones. Pharmacological pretreatment with somatostatin analogues caused the substantial reduction of GH and TSH plasma levels. Histological and immunohistochemical examination of the tissue obtained at transsphenoidal surgery showed GH and TSH secreting adenoma. The laboratory examinations after surgery showed normal GH and IGF-1 plasma levels and reduced insulin requirement, what indicates radical operation. The very low plasma levels of TSH and free thyroid hormones after surgery and immunohistochemical examination suggest central hyperthyroidism due to TSH secreting pituitary tumor (thyrotropinoma).

  7. A new specific reference gene based on growth hormone gene (GH1) used for detection and relative quantification of Aquadvantage® GM salmon (Salmo salar L.) in food products.

    Science.gov (United States)

    Hafsa, Ahmed Ben; Nabi, Nesrine; Zellama, Mohamed Salem; Said, Khaled; Chaouachi, Maher

    2016-01-01

    Genetic transformation of fish is mainly oriented towards the improvement of growth for the benefit of the aquaculture. Actually, Atlantic salmon (Salmo salar) is the species most transformed to achieve growth rates quite large compared to the wild. To anticipate the presence of contaminations with GM salmon in fish markets and the lack of labeling regulations with a mandatory threshold, the proper methods are needed to test the authenticity of the ingredients. A quantitative real-time polymerase chain reaction (QRT-PCR) method was used in this study. Ct values were obtained and validated using 15 processed food containing salmon. The relative and absolute limits of detection were 0.01% and 0.01 ng/μl of genomic DNA, respectively. Results demonstrate that the developed QRT-PCR method is suitable specifically for identification of S. salar in food ingredients based on the salmon growth hormone gene 1 (GH1). The processes used to develop the specific salmon reference gene case study are intended to serve as a model for performing quantification of Aquadvantage® GM salmon on future genetically modified (GM) fish to be commercialized. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Association between GH receptor polymorphism (exon 3 deletion), serum IGF1, semen quality, and reproductive hormone levels in 838 healthy young men

    DEFF Research Database (Denmark)

    Andreassen, M; Jensen, Rikke Bodin; Jørgensen, Niels

    2014-01-01

    =467) GHRd3/d3 homozygous individuals (n=69) tended to have larger semen volume (3.2 (2.4-4.3) vs 3.6 (2.6-4.7) ml, P=0.053) and higher serum inhibin-B levels (208 pg/ml (158-257) vs 227 pg/ml (185-264), P=0.050). Semen quality, levels of gonadotropins, testosterone, estradiol, sex hormone......-binding globulin, and IGF1 were not associated with GHRd3 genotype. A twofold increase in serum IGF1 was associated with a 13% (4-23) increase in calculated free testosterone (P=0.004). By contrast IGF1 was inversely associated with serum inhibin-B (P=0.027), but showed no associations to semen quality. GHR...

  9. Growth hormone and selective attention : A review

    NARCIS (Netherlands)

    Quik, Elise H.; van Dam, P. Sytze; Kenemans, J. Leon

    Introduction: The relation between growth hormone (GH) secretion and general cognitive function has been established. General cognitive functioning depends on core functions including selective attention, which have not been addressed specifically in relation to GH. The present review addresses

  10. Interpretation of growth hormone provocative tests

    DEFF Research Database (Denmark)

    Andersson, A M; Orskov, H; Ranke, M B

    1995-01-01

    To compare interpretations of growth hormone (GH) provocative tests in laboratories using six different GH immunoassays (one enzymeimmunometric assay (EIMA, assay 1), one immunoradiometric assay (IRMA, assay 5), one time-resolved fluorimmunometric assay (TRFIA, assay 3) and three radioimmunoassays...

  11. Energy homeostasis targets chromosomal reconfiguration of the human GH1 locus.

    Science.gov (United States)

    Vakili, Hana; Jin, Yan; Cattini, Peter A

    2014-11-01

    Levels of pituitary growth hormone (GH), a metabolic homeostatic factor with strong lipolytic activity, are decreased in obese individuals. GH declines prior to the onset of weight gain in response to excess caloric intake and hyperinsulinemia; however, the mechanism by which GH is reduced is not clear. We used transgenic mice expressing the human GH (hGH) gene, GH1, to assess the effect of high caloric intake on expression as well as the local chromosome structure of the intact GH1 locus. Animals exposed to 3 days of high caloric intake exhibited hyperinsulinemia without hyperglycemia and a decrease in both hGH synthesis and secretion, but no difference in endogenous production of murine GH. Efficient GH1 expression requires a long-range intrachromosomal interaction between remote enhancer sequences and the proximal promoter region through "looping" of intervening chromatin. High caloric intake disrupted this interaction and decreased both histone H3/H4 hyperacetylation and RNA polymerase II occupancy at the GH1 promoter. Incorporation of physical activity muted the effects of excess caloric intake on insulin levels, GH1 promoter hyperacetylation, chromosomal architecture, and expression. These results indicate that energy homeostasis alters postnatal hGH synthesis through dynamic changes in the 3-dimensional chromatin structure of the GH1 locus, including structures required for cell type specificity during development.

  12. Plasma lactate, GH and GH-binding protein levels in exercise following BCAA supplementation in athletes.

    Science.gov (United States)

    De Palo, E F; Gatti, R; Cappellin, E; Schiraldi, C; De Palo, C B; Spinella, P

    2001-01-01

    Branched chain amino acids (BCAA) stimulate protein synthesis, and growth hormone (GH) is a mediator in this process. A pre-exercise BCAA ingestion increases muscle BCAA uptake and use. Therefore after one month of chronic BCAA treatment (0.2 gkg(-1) of body weight), the effects of a pre-exercise oral supplementation of BCAA (9.64 g) on the plasma lactate (La) were examined in triathletes, before and after 60 min of physical exercise (75% of VO2 max). The plasma levels of GH (pGH) and of growth hormone binding protein (pGHBP) were also studied. The end-exercise La of each athlete was higher than basal. Furthermore, after the chronic BCAA treatment, these end-exercise levels were lower than before this treatment (8.6+/-0.8 mmol L(-1) after vs 12.8+/-1.0 mmol L(-1) before treatment; p BCAA chronic treatment, this end-exercise pGHBP was 738+/-85 pmol L(-1) before vs 1691+/-555 pmol L(-1) after. pGH/pGHBP ratio was unchanged in each athlete and between the groups, but a tendency to increase was observed at end-exercise. The lower La at the end of an intense muscular exercise may reflect an improvement of BCAA use, due to the BCAA chronic treatment. The chronic BCAA effects on pGH and pGHBP might suggest an improvement of muscle activity through protein synthesis.

  13. Messengers of the universe

    International Nuclear Information System (INIS)

    Becker, J.K.; Spurio, M.

    2011-01-01

    The observation of the solar neutrinos and of a neutrino burst from the supernova explosion 1987A opened a new observation field which in the next years could be complemented with the detection of astrophysical highenergy neutrinos. Neutrino astronomy is a young discipline derived from the fundamental necessity of extending conventional astronomy beyond the usual electro-magnetic messengers. This is a summary of recent results on those new 'messengers of the universe', based on the presentations in Branch IV of the Neutrino Oscillation Workshop 2010 (NOW2010).

  14. Phosphorylation of chicken growth hormone

    International Nuclear Information System (INIS)

    Aramburo, C.; Montiel, J.L.; Donoghue, D.; Scanes, C.G.; Berghman, L.R.

    1990-01-01

    The possibility that chicken growth hormone (cGH) can be phosphorylated has been examined. Both native and biosynthetic cGH were phosphorylated by cAMP-dependent protein kinase (and γ- 32 P-ATP). The extent of phosphorylation was however less than that observed with ovine prolactin. Under the conditions employed, glycosylated cGH was not phosphorylated. Chicken anterior pituitary cells in primary culture were incubated in the presence of 32 P-phosphate. Radioactive phosphate was incorporated in vitro into the fraction immunoprecipitable with antisera against cGH. Incorporation was increased with cell number and time of incubation. The presence of GH releasing factor (GRF) increased the release of 32 P-phosphate labeled immunoprecipitable GH into the incubation media but not content of immunoprecipitable GH in the cells. The molecular weight of the phosphorylated immunoreactive cGH in the cells corresponded to cGH dimer

  15. Sex steroids and the GH axis: Implications for the management of hypopituitarism.

    Science.gov (United States)

    Birzniece, Vita; Ho, Ken K Y

    2017-02-01

    Growth hormone (GH) regulates somatic growth, substrate metabolism and body composition. Sex hormones exert profound effect on the secretion and action of GH. Estrogens stimulate the secretion of GH, but inhibit the action of GH on the liver, an effect that occurs when administered orally. Estrogens suppress GH receptor signaling by stimulating the expression proteins that inhibit cytokine receptor signaling. This effect of estrogens is avoided when physiological doses of estrogens are administered via a non-oral route. Estrogen-like compounds, such as selective estrogen receptor modulators, possess dual properties of inhibiting the secretion as well as the action of GH. In contrast, androgens stimulate GH secretion, driving IGF-1 production. In the periphery, androgens enhance the action of GH. The differential effects of estrogens and androgens influence the dose of GH replacement in patients with hypopituitarism on concomitant treatment with sex steroids. Where possible, a non-oral route of estrogen replacement is recommended for optimizing cost-benefit of GH replacement in women with GH deficiency. Adequate androgen replacement in conjunction with GH replacement is required to achieve the full anabolic effect in men with hypopituitarism. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. ESTRADIOL-INDUCED SYNTHESIS OF VITELLOGENIN .3. ISOLATION AND CHARACTERIZATION OF VITELLOGENIN MESSENGER-RNA FROM AVIAN LIVER

    NARCIS (Netherlands)

    AB, G.; Roskam, W. G.; Dijkstra, J.; Mulder, J.; Willems, M.; van der Ende, A.; Gruber, M.

    1976-01-01

    The messenger RNA of the hormone-induced protein vitellogenin was isolated from the liver of estrogen-treated roosters. Starting from total polysomal RNA, the vitellogenin messenger was purified 67-fold by oligo (dT)-cellulose chromatography and sizing on a sucrose gradient. The messenger was

  17. Effect of GH/IGF-1 on Bone Metabolism and Osteoporsosis

    Directory of Open Access Journals (Sweden)

    Vittorio Locatelli

    2014-01-01

    Full Text Available Background. Growth hormone (GH and insulin-like growth factor (IGF-1 are fundamental in skeletal growth during puberty and bone health throughout life. GH increases tissue formation by acting directly and indirectly on target cells; IGF-1 is a critical mediator of bone growth. Clinical studies reporting the use of GH and IGF-1 in osteoporosis and fracture healing are outlined. Methods. A Pubmed search revealed 39 clinical studies reporting the effects of GH and IGF-1 administration on bone metabolism in osteopenic and osteoporotic human subjects and on bone healing in operated patients with normal GH secretion. Eighteen clinical studies considered the effect with GH treatment, fourteen studies reported the clinical effects with IGF-1 administration, and seven related to the GH/IGF-1 effect on bone healing. Results. Both GH and IGF-1 administration significantly increased bone resorption and bone formation in the most studies. GH/IGF-1 administration in patients with hip or tibial fractures resulted in increased bone healing, rapid clinical improvements. Some conflicting results were evidenced. Conclusions. GH and IGF-1 therapy has a significant anabolic effect. GH administration for the treatment of osteoporosis and bone fractures may greatly improve clinical outcome. GH interacts with sex steroids in the anabolic process. GH resistance process is considered.

  18. Effect of GH/IGF-1 on Bone Metabolism and Osteoporsosis

    Science.gov (United States)

    Locatelli, Vittorio; Bianchi, Vittorio E.

    2014-01-01

    Background. Growth hormone (GH) and insulin-like growth factor (IGF-1) are fundamental in skeletal growth during puberty and bone health throughout life. GH increases tissue formation by acting directly and indirectly on target cells; IGF-1 is a critical mediator of bone growth. Clinical studies reporting the use of GH and IGF-1 in osteoporosis and fracture healing are outlined. Methods. A Pubmed search revealed 39 clinical studies reporting the effects of GH and IGF-1 administration on bone metabolism in osteopenic and osteoporotic human subjects and on bone healing in operated patients with normal GH secretion. Eighteen clinical studies considered the effect with GH treatment, fourteen studies reported the clinical effects with IGF-1 administration, and seven related to the GH/IGF-1 effect on bone healing. Results. Both GH and IGF-1 administration significantly increased bone resorption and bone formation in the most studies. GH/IGF-1 administration in patients with hip or tibial fractures resulted in increased bone healing, rapid clinical improvements. Some conflicting results were evidenced. Conclusions. GH and IGF-1 therapy has a significant anabolic effect. GH administration for the treatment of osteoporosis and bone fractures may greatly improve clinical outcome. GH interacts with sex steroids in the anabolic process. GH resistance process is considered. PMID:25147565

  19. The GH/IGF-1 axis in ageing and longevity

    Science.gov (United States)

    List, Edward O.; Berryman, Darlene E.; Murrey, John W.

    2014-01-01

    Secretion of growth hormone (GH), and consequently that of insulin-like growth factor 1 (IGF-1), declines over time until only low levels can be detected in individuals aged ≥60 years. This phenomenon, which is known as the ‘somatopause’, has led to recombinant human GH being widely promoted and abused as an antiageing drug, despite lack of evidence of efficacy. By contrast, several mutations that decrease the tone of the GH/IGF-1 axis are associated with extended longevity in mice. In humans, corresponding or similar mutations have been identified, but whether these mutations alter longevity has yet to be established. The powerful effect of reduced GH activity on lifespan extension in mice has generated the hypothesis that pharmaceutically inhibiting, rather than increasing, GH action might delay ageing. Moreover, mice as well as humans with reduced activity of the GH/IGF-1 axis are protected from cancer and diabetes mellitus, two major ageing-related morbidities. Here, we review data on mouse strains with alterations in the GH/IGF-1 axis and their effects on lifespan. The outcome of corresponding or similar mutations in humans is described, as well as the potential mechanisms underlying increased longevity and the therapeutic benefits and risks of medical disruption of the GH/IGF-1 axis in humans. PMID:23591370

  20. Immune function during GH treatment in GH-deficient adults

    DEFF Research Database (Denmark)

    Sneppen, S B; Mersebach, H; Ullum, H

    2002-01-01

    investigated were unaltered. CONCLUSIONS: GH deficiency was associated with changes in lymphocyte subsets and impaired unstimulated and stimulated natural killer cell activity, but these remained abnormal during 18 months of GH replacement therapy. Extra-pituitary GH gene expression in, e.g. lymphoid tissues...

  1. Obesity, growth hormone and weight loss

    DEFF Research Database (Denmark)

    Rasmussen, Michael Højby

    2009-01-01

    Growth hormone (GH) is the most important hormonal regulator of postnatal longitudinal growth in man. In adults GH is no longer needed for longitudinal growth. Adults with growth hormone deficiency (GHD) are characterised by perturbations in body composition, lipid metabolism, cardiovascular risk...

  2. Gender influences short-term growth hormone treatment response in children

    DEFF Research Database (Denmark)

    Sävendahl, Lars; Blankenstein, Oliver; Oliver, Isabelle

    2012-01-01

    Gender may affect growth hormone (GH) treatment outcome. This study assessed gender-related differences in change from baseline height standard deviation scores (ΔHSDS) after 2 years' GH treatment.......Gender may affect growth hormone (GH) treatment outcome. This study assessed gender-related differences in change from baseline height standard deviation scores (ΔHSDS) after 2 years' GH treatment....

  3. Recombinant-derived chicken growth hormone used for radioimmunoassay

    International Nuclear Information System (INIS)

    Proudman, J.A.

    1984-01-01

    The use of recombinant-derived chicken growth hormone (rcGH) in an avian growth hormone (GH) radioimmunoassay (RIA) procedure is described. Antiserum to turkey GH bound 125 I-labeled rcGH, and unlabeled rcGH or turkey GH displaced binding in a dose-related manner. The dose-response curves of sera and pituitary extract from chickens and turkeys were parallel to the rcGH standard curve. Sera from hypophysectomized (hypox) chickens and turkeys produced no dose-response and did not inhibit binding of labeled rcGH. Recovery of rcGH added to hypox sera was quantitative. Modification of the homologous turkey GH RIA protocol of Proudman and Wentworth (1) to use rcGH made possible either an increase in assay sensitivity or a 3-day reduction in incubation time

  4. Growth hormone test

    Science.gov (United States)

    ... is called acromegaly . In children it is called gigantism . Too little growth hormone can cause a slow ... growth due to excess GH during childhood, called gigantism. (A special test is done to confirm this ...

  5. Binding properties of beetal recombinant caprine growth hormone to ...

    African Journals Online (AJOL)

    The aim of the study was to illustrate the radio-receptor assay of beetal recombinant caprine growth hormone (rcGH). Tracer (125I-rcGH) was prepared by iodinating beetal rcGH with iodine-125 and its biological activity was analyzed by rabbit anti-rcGH antibodies. Liver microsomal membranes of the Bovidae species ...

  6. Effect of growth hormone replacement therapy on pituitary hormone secretion and hormone replacement therapies in GHD adults

    DEFF Research Database (Denmark)

    Hubina, Erika; Mersebach, Henriette; Rasmussen, Ase Krogh

    2004-01-01

    We tested the impact of commencement of GH replacement therapy in GH-deficient (GHD) adults on the circulating levels of other anterior pituitary and peripheral hormones and the need for re-evaluation of other hormone replacement therapies, especially the need for dose changes.......We tested the impact of commencement of GH replacement therapy in GH-deficient (GHD) adults on the circulating levels of other anterior pituitary and peripheral hormones and the need for re-evaluation of other hormone replacement therapies, especially the need for dose changes....

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

    DEFF Research Database (Denmark)

    Billestrup, N; Møldrup, A; Serup, P

    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, we have transfected ...

  8. Insulin, IGF-1, and GH Receptors Are Altered in an Adipose Tissue Depot-Specific Manner in Male Mice With Modified GH Action.

    Science.gov (United States)

    Hjortebjerg, Rikke; Berryman, Darlene E; Comisford, Ross; Frank, Stuart J; List, Edward O; Bjerre, Mette; Frystyk, Jan; Kopchick, John J

    2017-05-01

    Growth hormone (GH) is a determinant of glucose homeostasis and adipose tissue (AT) function. Using 7-month-old transgenic mice expressing the bovine growth hormone (bGH) gene and growth hormone receptor knockout (GHR-/-) mice, we examined whether changes in GH action affect glucose, insulin, and pyruvate tolerance and AT expression of proteins involved in the interrelated signaling pathways of GH, insulinlike growth factor 1 (IGF-1), and insulin. Furthermore, we searched for AT depot-specific differences in control mice. Glycated hemoglobin levels were reduced in bGH and GHR-/- mice, and bGH mice displayed impaired gluconeogenesis as judged by pyruvate tolerance testing. Serum IGF-1 was elevated by 90% in bGH mice, whereas IGF-1 and insulin were reduced by 97% and 61% in GHR-/- mice, respectively. Igf1 RNA was increased in subcutaneous, epididymal, retroperitoneal, and brown adipose tissue (BAT) depots in bGH mice (mean increase ± standard error of the mean in all five depots, 153% ± 27%) and decreased in all depots in GHR-/- mice (mean decrease, 62% ± 4%). IGF-1 receptor expression was decreased in all AT depots of bGH mice (mean decrease, 49% ± 6%) and increased in all AT depots of GHR-/- mice (mean increase, 94% ± 8%). Insulin receptor expression was reduced in retroperitoneal, mesenteric, and BAT depots in bGH mice (mean decrease in all depots, 56% ± 4%) and augmented in subcutaneous, retroperitoneal, mesenteric, and BAT depots in GHR-/- mice (mean increase: 51% ± 1%). Collectively, our findings indicate a role for GH in influencing hormone signaling in AT in a depot-dependent manner. Copyright © 2017 Endocrine Society.

  9. Detection of GH abuse in sport: Past, present and future.

    Science.gov (United States)

    Barroso, Osquel; Schamasch, Patrick; Rabin, Olivier

    2009-08-01

    Due to its considered performance enhancing effects, human growth hormone (hGH) is abused as a doping agent in sport. Its misuse also carries potentially serious side effects to a person's health. Consequently, hGH and its releasing factors are prohibited in sport, as established in the Prohibited List which is updated and published yearly by the World Anti-Doping Agency (WADA). In order to fight the menace that hGH doping poses to the spirit of sport and to the health of athletes, the sport movement and the anti-doping authorities, initially led by the International Olympic Committee (IOC) and later by WADA, have put substantial efforts into developing tests for its detection. Currently, a primary analytical approach, the isoform differential immunoassay, has been implemented in WADA-accredited laboratories. In parallel, a second, indirect approach for the detection of hGH abuse, based on the quantification of hGH-associated biological markers, has been developed. The final aim is to combine both methodologies to improve the sensitivity and expand the time window to detect doping with hGH. In addition, novel analytical procedures, based on proteomic and genomic technologies as well as the use of mass spectrometry-based methods of detection, are being investigated for future application in hGH anti-doping tests.

  10. Endurance training and GH administration in elderly women

    DEFF Research Database (Denmark)

    Lange, K H; Lorentsen, J; Isaksson, F

    2001-01-01

    and after completion of the training program. Similarly, no effect on subcutaneous abdominal adipose tissue lipolysis was observed when combining endurance training with rhGH administration. However, in both the placebo and the GH groups, fat oxidation was significantly increased during exercise performed......In the present study, the effect of endurance training alone and endurance training combined with recombinant human growth hormone (rhGH) administration on subcutaneous abdominal adipose tissue lipolysis was investigated. Sixteen healthy women [age 75 +/- 2 yr (mean +/- SE)] underwent a 12-wk...... endurance training program on a cycle ergometer. rhGH was administered in a randomized, double-blinded, placebo-controlled design in addition to the training program. Subcutaneous abdominal adipose tissue lipolysis was estimated by means of microdialysis combined with measurements of subcutaneous abdominal...

  11. Dynamical Messengers for Gauge Mediation

    Energy Technology Data Exchange (ETDEWEB)

    Hook, Anson; Torroba, Gonzalo; /SLAC /Stanford U., Phys. Dept.

    2011-08-17

    We construct models of indirect gauge mediation where the dynamics responsible for breaking supersymmetry simultaneously generates a weakly coupled subsector of messengers. This provides a microscopic realization of messenger gauge mediation where the messenger and hidden sector fields are unified into a single sector. The UV theory is SQCD with massless and massive quarks plus singlets, and at low energies it flows to a weakly coupled quiver gauge theory. One node provides the primary source of supersymmetry breaking, which is then transmitted to the node giving rise to the messenger fields. These models break R-symmetry spontaneously, produce realistic gaugino and sfermion masses, and give a heavy gravitino.

  12. MESSENGER: Exploring Mercury's Magnetosphere

    Science.gov (United States)

    Slavin, James A.

    2008-01-01

    The MESSENGER mission to Mercury offers our first opportunity to explore this planet's miniature magnetosphere since Mariner 10's brief fly-bys in 1974-5. Mercury's magnetosphere is unique in many respects. The magnetosphere of Mercury is the smallest in the solar system with its magnetic field typically standing off the solar wind only - 1000 to 2000 km above the surface. For this reason there are no closed dri-fi paths for energetic particles and, hence, no radiation belts; the characteristic time scales for wave propagation and convective transport are short possibly coupling kinetic and fluid modes; magnetic reconnection at the dayside magnetopause may erode the subsolar magnetosphere allowing solar wind ions to directly impact the dayside regolith; inductive currents in Mercury's interior should act to modify the solar In addition, Mercury's magnetosphere is the only one with its defining magnetic flux tubes rooted in a planetary regolith as opposed to an atmosphere with a conductive ionosphere. This lack of an ionosphere is thought to be the underlying reason for the brevity of the very intense, but short lived, approx. 1-2 min, substorm-like energetic particle events observed by Mariner 10 in Mercury's magnetic tail. In this seminar, we review what we think we know about Mercury's magnetosphere and describe the MESSENGER science team's strategy for obtaining answers to the outstanding science questions surrounding the interaction of the solar wind with Mercury and its small, but dynamic magnetosphere.

  13. Effects of Huang Bai (Phellodendri Cortex and Three Other Herbs on GnRH and GH Levels in GT1–7 and GH3 Cells

    Directory of Open Access Journals (Sweden)

    Sun Haeng Lee

    2016-01-01

    Full Text Available The present study was to evaluate the effects of Huang Bai, Zhi Mu, Mai Ya, and Xia Ku Cao on hormone using the GT1–7 and GH3 cells. The GT1–7 and GH3 cell lines were incubated with DW; DMSO; and 30, 100, or 300 μg/mL of one of the four extract solutions in serum-free media for 24 hours. The MTT assay was performed to determine the cytotoxicity of the four herbs. The GT1–7 and GH3 cells were incubated in DW, estradiol (GT1–7 only, or noncytotoxic herb solutions in serum-free medium for 24 hours. A quantitative RT-PCR and western blot were performed to measure the GnRH expression in GT1–7 cells and GH expression in GH3 cells. Huang Bai, Zhi Mu, Xia Ku Cao, and Mai Ya inhibited the GnRH mRNA expression in GT1–7 cells, whereas Huang Bai enhanced GH mRNA expression in GH3 cells. Additionally, Xia Ku Cao inhibited GnRH protein expression in GT1–7 cells and Huang Bai promoted GH protein expression in GH3 cells. The findings suggest that Huang Bai can delay puberty by inhibiting GnRH synthesis in the hypothalamus while also accelerating growth by promoting GH synthesis and secretion in the pituitary.

  14. Duchenne muscular dystrophy with associated growth hormone deficiency

    International Nuclear Information System (INIS)

    Ghafoor, T.; Mahmood, A.; Shams, S.

    2003-01-01

    A patient with duchenne muscular dystrophy (DMD) and growth hormone (GH) deficiency is described who had no clinical evidence of muscular weakness before initiation of GH replacement therapy. Treatment with human GH resulted in appearance of symptoms of easy fatigability and muscle weakness. Thorough investigations including serum creating phosphokinase (CK) levels in recommended in every patient with GH deficiency before starting GH replacement therapy. (author)

  15. Association of genetic polymorphism in GH gene with milk ...

    Indian Academy of Sciences (India)

    Associations were analysed between polymorphisms of the growth hormone gene (GH-MspI) (localized in intron 3) and milk production traits of Beijing Holstein cows (a total of 543 cows). Polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method was used for identification of various ...

  16. Use of human GH in elderly patients with accidental hip fracture

    NARCIS (Netherlands)

    A-J. van der Lely (Aart-Jan); S.W.J. Lamberts (Steven); K.W. Jauch; B.A. Swierstra (Bart); H. Hertlein; D. de Vries (Danielle); M.A. Birkett; P.C. Bates; W.F. Blum (Werner); A.F. Attanasio (Andrea)

    2000-01-01

    textabstractOBJECTIVE: To investigate whether early intervention with recombinant human growth hormone (hGH) after hip fracture improves functional recovery and long-term outcome. SUBJECTS AND METHODS: Functional recovery after hip fracture is often incomplete. The catabolic

  17. Translational Influence on Messenger Stability

    DEFF Research Database (Denmark)

    Eriksen, Mette

    -termination to be a global phenomena in gene regulation. The influence of codon usage in the early coding region on messenger stability was examined, in order to establish how fast or slow the ribosome has to decode the sequence for it to protect the messenger from degradation. The experiments demonstrated that very fast...

  18. Segundos mensajeros Second messengers

    Directory of Open Access Journals (Sweden)

    Diana Patricia Díaz Hernández

    1989-01-01

    Full Text Available

    En esta revisión se describen, de manera esquemática, los mecanismos de acción empleados por los SEGUNDOS MENSAJEROS comenzando por el estimulo del receptor y continuando con las reacciones en cadena que conducen finalmente a una respuesta celular.

    This review schematically describes the different mechanisms of action that Second Messengers employ to stimulate receptors and then Initiate a chain of reactions that finally lead to appropriate cellular responses.

  19. Effect of cessation of GH treatment on cognition during transition phase in Prader-Willi syndrome: results of a 2-year crossover GH trial

    Directory of Open Access Journals (Sweden)

    R. J. Kuppens

    2016-11-01

    Full Text Available Abstract Background Patients with Prader-Willi syndrome (PWS have a cognitive impairment. Growth hormone (GH treatment during childhood improves cognitive functioning, while cognition deteriorates in GH-untreated children with PWS. Cessation of GH treatment at attainment of adult height (AH might deteriorate their GH-induced improved cognition, while continuation might benefit them. We, therefore, investigated the effects of placebo versus GH administration on cognition in young adults with PWS who were GH-treated for many years during childhood and had attained AH. Method Two-year, randomized, double-blind, placebo-controlled cross-over study in 25 young adults with PWS. Cross-over intervention with placebo and GH (0.67 mg/m2/day, both during 1 year. Results Total (TIQ, verbal (VIQ and performance IQ (PIQ did not deteriorate during 1 year of placebo, compared to GH treatment (p > 0.322. Young adults with a lower TIQ had significantly more loss of TIQ points during placebo versus GH, in particular VIQ decreased more in those with a lower VIQ. The effect of placebo versus GH on TIQ, VIQ and PIQ was not different for gender or genotype. Conclusions Compared to GH treatment, 1 year of placebo did not deteriorate cognitive functioning of GH-treated young adults with PWS who have attained AH. However, patients with a lower cognitive functioning had more loss in IQ points during placebo versus GH treatment. The reassuring finding that 1 year of placebo does not deteriorate cognitive functioning does, however, not exclude a gradual deterioration of cognitive functioning on the long term. Trial registration ISRCTN24648386 , NTR1038 , Dutch Trial Register, www.trialregister.nl . Registered 16 August 2007.

  20. Effect of cessation of GH treatment on cognition during transition phase in Prader-Willi syndrome: results of a 2-year crossover GH trial.

    Science.gov (United States)

    Kuppens, R J; Mahabier, E F; Bakker, N E; Siemensma, E P C; Donze, S H; Hokken-Koelega, A C S

    2016-11-16

    Patients with Prader-Willi syndrome (PWS) have a cognitive impairment. Growth hormone (GH) treatment during childhood improves cognitive functioning, while cognition deteriorates in GH-untreated children with PWS. Cessation of GH treatment at attainment of adult height (AH) might deteriorate their GH-induced improved cognition, while continuation might benefit them. We, therefore, investigated the effects of placebo versus GH administration on cognition in young adults with PWS who were GH-treated for many years during childhood and had attained AH. Two-year, randomized, double-blind, placebo-controlled cross-over study in 25 young adults with PWS. Cross-over intervention with placebo and GH (0.67 mg/m 2 /day), both during 1 year. Total (TIQ), verbal (VIQ) and performance IQ (PIQ) did not deteriorate during 1 year of placebo, compared to GH treatment (p > 0.322). Young adults with a lower TIQ had significantly more loss of TIQ points during placebo versus GH, in particular VIQ decreased more in those with a lower VIQ. The effect of placebo versus GH on TIQ, VIQ and PIQ was not different for gender or genotype. Compared to GH treatment, 1 year of placebo did not deteriorate cognitive functioning of GH-treated young adults with PWS who have attained AH. However, patients with a lower cognitive functioning had more loss in IQ points during placebo versus GH treatment. The reassuring finding that 1 year of placebo does not deteriorate cognitive functioning does, however, not exclude a gradual deterioration of cognitive functioning on the long term. ISRCTN24648386 , NTR1038 , Dutch Trial Register, www.trialregister.nl . Registered 16 August 2007.

  1. Pituitary-hormone secretion by thyrotropinomas

    NARCIS (Netherlands)

    Roelfsema, Ferdinand; Kok, Simon; Kok, Petra; Pereira, Alberto M.; Biermasz, Nienke R.; Smit, Jan W.; Frolich, Marijke; Keenan, Daniel M.; Veldhuis, Johannes D.; Romijn, Johannes A.

    2009-01-01

    Hormone secretion by somatotropinomas, corticotropinomas and prolactinomas exhibits increased pulse frequency, basal and pulsatile secretion, accompanied by greater disorderliness. Increased concentrations of growth hormone (GH) or prolactin (PRL) are observed in about 30% of thyrotropinomas leading

  2. Pathophysiological implications of the chemical messengers

    International Nuclear Information System (INIS)

    Blazquez Fernandez, E.

    2009-01-01

    To maintain a physical organization and a different composition of its surroundings environment, living beings use a great part of the energy that they produce. Vital processes require an elevated number of reactions which are regulated and integrated by chemical messengers. They use autocrine, paracrine, endocrine and synaptic signals through receptors of cell surface, nuclear or associated with ionic channels, enzymes, trim eric G proteins and to intracellular kinases. Through these mechanisms pheromones play an important role in the relationships between different individuals, and hormones are able to regulate the integrative functions of our organism. In the nervous system, neurotransmitters, neuromodulators, sensors and receptors between other messengers, play functions of great relevance, while growth factors stimulate cell proliferation and cytokines have many effects but the most important is the ones related with the control of the immflamatory process. Alterations of these messengers permit us a better understanding of the diseases and possibly of its treatments in a near future. Modifications of the expression of genes from the nuclear and mitochondrial genomes are responsible of monogenic, polygenic and mitochondrial diseases, while alterations in the activities of dopamine and serotonin neurotransmitters are related with schizophrenia, Parkinson disease and depression, respectively. Other example is the hyperthyroidism of the Graves-Bassedow disease due to the competitive interference of the LATS immunoglobulin with TSH at the level of the follicular cells producing thyroid hormones Twenty five years ago in the reviews on the mechanisms of insulin action, there was presentations in which the insulin receptor was located in the plasma membrane of the target cells while in the cytoplasm only a big interrogative was observed, that at present is replaced by chemical mediators cascades responsible of the multiple effects of insulin. This finding is similar

  3. Growth hormone treatment during pregnancy in a growth hormone-deficient woman

    DEFF Research Database (Denmark)

    Müller, J; Starup, J; Christiansen, J S

    1995-01-01

    Information on the course and outcome of pregnancies in growth hormone (GH)-deficient patients is sparse, and GH treatment during pregnancy in such women has not been described previously. We have studied fetal growth and serum levels of GH, insulin-like growth factor I (IGF-I) and IGF binding...

  4. Continuation of growth hormone therapy versus placebo in transition-phase patients with growth hormone deficiency

    DEFF Research Database (Denmark)

    Jørgensen, Jens; Nørrelund, Helene; Vahl, Nina

    2002-01-01

    In a placebo-controlled, parallel study of 18 patients with a mean age of 20 years who had confirmed growth hormone (GH) deficiency, we evaluated body composition, insulin sensitivity, and glucose turnover at baseline (when all were receiving GH replacement); after 12 months of continued GH therapy...

  5. GH receptor blocker administration and muscle-tendon collagen synthesis in humans

    DEFF Research Database (Denmark)

    Nielsen, Rie Harboe; Doessing, Simon; Goto, Kazushige

    2011-01-01

    The growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis stimulates collagen synthesis in tendon and skeletal muscle, but no studies have investigated the effect of reducing IGF-I on collagen synthesis in healthy humans.......The growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis stimulates collagen synthesis in tendon and skeletal muscle, but no studies have investigated the effect of reducing IGF-I on collagen synthesis in healthy humans....

  6. Heterologous humoral immune response in patients treated with human growth hormone from different sources

    International Nuclear Information System (INIS)

    Cardoso, A.I.; Llera, A.S.; Iacono, R.F.

    1993-01-01

    The existence of homologous anti-human growth hormone (anti-hGH) and heterologous anti-bovine growth hormone (anti-bGH) humoral immune responses in hypopituitary patients under hGH therapy has been reported previously. In order to study the influence of the hormone source, both responses were compared by radiobinding assays performed with [ 125 I]hGH or [ 125 I]bGH as tracers. 57 hypopituitary patients treated with extractive hGH, recombinant methionyl hGH or authentic recombinant hGH were studied. A very low incidence of heterologous antibodies was found in patients under recombinant hGH therapy, contrary to the high incidence observed in patients treated with extractive hGH preparations. In addition, immunochemical studies performed with a synthetic peptide (hGH 44-128) indicated that this peptide exhibited, in the anti-bGH/[ 125 I]bGH radioimmunoassay system, higher reactivity than the native hGH, suggesting that such fragment resembled an altered conformation of the hormone. The high heterologous response elicited only by the extractive hGH along with the behaviour of the hGH 44-128 fragment supports the fact that the extraction and purification procedures in extractive preparations may alter slightly the structure of the hGH molecule and trigger a heterologous immune response. 16 refs., 4 figs., 1 tab

  7. Heterologous humoral immune response in patients treated with human growth hormone from different sources

    Energy Technology Data Exchange (ETDEWEB)

    Cardoso, A.I.; Llera, A.S.; Iacono, R.F. (and others) (Inst. de Estudios de la Inmunidad Humoral, Buenos Aires (Argentina))

    1993-07-01

    The existence of homologous anti-human growth hormone (anti-hGH) and heterologous anti-bovine growth hormone (anti-bGH) humoral immune responses in hypopituitary patients under hGH therapy has been reported previously. In order to study the influence of the hormone source, both responses were compared by radiobinding assays performed with [[sup 125]I]hGH or [[sup 125]I]bGH as tracers. 57 hypopituitary patients treated with extractive hGH, recombinant methionyl hGH or authentic recombinant hGH were studied. A very low incidence of heterologous antibodies was found in patients under recombinant hGH therapy, contrary to the high incidence observed in patients treated with extractive hGH preparations. In addition, immunochemical studies performed with a synthetic peptide (hGH 44-128) indicated that this peptide exhibited, in the anti-bGH/[[sup 125]I]bGH radioimmunoassay system, higher reactivity than the native hGH, suggesting that such fragment resembled an altered conformation of the hormone. The high heterologous response elicited only by the extractive hGH along with the behaviour of the hGH 44-128 fragment supports the fact that the extraction and purification procedures in extractive preparations may alter slightly the structure of the hGH molecule and trigger a heterologous immune response. 16 refs., 4 figs., 1 tab.

  8. MESSENGER'S First Flyby of Mercury

    Science.gov (United States)

    Slavin, James A.

    2008-01-01

    The MESSENGER mission to Mercury offers our first opportunity to explore this planet's miniature magnetosphere since Mariner 10's brief fly-bys in 1974-5. The magnetosphere of Mercury is the smallest in the solar system with its magnetic field typically standing off the solar wind only - 1000 to 2000 km above the surface. An overview of the MESSENGER mission and its January 14th close flyby of Mercury will be provided. Primary science objectives and the science instrumentation will be described. Initial results from MESSENGER'S first flyby on January 14th, 2008 will be discussed with an emphasis on the magnetic field and charged particle measurements.

  9. contribution of growth hormone-releasing hormone and

    African Journals Online (AJOL)

    The strategy used was to stimulate GH secretion in 8 young ... treatment with two oral doses of 50 mg atenolol (to inhibit .... had normal baseline thyroid-stimulating hormone (TSH) ..... production rate of 14% per decade has been documented.'".

  10. Obesity, growth hormone and exercise.

    Science.gov (United States)

    Thomas, Gwendolyn A; Kraemer, William J; Comstock, Brett A; Dunn-Lewis, Courtenay; Maresh, Carl M; Volek, Jeff S

    2013-09-01

    Growth hormone (GH) is regulated, suppressed and stimulated by numerous physiological stimuli. However, it is believed that obesity disrupts the physiological and pathological factors that regulate, suppress or stimulate GH release. Pulsatile GH has been potently stimulated in healthy subjects by both aerobic and resistance exercise of the right intensity and duration. GH modulates fuel metabolism, reduces total fat mass and abdominal fat mass, and could be a potent stimulus of lipolysis when administered to obese individuals exogenously. Only pulsatile GH has been shown to augment adipose tissue lipolysis and, therefore, increasing pulsatile GH response may be a therapeutic target. This review discusses the factors that cause secretion of GH, how obesity may alter GH secretion and how both aerobic and resistance exercise stimulates GH, as well as how exercise of a specific intensity may be used as a stimulus for GH release in individuals who are obese. Only five prior studies have investigated exercise as a stimulus of endogenous GH in individuals who are obese. Based on prior literature, resistance exercise may provide a therapeutic target for releasing endogenous GH in individuals who are obese if specific exercise programme variables are utilized. Biological activity of GH indicates that this may be an important precursor to beneficial changes in body fat and lean tissue mass in obese individuals. However, additional research is needed including what molecular GH variants are acutely released and involved at target tissues as a result of different exercise stimuli and what specific exercise programme variables may serve to stimulate GH in individuals who are obese.

  11. The Messenger Mission to Mercury

    CERN Document Server

    Domingue, D. L

    2007-01-01

    NASA’s MESSENGER mission, launched on 3 August, 2004 is the seventh mission in the Discovery series. MESSENGER encounters the planet Mercury four times, culminating with an insertion into orbit on 18 March 2011. It carries a comprehensive package of geophysical, geological, geochemical, and space environment experiments to complete the complex investigations of this solar-system end member, which begun with Mariner 10. The articles in this book, written by the experts in each area of the MESSENGER mission, describe the mission, spacecraft, scientific objectives, and payload. The book is of interest to all potential users of the data returned by the MESSENGER mission, to those studying the nature of the planet Mercury, and by all those interested in the design and implementation of planetary exploration missions.

  12. The rationale and design of TransCon Growth Hormone for the treatment of growth hormone deficiency

    Directory of Open Access Journals (Sweden)

    Kennett Sprogøe

    2017-10-01

    Full Text Available The fundamental challenge of developing a long-acting growth hormone (LAGH is to create a more convenient growth hormone (GH dosing profile while retaining the excellent safety, efficacy and tolerability of daily GH. With GH receptors on virtually all cells, replacement therapy should achieve the same tissue distribution and effects of daily (and endogenous GH while maintaining levels of GH and resulting IGF-1 within the physiologic range. To date, only two LAGHs have gained the approval of either the Food and Drug Administration (FDA or the European Medicines Agency (EMA; both released unmodified GH, thus presumably replicating distribution and pharmacological actions of daily GH. Other technologies have been applied to create LAGHs, including modifying GH (for example, protein enlargement or albumin binding such that the resulting analogues possess a longer half-life. Based on these approaches, nearly 20 LAGHs have reached various stages of clinical development. Although most have failed, lessons learned have guided the development of a novel LAGH. TransCon GH is a LAGH prodrug in which GH is transiently bound to an inert methoxy polyethylene glycol (mPEG carrier. It was designed to achieve the same safety, efficacy and tolerability as daily GH but with more convenient weekly dosing. In phase 2 trials of children and adults with growth hormone deficiency (GHD, similar safety, efficacy and tolerability to daily GH was shown as well as GH and IGF-1 levels within the physiologic range. These promising results support further development of TransCon GH.

  13. Nuclear translocation and retention of growth hormone

    DEFF Research Database (Denmark)

    Mertani, Hichem C; Raccurt, Mireille; Abbate, Aude

    2003-01-01

    We have previously demonstrated that GH is subject to rapid receptor-dependent nuclear translocation. Here, we examine the importance of ligand activation of the GH-receptor (GHR)-associated Janus kinase (JAK) 2 and receptor dimerization for hormone internalization and nuclear translocation by use...... of cells stably transfected with cDNA for the GHR. Staurosporine and herbimycin A treatment of cells did not affect the ability of GH to internalize but resulted in increased nuclear accumulation of hormone. Similarly, receptor mutations, which prevent the association and activation of JAK2, did not affect...... the ability of the hormone to internalize or translocate to the nucleus but resulted in increased nuclear accumulation of GH. These results were observed both by nuclear isolation and confocal laser scanning microscopy. Staurosporine treatment of cells in which human GH (hGH) was targeted to the cytoplasm...

  14. Increased fibrosis: A novel means by which GH influences white adipose tissue function.

    Science.gov (United States)

    Householder, Lara A; Comisford, Ross; Duran-Ortiz, Silvana; Lee, Kevin; Troike, Katie; Wilson, Cody; Jara, Adam; Harberson, Mitchell; List, Edward O; Kopchick, John J; Berryman, Darlene E

    2018-04-01

    White adipose tissue (WAT) fibrosis - the buildup of extracellular matrix (ECM) proteins, primarily collagen - is now a recognized hallmark of tissue dysfunction and is increased with obesity and lipodystrophy. While growth hormone (GH) is known to increase collagen in several tissues, no previous research has addressed its effect on ECM in WAT. Thus, the purpose of this study is to determine if GH influences WAT fibrosis. This study examined WAT from four distinct strains of GH-altered mice (bGH and GHA transgenic mice as well as two tissue specific GH receptor gene disrupted lines, fat growth hormone receptor knockout or FaGHRKO and liver growth hormone receptor knockout or LiGHRKO mice). Collagen content and adipocyte size were studied in all cohorts and compared to littermate controls. In addition, mRNA expression of fibrosis-associated genes was assessed in one cohort (6month old male bovine GH transgenic and WT mice) and cultured 3T3-L1 adipocytes treated with GH. Collagen stained area was increased in WAT from bGH mice, was depot-dependent, and increased with age. Furthermore, increased collagen content was associated with decreased adipocyte size in all depots but more dramatic changes in the subcutaneous fat pad. Notably, the increase in collagen was not associated with an increase in collagen gene expression or other genes known to promote fibrosis in WAT, but collagen gene expression was increased with acute GH administration in 3T3-LI cells. In contrast, evaluation of 6month old GH antagonist (GHA) male mice showed significantly decreased collagen in the subcutaneous depot. Lastly, to assess if GH induced collagen deposition directly or indirectly (via IGF-1), fat (Fa) and liver (Li) specific GHRKO mice were evaluated. Decreased fibrosis in FaGHRKO and increased fibrosis in LiGHRKO mice suggest GH is primarily responsible for the alterations in collagen. Our results show that GH action is positively associated with an increase in WAT collagen content as

  15. The characterization of six auxin-induced tomato GH3 genes uncovers a member, SlGH3.4, strongly responsive to arbuscular mycorrhizal symbiosis.

    Science.gov (United States)

    Liao, Dehua; Chen, Xiao; Chen, Aiqun; Wang, Huimin; Liu, Jianjian; Liu, Junli; Gu, Mian; Sun, Shubin; Xu, Guohua

    2015-04-01

    In plants, the GH3 gene family is widely considered to be involved in a broad range of plant physiological processes, through modulation of hormonal homeostasis. Multiple GH3 genes have been functionally characterized in several plant species; however, to date, limited works to study the GH3 genes in tomato have been reported. Here, we characterize the expression and regulatory profiles of six tomato GH3 genes, SlGH3.2, SlGH3.3, SlGH3.4, SlGH3.7, SlGH3.9 and SlGH3.15, in response to different phytohormone applications and arbuscular mycorrhizal (AM) fungal colonization. All six GH3 genes showed inducible responses to external IAA, and three members were significantly up-regulated in response to AM symbiosis. In particular, SlGH3.4, the transcripts of which were barely detectable under normal growth conditions, was strongly activated in the IAA-treated and AM fungal-colonized roots. A comparison of the SlGH3.4 expression in wild-type plants and M161, a mutant with a defect in AM symbiosis, confirmed that SlGH3.4 expression is highly correlated to mycorrhizal colonization. Histochemical staining demonstrated that a 2,258 bp SlGH3.4 promoter fragment could drive β-glucuronidase (GUS) expression strongly in root tips, steles and cortical cells of IAA-treated roots, but predominantly in the fungal-colonized cells of mycorrhizal roots. A truncated 654 bp promoter failed to direct GUS expression in IAA-treated roots, but maintained the symbiosis-induced activity in mycorrhizal roots. In summary, our results suggest that a mycorrhizal signaling pathway that is at least partially independent of the auxin signaling pathway has evolved for the co-regulation of the auxin- and mycorrhiza-activated GH3 genes in plants. © The Author 2014. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  16. Mortality and GH deficiency

    DEFF Research Database (Denmark)

    Stochholm, Kirstine; Gravholt, Claus Højbjerg; Laursen, Torben

    2007-01-01

    into childhood onset (CO) and adult onset (AO), discriminated by an age cutoff below or above 18 years at onset of GHD. METHOD: Data on death were identified in national registries. Sex- and cause-specific mortalities were identified in CO and AO GHD when compared with controls. RESULTS: Mortality was increased......OBJECTIVE: To estimate the mortality in Denmark in patients suffering from GH deficiency (GHD). DESIGN: Mortality was analyzed in 1794 GHD patients and 8014 controls matched on age and gender. All records in GHD patients were studied and additional morbidity noted. Patients were divided...... in CO and AO GHD in both genders, when compared with controls. The hazard ratio (HR) for CO males was 8.3 (95% confidence interval (CI) 4.5-15.1) and for females 9.4 (CI 4.6-19.4). For AO males, HR was 1.9 (CI 1.7-2.2) and for females 3.4 (CI 2.9-4.0). We found a significantly higher HR in AO females...

  17. Substrate Metabolism and Insulin Sensitivity During Fasting in Obese Human Subjects: Impact of GH Blockade.

    Science.gov (United States)

    Pedersen, Morten Høgild; Svart, Mads Vandsted; Lebeck, Janne; Bidlingmaier, Martin; Stødkilde-Jørgensen, Hans; Pedersen, Steen Bønløkke; Møller, Niels; Jessen, Niels; Jørgensen, Jens O L

    2017-04-01

    Insulin resistance and metabolic inflexibility are features of obesity and are amplified by fasting. Growth hormone (GH) secretion increases during fasting and GH causes insulin resistance. To study the metabolic effects of GH blockade during fasting in obese subjects. Nine obese males were studied thrice in a randomized design: (1) after an overnight fast (control), (2) after 72 hour fasting (fasting), and (3) after 72 hour fasting with GH blockade (pegvisomant) [fasting plus GH antagonist (GHA)]. Each study day consisted of a 4-hour basal period followed by a 2-hour hyperinsulinemic, euglycemic clamp combined with indirect calorimetry, assessment of glucose and palmitate turnover, and muscle and fat biopsies. GH levels increased with fasting (P fasting-induced reduction of serum insulin-like growth factor I was enhanced by GHA (P Fasting increased lipolysis and lipid oxidation independent of GHA, but fasting plus GHA caused a more pronounced suppression of lipid intermediates in response to hyperinsulinemic, euglycemic clamp. Fasting-induced insulin resistance was abrogated by GHA (P Fasting plus GHA also caused elevated glycerol levels and reduced levels of counterregulatory hormones. Fasting significantly reduced the expression of antilipolytic signals in adipose tissue independent of GHA. Suppression of GH activity during fasting in obese subjects reverses insulin resistance and amplifies insulin-stimulated suppression of lipid intermediates, indicating that GH is an important regulator of substrate metabolism, insulin sensitivity, and metabolic flexibility also in obese subjects. Copyright © 2017 by the Endocrine Society

  18. [Secretion of growth hormone in hyperthyroidism].

    Science.gov (United States)

    Hervás, F; Morreale de Escobar, G; Escobar Del Rey, F; Pozuelo, V

    1976-01-01

    The authors studied growth hormone (GH) secretion in a group of adult controls and another group of hyperthyroid patients after stimulation with intravenous insulin-induced (0,1 IU/kg) hypoglycemia, aiming to clear out the problem of discrepancies in literature concerning GH secretion in hyperthyroidism. They concluded that in this syndrome, GH levels are significantly higher than those of controls. The GH releasing response is normal, though it could be expected to be decreased due to decreased pituitary GH contents as a result of permanent somatotrophic cell stimulation.

  19. GH Travel & Mission Support System

    Data.gov (United States)

    US Agency for International Development — HTRAMS is a travel data collection system for GH that collects information on both the basic details of an employee's trips (destination, length, purpose, etc.) and...

  20. Improved growth response to GH treatment in irradiated children

    International Nuclear Information System (INIS)

    Lannering, B.; Albertsson-Wikland, K.

    1989-01-01

    The growth response to two years of GH treatment was studied in fifteen children after radiotherapy for a cranial tumour. The growth response was compared to that of short children (-2 SD) and that of children with idiopathic growth hormone deficiency (GHD) of similar ages. All children were treated with hGH 0.1 IU/kg/day s.c.; which is a higher dose and frequency than previously reported for irradiated children. On this protocol the growth rate increased 5.0 +- 0.5 cm/y (mean +- SEM) the first year and 3.8 +- 0.7 cm/y the second year compared to the growth rate the year before GH-treatment. Although the net gain in growth was higher than previously reported, the first year growth response was significantly reduced (p less than 0.05) compared to that of GHD-children (7.6 +- 0.5 cm/y) but exceeded (p less than 0.05) that of short children (3.4 +- 0.3 cm/y). The median spontaneous 24 h-GH secretion was 209 mU/l in the short children, 52 mU/l in the irradiated children and 16 mU/l in the idiopathic GHD children. Thus the growth increment varied inversely to the spontaneous GH secretion observed in the three groups

  1. The GH/IGF-1 axis in obesity: pathophysiology and therapeutic considerations.

    Science.gov (United States)

    Berryman, Darlene E; Glad, Camilla A M; List, Edward O; Johannsson, Gudmundur

    2013-06-01

    Obesity has become one of the most common medical problems in developed countries, and this disorder is associated with high incidences of hypertension, dyslipidaemia, cardiovascular disease, type 2 diabetes mellitus and specific cancers. Growth hormone (GH) stimulates the production of insulin-like growth factor 1 in most tissues, and together GH and insulin-like growth factor 1 exert powerful collective actions on fat, protein and glucose metabolism. Clinical trials assessing the effects of GH treatment in patients with obesity have shown consistent reductions in total adipose tissue mass, in particular abdominal and visceral adipose tissue depots. Moreover, studies in patients with abdominal obesity demonstrate a marked effect of GH therapy on body composition and on lipid and glucose homeostasis. Therefore, administration of recombinant human GH or activation of endogenous GH production has great potential to influence the onset and metabolic consequences of obesity. However, the clinical use of GH is not without controversy, given conflicting results regarding its effects on glucose metabolism. This Review provides an introduction to the role of GH in obesity and summarizes clinical and preclinical data that describe how GH can influence the obese state.

  2. GH mediates exercise-dependent activation of SVZ neural precursor cells in aged mice.

    Directory of Open Access Journals (Sweden)

    Daniel G Blackmore

    Full Text Available Here we demonstrate, both in vivo and in vitro, that growth hormone (GH mediates precursor cell activation in the subventricular zone (SVZ of the aged (12-month-old brain following exercise, and that GH signaling stimulates precursor activation to a similar extent to exercise. Our results reveal that both addition of GH in culture and direct intracerebroventricular infusion of GH stimulate neural precursor cells in the aged brain. In contrast, no increase in neurosphere numbers was observed in GH receptor null animals following exercise. Continuous infusion of a GH antagonist into the lateral ventricle of wild-type animals completely abolished the exercise-induced increase in neural precursor cell number. Given that the aged brain does not recover well after injury, we investigated the direct effect of exercise and GH on neural precursor cell activation following irradiation. This revealed that physical exercise as well as infusion of GH promoted repopulation of neural precursor cells in irradiated aged animals. Conversely, infusion of a GH antagonist during exercise prevented recovery of precursor cells in the SVZ following irradiation.

  3. GH Mediates Exercise-Dependent Activation of SVZ Neural Precursor Cells in Aged Mice

    Science.gov (United States)

    Blackmore, Daniel G.; Vukovic, Jana; Waters, Michael J.; Bartlett, Perry F.

    2012-01-01

    Here we demonstrate, both in vivo and in vitro, that growth hormone (GH) mediates precursor cell activation in the subventricular zone (SVZ) of the aged (12-month-old) brain following exercise, and that GH signaling stimulates precursor activation to a similar extent to exercise. Our results reveal that both addition of GH in culture and direct intracerebroventricular infusion of GH stimulate neural precursor cells in the aged brain. In contrast, no increase in neurosphere numbers was observed in GH receptor null animals following exercise. Continuous infusion of a GH antagonist into the lateral ventricle of wild-type animals completely abolished the exercise-induced increase in neural precursor cell number. Given that the aged brain does not recover well after injury, we investigated the direct effect of exercise and GH on neural precursor cell activation following irradiation. This revealed that physical exercise as well as infusion of GH promoted repopulation of neural precursor cells in irradiated aged animals. Conversely, infusion of a GH antagonist during exercise prevented recovery of precursor cells in the SVZ following irradiation. PMID:23209615

  4. New York Milk Supply with Bovine Growth Hormone

    OpenAIRE

    Magrath, William B.; Tauer, Loren W.

    1986-01-01

    New York milk supply functions with ans without Bovine Growth Hormone were estimated by a sector linear programming model. High Government price supports make bGH profitable and induces significant increases in output. Reduction or elimination of Price supports greatly diminishes bGH as a variable technology except at low bGH prices

  5. GH response to intravenous clonidine challenge correlates with history of childhood trauma in personality disorder.

    Science.gov (United States)

    Lee, Royce J; Fanning, Jennifer R; Coccaro, Emil F

    2016-05-01

    Childhood trauma is a risk factor for personality disorder. We have previously shown that childhood trauma is associated with increased central corticotrophin-releasing hormone concentration in adults with personality disorder. In the brain, the release of corticotrophin-releasing hormone can be stimulated by noradrenergic neuronal activity, raising the possibility that childhood trauma may affect the hypothalamic-pituitary adrenal (HPA) axis by altering brain noradrenergic function. In this study, we sought to test the hypothesis that childhood trauma is associated with blunted growth hormone response to the α-2 adrenergic autoreceptor agonist clonidine. All subjects provided written informed consent. Twenty personality disordered and twenty healthy controls (without personality disorder or Axis I psychopathology) underwent challenge with clonidine, while plasma Growth Hormone (GH) concentration was monitored by intravenous catheter. On a different study session, subjects completed the Childhood Trauma Questionnaire and underwent diagnostic interviews. Contrary to our a priori hypothesis, childhood trauma was associated with enhanced GH response to clonidine. This positive relationship was present in the group of 40 subjects and in the subgroup 20 personality disordered subjects, but was not detected in the healthy control subjects when analyzed separately. The presence of personality disorder was unrelated to the magnitude of GH response. Childhood trauma is positively correlated with GH response to clonidine challenge in adults with personality disorder. Enhanced rather that blunted GH response differentiates childhood trauma from previously identified negative predictors of GH response, such as anxiety or mood disorder. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Long-term maintenance of the anabolic effects of GH on the skeleton in successfully treated patients with acromegaly

    NARCIS (Netherlands)

    Biermasz, Nienke R.; Hamdy, Neveen A. T.; Pereira, Alberto M.; Romijn, Johannes A.; Roelfsema, Ferdinand

    2005-01-01

    The anabolic actions of growth hormone (GH) are well documented. In acromegaly, the skeletal effects of chronic GH excess have been mainly addressed by evaluating bone mineral density (BMD). Most data were obtained in patients with active acromegaly, and apparently high or normal BMD was observed in

  7. Effect of long-term growth hormone treatment on bone mass and bone metabolism in growth hormone-deficient men

    NARCIS (Netherlands)

    Bravenboer, N; Holzmann, PJ; ter Maaten, JC; Stuurman, LM; Roos, JC; Lips, P

    2005-01-01

    Long-term GH treatment in GH-deficient men resulted in a continuous increase in bone turnover as shown by histomorphometry. BMD continuously increased in all regions of interest, but more in the regions with predominantly cortical bone. Introduction: Adults with growth hormone (GH) deficiency have

  8. Auxological criteria for the diagnosis of GH-dependent short stature and prescription of rGH: problems and pitfalls

    Directory of Open Access Journals (Sweden)

    Giulio Gilli

    2007-12-01

    Full Text Available Recombinant growth hormone (rGH administration is a cornerstone in the treatment of short stature secondary to GH deficit. Since its introduction in the 80s, the population of short patients with an indication to rGH therapy has clearly broadened, probably because of increased awareness by patients and physicians. Since rGH therapy is demanding for patients and expensive, the Italian National Health Service, like other third payers and regulatory authorities, regulates its prescription according to criteria listed in the Nota AIFA 39. This paper illustrates pitfalls and difficulties paediatricians may encounter when assessing short stature patients in order to decide upon the opportunity and possibility to initiate rGH therapy through the exposition of four emblematic, though hypothetical, clinical histories. In the discussion, the Authors highlight some of the most critical points in the formulation of the Nota 39, among which are the lack of clear reference values, neglecting of parental height targets and therapeutic responses, as well as some omissions in methodology specifications.

  9. Relationship between thyroid functions and urinary growth hormone secretion in patients with hyper- and hypothyroidism.

    Science.gov (United States)

    Murao, K; Takahara, J; Sato, M; Tamaki, M; Niimi, M; Ishida, T

    1994-10-01

    Thyroid hormone plays an important role in growth hormone (GH) synthesis and secretion. To study the relationship between thyroid function and urinary GH secretion in the hyperthyroid and hypothyroid states, we measured thyroid hormones, simultaneously with serum and urinary GH levels, in 54 patients with thyroid diseases. GH-releasing hormone (GRH) test was performed in 18 patients in order to evaluate serum and urinary GH responses to GRH in hyper- and hypothyroid states. Serum thyroid hormone levels were strongly correlated with the urinary GH levels in the patients, and the correlation was greater than that between serum thyroid hormone and serum GH levels. Urinary GH levels were significantly higher in the hyperthyroid patients than in the euthyroid and hypothyroid patients, although serum GH levels were not significantly different among these three groups. Serum GH response to GRH was significantly decreased in hyperthyroid patients as compared to euthyroid patients. However, urinary GH levels after GRH administration were not decreased in the hyperthyroid patients. These results suggest that hyperthyroid states increase GH in urine and may accelerate the urinary clearance of GH.

  10. 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

  11. Effects of growth hormone and insulin-like growth factor 1 deficiency on ageing and longevity.

    Science.gov (United States)

    Laron, Zvi

    2002-01-01

    Present knowledge on the effects of growth hormone (GH)/insulin-like growth hormone (IGF)1 deficiency on ageing and lifespan are reviewed. Evidence is presented that isolated GH deficiency (IGHD), multiple pituitary hormone deficiencies (MPHD) including GH, as well as primary IGE1 deficiency (GH resistance, Laron syndrome) present signs of early ageing such as thin and wrinkled skin, obesity, hyperglycemia and osteoporosis. These changes do not seem to affect the lifespan, as patients reach old age. Animal models of genetic MPHD (Ames and Snell mice) and GH receptor knockout mice (primary IGF1 deficiency) also have a statistically significant higher longevity compared to normal controls. On the contrary, mice transgenic for GH and acromegalic patients secreting large amounts of GH have premature death. In conclusion longstanding GH/IGF1 deficiency affects several parameters of the ageing process without impairing lifespan, and as shown in animal models prolongs longevity. In contrast high GH/IGF1 levels accelerate death.

  12. Growth hormone effects on cortical bone dimensions in young adults with childhood-onset growth hormone deficiency

    DEFF Research Database (Denmark)

    Hyldstrup, L; Conway, G S; Racz, K

    2012-01-01

    Growth hormone (GH) treatment in young adults with childhood-onset GH deficiency has beneficial effects on bone mass. The present study shows that cortical bone dimensions also benefit from GH treatment, with endosteal expansion and increased cortical thickness leading to improved bone strength....... INTRODUCTION: In young adults with childhood-onset growth hormone deficiency (CO GHD), GH treatment after final height is reached has been shown to have beneficial effects on spine and hip bone mineral density. The objective of the study was to evaluate the influence of GH on cortical bone dimensions. METHODS...

  13. Luteinizing hormone (LH)-responsive Cushing's syndrome: the demonstration of LH receptor messenger ribonucleic acid in hyperplastic adrenal cells, which respond to chorionic gonadotropin and serotonin agonists in vitro

    NARCIS (Netherlands)

    R.A. Feelders (Richard); W.W. de Herder (Wouter); S.W.J. Lamberts (Steven); L.J. Hofland (Leo); P.M. van Koetsveld (Peter); M. Verhoef-Post (Miriam); A.P.N. Themmen (Axel); F.H. de Jong (Frank); H.J. Bonjer (Jaap); A.J. Clark (Adrian); A-J. van der Lely (Aart-Jan)

    2003-01-01

    textabstractIn a substantial part of adrenal adenomas and hyperplasias from patients with Cushing's syndrome, cortisol production is controlled by the expression of aberrant hormone receptors on adrenocortical cells. We present in vivo and in vitro data of two patients with a

  14. Growth hormone therapy: emerging dilemmas.

    Science.gov (United States)

    Laron, Zvi

    2011-06-01

    The history of pituitary growth hormone (GH) started 100 years ago but the isolation purification and determination of the chemical structure of the human GH (hGH) took another 50 years. Starting in 1957 hGH was extracted from cadaver pituitaries and its clinical use was restricted to severe GH deficient patient. With the invention of recombinant biosynthetic hGH in 1985; the indications for its use were extended. The major approved medications are GH deficiency and short statured children of various etiologies. This is a critical review of present and future use of human GH. To evaluate the effectiveness of the hGH treatment several pharmaceutical companies established postmarketing follow-up programs which are based on the reliability and cooperation of the treating physicians. Unfortunately they stop when the treatment is terminated and most studies refer to growth stimulation effectiveness during initial years but do not follow the children until final height. The long-term experience enabled to evaluate adverse effects (AE), the majority being due to large dosage. The most serious AE reported are increases in malignancies and early or late mortality in adult age. There is consensus that GH deficient children need replacement therapy. As long-term hGH treatment is expensive and the final height gains in non-GH deficient children small the cost-benefit indications to treat short children without a disease has been questioned. To avoid the need of daily injections, long-acting hGH preparations undergo clinical trials. The future will show their effectiveness and eventual adverse effects.

  15. Does the GH/IGF-1 axis contribute to skeletal sexual dimorphism? Evidence from mouse studies.

    Science.gov (United States)

    Liu, Zhongbo; Mohan, Subburaman; Yakar, Shoshana

    2016-04-01

    The contribution of the gonadotropic axis to skeletal sexual dimorphism (SSD) was clarified in recent years. Studies with animal models of estrogen receptor (ER) or androgen receptor (AR) null mice, as well as mice with bone cell-specific ablation of ER or AR, revealed that both hormones play major roles in skeletal acquisition, and that estrogen regulates skeletal accrual in both sexes. The growth hormone (GH) and its downstream effector, the insulin-like growth factor-1 (IGF-1) are also major determinants of peak bone mass during puberty and young adulthood, and play important roles in maintaining bone integrity during aging. A few studies in both humans and animal models suggest that in addition to the differences in sex steroid actions on bone, sex-specific effects of GH and IGF-1 play essential roles in SSD. However, the contributions of the somatotropic (GH/IGF-1) axis to SSD are controversial and data is difficult to interpret. GH/IGF-1 are pleotropic hormones that act in an endocrine and autocrine/paracrine fashion on multiple tissues, affecting body composition as well as metabolism. Thus, understanding the contribution of the somatotropic axis to SSD requires the use of mouse models that will differentiate between these two modes of action. Elucidation of the relative contribution of GH/IGF-1 axis to SSD is significant because GH is approved for the treatment of normal children with short stature and children with congenital growth disorders. Thus, if the GH/IGF-1 axis determines SSD, treatment with GH may be tailored according to sex. In the following review, we give an overview of the roles of sex steroids in determining SSD and how they may interact with the GH/IGF-1 axis in bone. We summarize several mouse models with impaired somatotropic axis and speculate on the possible contribution of that axis to SSD. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Genome-wide analysis of the GH3 family in apple (Malus × domestica).

    Science.gov (United States)

    Yuan, Huazhao; Zhao, Kai; Lei, Hengjiu; Shen, Xinjie; Liu, Yun; Liao, Xiong; Li, Tianhong

    2013-05-02

    Auxin plays important roles in hormone crosstalk and the plant's stress response. The auxin-responsive Gretchen Hagen3 (GH3) gene family maintains hormonal homeostasis by conjugating excess indole-3-acetic acid (IAA), salicylic acid (SA), and jasmonic acids (JAs) to amino acids during hormone- and stress-related signaling pathways. With the sequencing of the apple (Malus × domestica) genome completed, it is possible to carry out genomic studies on GH3 genes to indentify candidates with roles in abiotic/biotic stress responses. Malus sieversii Roem., an apple rootstock with strong drought tolerance and the ancestral species of cultivated apple species, was used as the experimental material. Following genome-wide computational and experimental identification of MdGH3 genes, we showed that MdGH3s were differentially expressed in the leaves and roots of M. sieversii and that some of these genes were significantly induced after various phytohormone and abiotic stress treatments. Given the role of GH3 in the negative feedback regulation of free IAA concentration, we examined whether phytohormones and abiotic stresses could alter the endogenous auxin level. By analyzing the GUS activity of DR5::GUS-transformed Arabidopsis seedlings, we showed that ABA, SA, salt, and cold treatments suppressed the auxin response. These findings suggest that other phytohormones and abiotic stress factors might alter endogenous auxin levels. Previous studies showed that GH3 genes regulate hormonal homeostasis. Our study indicated that some GH3 genes were significantly induced in M. sieversii after various phytohormone and abiotic stress treatments, and that ABA, SA, salt, and cold treatments reduce the endogenous level of axuin. Taken together, this study provides evidence that GH3 genes play important roles in the crosstalk between auxin, other phytohormones, and the abiotic stress response by maintaining auxin homeostasis.

  17. The kidneys play a central role in the clearance of rhGH in rats

    DEFF Research Database (Denmark)

    Vestergaard, Bill; Thygesen, Peter; Kreilgaard, Mads

    2016-01-01

    at treatment of patients with growth hormone disorders. The purpose of this study was to investigate the relative importance of the kidneys in the clearance of rhGH. The study employed a newly validated nephrectomy rat model and a population based pharmacokinetic approach to assess renal clearance of rh...... that renal clearance plays a pivotal role in the elimination of rhGH in rats....

  18. Mercury's Reference Frames After the MESSENGER Mission

    Science.gov (United States)

    Stark, A.; Oberst, J.; Preusker, F.; Burmeister, S.; Steinbrügge, G.; Hussmann, H.

    2018-05-01

    We provide an overview of Mercury's reference frames based on MESSENGER observations. We discuss the dynamical, the principal-axes, the ellipsoid, as well as the cartographic frame, which was adopted for MESSENGER data products.

  19. Effects of growth hormone deficiency and recombinant growth hormone therapy on postprandial gallbladder motility and cholecystokinin release.

    NARCIS (Netherlands)

    Moschetta, A.; Twickler, M.; Rehfeld, J.F.; Ooteghem, N.A. van; Castro Cabezas, M.; Portincasa, P.; Berge-Henegouwen, G.P. van; Erpecum, K.J. van

    2004-01-01

    In addition to cholecystokinin, other hormones have been suggested to be involved in regulation of postprandial gallbladder contraction. We aimed to evaluate effects of growth hormone (GH) on gallbladder contractility and cholecystokinin release. Gallbladder and gastric emptying (by ultrasound) and

  20. GH/IGF-I Transgene Expression on Muscle Homeostasis

    Science.gov (United States)

    Schwartz, Robert J.

    1999-01-01

    We propose to test the hypothesis that the growth hormone/ insulin like growth factor-I axis through autocrine/paracrine mechanisms may provide long term muscle homeostasis under conditions of prolonged weightlessness. As a key alternative to hormone replacement therapy, ectopic production of hGH, growth hormone releasing hormone (GHRH), and IGF-I will be studied for its potential on muscle mass impact in transgenic mice under simulated microgravity. Expression of either hGH or IGF-I would provide a chronic source of a growth-promoting protein whose biosynthesis or secretion is shut down in space. Muscle expression of the IGF-I transgene has demonstrated about a 20% increase in hind limb muscle mass over control nontransgenic litter mates. These recent experiments, also establish the utility of hind-limb suspension in mice as a workable model to study atrophy in weight bearing muscles. Thus, transgenic mice will be used in hind-limb suspension models to determine the role of GH/IGF-I on maintenance of muscle mass and whether concentric exercises might act in synergy with hormone treatment. As a means to engineer and ensure long-term protein production that would be workable in humans, gene therapy technology will be used by to monitor muscle mass preservation during hind-limb suspension, after direct intramuscular injection of a genetically engineered muscle-specific vector expressing GHRH. Effects of this gene-based therapy will be assessed in both fast twitch (medial gastrocnemius) and slow twitch muscle (soleus). End-points include muscle size, ultrastructure, fiber type, and contractile function, in normal animals, hind limb suspension, and reambutation.

  1. Analysis of Surface Binding Sites (SBS) within GH62, GH13, and GH77

    DEFF Research Database (Denmark)

    Wilkens, Casper; Cockburn, Darrell; Andersen, Susan

    2015-01-01

    Certain interactions between carbohydrate active enzymes and polysaccharides involve surface binding sites (SBS) situated on catalytic domains outside of the active site. We recently undertook to develop a toolbox for SBS identification and characterization. In affinity gel electrophoresis (AGE...... of the reported SBSs. In GH13 SBSs have been seen in 17 subfamilies including SBSs with highly diverse functions in the same enzyme. Circumstantial evidence is provided for an SBS in the GH77 MalQ from Escherichia coli, the bacterial orthologue of Arabidopsis DPE2 involved in starch metabolism. Furthermore...

  2. Pituitary and mammary growth hormone in dogs

    NARCIS (Netherlands)

    Bhatti, Sofie Fatima Mareyam

    2006-01-01

    Several pathological (e.g. obesity and chronic hypercortisolism) and non-pathological (e.g. ageing) states in humans are characterized by a reduction in pituitary growth hormone (GH) secretion. Chronic hypercortisolism in humans is also associated with an impaired GH response to various stimuli.

  3. Phenomenologies of Higgs messenger models

    Energy Technology Data Exchange (ETDEWEB)

    Zheng Sibo; Yu Yao; Wu Xinggang [Department of Physics, Chongqing University, Chongqing 401331 (China)

    2011-08-11

    In this Letter, we investigate the phenomenologies of models where the Higgs sector plays the role of messengers in gauge mediation. The minimal Higgs sector and its extension are considered respectively. We find that there exist viable models when an appropriate parity is imposed. Phenomenological features in these kind of models include three sum rules for scalar masses, light gluino as well as one-loop {mu} and two-loop B{mu} terms.

  4. Evidence for association of the cloned liver growth hormone receptor with a tyrosine kinase

    DEFF Research Database (Denmark)

    Wang, X; Uhler, M D; Billestrup, N

    1992-01-01

    The ability of the cloned liver growth hormone (GH) receptor, when expressed in mammalian cell lines, to copurify with tyrosine kinase activity and be tyrosyl phosphorylated was examined. 125I-human growth hormone-GH receptor complexes isolated from COS-7 cells transiently expressing high levels...... of tyrosine kinase activity with cloned liver GH receptor. The level of phosphorylation of the GH receptor was very low, as compared with the endogenous GH receptor in 3T3-F442A cells, suggesting that tyrosine kinase activity is not intrinsic to the cloned GH receptor but rather resides with a kinase present...... in a variety of cell types. The finding that the level of phosphorylation of GH receptor appears to vary with cell type is consistent with the cloned liver GH receptor being a substrate for an associated tyrosine kinase and with the amount of such a GH receptor-associated tyrosine kinase being cell type-specific....

  5. Regulation of skeletal growth and mineral acquisition by the GH/IGF-1 axis: Lessons from mouse models.

    Science.gov (United States)

    Yakar, Shoshana; Isaksson, Olle

    2016-06-01

    The growth hormone (GH) and its downstream mediator, the insulin-like growth factor-1 (IGF-1), construct a pleotropic axis affecting growth, metabolism, and organ function. Serum levels of GH/IGF-1 rise during pubertal growth and associate with peak bone acquisition, while during aging their levels decline and associate with bone loss. The GH/IGF-1 axis was extensively studied in numerous biological systems including rodent models and cell cultures. Both hormones act in an endocrine and autocrine/paracrine fashion and understanding their distinct and overlapping contributions to skeletal acquisition is still a matter of debate. GH and IGF-1 exert their effects on osteogenic cells via binding to their cognate receptor, leading to activation of an array of genes that mediate cellular differentiation and function. Both hormones interact with other skeletal regulators, such as sex-steroids, thyroid hormone, and parathyroid hormone, to facilitate skeletal growth and metabolism. In this review we summarized several rodent models of the GH/IGF-1 axis and described key experiments that shed new light on the regulation of skeletal growth by the GH/IGF-1 axis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Growth hormone and the heart.

    Science.gov (United States)

    Cittadini, A; Longobardi, S; Fazio, S; Saccà, L

    1999-01-01

    Until a few years ago, growth hormone (GH) and insulin-like growth factor-1 (IGF-1) were considered essential only to the control of linear growth, glucose homeostasis, and for the maintenance of skeletal muscle mass. A large body of evidence recently coming from animal and human studies has unequivocally proven that the heart is a target organ for the GH/IGF-1 axis. Specifically GH exerts both direct and indirect cardiovascular actions. Among the direct effects, the ability of GH to trigger cardiac tissue growth plays a pivotal role. Another direct effect is to augment cardiac contractility, independent of myocardial growth. Direct effects of GH also include the improvement of myocardial energetics and mechanical efficiency. Indirect effects of GH on the heart include decreased peripheral vascular resistance (PVR), expansion of blood volume, increased glomerular filtration rate, enhanced respiratory activity, increased skeletal muscle performance, and psychological well-being. Among them, the most consistently found is the decrease of PVR. GH may also raise preload through its sodium-retaining action and its interference with the hormonal system that regulates water and electrolyte metabolism. Particularly important is the effect of GH on skeletal muscle mass and performance. Taking into account that heart failure is characterized by left ventricular dilation, reduced cardiac contractility, and increase of wall stress and peripheral vascular resistance, GH may be beneficial for treatment of heart failure. Animal studies and preliminary human trials have confirmed the validity of the GH approach to the treatment of heart failure. Larger placebo-controlled human studies represent the main focus of future investigations.

  7. [Effects of growth hormone replacement therapy on bone metabolism].

    Science.gov (United States)

    Yamamoto, Masahiro; Sugimoto, Toshitsugu

    2014-06-01

    Growth hormone (GH) as well as insulin like growth factor-1 (IGF-1) are essential hormones to maintain homeostasis of bone turnover by activating osteoblastogenesis and osteoclastogenesis. Results from GH replacement therapy for primary osteoporosis and adult-onset GH deficiency (AGHD) suggest that one year or more treatment period by this agent is required to gain bone mineral density (BMD) over the basal level after compensating BMD loss caused by dominant increase in bone resorption which was observed at early phase of GH treatment. A recent meta-analysis demonstrates the efficacy of GH replacement therapy on increases in BMD in male patients with AGHD. Additional analyses are needed to draw firm conclusions in female patients with AGHD, because insufficient amounts of GH might be administrated to them without considerations of influence of estrogen replacement therapy on IGF-1 production. Further observational studies are needed to clarify whether GH replacement therapy prevent fracture risk in these patients.

  8. Geodesy at Mercury with MESSENGER

    Science.gov (United States)

    Smith, David E.; Zuber, Maria t.; Peale, Stanley J.; Phillips, Roger J.; Solomon, Sean C.

    2006-01-01

    In 2011 the MESSENGER (MErcury Surface, Space ENvironment, GEochemistry, and Ranging) spacecraft will enter Mercury orbit and begin the mapping phase of the mission. As part of its science objectives the MESSENGER mission will determine the shape and gravity field of Mercury. These observations will enable the topography and the crustal thickness to be derived for the planet and will determine the small libration of the planet about its axis, the latter critical to constraining the state of the core. These measurements require very precise positioning of the MESSENGER spacecraft in its eccentric orbit, which has a periapsis altitude as low as 200 km, an apoapsis altitude near 15,000 km, and a closest approach to the surface varying from latitude 60 to about 70 N. The X-band tracking of MESSENGER and the laser altimetry are the primary data that will be used to measure the planetary shape and gravity field. The laser altimeter, which has an expected range of 1000 to 1200 km, is expected to provide significant data only over the northern hemisphere because of MESSENGER's eccentric orbit. For the southern hemisphere, radio occultation measurements obtained as the spacecraft passes behind the planet as seen from Earth and images obtained with the imaging system will be used to provide the long-wavelength shape of the planet. Gravity, derived from the tracking data, will also have greater resolution in the northern hemisphere, but full global models for both topography and gravity will be obtained at low harmonic order and degree. The limiting factor for both gravity and topography is expected to be knowledge of the spacecraft location. Present estimations are that in a combined tracking, altimetry, and occultation solution the spacecraft position uncertainty is likely to be of order 10 m. This accuracy should be adequate for establishing an initial geodetic coordinate system for Mercury that will enable positioning of imaged features on the surface, determination of

  9. Response of Indian growth hormone deficient children to growth hormone therapy: association with pituitary size.

    Science.gov (United States)

    Khadilkar, Vaman V; Prasad, Hemchand Krishna; Ekbote, Veena H; Rustagi, Vaishakhi T; Singh, Joshita; Chiplonkar, Shashi A; Khadilkar, Anuradha V

    2015-05-01

    To ascertain the impact of pituitary size as judged by Magnetic Resonance Imaging (MRI), on response to Growth Hormone (GH) therapy in GH deficient children. Thirty nine children (9.1 ± 2.7 y, 22 boys) with non-acquired GH deficiency (21 Isolated GH deficiency and 18 Combined pituitary hormone deficiency) were consecutively recruited and followed up for one year. Clinical, radiological (bone age and MRI) and biochemical parameters were studied. Children with hypoplastic pituitary (pituitary height deficit (height for age Z-score -6.0 vs. -5.0) and retardation of skeletal maturation (bone age chronological age ratio of 0.59 vs. 0.48) at baseline as compared to children with normal pituitary heights (p growth hormone deficient children with hypoplastic pituitary respond better to therapy with GH in short term.

  10. Effects of hyperthyroidism and hypothyroidism on rat growth hormone release induced by thyrotropin-releasing hormone.

    Science.gov (United States)

    Chihara, K; Kato, Y; Ohgo, S; Iwasaki, Y; Maeda, K

    1976-06-01

    The effect of synthetic thyrotropin-releasing hormone (TRH) on the release of growth hormone (GH) and thyroid-stimulating hormone (TSH) was investigated in euthyroid, hypothyroid, and hyperthyroid rats under urethane anesthesia. In euthyroid control rats, intravenous injection of TRH (200 ng/100 g BW) resulted in a significant increase in both plasma GH and TSH. In rats made hypothyroid by treatment with propylthiouracil or by thyroidectomy, basal GH and TSH levels were significantly elevated with exaggerated responses to TRH. In contrast, plasma GH and TSH responses to TRH were both significantly inhibited in rats made hyperthyroid by L-thyroxine (T4) treatment. These results suggest that altered thyroid status influences GH release as well as TSH secretion induced by TRH in rats.

  11. Ames dwarf (Prop1(df)/Prop1(df)) mice display increased sensitivity of the major GH-signaling pathways in liver and skeletal muscle.

    Science.gov (United States)

    Miquet, Johanna G; Muñoz, Marina C; Giani, Jorge F; González, Lorena; Dominici, Fernando P; Bartke, Andrzej; Turyn, Daniel; Sotelo, Ana I

    2010-04-01

    Growth hormone (GH) is an anabolic hormone that regulates growth and metabolism. Ames dwarf mice are natural mutants for Prop1, with impaired development of anterior pituitary and undetectable levels of circulating GH, prolactin and TSH. They constitute an endocrine model of life-long GH-deficiency. The main signaling cascades activated by GH binding to its receptor are the JAK2/STATs, PI-3K/Akt and the MAPK Erk1/2 pathways. We have previously reported that GH-induced STAT5 activation was higher in Ames dwarf mice liver compared to non-dwarf controls. The aim of this study was to evaluate the principal components of the main GH-signaling pathways under GH-deficiency in liver and skeletal muscle, another GH-target tissue. Ames dwarf mice and their non-dwarf siblings were assessed. Animals were injected i.p. with GH or saline 15min before tissue removal. Protein content and phosphorylation of signaling mediators were determined by immunoblotting of tissue solubilizates. GH was able to induce STAT5 and STAT3 tyrosine phosphorylation in both liver and muscle, but the response was higher for Ames dwarf mice than for non-dwarf controls. When Erk1/2 activation was assessed in liver, only dwarf mice showed GH-induced phosphorylation, while in muscle no response to the hormone was found in either genotype. GH-induced Akt phosphorylation at Ser473 in liver was only detected in dwarf mice. In skeletal muscle, both normal and dwarf mice responded to a GH stimulus, although dwarf mice presented higher GH activation levels. The phosphorylation of GSK-3, a substrate of Akt, increased upon hormone stimulation only in dwarf mice in both tissues. In contrast, no differences in the phosphorylation of mTOR, another substrate of Akt, were observed after GH stimulus, either in normal or dwarf mice in liver, while we were unable to determine mTOR in muscle. Protein content of GH-receptor and of the signaling mediators studied did not vary between normal and dwarf animals in the assessed

  12. The effect of short-term cortisol changes on growth hormone responses to the pyridostigmine-growth-hormone-releasing-hormone test in healthy adults and patients with suspected growth hormone deficiency

    DEFF Research Database (Denmark)

    Andersen, M; Støving, R K; Hangaard, J

    1998-01-01

    BACKGROUND AND AIMS: The interaction between cortisol and growth hormone (GH)-levels may significantly influence GH-responses to a stimulation test. In order to systematically analyse the interaction in a paired design, it is necessary to use a test, which has been proven safe and reliable...... such as the pyridostigmine-growth-hormone-releasing-hormone (PD-GHRH) test. Three groups of subjects with a different GH-secretory capacity were included. STUDY A: Eight healthy adults were tested seven times, once with placebo throughout the examination and six times with the PD-GHRH test following no glucocorticoid......-responses to a PD-GHRH test were reduced in all individuals during acute stress-appropriate cortisol levels and the percentage reduction in GH-levels was independent of the GH-secretory capacity. Clinically, we found that peak GH-responses were not significantly affected by a short break in conventional HC therapy...

  13. Impact of GH administration on athletic performance in healthy young adults: A systematic review and meta-analysis of placebo-controlled trials

    DEFF Research Database (Denmark)

    Hermansen, Kasper; Bengtsen, Mads; Kjaer, Michael

    2017-01-01

    OBJECTIVE: Illicit use of growth hormone (GH) as a performance-enhancing drug among athletes is prevalent, although the evidence of such effects in healthy, young subjects is sparse. We therefore performed a meta-analysis of published studies on the effect of GH administration on body composition...... relevant articles were retrieved of which 11 were included in this analysis comprising 254 subjects. RESULTS: Administration of GH significantly increased lean body mass (p

  14. A remote but significant sequence homology between glycoside hydrolase clan GH-H and glycoside hydrolase family GH 31

    DEFF Research Database (Denmark)

    Janecek, S.; Svensson, Birte; MacGregor, E.A.

    2007-01-01

    Although both the α-amylase super-family, i.e. the glycoside hydrolase (GH) clan GH-H (the GH families 13, 70 and 77), and family GH31 share some characteristics, their different catalytic machinery prevents classification of GH31 in clan GH-H. A significant but remote evolutionary relatedness is...

  15. Growth hormone treatment during pregnancy in a growth hormone-deficient woman

    DEFF Research Database (Denmark)

    Müller, J; Starup, J; Christiansen, J S

    1995-01-01

    protein 3 (IGFBP-3) during pregnancy, as well as birth weight and hormone levels after delivery in a 25-year-old woman with idiopathic, isolated GH deficiency diagnosed at the age of 7 years. As part of a clinical trial, the patient was treated with 2 IU/M2 GH for a period of 5 years. At this time she...

  16. IDENTIFICATION OF GH|ALUI AND GHR|ALUI GENES POLYMORPHISMS IN INDONESIAN BUFFALO

    Directory of Open Access Journals (Sweden)

    E. Andreas

    2014-10-01

    Full Text Available Growth hormone (GH is an anabolic hormone which sintesized and secreted by somatrotop cell inpituitary anterior lobe. GH exert its effect on growth and metabolism by interacting with a specificreceptor on the surface of the target cells. Growth hormone receptor (GHR has been suggested ascandidate gene for traits related to meat production in Bovidae. The objectives of this study were toidentify polymorphism of GH and GHR genes in buffalo. The 452 DNA samples buffalo were collectedfrom five populations in Indonesia (Siborong-Borong-Medan (65, Lebak-Banten (29, Pandeglang-Banten (180, Semarang-Central Java, and Mataram-West Nusa Tenggara (103. A gene fragment of theGH|AluI gene at 432 bp located on exon 3 and GHR|AluI gene at 298 bp on exon 10 were successfullyamplified by using the techniques of a PCR (polymerase chain reaction and genotyped by PCR-RFLP(restriction fragment length polymorphism then -SSCP (single strand conformation polymorphism. Theresults showed no polymorphisms were detected in these genes. All buffaloes tested had LL genotype forlocus GH|AluI and AA genotype for locus GHR|AluI.

  17. The physiology of growth hormone and sport.

    LENUS (Irish Health Repository)

    Widdowson, W Matthew

    2012-02-01

    The growth hormone (GH)\\/ insulin-like growth factor-I (IGF-I) axis exerts short-and long-term metabolic effects that are potentially important during exercise. Exercise is a potent stimulus to GH release and there is some evidence that the acute increase in GH is important in regulating substrate metabolism post-exercise. Regular exercise also increases 24-hour GH secretion rates, which potentially contributes to the physiologic changes induced by training. The effects of GH replacement in GH-deficient adults provide a useful model with which to study the effects of the more long-term effects of the GH\\/ IGF-I axis. There is convincing evidence that GH replacement increases exercise capacity. Measures of exercise performance including maximal oxygen uptake (VO2max) and ventilatory threshold (VeT) are impaired in GH deficiency and improved by GH replacement, probably through some combination of increased oxygen delivery to exercising muscle, increased fatty acid availability with glycogen sparing, increased muscle strength, improved body composition and improved thermoregulation. Administration of supraphysiologic doses of GH to athletes increases fatty acid availability and reduces oxidative protein loss particularly during exercise, and increases lean body mass. It is not known whether these effects translate to improved athletic performance, although recombinant human GH is known to be widely abused in sport. The model of acromegaly provides evidence that long-term GH excess does not result in improved performance but it is possible that a "window" exists in which the protein anabolic effects of supraphysiologic GH might be advantageous.

  18. Effects of Growth Hormone on Bone.

    Science.gov (United States)

    Tritos, Nicholas A; Klibanski, Anne

    2016-01-01

    Describe the effects of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) on the skeleton. The GH and IGF-1 axis has pleiotropic effects on the skeleton throughout the lifespan by influencing bone formation and resorption. GH deficiency leads to decreased bone turnover, delayed statural growth in children, low bone mass, and increased fracture risk in adults. GH replacement improves adult stature in GH deficient children, increases bone mineral density (BMD) in adults, and helps to optimize peak bone acquisition in patients, during the transition from adolescence to adulthood, who have persistent GH deficiency. Observational studies suggest that GH replacement may mitigate the excessive fracture risk associated with GH deficiency. Acromegaly, a state of GH and IGF-1 excess, is associated with increased bone turnover and decreased BMD in the lumbar spine observed in some studies, particularly in patients with hypogonadism. In addition, patients with acromegaly appear to be at an increased risk of morphometric-vertebral fractures, especially in the presence of active disease or concurrent hypogonadism. GH therapy also has beneficial effects on statural growth in several conditions characterized by GH insensitivity, including chronic renal failure, Turner syndrome, Prader-Willi syndrome, postnatal growth delay in patients with intrauterine growth retardation who do not demonstrate catchup growth, idiopathic short stature, short stature homeobox-containing (SHOX) gene mutations, and Noonan syndrome. GH and IGF-1 have important roles in skeletal physiology, and GH has an important therapeutic role in both GH deficiency and insensitivity states. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. The liver taxis of receptor mediated lactosaminated human growth hormone

    International Nuclear Information System (INIS)

    Chen Zelian; Shi Lin; Li Tongling; Pang Qijie; He Juying; Guan Changtian

    2002-01-01

    Radiography imaging is used to assess liver taxis mechanism of anti-dwarfism drug lactosaminated human growth hormone (L-rhGH). Both L-rhGH and rhGH labelled with 131 I are used to study their biodistribution in animals (including rabbits, cocks and rats). The results show that L-rhGH is of specific hepatic targeting property, and the maximum hepatic concentration rate is 76.8%, which is two times of rhGH. Its hepatic binding is receptor mediated

  20. Cell transfection as a tool to study growth hormone action

    DEFF Research Database (Denmark)

    Norstedt, G; Enberg, B; Francis, S

    1994-01-01

    The isolation of growth hormone receptor (GHR) cDNA clones has made possible the transfection of GHRs into cultured cells. Our aim in this minireview is to show how the application of such approaches have benefited GHR research. GH stimulation of cells expressing GHR cDNAs can cause an alteration...... is important in GH action. The GH signals are transmitted to the nucleus and GH regulated genes have now begun to be characterized. The ability to use cell transfection for mechanistic studies of GH action will be instrumental to define domains within the receptor that are of functional importance...

  1. Effects of GhWUS from upland cotton (Gossypium hirsutum L.) on somatic embryogenesis and shoot regeneration.

    Science.gov (United States)

    Xiao, Yanqing; Chen, Yanli; Ding, Yanpeng; Wu, Jie; Wang, Peng; Yu, Ya; Wei, Xi; Wang, Ye; Zhang, Chaojun; Li, Fuguang; Ge, Xiaoyang

    2018-05-01

    The WUSCHEL (WUS) gene encodes a plant-specific homeodomain-containing transcriptional regulator, which plays important roles during embryogenesis, as well as in the formation of shoot and flower meristems. Here, we isolated two homologues of Arabidopsis thaliana WUS (AtWUS), GhWUS1a_At and GhWUS1b_At, from upland cotton (Gossypium hirsutum). Domain analysis suggested that the two putative GhWUS proteins contained a highly conserved DNA-binding HOX domain and a WUS-box. Expression profile analysis showed that GhWUSs were predominantly expressed during the embryoid stage. Ectopic expression of GhWUSs in Arabidopsis could induce somatic embryo and shoot formation from seedling root tips. Furthermore, in the absence of exogenous hormone, overexpression of GhWUSs in Arabidopsis could promote shoot regeneration from excised roots, and in the presence of exogenous auxin, excised roots expressing GhWUS could be induced to produce somatic embryo. In addition, expression of the chimeric GhWUS repressor in cotton callus inhibited embryogenic callus formation. Our results show that GhWUS is an important regulator of somatic embryogenesis and shoot regeneration. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Growth hormone concentrations in mammary secretions and plasma of the periparturient bitch and in plasma of the neonate.

    Science.gov (United States)

    Schoenmakers, I; Kooistra, H S; Okkens, A C; Hazewinkel, H A; Bevers, M M; Mol, J A

    1997-01-01

    The presence of growth hormone (GH) in mammary secretions of bitches was investigated in relation to plasma GH concentrations at about the time of parturition and during the first weeks of lactation. Plasma GH concentrations in neonates were measured during the first weeks of lactation, to determine whether GH in maternal milk contributes to plasma concentrations of GH in the neonate. Gastrointestinal uptake of GH was studied by measurement of plasma bovine GH (bGH) concentrations after intragastric administration of bGH. High concentrations of GH were found in the mammary secretions of the bitches, particularly before parturition and in colostrum, exceeding maternal plasma concentration up to 100-1000 times. GH concentrations in milk were not not significantly correlated with GH concentrations in plasma of bitches or neonates. Bovine GH could not be detected in neonatal plasma for 4 h after intragastric administration of bGH. The presence of high concentrations of canine GH (cGH) in ante-partum and colostral mammary secretions is consistent with the progesterone-induced mammary biosynthesis of GH. GH in milk is probably not absorbed from the gastrointestinal tract into the blood circulation of the newborn in its intact form.

  3. Developmental programming: the role of growth hormone.

    Science.gov (United States)

    Oberbauer, Anita M

    2015-01-01

    Developmental programming of the fetus has consequences for physiologic responses in the offspring as an adult and, more recently, is implicated in the expression of altered phenotypes of future generations. Some phenotypes, such as fertility, bone strength, and adiposity are highly relevant to food animal production and in utero factors that impinge on those traits are vital to understand. A key systemic regulatory hormone is growth hormone (GH), which has a developmental role in virtually all tissues and organs. This review catalogs the impact of GH on tissue programming and how perturbations early in development influence GH function.

  4. GH dysfunction in Engrailed-2 knockout mice, a model for autism spectrum disorders

    Directory of Open Access Journals (Sweden)

    Giovanni eProvenzano

    2014-09-01

    Full Text Available Insulin-like growth factor 1 (IGF-1 signaling promotes brain development and plasticity. Altered IGF-1 expression has been associated to autism spectrum disorders (ASD. IGF-1 levels were found increased in the blood and decreased in the cerebrospinal fluid of ASD children. Accordingly, IGF-1 treatment can rescue behavioral deficits in mouse models of ASD, and IGF-1 trials have been proposed for ASD children. IGF-1 is mainly synthesized in the liver, and its synthesis is dependent on growth hormone (GH produced in the pituitary gland. GH also modulates cognitive functions, and altered levels of GH have been detected in ASD patients.Here we analyzed the expression of GH, IGF-1, their receptors and regulatory hormones in the neuroendocrine system of adult male mice lacking the homeobox transcription factor Engrailed-2 (En2-/- mice. En2-/- mice display ASD-like behaviors (social interactions, defective spatial learning, increased seizure susceptibility accompanied by relevant neuropathological changes (loss of cerebellar and forebrain inhibitory neurons. Recent studies showed that En2 modulates IGF-1 activity during postnatal cerebellar development.We found that GH mRNA expression was markedly deregulated throughout the neuroendocrine axis in En2-/- mice, as compared to wild-type (WT controls. In mutant mice, GH mRNA levels were significantly increased in the pituitary gland, blood and liver, whereas decreased levels were detected in the hippocampus. These changes were paralleled by decreased levels of GH protein in the hippocampus but not other tissues of En2-/- mice. IGF-1 mRNA was significantly up-regulated in the liver and down-regulated in the En2-/- hippocampus, but no differences were detected in the levels of IGF-1 protein between the two genotypes. Our data strengthen the notion that altered GH levels in the hippocampus may be involved in learning disabilities associated to ASD.

  5. Absence of serum growth hormone binding protein in patients with growth hormone receptor deficiency (Laron dwarfism)

    Energy Technology Data Exchange (ETDEWEB)

    Daughaday, W.H.; Trivedi, B.

    1987-07-01

    It has recently been recognized that human serum contains a protein that specifically binds human growth hormone (hGH). This protein has the same restricted specificity for hGH as the membrane-bound GH receptor. To determine whether the GH-binding protein is a derivative of, or otherwise related to, the GH receptor, the authors have examined the serum of three patients with Laron-type dwarfism, a condition in which GH refractoriness has been attributed to a defect in the GH receptor. The binding of /sup 125/I-labeled hGH incubated with serum has been measured after gel filtration of the serum through an Ultrogel AcA 44 minicolumn. Results are expressed as percent of specifically bound /sup 125/I-hGH and as specific binding relative to that of a reference serum after correction is made for endogenous GH. The mean +/- SEM of specific binding of sera from eight normal adults (26-46 years of age) was 21.6 +/- 0.45%, and the relative specific binding was 101.1 +/- 8.6%. Sera from 11 normal children had lower specific binding of 12.5 +/- 1.95% and relative specific binding of 56.6 +/- 9.1%. Sera from three children with Laron-type dwarfism lacked any demonstrable GH binding, whereas sera from 10 other children with other types of nonpituitary short stature had normal relative specific binding. They suggest that the serum GH-binding protein is a soluble derivative of the GH receptor. Measurement of the serum GH-binding protein may permit recognition of other abnormalities of the GH receptor.

  6. Absence of serum growth hormone binding protein in patients with growth hormone receptor deficiency (Laron dwarfism)

    International Nuclear Information System (INIS)

    Daughaday, W.H.; Trivedi, B.

    1987-01-01

    It has recently been recognized that human serum contains a protein that specifically binds human growth hormone (hGH). This protein has the same restricted specificity for hGH as the membrane-bound GH receptor. To determine whether the GH-binding protein is a derivative of, or otherwise related to, the GH receptor, the authors have examined the serum of three patients with Laron-type dwarfism, a condition in which GH refractoriness has been attributed to a defect in the GH receptor. The binding of 125 I-labeled hGH incubated with serum has been measured after gel filtration of the serum through an Ultrogel AcA 44 minicolumn. Results are expressed as percent of specifically bound 125 I-hGH and as specific binding relative to that of a reference serum after correction is made for endogenous GH. The mean +/- SEM of specific binding of sera from eight normal adults (26-46 years of age) was 21.6 +/- 0.45%, and the relative specific binding was 101.1 +/- 8.6%. Sera from 11 normal children had lower specific binding of 12.5 +/- 1.95% and relative specific binding of 56.6 +/- 9.1%. Sera from three children with Laron-type dwarfism lacked any demonstrable GH binding, whereas sera from 10 other children with other types of nonpituitary short stature had normal relative specific binding. They suggest that the serum GH-binding protein is a soluble derivative of the GH receptor. Measurement of the serum GH-binding protein may permit recognition of other abnormalities of the GH receptor

  7. Interactions between the thyroid hormones and the hormones of the growth hormone axis.

    Science.gov (United States)

    Laron, Zvi

    2003-12-01

    The normal secretion and action of the thyroid hormones and the hormones of the GH/IGF-I (growth hormone/ insulin-like growth factor I) axis are interdependent. Their interactions often differ in man from animal studies in rodents and sheep. Thus neonates with congenital hypothyroidism are of normal length in humans but IUGR (intrauterine growth retardation) in sheep. Postnatally normal GH/IGF-I secretion and action depends on an euthyroid state. Present knowledge on the interactions between the two axes is reviewed in states of hypo- and hyperthyroidism, states of GH/IGF-I deprivation and hypersecretion, as well as the relationship between IGF-I and thyroid cancer. Emphasis is given to data in children and aspects of linear growth and skeletal maturation.

  8. Nuclear Export of Messenger RNA

    Directory of Open Access Journals (Sweden)

    Jun Katahira

    2015-03-01

    Full Text Available Transport of messenger RNA (mRNA from the nucleus to the cytoplasm is an essential step of eukaryotic gene expression. In the cell nucleus, a precursor mRNA undergoes a series of processing steps, including capping at the 5' ends, splicing and cleavage/polyadenylation at the 3' ends. During this process, the mRNA associates with a wide variety of proteins, forming a messenger ribonucleoprotein (mRNP particle. Association with factors involved in nuclear export also occurs during transcription and processing, and thus nuclear export is fully integrated into mRNA maturation. The coupling between mRNA maturation and nuclear export is an important mechanism for providing only fully functional and competent mRNA to the cytoplasmic translational machinery, thereby ensuring accuracy and swiftness of gene expression. This review describes the molecular mechanism of nuclear mRNA export mediated by the principal transport factors, including Tap-p15 and the TREX complex.

  9. Nitric oxide: a physiologic messenger.

    Science.gov (United States)

    Lowenstein, C J; Dinerman, J L; Snyder, S H

    1994-02-01

    To review the physiologic role of nitric oxide, an unusual messenger molecule that mediates blood vessel relaxation, neurotransmission, and pathogen suppression. A MEDLINE search of articles published from 1987 to 1993 that addressed nitric oxide and the enzyme that synthesizes it, nitric oxide synthase. Animal and human studies were selected from 3044 articles to analyze the clinical importance of nitric oxide. Descriptions of the structure and function of nitric oxide synthase were selected to show how nitric oxide acts as a biological messenger molecule. Biochemical and physiologic studies were analyzed if the same results were found by three or more independent observers. Two major classes of nitric oxide synthase enzymes produce nitric oxide. The constitutive isoforms found in endothelial cells and neurons release small amounts of nitric oxide for brief periods to signal adjacent cells, whereas the inducible isoform found in macrophages releases large amounts of nitric oxide continuously to eliminate bacteria and parasites. By diffusing into adjacent cells and binding to enzymes that contain iron, nitric oxide plays many important physiologic roles. It regulates blood pressure, transmits signals between neurons, and suppresses pathogens. Excess amounts, however, can damage host cells, causing neurotoxicity during strokes and causing the hypotension associated with sepsis. Nitric oxide is a simple molecule with many physiologic roles in the cardiovascular, neurologic, and immune systems. Although the general principles of nitric oxide synthesis are known, further research is necessary to determine what role it plays in causing disease.

  10. Nuclear Export of Messenger RNA

    Science.gov (United States)

    Katahira, Jun

    2015-01-01

    Transport of messenger RNA (mRNA) from the nucleus to the cytoplasm is an essential step of eukaryotic gene expression. In the cell nucleus, a precursor mRNA undergoes a series of processing steps, including capping at the 5' ends, splicing and cleavage/polyadenylation at the 3' ends. During this process, the mRNA associates with a wide variety of proteins, forming a messenger ribonucleoprotein (mRNP) particle. Association with factors involved in nuclear export also occurs during transcription and processing, and thus nuclear export is fully integrated into mRNA maturation. The coupling between mRNA maturation and nuclear export is an important mechanism for providing only fully functional and competent mRNA to the cytoplasmic translational machinery, thereby ensuring accuracy and swiftness of gene expression. This review describes the molecular mechanism of nuclear mRNA export mediated by the principal transport factors, including Tap-p15 and the TREX complex. PMID:25836925

  11. Relationship between the functional exon 3 deleted growth hormone receptor polymorphism and symptomatic osteoarthritis in women

    NARCIS (Netherlands)

    Claessen, K. M. J. A.; Kloppenburg, M.; Kroon, H. M.; Bijsterbosch, J.; Pereira, A. M.; Romijn, J. A.; van der Straaten, T.; Nelissen, R. G. H. H.; Hofman, A.; Uitterlinden, A. G.; Duijnisveld, B. J.; Lakenberg, N.; Beekman, M.; van Meurs, J. B.; Slagboom, P. E.; Biermasz, N. R.; Meulenbelt, I.

    2014-01-01

    Background Several studies suggest a role of the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis in the pathophysiology of primary osteoarthritis (OA). A common polymorphism of the GH receptor (exon 3 deletion, d3-GHR) is associated with increased GH/IGF-1 activity. Objective To study

  12. 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...

  13. Arginine induces GH gene expression by activating NOS/NO signaling in rat isolated hemi-pituitaries

    Directory of Open Access Journals (Sweden)

    S.C.F. Olinto

    2012-11-01

    Full Text Available The amino acid arginine (Arg is a recognized secretagogue of growth hormone (GH, and has been shown to induce GH gene expression. Arg is the natural precursor of nitric oxide (NO, which is known to mediate many of the effects of Arg, such as GH secretion. Arg was also shown to increase calcium influx in pituitary cells, which might contribute to its effects on GH secretion. Although the mechanisms involved in the effects of Arg on GH secretion are well established, little is known about them regarding the control of GH gene expression. We investigated whether the NO pathway and/or calcium are involved in the effects of Arg on GH gene expression in rat isolated pituitaries. To this end, pituitaries from approximately 170 male Wistar rats (~250 g were removed, divided into two halves, pooled (three hemi-pituitaries and incubated or not with Arg, as well as with different pharmacological agents. Arg (71 mM, the NO donor sodium nitroprusside (SNP, 1 and 0.1 mM and a cyclic guanosine monophosphate (cGMP analogue (8-Br-cGMP, 1 mM increased GH mRNA expression 60 min later. The NO acceptor hemoglobin (0.3 µM blunted the effect of SNP, and the combined treatment with Arg and L-NAME (a NO synthase (NOS inhibitor, 55 mM abolished the stimulatory effect of Arg on GH gene expression. The calcium channel inhibitor nifedipine (3 µM also abolished Arg-induced GH gene expression. The present study shows that Arg directly induces GH gene expression in hemi-pituitaries isolated from rats, excluding interference from somatostatinergic neurons, which are supposed to be inhibited by Arg. Moreover, the data demonstrate that the NOS/NO signaling pathway and calcium mediate the Arg effects on GH gene expression.

  14. Arginine induces GH gene expression by activating NOS/NO signaling in rat isolated hemi-pituitaries

    Energy Technology Data Exchange (ETDEWEB)

    Olinto, S.C.F. [Faculdade de Ciências Integradas do Pontal, Universidade Federal de Uberlândia, Ituiutaba, MG (Brazil); Adrião, M.G. [Departamento de Morfologia e Fisiologia, Universidade Federal Rural de Pernambuco, Recife, PE (Brazil); Castro-Barbosa, T.; Goulart-Silva, F.; Nunes, M.T. [Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP (Brazil)

    2012-06-01

    The amino acid arginine (Arg) is a recognized secretagogue of growth hormone (GH), and has been shown to induce GH gene expression. Arg is the natural precursor of nitric oxide (NO), which is known to mediate many of the effects of Arg, such as GH secretion. Arg was also shown to increase calcium influx in pituitary cells, which might contribute to its effects on GH secretion. Although the mechanisms involved in the effects of Arg on GH secretion are well established, little is known about them regarding the control of GH gene expression. We investigated whether the NO pathway and/or calcium are involved in the effects of Arg on GH gene expression in rat isolated pituitaries. To this end, pituitaries from approximately 170 male Wistar rats (∼250 g) were removed, divided into two halves, pooled (three hemi-pituitaries) and incubated or not with Arg, as well as with different pharmacological agents. Arg (71 mM), the NO donor sodium nitroprusside (SNP, 1 and 0.1 mM) and a cyclic guanosine monophosphate (cGMP) analogue (8-Br-cGMP, 1 mM) increased GH mRNA expression 60 min later. The NO acceptor hemoglobin (0.3 µM) blunted the effect of SNP, and the combined treatment with Arg and L-NAME (an NO synthase (NOS) inhibitor, 55 mM) abolished the stimulatory effect of Arg on GH gene expression. The calcium channel inhibitor nifedipine (3 µM) also abolished Arg-induced GH gene expression. The present study shows that Arg directly induces GH gene expression in hemi-pituitaries isolated from rats, excluding interference from somatostatinergic neurons, which are supposed to be inhibited by Arg. Moreover, the data demonstrate that the NOS/NO signaling pathway and calcium mediate the Arg effects on GH gene expression.

  15. Arginine induces GH gene expression by activating NOS/NO signaling in rat isolated hemi-pituitaries

    International Nuclear Information System (INIS)

    Olinto, S.C.F.; Adrião, M.G.; Castro-Barbosa, T.; Goulart-Silva, F.; Nunes, M.T.

    2012-01-01

    The amino acid arginine (Arg) is a recognized secretagogue of growth hormone (GH), and has been shown to induce GH gene expression. Arg is the natural precursor of nitric oxide (NO), which is known to mediate many of the effects of Arg, such as GH secretion. Arg was also shown to increase calcium influx in pituitary cells, which might contribute to its effects on GH secretion. Although the mechanisms involved in the effects of Arg on GH secretion are well established, little is known about them regarding the control of GH gene expression. We investigated whether the NO pathway and/or calcium are involved in the effects of Arg on GH gene expression in rat isolated pituitaries. To this end, pituitaries from approximately 170 male Wistar rats (∼250 g) were removed, divided into two halves, pooled (three hemi-pituitaries) and incubated or not with Arg, as well as with different pharmacological agents. Arg (71 mM), the NO donor sodium nitroprusside (SNP, 1 and 0.1 mM) and a cyclic guanosine monophosphate (cGMP) analogue (8-Br-cGMP, 1 mM) increased GH mRNA expression 60 min later. The NO acceptor hemoglobin (0.3 µM) blunted the effect of SNP, and the combined treatment with Arg and L-NAME (an NO synthase (NOS) inhibitor, 55 mM) abolished the stimulatory effect of Arg on GH gene expression. The calcium channel inhibitor nifedipine (3 µM) also abolished Arg-induced GH gene expression. The present study shows that Arg directly induces GH gene expression in hemi-pituitaries isolated from rats, excluding interference from somatostatinergic neurons, which are supposed to be inhibited by Arg. Moreover, the data demonstrate that the NOS/NO signaling pathway and calcium mediate the Arg effects on GH gene expression

  16. Endurance exercise modulates levodopa induced growth hormone release in patients with Parkinson's disease.

    Science.gov (United States)

    Müller, Thomas; Welnic, Jacub; Woitalla, Dirk; Muhlack, Siegfried

    2007-07-11

    Acute levodopa (LD) application and exercise release human growth hormone (GH). An earlier trial showed, that combined stimulus of exercise and LD administration is the best provocative test for GH response in healthy participants. Objective was to show this combined effect of LD application and exercise on GH response and to investigate the impact on LD metabolism in 20 previously treated patients with Parkinson's disease (PD). We measured GH- and LD plasma concentrations following soluble 200 mg LD/50 mg benserazide administration during endurance exercise and rest on two separate consecutive days. GH concentrations significantly increased on both days, but GH release was significantly delayed during rest. LD metabolism was not altered due to exercise in a clinical relevant manner. Exercise induced a significant faster LD stimulated GH release in comparison with the rest condition. We did not find the supposed increase of LD induced GH release by endurance exercise. We assume, that only a limited amount of GH is available for GH release in the anterior pituitary following an acute 200 mg LD administration. GH disposal also depends on growth hormone releasing hormone (GHRH), which is secreted into hypothalamic portal capillaries. During the exercise condition, the resulting higher blood pressure supports blood flow and thus GHRH transport towards the GH producing cells in the pituitary. This might additionally have caused the significant faster GH release during exercise.

  17. Algorithmic complexity of growth hormone release in humans

    Energy Technology Data Exchange (ETDEWEB)

    Prank, K.; Wagner, M.; Brabant, G. [Medical School Hannover (Germany)

    1996-12-31

    Most hormones are secreted in an pulsatile rather than in a constant manner. This temporal pattern of pulsatile hormone release plays an important role in the regulation of cellular function and structure. In healthy humans growth hormone (GH) secretion is characterized by distinct pulses whereas patients bearing a GH producing tumor accompanied with excessive secretion (acromegaly) exhibit a highly irregular pattern of GH release. It has been hypothesized that this highly disorderly pattern of GH release in acromegaly arises from random events in the GH-producing tumor under decreased normal control of GH secretion. Using a context-free grammar complexity measure (algorithmic complexity) in conjunction with random surrogate data sets we demonstrate that the temporal pattern of GH release in acromegaly is not significantly different from a variety of stochastic processes. In contrast, normal subjects clearly exhibit deterministic structure in their temporal patterns of GH secretion. Our results support the hypothesis that GH release in acromegaly is due to random events in the GH-producing tumorous cells which might become independent from hypothalamic regulation. 17 refs., 1 fig., 2 tabs.

  18. Acute GH and IGF-I responses to short vs. long rest period between ...

    African Journals Online (AJOL)

    In order to examine the effects of different rest intervals between the sets on acute growth hormone (GH) and insulin-like growth factor-1 (IGF-I) responses, ten recreationally resistance trained men served as subjects (Mean ± SD, age=22 ± 2 years, body mass= 84 ± 8 kg). Subjects performed two heavy-resistance training ...

  19. Pituitary adenomas in mice transgenic for growth hormone-releasing hormone

    DEFF Research Database (Denmark)

    Asa, S L; Kovacs, K; Stefaneanu, L

    1992-01-01

    It has been shown that mice transgenic for human GH-releasing hormone (GRH) develop hyperplasia of pituitary somatotrophs, lactotrophs, and mammosomatotrophs, cells capable of producing both GH and PRL, by 8 months of age. We now report that GRH transgenic mice 10-24 months of age develop pituitary...... adenomas, which we characterized by histology, immunohistochemistry, in situ hybridization, and electron microscopy. Of 13 animals examined, all developed GH-immunoreactive neoplasms that had diffuse positivity for GH mRNA by in situ hybridization. Eleven also contained PRL immunoreactivity; in situ...

  20. Ghrelin- and GH-induced insulin resistance

    DEFF Research Database (Denmark)

    Vestergaard, Esben Thyssen; Krag, Morten B; Poulsen, Morten M

    2013-01-01

    Supraphysiological levels of ghrelin and GH induce insulin resistance. Serum levels of retinol-binding protein-4 (RBP4) correlate inversely with insulin sensitivity in patients with type 2 diabetes. We aimed to determine whether ghrelin and GH affect RBP4 levels in human subjects.......Supraphysiological levels of ghrelin and GH induce insulin resistance. Serum levels of retinol-binding protein-4 (RBP4) correlate inversely with insulin sensitivity in patients with type 2 diabetes. We aimed to determine whether ghrelin and GH affect RBP4 levels in human subjects....

  1. Radiation sensitivity of messenger RNA

    International Nuclear Information System (INIS)

    Ponta, H.; Pfennig-Yeh, M.L.; Herrlich, P.; Karlsruhe Univ.; Wagner, E.F.; Schweiger, M.

    1979-01-01

    Messenger RNA function is inactivated by irradiation with ultraviolet light. A unit length mRNA (in bases) is 2-3 times more sensitive than a unit length of DNA (in base pairs) with respect to the inactivation of template function. These data stem from four experimental systems all of which do not repair DNA: the translation of E. coli mRNA in rifampicin-treated cells, of T7 mRNA in infected E.coli, of f2 phage RNA in vivo, and of stable mRNA in chromosomeless minicells. The comparison of relative sensitivities to UV is relevant to the technique of UV mapping of transcription units which enjoys increasing popularity in pro- and eukaryotic genetic research. (orig.) [de

  2. Radiation sensitivity of messenger RNA

    Energy Technology Data Exchange (ETDEWEB)

    Ponta, H; Pfennig-Yeh, M L; Herrlich, P [Kernforschungszentrum Karlsruhe G.m.b.H. (Germany, F.R.). Inst. fuer Genetik und Toxikologie von Spaltstoffen; Karlsruhe Univ. (TH) (Germany, F.R.). Inst. fuer Genetik); Wagner, E F; Schweiger, M [Innsbruck Univ. (Austria). Inst. fuer Biochemie

    1979-08-01

    Messenger RNA function is inactivated by irradiation with ultraviolet light. A unit length mRNA (in bases) is 2-3 times more sensitive than a unit length of DNA (in base pairs) with respect to the inactivation of template function. These data stem from four experimental systems all of which do not repair DNA: the translation of E. coli mRNA in rifampicin-treated cells, of T7 mRNA in infected E.coli, of f2 phage RNA in vivo, and of stable mRNA in chromosomeless minicells. The comparison of relative sensitivities to UV is relevant to the technique of UV mapping of transcription units which enjoys increasing popularity in pro- and eukaryotic genetic research.

  3. Growth hormone treatment in non-growth hormone-deficient children

    Directory of Open Access Journals (Sweden)

    Sandro Loche

    2014-03-01

    Full Text Available Until 1985 growth hormone (GH was obtained from pituitary extracts, and was available in limited amounts only to treat severe growth hormone deficiency (GHD. With the availability of unlimited quantities of GH obtained from recombinant DNA technology, researchers started to explore new modalities to treat GHD children, as well as to treat a number of other non-GHD conditions. Although with some differences between different countries, GH treatment is indicated in children with Turner syndrome, chronic renal insufficiency, Prader-Willi syndrome, deletions/mutations of the SHOX gene, as well as in short children born small for gestational age and with idiopathic short stature. Available data from controlled trials indicate that GH treatment increases adult height in patients with Turner syndrome, in patients with chronic renal insufficiency, and in short children born small for gestational age. Patients with SHOX deficiency seem to respond to treatment similarly to Turner syndrome. GH treatment in children with idiopathic short stature produces a modest mean increase in adult height but the response in the individual patient is unpredictable. Uncontrolled studies indicate that GH treatment may be beneficial also in children with Noonan syndrome. In patients with Prader-Willi syndrome GH treatment normalizes growth and improves body composition and cognitive function. In any indication the response to GH seems correlated to the dose and the duration of treatment. GH treatment is generally safe with no major adverse effects being recorded in any condition.

  4. Radioimmunoassay of canine growth hormone

    International Nuclear Information System (INIS)

    Eigenmann, J.E.; Eigenmann, R.Y.

    1981-01-01

    A sensitive radioimmunoassay (RIA) for canine growth hormone (GH) was developed. Antibodies were elicited in rhesus monkeys. One antiserum exhibited a working titer at a dilution of 1:500 000. Radioiodination was performed enzymatically employing lactoperoxidase. Logit-log transformation and least squares fitting resulted in straight line fitting of the standard curve between 0.39 and 50 ng/ml. Formation of large-molecular [ 125 I]GH during storage caused diminished assay sensitivity. Therefore [ 125 I]GH was re-purified by gel chromatography. Using this procedure, high and reproducible assay sensitivity was obtained. Tracer preparations were used for as long as 3 months after iodination. Diluted plasma from normal and acromegalic dogs resulted in a dose-response curve parallel to the standard curve. Canine prolactin exhibited a cross-reactivity of 2%. The within-assay coefficient of variation (CV) was 3.8 and the between-assay CV was 7.2%. Mean plasma GH concentration in normal dogs was 1.92 +- 0.14 ng/ml (mean +- SEM.) GH levels in acromegalic dogs were appreciably higher. Insulin-induced hypoglycaemia, arginine and ornithine administration resulted in inconsistent and sluggish GH increment. A better response was obtained by injecting a low dose of clonidine. Clonidine administration to hypopituitary dogs resulted in absent or poor GH increment. (author)

  5. The robustness of diagnostic tests for GH deficiency in adults

    DEFF Research Database (Denmark)

    Andersen, Marianne

    2015-01-01

    with recombinant human GH. There is, however, an ongoing debate on how to diagnose GHD, especially in adults. A GH response below the cut-off limit of a GH-stimulation test is required in most cases for establishing GHD in adults. No 'gold standard' GH-stimulation test exists, but some GH stimulation tests may...

  6. Effects of octreotide infusion, surgery and estrogen on suppression of height increase and 20K growth hormone ratio in a girl with gigantism due to a growth hormone-secreting macroadenoma.

    Science.gov (United States)

    Minagawa, M; Yasuda, T; Someya, T; Kohno, Y; Saeki, N; Hashimoto, Y

    2000-01-01

    We treated an extremely tall 13-year-old girl with a growth hormone (GH)-secreting macroadenoma and GH levels of 120-495 ng/ml with a combination of preoperative octreotide infusion, surgery and postoperative octreotide infusion plus estrogen, which resulted in reduced tumor size prior to surgery, reduced GH levels and completely suppressed growth after surgery. 20K GH is produced by alternative splicing of 22K GH mRNA and the ratio of 20K GH to 22K GH is within a small range in the normal population and high in a GH-secreting tumor. The 20K/22K GH ratio in this patient was persistently elevated during each phase of the treatment and may serve as a sensitive index of tumor-derived GH secretion. Copyright 2000 S. Karger AG, Basel.

  7. The sheep growth hormone gene polymorphism and its effects on milk traits.

    Science.gov (United States)

    Dettori, Maria Luisa; Pazzola, Michele; Pira, Emanuela; Paschino, Pietro; Vacca, Giuseppe Massimo

    2015-05-01

    Growth hormone (GH) is encoded by the GH gene, which may be single copy or duplicate in sheep. The two copies of the sheep GH gene (GH1/GH2-N and GH2-Z) were entirely sequenced in one 106 ewes of Sarda breed, in order to highlight sequence polymorphisms and investigate possible association between genetic variants and milk traits. Milk traits included milk yield, fat, protein, casein and lactose percentage. We evidenced 75 nucleotide changes. Transcription factor binding site prediction revealed two sequences potentially recognised by the pituitary-specific transcription factor POU1FI at the GH1/GH2-N gene, which were lost at the promoter of GH2-Z, which might explain the different tissues of expression of GH1/GH2-N (pituitary) and GH2-Z (placenta). Significant differences in milk traits were observed among genotypes at polymorphic loci only for the GH2-Z gene. Sheep with homozygote genotype ss748770547 CC had higher fat percentage (P < 0.01) than TT. SNP ss748770547 was part of a potential transcription factor binding site for C/EBP alpha (CCAAT/Enhancer Binding Protein), which is involved in the regulation of adipogenesis and adipoblast differentiation. SNP ss748770547, located in the GH2-Z gene 5' flanking region, may be a causal mutation affecting milk fat content. These findings might contribute to the knowledge of the sheep GH locus and might be useful in selection processes in sheep.

  8. Male bovine GH transgenic mice have decreased adiposity with an adipose depot-specific increase in immune cell populations.

    Science.gov (United States)

    Benencia, Fabian; Harshman, Stephanie; Duran-Ortiz, Silvana; Lubbers, Ellen R; List, Edward O; Householder, Lara; Al-Naeeli, Mawadda; Liang, Xiaoyu; Welch, Lonnie; Kopchick, John J; Berryman, Darlene E

    2015-05-01

    White adipose tissue (WAT) is composed of mature adipocytes and a stromal vascular fraction (SVF), which contains a variety of cells, including immune cells that vary among the different WAT depots. Growth hormone (GH) impacts immune function and adiposity in an adipose depot-specific manner. However, its effects on WAT immune cell populations remain unstudied. Bovine GH transgenic (bGH) mice are commonly used to study the in vivo effects of GH. These giant mice have an excess of GH action, impaired glucose metabolism, decreased adiposity, increased lean mass, and a shortened lifespan. Therefore, the purpose of this study was to characterize the WAT depot-specific differences in immune cell populations in the presence of excess GH in vivo. Three WAT depots were assessed: inguinal (sc), epididymal (EPI), and mesenteric (MES). Subcutaneous and MES bGH WAT depots showed a significantly higher number of total SVF cells, yet only MES bGH WAT had higher leukocyte counts compared with control samples. By means of flow cytometry analysis of the SVF, we detected greater macrophage and regulatory T-cell infiltration in sc and MES bGH WAT depots compared with controls. However, no differences were observed in the EPI WAT depot. RNA-sequencing confirmed significant alterations in pathways related to T-cell infiltration and activation in the sc depot with fewer significant changes in the EPI bGH WAT depot. These findings collectively point to a previously unrecognized role for GH in influencing the distribution of WAT immune cell populations in a depot-specific manner.

  9. Defective distal regulatory element at the 5' upstream of rat prolactin gene of steroid-nonresponsive GH-subclone.

    Science.gov (United States)

    Kumar, V; Wong, D T; Pasion, S G; Biswas, D K

    1987-12-08

    The prolactin-nonproducing (PRL-) GH cell strains (rat pituitary tumor cells in culture). GH12C1 and F1BGH12C1, do not respond to steroid hormones estradiol or hydrocortisone (HC). However, the stimulatory effect of estradiol and the inhibitory effect of hydrocortisone on prolactin synthesis can be demonstrated in the prolactin-producing GH cell strain, GH4C1. In this investigation we have examined the 5' end flanking region of rat prolactin (rat PRL) gene of steroid-responsive, GH4C1 cells to identify the positive and negative regulatory elements and to verify the status of these elements in steroid-nonresponsive F1BGH12C1 cells. Results presented in this report demonstrate that the basel level expression of the co-transferred Neo gene (neomycin phosphoribosyl transferase) is modulated by the distal upstream regulatory elements of rat PRL gene in response to steroid hormones. The expression of adjacent Neo gene is inhibited by dexamethasone and is stimulated by estradiol in transfectants carrying distal regulatory elements (SRE) of steroid-responsive cells. These responses are not observed in transfectants with the rat PRL upstream sequences derived from steroid-nonresponsive cells. The basal level expression of the host cell alpha-2 tubulin gene is not affected by dexamethasone. We report here the identification of the distal steroid regulatory element (SRE) located between 3.8 and 7.8 kb upstream of the transcription initiation site of rat PRL gene. Both the positive and the negative effects of steroid hormones can be identified within this upstream sequence. This distal SRE appears to be nonfunctional in steroid-nonresponsive cells. Though the proximal SRE is functional, the defect in the distal SRE makes the GH substrain nonresponsive to steroid hormones. These results suggest that both the proximal and the distal SREs are essential for the mediation of action of steroid hormones in GH cells.

  10. Vasoprotective effects of life span-extending peripubertal GH replacement in Lewis dwarf rats.

    Science.gov (United States)

    Ungvari, Zoltan; Gautam, Tripti; Koncz, Peter; Henthorn, Jim C; Pinto, John T; Ballabh, Praveen; Yan, Han; Mitschelen, Matthew; Farley, Julie; Sonntag, William E; Csiszar, Anna

    2010-11-01

    In humans, growth hormone deficiency (GHD) and low circulating levels of insulin-like growth factor 1 (IGF-1) significantly increase the risk for cerebrovascular disease. Genetic growth hormone (GH)/IGF-1 deficiency in Lewis dwarf rats significantly increases the incidence of late-life strokes, similar to the effects of GHD in elderly humans. Peripubertal treatment of Lewis dwarf rats with GH delays the occurrence of late-life stroke, which results in a significant extension of life span. The present study was designed to characterize the vascular effects of life span-extending peripubertal GH replacement in Lewis dwarf rats. Here, we report, based on measurements of dihydroethidium fluorescence, tissue isoprostane, GSH, and ascorbate content, that peripubertal GH/IGF-1 deficiency in Lewis dwarf rats increases vascular oxidative stress, which is prevented by GH replacement. Peripubertal GHD did not alter superoxide dismutase or catalase activities in the aorta nor the expression of Cu-Zn-SOD, Mn-SOD, and catalase in the cerebral arteries of dwarf rats. In contrast, cerebrovascular expression of glutathione peroxidase 1 was significantly decreased in dwarf vessels, and this effect was reversed by GH treatment. Peripubertal GHD significantly decreases expression of the Nrf2 target genes NQO1 and GCLC in the cerebral arteries, whereas it does not affect expression and activity of endothelial nitric oxide synthase and vascular expression of IGF-1, IGF-binding proteins, and inflammatory markers (tumor necrosis factor alpha, interluekin-6, interluekin-1β, inducible nitric oxide synthase, intercellular adhesion molecule 1, and monocyte chemotactic protein-1). In conclusion, peripubertal GH/IGF-1 deficiency confers pro-oxidative cellular effects, which likely promote an adverse functional and structural phenotype in the vasculature, and results in accelerated vascular impairments later in life.

  11. GH activity and markers of inflammation

    DEFF Research Database (Denmark)

    Andreassen, Mikkel; Frystyk, Jan; Faber, Jens

    2012-01-01

    The GH/IGF1 axis may modulate inflammatory processes. However, the relationship seems complicated as both pro- and anti-inflammatory effects have been demonstrated.......The GH/IGF1 axis may modulate inflammatory processes. However, the relationship seems complicated as both pro- and anti-inflammatory effects have been demonstrated....

  12. Effects of dietary genistein on GH/IGF-I axis of Nile tilapia Oreochromis niloticus

    Science.gov (United States)

    Chen, Dong; Wang, Wei; Ru, Shaoguo

    2016-09-01

    There is considerable concern that isoflavones, such as genistein in fish feed composed of soybean protein, aff ects somatic growth in fish. Our previous works demonstrated that 30 and 300 μg/g dietary genistein had no significant eff ect on growth performance in Nile tilapia ( Oreochromis niloticus), but the higher level of genistein (3 000 μg/g) significantly depressed growth. This study was conducted to further examine the eff ects of dietary genistein on the endocrine disruption on growth hormone/insulin-like growth factor-I (GH/IGF-I) axis in Nile tilapia ( O. niloticus). Juvenile fish were fed by hand twice daily to satiation with one of four isonitrogenous and isoenergetic diets, each containing either 0, 30, 300 or 3 000 μg/g genistein. Following an 8-week feeding period, plasma GH and IGF-I levels were investigated by radioimmunoassay and gene expression levels of gh, ghrelin, gnrhs, ghr, npy, npyrs, pacap, ghrs, i gf-I, igf-Ir, and igfbp3 were examined by real-time PCR. The results show that no significant change in plasma GH and IGF-I levels in fish fed with diets containing 30 μg/g and 300 μg/g genistein. mRNA expression of genes along the GH/IGF-I axis remained unaff ected, except for igf-Ir, which was stimulated by the 300 μg/g genistein diet. While in fish fed the 3 000 μg/g genistein diet, the plasma GH and IGF-I levels decreased, and mRNA expression of gh, ghr2, npyr1, igf-I, and igf-Ir were also significantly depressed. In contrast, npy and igfbp3 mRNA expression were enhanced. This study provides convincing evidence for growth impediment by genistein by disturbing the GH/IGF-I axis in Nile tilapia O. niloticus.

  13. Microarchitecture, but Not Bone Mechanical Properties, Is Rescued with Growth Hormone Treatment in a Mouse Model of Growth Hormone Deficiency

    OpenAIRE

    Kristensen, Erika; Hallgrímsson, Benedikt; Morck, Douglas W.; Boyd, Steven K.

    2012-01-01

    Growth hormone (GH) deficiency is related to an increased fracture risk although it is not clear if this is due to compromised bone quality or a small bone size. We investigated the relationship between bone macrostructure, microarchitecture and mechanical properties in a GH-deficient (GHD) mouse model undergoing GH treatment commencing at an early (prepubertal) or late (postpubertal) time point. Microcomputed tomography images of the femur and L4 vertebra were obtained to quantify macrostruc...

  14. Mortality and reduced growth hormone secretion

    DEFF Research Database (Denmark)

    Stochholm, Kirstine; Christiansen, Jens; Laursen, Torben

    2007-01-01

    BACKGROUND: Data regarding the mortality rates of patients with growth hormone deficiency (GHD), whether or not treated with growth hormone (GH), are limited, but an increased mortality rate among hypopituitary patients compared with the general population has been documented. Cardiovascular dise...

  15. Sweet Spot Supersymmetry and Composite Messengers

    International Nuclear Information System (INIS)

    Ibe, Masahiro; Kitano, Ryuichiro

    2007-01-01

    Sweet spot supersymmetry is a phenomenologically and cosmologically perfect framework to realize a supersymmetric world at short distance. We discuss a class of dynamical models of supersymmetry breaking and its mediation whose low-energy effective description falls into this framework. Hadron fields in the dynamical models play a role of the messengers of the supersymmetry breaking. As is always true in the models of the sweet spot supersymmetry, the messenger scale is predicted to be 10 5 GeV ∼ mess ∼ 10 GeV. Various values of the effective number of messenger fields N mess are possible depending on the choice of the gauge group

  16. MESSENGER'S First and Second Flybys of Mercury

    Science.gov (United States)

    Slavin, James A.

    2009-01-01

    The MESSENGER mission to Mercury offers our first opportunity to explore this planet's miniature magnetosphere since Mariner 10's brief fly-bys in 1974-5. The magnetosphere of Mercury is the smallest in the solar system with its magnetic field typically standing off the solar wind only approximately 1000 km above the surface. An overview of the MESSENGER mission and its January 14th and October 6th, 2008 close flybys of Mercury will be provided. Primary science objectives and the science instrumentation will be described. Initial results from MESSENGER will be discussed with an emphasis on the magnetic field and charged particle measurements.

  17. Growth hormone-releasing factor stimulates proliferation of somatotrophs in vitro

    DEFF Research Database (Denmark)

    Billestrup, Nils; Swanson, L W; Vale, W

    1986-01-01

    The mitogenic effect of the hypothalamic peptides growth hormone-releasing factor (GRF) and somatostatin on cultured growth hormone (GH)-producing cells (somatotrophs) was studied. Using autoradiographic detection of [3H]thymidine uptake and immunocytochemical identification of GH-producing cells...

  18. Cholecystokinin-From Local Gut Hormone to Ubiquitous Messenger

    DEFF Research Database (Denmark)

    Rehfeld, Jens F

    2017-01-01

    pancreatic enzyme secretion and growth, gallbladder contraction, and gut motility, satiety and inhibit acid secretion from the stomach. Moreover, they are major neurotransmitters in the brain and the periphery. CCK peptides also stimulate calcitonin, insulin, and glucagon secretion, and they may act...

  19. Cholecystokinin-From Local Gut Hormone to Ubiquitous Messenger

    DEFF Research Database (Denmark)

    Rehfeld, Jens F

    2017-01-01

    Cholecystokinin (CCK) was discovered in 1928 in jejunal extracts as a gallbladder contraction factor. It was later shown to be member of a peptide family, which are all ligands for the CCK1 and CCK2 receptors. CCK peptides are known to be synthetized in small intestinal endocrine I-cells and cere...

  20. Increased neck soft tissue mass and worsening of obstructive sleep apnea after growth hormone treatment in men with abdominal obesity

    DEFF Research Database (Denmark)

    Karimi, Mahssa; Koranyi, Josef; Franco, Celina

    2010-01-01

    Risk factors for obstructive sleep apnea (OSA) are male gender, obesity and abnormalities in neck soft tissue mass. OSA is associated with both growth hormone (GH) excess and severe GH deficiency in adults. Adults with abdominal obesity have markedly suppressed GH secretion....

  1. Effects of ionizing radiation and partial hepatectomy on messenger RNA synthesis

    International Nuclear Information System (INIS)

    Abdel-Halim, M.N.

    1979-01-01

    Newly synthesized messenger RNA, as measured by a 40 min uptake of the radioactive precursor (6- 14 C) orotic acid, was studied in the regenerating livers of non-irradiated and gamma-irradiated (1800 rad) adrenal-intact and adrenalectomized rats 24 and 48 hours after partial hepatectomy. Two groups of rats, one with and one without adrenal glands were each divided into four subgroups: (1) control rats, (2) irradiated rats, (3) partially hepatectomized rats and (4) irradiated, partially hepatectomized rats. The radioactive profile of polyribosome formation and distribution was determined by sucrose density gradient centrifugation (10 to 40 per cent). The result of this study indicates that ionizing radiation decreases the synthesis of newly formed messenger RNA in regenerating livers of adrenal-intact rats. However, adrenalectomy largely abolished that inhibition. These data suggest that the decrease in messenger RNA synthesis may be explained by the disturbance of adrenal hormones induced by partial hepatectomy and ionizing radiation. (author)

  2. Thyroid hormone receptor binds to a site in the rat growth hormone promoter required for induction by thyroid hormone

    International Nuclear Information System (INIS)

    Koenig, R.J.; Brent, G.A.; Warne, R.L.; Larsen, P.R.; Moore, D.D.

    1987-01-01

    Transcription of the rat growth hormone (rGH) gene in pituitary cells is increased by addition of thyroid hormone (T3). This induction is dependent on the presence of specific sequences just upstream of the rGH promoter. The authors have partially purified T3 receptor from rat liver and examined its interaction with these rGH sequences. They show here that T3 receptor binds specifically to a site just upstream of the basal rGH promoter. This binding site includes two copies of a 7-base-pair direct repeat, the centers of which are separated by 10 base pairs. Deletions that specifically remove the T3 receptor binding site drastically reduce response to T3 in transient transfection experiments. These results demonstrate that T3 receptor can recognize specific DNA sequences and suggest that it can act directly as a positive transcriptional regulatory factor

  3. In vivo effect of 3,5,3'-triiodothyronine on calcium uptake in several tissues in the rat: Evidence for a physiological role for calcium as the first messenger for the prompt action of thyroid hormone at the level of the plasma membrane

    International Nuclear Information System (INIS)

    Segal, J.

    1990-01-01

    Calcium has been shown in vitro to serve as the first messenger for the rapid effect of thyroid hormone at the level of the plasma membrane. In the present study the physiological relevance of this mechanism is examined in the whole animal. To this end, the effect of T3 on 45calcium uptake and sugar 2-deoxyglucose (2-DG) uptake, an effect that requires extracellular calcium, and the influence of calcium blockers thereon were measured in ventricles, atria, diaphragm, fat, and liver in the rat. In the first three tissues, T3 produced comparable changes in 45Ca uptake and 2-DG uptake (T3 increased 2-DG uptake in fat, where 45Ca uptake was undetected, and had no effect in liver); this activity was blocked by the calcium channel blocker cadmium. The effect of T3 on 45Ca uptake, like its effect on the in vivo uptake of 2-DG described previously, was biphasic and time related; at physiological doses of 0.01 and 0.1 micrograms/100 g BW, T3 increased 45Ca uptake, whereas at greater (pharmacological) doses of 1 and 100 micrograms/100 g BW, T3 was without effect or inhibited 45Ca uptake. In ventricles and atria, the stimulatory effect of T3 on 45Ca uptake was very rapid within 2 min, at which time it was at or near maximum (50-90% above control) and then declined gradually and was not seen after 10-20 min. Of the several calcium blockers employed, verapamil (organic) and cadmium (inorganic) were found to be the most effective. Verapamil and cadmium produced a rapid, transient, and dose-related inhibition of 45Ca uptake in the tissues examined (except fat tissue where, under the experimental conditions employed, 45Ca uptake was undetected). Verapamil, given iv (200 micrograms/100 g BW) or ip (1 mg/100 g BW), reduced tissue 45Ca uptake by 50-90% within 2 or 10 min, respectively, and then its inhibitory effect diminished rapidly and was not seen after 20-30 min

  4. PCR-RFLP analyses for studying the diversity of GH and Pit-1 genes in Slovak Simmental cattle

    Directory of Open Access Journals (Sweden)

    Anna Trakovická

    2013-10-01

    Full Text Available The aim of this study was evaluation of growth hormone (GH and specific pituitary transcription factor (Pit-1 genes diversity in population of 353 Slovak Simmental cows. The analyses were based on single nucleotide polymorphisms GH/AluI and Pit-1/HinfI detections. A polymorphic site of GH gene (AluI has been linked to differences in circulating metabolites, metabolic hormones and milk yield. Bovine Pit-1 is responsible for pituitary development and hormone secreting gene expression, including GH gene. The Pit-1/HinfI locus was associated with growth, milk production and reproduction performance in cattle. Samples of genomic DNA were analyzed by PCR-RFLP method. Digestion of GH gene PCR products with restriction enzyme AluI revealed allele L and V with frequency 0.695 and 0.305, respectively. The digested Pit-1 gene PCR products with enzyme HinfI revealed alleles A (0.249 and B (0.751. Dominant genotypes were for GH gene heterozygous LV (0.47 and for Pit-1 gene homozygous BB (0.56 animals. The observed heterozygosity, effective allele numbers and polymorphism information content of GH/AluI and Pit-1/HinfI bovine loci population were 0.42/0.37, 1.73/1.59 and 0.33/0.30, respectively. The median polymorphic information content of loci was also transferred to the higher observed homozygosity in population (0.58/0.63. Keywords: cattle, growth hormone, leptin, PCR, Pit-1, polymorphism.

  5. [Hormones and hair growth].

    Science.gov (United States)

    Trüeb, R M

    2010-06-01

    With respect to the relationship between hormones and hair growth, the role of androgens for androgenetic alopecia (AGA) and hirsutism is best acknowledged. Accordingly, therapeutic strategies that intervene in androgen metabolism have been successfully developed for treatment of these conditions. Clinical observations of hair conditions involving hormones beyond the androgen horizon have determined their role in regulation of hair growth: estrogens, prolactin, thyroid hormone, cortisone, growth hormone (GH), and melatonin. Primary GH resistance is characterized by thin hair, while acromegaly may cause hypertrichosis. Hyperprolactinemia may cause hair loss and hirsutism. Partial synchronization of the hair cycle in anagen during late pregnancy points to an estrogen effect, while aromatase inhibitors cause hair loss. Hair loss in a causal relationship to thyroid disorders is well documented. In contrast to AGA, senescent alopecia affects the hair in a diffuse manner. The question arises, whether the hypothesis that a causal relationship exists between the age-related reduction of circulating hormones and organ function also applies to hair and the aging of hair.

  6. Growing up with short stature : Psychosocial consequences of hormone treatment

    NARCIS (Netherlands)

    Visser-van Balen, J.

    2007-01-01

    Growing up with short stature. Psychosocial consequences of hormone treatment To enhance height in children with short stature, growth hormone (GH) can be used. In short children without a detectable pathology underlying their short stature, there is no medical rationale for growth hormone

  7. Cognitive impairments and mood disturbances in growth hormone deficient men

    NARCIS (Netherlands)

    Deijen, J.B.; de Boer, H.; Blok, G.J.; van der Veen, E.A.

    1996-01-01

    In order to establish whether reported psychological complaints in hypopituitary adults are related to growth hormone (GH) deficiency or other pituitary hormone deficiencies, emotional well-being and cognitive performance were evaluated in 31 men with multiple pituitary hormone deficiencies (MPHD)

  8. Growth hormone in sports: detecting the doped or duped.

    Science.gov (United States)

    Ho, Ken K Y; Nelson, Anne E

    2011-01-01

    Doping with growth hormone (GH) is banned; however, there is anecdotal evidence that it is widely abused. GH is reportedly often used in combination with anabolic steroids at high doses for several months. Development of a robust test for detecting GH has been challenging since recombinant human 22-kDa GH used in doping is indistinguishable analytically from endogenous GH and there are wide physiological fluctuations in circulating GH concentrations. One approach to GH testing is based on measurement of different circulating GH isoforms using immunoassays that differentiate between 22-kDa and other GH isoforms. Administration of 22-kDa GH results in a change in its abundance relative to other endogenous pituitary GH isoforms. The differential isoform method is, however, limited by its short time window of detection. A second approach that extends the time window of detection is based on detection of increased levels of circulating GH-responsive proteins, such as the insulin-like growth factor (IGF) axis and collagen peptides. As age and gender are the major determinants of variability for IGF-I and the collagen markers, a test based on these markers must take these factors into account. Extensive data now validate the GH-responsive marker approach, and implementation is largely dependent on establishing an assured supply of standardized assays. Robust tests are available to detect GH and enforce the ban on its abuse in sports. Novel approaches that include gene expression and proteomic profiling must continue to be pursued to expand the repertoire of testing approaches available and to maintain deterrence of GH doping. Copyright © 2011 S. Karger AG, Basel.

  9. Increased linear bone growth by GH in the absence of SOCS2 is independent of IGF-1.

    Science.gov (United States)

    Dobie, Ross; Ahmed, Syed F; Staines, Katherine A; Pass, Chloe; Jasim, Seema; MacRae, Vicky E; Farquharson, Colin

    2015-11-01

    Growth hormone (GH) signaling is essential for postnatal linear bone growth, but the relative importance of GHs actions on the liver and/or growth plate cartilage remains unclear. The importance of liver derived insulin like-growth factor-1 (IGF-1) for endochondral growth has recently been challenged. Here, we investigate linear growth in Suppressor of Cytokine Signaling-2 (SOCS2) knockout mice, which have enhanced growth despite normal systemic GH/IGF-1 levels. Wild-type embryonic ex vivo metatarsals failed to exhibit increased linear growth in response to GH, but displayed increased Socs2 transcript levels (P growth over a 12 day period. Despite this increase, IGF-1 transcript and protein levels were not increased in response to GH. In accordance with these data, IGF-1 levels were unchanged in GH-challenged postnatal Socs2(-/-) conditioned medium despite metatarsals showing enhanced linear growth. Growth-plate Igf1 mRNA levels were not elevated in juvenile Socs2(-/-) mice. GH did however elevate IGF-binding protein 3 levels in conditioned medium from GH challenged metatarsals and this was more apparent in Socs2(-/-) metatarsals. GH did not enhance the growth of Socs2(-/-) metatarsals when the IGF receptor was inhibited, suggesting that IGF receptor mediated mechanisms are required. IGF-2 may be responsible as IGF-2 promoted metatarsal growth and Igf2 expression was elevated in Socs2(-/-) (but not WT) metatarsals in response to GH. These studies emphasise the critical importance of SOCS2 in regulating GHs ability to promote bone growth. Also, GH appears to act directly on the metatarsals of Socs2(-/-) mice, promoting growth via a mechanism that is independent of IGF-1. © 2014 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.

  10. Autosomal Dominant Growth Hormone Deficiency (Type II).

    Science.gov (United States)

    Alatzoglou, Kyriaki S; Kular, Dalvir; Dattani, Mehul T

    2015-06-01

    Isolated growth hormone deficiency (IGHD) is the commonest pituitary hormone deficiency resulting from congenital or acquired causes, although for most patients its etiology remains unknown. Among the known factors, heterozygous mutations in the growth hormone gene (GH1) lead to the autosomal dominant form of GHD, also known as type II GHD. In many cohorts this is the commonest form of congenital isolated GHD and is mainly caused by mutations that affect the correct splicing of GH-1. These mutations cause skipping of the third exon and lead to the production of a 17.5-kDa GH isoform that exerts a dominant negative effect on the secretion of the wild type GH. The identification of these mutations has clinical implications for the management of patients, as there is a well-documented correlation between the severity of the phenotype and the increased expression of the 17.5-kDa isoform. Patients with type II GHD have a variable height deficit and severity of GHD and may develop additional pituitary hormone defiencies over time, including ACTH, TSH and gonadotropin deficiencies. Therefore, their lifelong follow-up is recommended. Detailed studies on the effect of heterozygous GH1 mutations on the trafficking, secretion and action of growth hormone can elucidate their mechanism on a cellular level and may influence future treatment options for GHD type II.

  11. Skin morphological changes in growth hormone deficiency and acromegaly

    DEFF Research Database (Denmark)

    Lange, Merete Wolder; Thulesen, J; Feldt-Rasmussen, U

    2001-01-01

    To evaluate the histomorphology of skin and its appendages, especially eccrine sweat glands, in patients with GH disorders, because reduced sweating ability in patients with growth hormone deficiency (GHD) is associated with increased risk of hyperthermia under stressed conditions....

  12. Information for People Treated with Human Growth Hormone (Summary)

    Science.gov (United States)

    ... person in Austria received hormone made by a pharmaceutical company. Are people treated with pituitary hGH at ... are the electroencephalogram (EEG) and magnetic resonance imaging (MRI). While these brain tests are useful if they ...

  13. Immobilization of Glycoside Hydrolase Families GH1, GH13, and GH70: State of the Art and Perspectives

    Directory of Open Access Journals (Sweden)

    Natália G. Graebin

    2016-08-01

    Full Text Available Glycoside hydrolases (GH are enzymes capable to hydrolyze the glycosidic bond between two carbohydrates or even between a carbohydrate and a non-carbohydrate moiety. Because of the increasing interest for industrial applications of these enzymes, the immobilization of GH has become an important development in order to improve its activity, stability, as well as the possibility of its reuse in batch reactions and in continuous processes. In this review, we focus on the broad aspects of immobilization of enzymes from the specific GH families. A brief introduction on methods of enzyme immobilization is presented, discussing some advantages and drawbacks of this technology. We then review the state of the art of enzyme immobilization of families GH1, GH13, and GH70, with special attention on the enzymes β-glucosidase, α-amylase, cyclodextrin glycosyltransferase, and dextransucrase. In each case, the immobilization protocols are evaluated considering their positive and negative aspects. Finally, the perspectives on new immobilization methods are briefly presented.

  14. Growth hormone insensitivity: Mexican case report

    Directory of Open Access Journals (Sweden)

    I Castilla-Cortazar

    2017-11-01

    Full Text Available Herein, we present a 14-year-old patient with short stature (134 cm referred from Paediatrics to our department for complementary evaluation since growth hormone (GH treatment failed to show any improvement. He was born premature and small for gestational age. Genital examination classified the patient as Tanner I–II with small penis and testicular size for his age. Biochemical analyses revealed normal GH levels with low serum insulin-like growth factor-1 (IGF-1. Molecular diagnosis confirmed several mutations in IGF1R and IGFALS, and so he was diagnosed with Laron Syndrome or GH insensibility and treated with IGF-1 substitutive therapy.

  15. Characterization of pituitary function with emphasis on GH secretion in the chronic fatigue syndrome.

    Science.gov (United States)

    Moorkens, G; Berwaerts, J; Wynants, H; Abs, R

    2000-07-01

    Previous studies have revealed that hormonal disturbances may accompany the chronic fatigue syndrome (CFS). Changes in the secretion of the pituitary-adrenal axis have been demonstrated, as well as abnormalities in the GH-IGF-I axis. However, data have not always been well characterized and were sometimes conflicting. The small number of CFS patients investigated in earlier studies may have played a role in the interpretation of the results. Hormonal testing was performed in 73 nonobese CFS patients and nonobese 21 age-and gender-matched healthy controls. We investigated GH, ACTH and cortisol responses to insulin-induced hypoglycaemia. In a subgroup of patients arginine and clonidine stimulation for GH was also performed. Nocturnal secretion of GH, ACTH and cortisol were determined. Serum levels of IGF-I, prolactin, TSH, and free thyroxine were also measured. Visceral fat mass was assessed by CT scanning. GH response to insulin induced hypoglycaemia assessed by peak value (17.0 +/- 13.1 microg/l vs. 22. 1 +/- 9.8 microg/l; P = 0.01) and by AUC (450.0 +/- 361.3 microg/l vs. 672.3 +/- 393.0 microg/l; P = 0.002) was significantly decreased in CFS patients vs. controls. Nocturnal GH secretion assessed by GH peak value (5.4 +/- 3.7 vs. 9.0 +/- 5.1 microg/l; P = 0.44) and by AUC (34.4 +/- 20.2 vs. 67.4 +/- 43.1; P = 0.045) was also significantly impaired in CFS patients. Arginine and clonidine administration showed no differences in GH secretion between CFS patients and controls. In the CFS group, GH peak values were significantly higher after ITT than after arginine (P = 0.017) or clonidine (P = 0.001). No differences in serum IGF-I levels were found between CFS patients and controls. Except for a significantly lower nocturnal cortisol peak value, no differences were found in ACTH and cortisol secretion between CFS patients and controls. Significantly higher serum prolactin levels (7.4 +/- 4.7 microg/l vs. 4.4 +/- 1.3 microg/l; P = 0.004) and significantly higher serum

  16. Arterial pulse wave velocity, inflammatory markers, pathological GH and IGF states, cardiovascular and cerebrovascular disease

    Directory of Open Access Journals (Sweden)

    Michael R Graham

    2008-12-01

    Full Text Available Michael R Graham1, Peter Evans2, Bruce Davies1, Julien S Baker11Health and Exercise Science Research Unit, Faculty of Health Sport and Science, University of Glamorgan, Pontypridd, Wales, United Kingdom; 2Royal Gwent Hospital, Newport, Gwent, United KingdomAbstract: Blood pressure (BP measurements provide information regarding risk factors associated with cardiovascular disease, but only in a specific artery. Arterial stiffness (AS can be determined by measurement of arterial pulse wave velocity (APWV. Separate from any role as a surrogate marker, AS is an important determinant of pulse pressure, left ventricular function and coronary artery perfusion pressure. Proximal elastic arteries and peripheral muscular arteries respond differently to aging and to medication. Endogenous human growth hormone (hGH, secreted by the anterior pituitary, peaks during early adulthood, declining at 14% per decade. Levels of insulin-like growth factor-I (IGF-I are at their peak during late adolescence and decline throughout adulthood, mirror imaging GH. Arterial endothelial dysfunction, an accepted cause of increased APWV in GH deficiency (GHD is reversed by recombinant human (rh GH therapy, favorably influencing the risk for atherogenesis. APWV is a noninvasive method for measuring atherosclerotic and hypertensive vascular changes increases with age and atherosclerosis leading to increased systolic blood pressure and increased left ventricular hypertrophy. Aerobic exercise training increases arterial compliance and reduces systolic blood pressure. Whole body arterial compliance is lowered in strength-trained individuals. Homocysteine and C-reactive protein are two infl ammatory markers directly linked with arterial endothelial dysfunction. Reviews of GH in the somatopause have not been favorable and side effects of treatment have marred its use except in classical GHD. Is it possible that we should be assessing the combined effects of therapy with rhGH and rh

  17. [Issues related to secondary osteoporosis associated with growth hormone deficiency in adulthood].

    Science.gov (United States)

    Kužma, Martin; Jackuliak, Peter; Killinger, Zdenko; Vaňuga, Peter; Payer, Juraj

    Growth hormone (GH) increases linear bone growth through complex hormonal reactions, mainly mediated by insulin like growth factor 1 (IGF1) that is produced mostly by hepatocytes under influence of GH and stimulates differentiation of epiphyseal prechondrocytes. IGF1 and GH play a key role in the linear bone growth after birth and regulation of bone remodelation during the entire lifespan. It is known that adult GH deficient (GHD) patients have decreased BMD and increased risk of low-impact fractures. Most data gathered thus far on the effect of GH replacement on bone status comprise the measurement of quantitative changes of bone mass. Some animal studies with GHD showed that the bone microarchitecture, measured using computed tomography methods, is significantly compromised and improve after GH replacement. However, human studies did not show significantly decreased bone microarchitecture, but limited methodological quality does not allow firm conclusions on this subject.Key words: bone mass - bone quality - fracture - growth hormone - IGF1.

  18. Thyroxine modifies the effects of growth hormone in Ames dwarf mice.

    Science.gov (United States)

    Do, Andrew; Menon, Vinal; Zhi, Xu; Gesing, Adam; Wiesenborn, Denise S; Spong, Adam; Sun, Liou; Bartke, Andrzej; Masternak, Michal M

    2015-04-01

    Ames dwarf (df/df) mice lack growth hormone (GH), thyroid stimulating hormone and prolactin. Treatment of juvenile df/df mice with GH alone stimulates somatic growth, reduces insulin sensitivity and shortens lifespan. Early-life treatment with thyroxine (T4) alone produces modest growth stimulation but does not affect longevity. In this study, we examined the effects of treatment of juvenile Ames dwarf mice with a combination of GH + T4 and compared them to the effects of GH alone. Treatment of female and male dwarfs with GH + T4 between the ages of 2 and 8 weeks rescued somatic growth yet did not reduce lifespan to match normal controls, thus contrasting with the previously reported effects of GH alone. While the male dwarf GH + T4 treatment group had no significant effect on lifespan, the female dwarfs undergoing treatment showed a decrease in maximal longevity. Expression of genes related to GH and insulin signaling in the skeletal muscle and white adipose tissue (WAT) of female dwarfs was differentially affected by treatment with GH + T4 vs. GH alone. Differences in the effects of GH + T4 vs. GH alone on insulin target tissues may contribute to the differential effects of these treatments on longevity.

  19. Gigantism caused by growth hormone secreting pituitary adenoma

    OpenAIRE

    Rhee, Noorisaem; Jeong, Kumi; Yang, Eun Mi; Kim, Chan Jong

    2014-01-01

    Gigantism indicates excessive secretion of growth hormones (GH) during childhood when open epiphyseal growth plates allow for excessive linear growth. Case one involved a 14.7-year-old boy presented with extreme tall stature. His random serum GH level was 38.4 ng/mL, and failure of GH suppression was noted during an oral glucose tolerance test (OGTT; nadir serum GH, 22.7 ng/mL). Magnetic resonance imaging (MRI) of the brain revealed a 12-mm-sized pituitary adenoma. Transsphenoidal surgery was...

  20. Characterization of Growth Hormone Resistance in Experimental and Ulcerative Colitis

    DEFF Research Database (Denmark)

    Soendergaard, Christoffer; Kvist, Peter Helding; Thygesen, Peter

    2017-01-01

    Growth hormone (GH) resistance may develop as a consequence of inflammation during conditions such as inflammatory bowel disease, encompassing ulcerative colitis (UC). However, the specific role of the GH-insulin growth factor (IGF)-1-axis and/or the functional consequences of GH resistance......) proteins. These effects are driven by pro-inflammatory mediators (tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6) as confirmed using primary epithelial cells. Treatment of experimental colitis with GH increased IGF-1 and body weight of the mice, but had no effects on colonic inflammation...

  1. A radioimmunoassay of chicken growth hormone using growth hormone produced by recombinant DNA technology: validation and observations of plasma hormone variations in genetically fat and lean chickens

    International Nuclear Information System (INIS)

    Picaper, G.; Leclercq, B.; Saadoun, A.; Mongin, P.

    1986-01-01

    A radioimmunoassay (RIA) of chicken growth hormone (c-GH) has been developed using growth hormone produced by recombinant DNA technology. The best rabbit antiserum was used at 1/300,000 final dilution. Hormone labelling by iodine-125, achieved by chloramine T, allowed a specific activity of 3.7 MBq/μg. The equilibrium curves show that optimal conditions of incubation were reached at room temperature for 24h. This RIA used a second sheep antibody which precipitated the whole c-GH bound to the first antibody in the presence of polyethylene glycol solution (6%) at room temperature for 30 min. In our conditions, sensitivity was about 30 pg of c-GH per tube. Coefficient of variation was around 10%. No cross reaction was found with avian LH and prolactin. Thyrotrophin-releasing hormone (TRH) injection to young chickens induced 20-fold higher plasma c-GH concentrations. Simultaneous injection of somatostatin and TRH slightly reduced these concentrations. Hypoglycemia induced by insulin led to a drop of the plasma c-GH concentration. Conversely, refeeding or glucose load induced slight increases of the c-GH level. Genetically fat chickens tended to exhibit higher plasma c-GH concentrations than lean chickens

  2. Pituitary-hormone secretion by thyrotropinomas

    OpenAIRE

    Roelfsema, Ferdinand; Kok, Simon; Kok, Petra; Pereira, Alberto M.; Biermasz, Nienke R.; Smit, Jan W.; Frolich, Marijke; Keenan, Daniel M.; Veldhuis, Johannes D.; Romijn, Johannes A.

    2008-01-01

    Hormone secretion by somatotropinomas, corticotropinomas and prolactinomas exhibits increased pulse frequency, basal and pulsatile secretion, accompanied by greater disorderliness. Increased concentrations of growth hormone (GH) or prolactin (PRL) are observed in about 30% of thyrotropinomas leading to acromegaly or disturbed sexual functions beyond thyrotropin (TSH)-induced hyperthyroidism. Regulation of non-TSH pituitary hormones in this context is not well understood. We there therefore ev...

  3. Slipped Capital Femoral Epiphysis as a Complication of Growth Hormone Therapy

    Directory of Open Access Journals (Sweden)

    Shuo-Yu Wang

    2007-01-01

    Full Text Available Slipped capital femoral epiphysis (SCFE is a rare complication of growth hormone (GH therapy. Here, we report three patients who developed SCFE during GH therapy. The first two patients had hypopituitarism and had started GH therapy at the age of 15 years 6 months and 13 years 9 months, respectively. SCFE developed 4 years and 1 year after GH therapy, respectively. The third patient had Prader-Willi syndrome with obesity and hypogonadism and began GH therapy at the age of 12 years and 11 months. SCFE developed 2 months after starting GH therapy. Pain over the hip joints or over the knees is an early sign of SCFE. Despite recommendation, none of the three patients continued GH therapy. A high index of suspicion during GH therapy in patients at high risk of SCFE is important for early diagnosis and appropriate management. [J Formos Med Assoc 2007;106(2 Suppl:S46-S50

  4. Human GH Receptor-IGF-1 Receptor Interaction: Implications for GH Signaling

    Science.gov (United States)

    Gan, Yujun; Buckels, Ashiya; Liu, Ying; Zhang, Yue; Paterson, Andrew J.; Jiang, Jing; Zinn, Kurt R.

    2014-01-01

    GH signaling yields multiple anabolic and metabolic effects. GH binds the transmembrane GH receptor (GHR) to activate the intracellular GHR-associated tyrosine kinase, Janus kinase 2 (JAK2), and downstream signals, including signal transducer and activator of transcription 5 (STAT5) activation and IGF-1 gene expression. Some GH effects are partly mediated by GH-induced IGF-1 via IGF-1 receptor (IGF-1R), a tyrosine kinase receptor. We previously demonstrated in non-human cells that GH causes formation of a GHR-JAK2-IGF-1R complex and that presence of IGF-1R (even without IGF-1 binding) augments proximal GH signaling. In this study, we use human LNCaP prostate cancer cells as a model system to further study the IGF-1R's role in GH signaling. GH promoted JAK2 and GHR tyrosine phosphorylation and STAT5 activation in LNCaP cells. By coimmunoprecipitation and a new split luciferase complementation assay, we find that GH augments GHR/IGF-1R complex formation, which is inhibited by a Fab of an antagonistic anti-GHR monoclonal antibody. Short hairpin RNA-mediated IGF-1R silencing in LNCaP cells reduced GH-induced GHR, JAK2, and STAT5 phosphorylation. Similarly, a soluble IGF-1R extracellular domain fragment (sol IGF-1R) interacts with GHR in response to GH and blunts GH signaling. Sol IGF-1R also markedly inhibits GH-induced IGF-1 gene expression in both LNCaP cells and mouse primary osteoblast cells. On the basis of these and other findings, we propose a model in which IGF-1R augments GH signaling by allowing a putative IGF-1R-associated molecule that regulates GH signaling to access the activated GHR/JAK2 complex and envision sol IGF-1R as a dominant-negative inhibitor of this IGF-1R-mediated augmentation. Physiological implications of this new model are discussed. PMID:25211187

  5. Nonalcoholic fatty liver in patients with Laron syndrome and GH gene deletion - preliminary report.

    Science.gov (United States)

    Laron, Zvi; Ginsberg, Shira; Webb, Muriel

    2008-10-01

    There is little information on the relationship between growth hormone/insulin-like growth factor-I (GH/IGF-I) deficiency or IGF-I treatment on nonalcoholic fatty liver disease (NAFLD) a disorder linked to obesity and insulin resistance. To find out whether the markedly obese patients with Laron syndrome (LS) and GH gene deletion have fatty livers. We studied 11 untreated adult patients with LS (5M, 6F), five girls with LS treated by IGF-I and five adult patients with GH gene deletion (3M, 3F), four previously treated by hGH in childhood. Fatty liver was quantitatively evaluated by ultrasonography using a phase array US system (HITACHI 6500, Japan). Body adiposity was determined by DEXA, and insulin resistance was estimated by HOMA-IR using the fasting serum glucose and insulin values. Six out of 11 adult patients with LS, two out of the five IGF-I treated girls with LS and three out of five adult hGH gene deletion patients were found to have NAFLD (nonalcoholic fatty liver disease). NAFLD is a frequent complication in untreated and treated congenital IGF-I deficiency. No correlation between NAFLD and age, sex, degree of obesity, blood lipids, or degree of insulin resistance was observed.

  6. Effects of High Intensity Interval Training on Plasma Levels of GH and IGF-I

    Directory of Open Access Journals (Sweden)

    Seyyed Mahmoud Hejazi

    2017-04-01

    Full Text Available Introduction: It is well-recognized that exercise has a significant impact on the GH/IGF system but less is known about the effects of HIIT on this axis. Aim of the present study was to evaluate the effect of ten weeks of HIIT on plasma levels of GH and IGF-I in healthy men. Methods: Twenty young men (age 23.34 ± 2.56 weight 72.47 ± 12.01 height 174.10 ± 5.75 recruited and randomly assigned into control (n=10 and HIIT (n=12 groups. HIIT protocol was started with 4 cycles. Then, every two weeks one cycle was added to the previous ones. Finally, it was to 8 cycles/ session in tenth weeks that lasted 16 minutes. Blood samples were collected prior to and after HIIT program for all subjects and IGF-I and GH levels were measured. Result: HIIT subjects showed a significant increase in IGF-I (P=0.002, F=12.38. However, no significant change was shown in GH levels (P=0.716, F=0.62. Discussion and conclusion: Our findings indicate that the HIIT caused increase in circulating levels of IGF-I independently from GH levels. Both hormones may contribute to positive effects of anabolic conditions.

  7. Efficacy of growth hormone therapy in adults with childhood-onset growth hormone deficiency

    Directory of Open Access Journals (Sweden)

    Ja Hye Kim

    2014-03-01

    Full Text Available PurposeGrowth hormone (GH plays a key role in the regulation of body composition, lipid metabolism, and quality of life in adults with GH deficiency (GHD. This study investigated changes in laboratory findings and body composition after GH recommencement for adult GHD and analyzed correlation between GH interruption period and endocrine or anthropometric parameters.MethodsA total of 45 patients (17 females and 28 males diagnosed with childhood-onset GHD (CO-GHD were investigated and all patients had organic brain lesions. Patients diagnosed CO-GHD were retested to confirm adult GHD at age 20.4±5.0 years (18.0-32.1 years. Recombinant human GH was administered at a dose of 0.44 mg/day. Clinical and laboratory parameters such as weight, height, body mass index (BMI, serum insulin-like growth factor 1 (IGF-1, serum total cholesterol, high-density lipoprotein (HDL cholesterol, low-density lipoprotein (LDL cholesterol, and triglyceride levels, were compared between baseline and 12 months after treatment using paired t-test. In addition, correlation between GH interruption period and clinical parameters including BMI, lipid profile, IGF-1, and IGFBP-3, was analyzed.ResultsOf 45 patients, 33 patients had GH interruption period of 4.3±3.6 years (0.7-12.5 years. Serum HDL-cholesterol level increased significantly, whereas LDL-cholesterol decreased after 1 year of GH replacement therapy. However, body weight and BMI showed no significant changes after 1 year of GH replacement therapy. There were no significant correlations between GH interruption period and lipid profile or anthropometric parameters.ConclusionBMI and body weight were not affected by GH replacement. However, GH replacement in adults with GHD offers benefits in lipid metabolism.

  8. 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...

  9. A mathematical model for interpreting in vitro rhGH release from laminar implants.

    Science.gov (United States)

    Santoveña, A; García, J T; Oliva, A; Llabrés, M; Fariña, J B

    2006-02-17

    Recombinant human growth hormone (rhGH), used mainly for the treatment of growth hormone deficiency in children, requires daily subcutaneous injections. The use of controlled release formulations with appropriate rhGH release kinetics reduces the frequency of medication, improving patient compliance and quality of life. Biodegradable implants are a valid alternative, offering the feasibility of a regular release rate after administering a single dose, though it exists the slight disadvantage of a very minor surgical operation. Three laminar implant formulations (F(1), F(2) and F(3)) were produced by different manufacture procedures using solvent-casting techniques with the same copoly(D,L-lactic) glycolic acid (PLGA) polymer (Mw=48 kDa). A correlation in vitro between polymer matrix degradation and drug release rate from these formulations was found and a mathematical model was developed to interpret this. This model was applied to each formulation. The obtained results where explained in terms of manufacture parameters with the aim of elucidate whether drug release only occurs by diffusion or erosion, or by a combination of both mechanisms. Controlling the manufacture method and the resultant changes in polymer structure facilitates a suitable rhGH release profile for different rhGH deficiency treatments.

  10. Impact of Growth Hormone on Regulation of Adipose Tissue.

    Science.gov (United States)

    Troike, Katie M; Henry, Brooke E; Jensen, Elizabeth A; Young, Jonathan A; List, Edward O; Kopchick, John J; Berryman, Darlene E

    2017-06-18

    Increasing prevalence of obesity and obesity-related conditions worldwide has necessitated a more thorough understanding of adipose tissue (AT) and expanded the scope of research in this field. AT is now understood to be far more complex and dynamic than previously thought, which has also fueled research to reevaluate how hormones, such as growth hormone (GH), alter the tissue. In this review, we will introduce properties of AT important for understanding how GH alters the tissue, such as anatomical location of depots and adipokine output. We will provide an overview of GH structure and function and define several human conditions and cognate mouse lines with extremes in GH action that have helped shape our understanding of GH and AT. A detailed discussion of the GH/AT relationship will be included that addresses adipokine production, immune cell populations, lipid metabolism, senescence, differentiation, and fibrosis, as well as brown AT and beiging of white AT. A brief overview of how GH levels are altered in an obese state, and the efficacy of GH as a therapeutic option to manage obesity will be given. As we will reveal, the effects of GH on AT are numerous, dynamic and depot-dependent. © 2017 American Physiological Society. Compr Physiol 7:819-840, 2017. Copyright © 2017 John Wiley & Sons, Inc.

  11. Higgs mass from neutrino-messenger mixing

    International Nuclear Information System (INIS)

    Byakti, Pritibhajan; Khosa, Charanjit K.; Mummidi, V.S.; Vempati, Sudhir K.

    2017-01-01

    The discovery of the Higgs particle at 125 GeV has put strong constraints on minimal messenger models of gauge mediation, pushing the stop masses into the multi-TeV regime. Extensions of these models with matter-messenger mixing terms have been proposed to generate a large trilinear parameter, A t , relaxing these constraints. The detailed survey of these models (DOI: 10.1007/JHEP05(2013)055; 10.1007/JHEP08(2013)093 ) so far considered messenger mixings with only MSSM superfields. In the present work, we extend the survey to MSSM with inverse-seesaw mechanism. The neutrino-sneutrino corrections to the Higgs mass in the inverse seesaw model are not significant in the minimal gauge mediation model, unless one considers messenger-matter interaction terms. We classify all possible models with messenger-matter interactions and perform thorough numerical analysis to find out the promising models. We found that out of the 17 possible models 9 of them can lead to Higgs mass within the observed value without raising the sfermion masses significantly. The successful models have stop masses ∼1.5 TeV with small or negligible mixing and yet a light CP even Higgs at 125 GeV.

  12. Higgs mass from neutrino-messenger mixing

    Energy Technology Data Exchange (ETDEWEB)

    Byakti, Pritibhajan [Center for High Energy Physics, Indian Institute of Science,C.V. Raman Ave, Bangalore 560012 (India); Department of Theoretical Physics, Indian Association for the Cultivation of Science,2A & 2B Raja S.C. Mullick Road, Kolkata 700 032 (India); Khosa, Charanjit K. [Center for High Energy Physics, Indian Institute of Science,C.V. Raman Ave, Bangalore 560012 (India); Mummidi, V.S. [Harish-Chandra Research Institute,Chhatnag Road, Jhusi, Allahabad 211019 (India); Vempati, Sudhir K. [Center for High Energy Physics, Indian Institute of Science,C.V. Raman Ave, Bangalore 560012 (India)

    2017-03-06

    The discovery of the Higgs particle at 125 GeV has put strong constraints on minimal messenger models of gauge mediation, pushing the stop masses into the multi-TeV regime. Extensions of these models with matter-messenger mixing terms have been proposed to generate a large trilinear parameter, A{sub t}, relaxing these constraints. The detailed survey of these models (DOI: 10.1007/JHEP05(2013)055; 10.1007/JHEP08(2013)093 ) so far considered messenger mixings with only MSSM superfields. In the present work, we extend the survey to MSSM with inverse-seesaw mechanism. The neutrino-sneutrino corrections to the Higgs mass in the inverse seesaw model are not significant in the minimal gauge mediation model, unless one considers messenger-matter interaction terms. We classify all possible models with messenger-matter interactions and perform thorough numerical analysis to find out the promising models. We found that out of the 17 possible models 9 of them can lead to Higgs mass within the observed value without raising the sfermion masses significantly. The successful models have stop masses ∼1.5 TeV with small or negligible mixing and yet a light CP even Higgs at 125 GeV.

  13. A growth hormone receptor SNP promotes lung cancer by impairment of SOCS2-mediated degradation

    DEFF Research Database (Denmark)

    Chhabra, Y.; Wong, H. Y.; Nikolajsen, Louise Fletcher

    2018-01-01

    Both humans and mice lacking functional growth hormone (GH) receptors are known to be resistant to cancer. Further, autocrine GH has been reported to act as a cancer promoter. Here we present the first example of a variant of the GH receptor (GHR) associated with cancer promotion, in this case lu......-mesenchymal transition and metastases (TWIST1, SNAI2, EGFR, MYC and CCND1) at 2 h after a GH pulse. This is consistent with prolonged GH signalling acting to promote cancer progression in lung cancer.Oncogene advance online publication, 2 October 2017; doi:10.1038/onc.2017.352....

  14. Molecular genetics of growth hormone deficient children: correlation with auxology and response to first year of growth hormone therapy.

    Science.gov (United States)

    Khadilkar, Vaman; Phadke, Nikhil; Khatod, Kavita; Ekbote, Veena; Gupte, Supriya Phanse; Nadar, Ruchi; Khadilkar, Anuradha

    2017-05-24

    With the paucity of available literature correlating genetic mutation and response to treatment, we aimed to study the genetic makeup of children with growth hormone (GH) deficiency in Western India and correlate the mutation with auxology and response to GH treatment at end of 1 year. Fifty-three (31 boys and 22 girls) children with severe short stature (height for age z-score imaging (MRI) brain scan was done in all. Genetic mutations were tested for in GH1, GHRH, LHX3, LHX4 and PROP1, POU1F1 and HESX1 genes. Mean age at presentation was 9.7±5.1 years. Thirty-seven children (Group A) had no genetic mutation detected. Six children (Group B) had mutations in the GH releasing hormone receptor (GHRHR) gene, while eight children (Group C) had mutation in the GH1 gene. In two children, one each had a mutation in PROP1 and LHX3. There was no statistically significant difference in baseline height, weight and BMI for age z-score and height velocity for age z-score (HVZ). HVZ was significantly lower, post 1 year GH treatment in the group with homozygous GH1 deletion than in children with no genetic defect. Response to GH at the end of 1 year was poor in children with the homozygous GH1 deletion as compared to those with GHRHR mutation or without a known mutation.

  15. Effects of 2 wk of GH administration on 24-h indirect calorimetry in young, healthy, lean men

    DEFF Research Database (Denmark)

    Hansen, Mette; Morthorst, Rikke; Larsson, Benny

    2005-01-01

    The present study was designed as a randomized, double-blind placebo (Plc)-controlled study to determine the effect of 2 wk of growth hormone administration (GH-adm.) on energy expenditure (EE) and substrate oxidation in healthy humans. Sixteen young healthy men were divided into two groups....... The study consisted of two 24-h measurements (indirect calorimetry), separated by 2 wk of either Plc or GH injections (6 IU/day). At baseline, no significant differences were observed between the two groups in any of the measured anthropometric, hormonal, or metabolic parameters, neither did the parameters...... change over time in the Plc group. GH-adm. resulted in a 4.4% increase in 24-h EE (P

  16. Growth Hormone Resistance—Special Focus on Inflammatory Bowel Disease

    Directory of Open Access Journals (Sweden)

    Christoffer Soendergaard

    2017-05-01

    Full Text Available Growth hormone (GH plays major anabolic and catabolic roles in the body and is important for regulating several aspects of growth. During an inflammatory process, cells may develop a state of GH resistance during which their response to GH stimulation is limited. In this review, we will emphasize specific mechanisms governing the formation of GH resistance in the active phase of inflammatory bowel disease. The specific molecular effects mediated through individual inflammatory mediators and processes will be highlighted to provide an overview of the transcriptional, translational and post-translational inflammation-mediated impacts on the GH receptor (GHR along with the impacts on GH-induced intracellular signaling. We also will review GH’s effects on mucosal healing and immune cells in the context of experimental colitis, human inflammatory bowel disease and in patients with short bowel syndrome.

  17. Optimizing patient management and adherence for children receiving growth hormone

    DEFF Research Database (Denmark)

    Acerini, Carlo L.; Wac, Katarzyna; Bang, Peter

    2017-01-01

    © 2017 Acerini, Wac, Bang and Lehwalder. Poor adherence with growth hormone (GH) therapy has been associated with worse clinical outcomes, which in children relates specifically to their linear growth and loss of quality of life. The "360° GH in Europe" meeting, held in Lisbon, Portugal, in June...... and are reported as a manuscript, authored by the speakers. Reported here is a summary of the proceedings of the second session, which reviewed the determinants of GH therapy response, factors affecting GH therapy adherence and the development of innovative technologies to improve GH treatment in children....... Response to GH therapy varies widely, particularly in regard to the underlying diagnosis, although there is little consensus on the definition of a poor response. If the growth response is seen to be less than expected, the possible reasons should be discussed with patients and their parents, including...

  18. Growth hormone therapy and craniofacial bones: a comprehensive review.

    Science.gov (United States)

    Litsas, G

    2013-09-01

    Growth hormone (GH) has significant effects on linear bone growth, bone mass and bone metabolism. The primary role of GH supplementation in children with GH deficiency, those born small for gestational age or with other types of disorders in somatic development is to increase linear growth. However, GH therapy seems to elicit varying responses in the craniofacial region. Whereas the effects of GH administration on somatic development are well documented, comparatively little is known of its effects on the craniofacial region. The purpose of this review was to search the literature and compile results from both animal and human studies related to the impact of GH on craniofacial growth. © 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Effect of growth hormone-releasing factor on growth hormone release in children with radiation-induced growth hormone deficiency

    International Nuclear Information System (INIS)

    Lustig, R.H.; Schriock, E.A.; Kaplan, S.L.; Grumbach, M.M.

    1985-01-01

    Five male children who received cranial irradiation for extrahypothalamic intracranial neoplasms or leukemia and subsequently developed severe growth hormone (GH) deficiency were challenged with synthetic growth hormone-releasing factor (GRF-44), in an attempt to distinguish hypothalamic from pituitary dysfunction as a cause of their GH deficiency, and to assess the readily releasable GH reserve in the pituitary. In response to a pulse of GRF-44 (5 micrograms/kg intravenously), mean peak GH levels rose to values higher than those evoked by the pharmacologic agents L-dopa or arginine (6.4 +/- 1.3 ng/mL v 1.5 +/- 0.4 ng/mL, P less than .05). The peak GH value occurred at a mean of 26.0 minutes after administration of GRF-44. These responses were similar to those obtained in children with severe GH deficiency due to other etiologies (peak GH 6.3 +/- 1.7 ng/mL, mean 28.0 minutes). In addition, there was a trend toward an inverse relationship between peak GH response to GRF-44 and the postirradiation interval. Prolactin and somatomedin-C levels did not change significantly after the administration of a single dose of GRF-44. The results of this study support the hypothesis that cranial irradiation in children can lead to hypothalamic GRF deficiency secondary to radiation injury of hypothalamic GRF-secreting neurons. This study also lends support to the potential therapeutic usefulness of GRF-44 or an analog for GH deficiency secondary to cranial irradiation

  20. Acute effects of clonidine and growth-hormone-releasing hormone on growth hormone secretion in patients with hyperthyroidism.

    Science.gov (United States)

    Giustina, A; Buffoli, M G; Bussi, A R; Wehrenberg, W B

    1991-01-01

    Patients with hyperthyroidism have reduced growth hormone (GH) responses to pharmacological stimuli and reduced spontaneous nocturnal GH secretion. The stimulatory effect of clonidine on GH secretion has been suggested to depend on an enhancement of hypothalamic GH-releasing hormone (GHRH) release. The aim of our study was to evaluate the effects of clonidine and GHRH on GH secretion in patients with hyperthyroidism. Eight hyperthyroid females with recent diagnosis of Graves' disease (age range 20-55 years, body mass index range 19.2-26.2 kg/m2) and 6 healthy female volunteers (age range 22-35 years, body mass index range 19-25 kg/m2) underwent two experimental trials at no less than 7-day intervals: (a) an intravenous infusion of clonidine 150 micrograms in 10 ml of saline, or (b) a bolus intravenous injection of human GHRH (1-29)NH2, 100 micrograms in 1 ml of saline. Hyperthyroid patients showed blunted GH peaks after clonidine (7.1 +/- 1.7 micrograms/l) as compared to normal subjects receiving clonidine (28.5 +/- 4.9 micrograms/l, p less than 0.05). GH peaks after GHRH were also significantly lower in hyperthyroid subjects (8.0 +/- 1.7 micrograms/l) as compared to normal subjects receiving GHRH (27.5 +/- 4.4 micrograms/l, p less than 0.05). No significant differences in the GH values either after clonidine or GHRH were observed in the two groups of subjects examined. Our data demonstrate that the GH responses to clonidine as well as to GHRH in patients with hyperthyroidism are inhibited in a similar fashion with respect to normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Effects of growth hormone on morphology of cardiac muscle and skeletal muscle and hormone levels in rats

    International Nuclear Information System (INIS)

    Yang Ping; Liu Cong; Meng Fanbo; Zhu Jinming; Ni Jinsong; Zhou Hong; Tang Yubo

    2005-01-01

    Objective: To study the effects of growth hormone (GH) on morphology of cardiac muscle and skeletal muscle and hormone levels in Wistar rats. Methods: The GH was given with subcutaneous injection for 15 days, the level of serum GH was determined by radiation-immune method; the body weight and the ratio of organ weight to body weight were determined; the cell appearances of cardiac muscle and skeletal muscle were observed under microscope. the control group was set up. Results; The level of serum GH and rat body weight in experimental group were obviously higher than that in the control group, but the ratio of organ weight to body weight was not obviously different in two groups; musculature hypertrophy and cell nucleolus increasing were observed under microscopy, there were no capillary vessel hyperplasia and inflammatory soakage. Conclusion: GH can induce hypertrophy of cardiac muscle cells and skeletal muscle cells but not interstitial proliferation. (authors)

  2. The Effects of GH Transgenic Goats on the Microflora of the Intestine, Feces and Surrounding Soil.

    Directory of Open Access Journals (Sweden)

    Zekun Bao

    Full Text Available The development of genetically engineered animals has brought with it increasing concerns about biosafety issues. We therefore evaluated the risks of growth hormone from transgenic goats, including the probability of horizontal gene transfer and the impact on the microbial community of the goats' gastrointestinal tracts, feces and the surrounding soil. The results showed that neither the GH nor the neoR gene could be detected in the samples. Moreover, there was no significant change in the microbial community of the gastrointestinal tracts, feces and soil, as tested with PCR-denaturing gradient gel electrophoresis and 16S rDNA sequencing. Finally, phylogenetic analysis showed that the intestinal content, feces and soil samples all contained the same dominant group of bacteria. These results demonstrated that expression of goat growth hormone in the mammary of GH transgenic goat does not influence the microflora of the intestine, feces and surrounding soil.

  3. Growth Hormone Deficiency in a Patient with Becker Muscular Dystrophy: A Pediatric Case Report

    Directory of Open Access Journals (Sweden)

    Valeria Calcaterra

    2013-01-01

    Full Text Available Objective. To describe a biochemical growth hormone (GH deficiency and to evaluate therapeutic result in a six-year-old male with Becker muscular dystrophy (BMD. Methods. GH peak was evaluated after response to arginine and insulin. Bone age was evaluated according to Greulich and Pyle method. Results. The GH-supplementary therapy was very effective in terms of growth gain. Conclusion. The possibility of a growth hormone deficiency and treatment with GH in patients with BMD cannot be excluded, especially considering the good therapeutic response.

  4. SOCS-3 is involved in the downregulation of the acute insulin-like effects of growth hormone in rat adipocytes by inhibition of Jak2/IRS-1 signaling

    DEFF Research Database (Denmark)

    Ridderstråle, M; Amstrup, J; Hilton, D J

    2003-01-01

    One of the long-term effects of growth hormone (GH) in adipocytes is to maintain a state of refractoriness to insulin-like effects, a refractoriness which otherwise declines within a few hours of GH starvation. Here, we examined differences in GH signaling and the possible role for the recently i...

  5. Identification of tyrosine residues in the intracellular domain of the growth hormone receptor required for transcriptional signaling and Stat5 activation

    DEFF Research Database (Denmark)

    Hansen, L. H.; Wang, X.; Kopchick, J J

    1996-01-01

    The binding of growth hormone (GH) to its receptor results in its dimerization followed by activation of Jak2 kinase and tyrosine phosphorylation of the GH receptor itself, as well as Jak2 and the transcription factors Stat1, -3, and -5. In order to study the role of GH receptor tyrosine phosphor...

  6. Low FT4 Concentrations around the Start of Recombinant Human Growth Hormone Treatment: Predictor of Congenital Structural Hypothalamic-Pituitary Abnormalities?

    NARCIS (Netherlands)

    van Iersel, Laura; van Santen, Hanneke M.; Zandwijken, Gladys R. J.; Zwaveling-Soonawala, Nitash; Hokken-Koelega, Anita C. S.; van Trotsenburg, A. S. Paul

    2018-01-01

    Growth hormone (GH) treatment may unmask central hypothyroidism (CeH). This was first observed in children with GH deficiency (GHD), later also in adults with GHD due to acquired "organic" pituitary disease. We hypothesized that newly diagnosed CeH in children after starting GH treatment for

  7. The GH/IGF-I axis and pituitary function and size in adults with Prader-Willi syndrome

    NARCIS (Netherlands)

    van Nieuwpoort, I.C.; Sinnema, M.; Castelijns, J.A.; Twisk, J.W.; Curfs, L.M.; Drent, M.L.

    2011-01-01

    Background: In adults with Prader-Willi syndrome (PWS), limited information is available about pituitary function, more specifically the prevalence of growth hormone deficiency (GHD). The aim of this study was to gain more insight into endocrine function in PWS adults, with emphasis on GH secretion.

  8. Timing of growth hormone treatment affects trabecular bone microarchitecture and mineralization in growth hormone deficient mice.

    Science.gov (United States)

    Kristensen, Erika; Hallgrímsson, Benedikt; Morck, Douglas W; Boyd, Steven K

    2010-08-01

    Growth hormone (GH) is essential in the development of bone mass, and a growth hormone deficiency (GHD) in childhood is frequently treated with daily injections of GH. It is not clear what effect GHD and its treatment has on bone. It was hypothesized that GHD would result in impaired microarchitecture, and an early onset of treatment would result in a better recovery than late onset. Growth hormone deficient homozygous (lit/lit) mice of both sexes were divided into two treatment groups receiving daily injections of GH, starting at an early (21 days of age) or a late time point (35 days of age, corresponding to the end of puberty). A group of heterozygous mice with normal levels of growth hormone served as controls. In vivo micro-computed tomography scans of the fourth lumbar vertebra were obtained at five time points between 21 and 60 days of age, and trabecular morphology and volumetric BMD were analyzed to determine the effects of GH on bone microarchitecture. Early GH treatment led to significant improvements in bone volume ratio (p=0.006), tissue mineral density (p=0.005), and structure model index (p=0.004) by the study endpoint (day 60), with no detected change in trabecular thickness. Trabecular number increased and trabecular separation decreased in GHD mice regardless of treatment compared to heterozygous mice. This suggests fundamental differences in the structure of trabecular bone in GHD and GH treated mice, reflected by an increased number of thinner trabeculae in these mice compared to heterozygous controls. There were no significant differences between the late treatment group and GHD mice except for connectivity density. Taken together, these results indicate that bone responds to GH treatment initiated before puberty but not to treatment commencing post-puberty, and that GH treatment does not rescue the structure of trabecular bone to that of heterozygous controls. Copyright 2010 Elsevier Inc. All rights reserved.

  9. Differential effects of hGH and IGF-I on body proportions.

    Science.gov (United States)

    Laron, Zvi; Silbergeld, Aviva; Kauli, Rivka

    2012-07-01

    The differential growth effects of hGH and IGF-I on the upper/lower (U/L) body segment in relation to height (Ht) were analyzed in 15 patients with isolated Growth hormone deficiency (IGHD,:7M, 8F) mean age 5.0 +/- 3.2 (SD) years treated with hGH; 21 patients with multiple pituitary hormone deficiency including growth hormone (MPHD: 14M, 7F) aged 10.0 +/- 3.8, treated with hGH; 9 patients with Laron Syndrome (LS) (4M,5F) aged 6.9 +/- 5.6 years treated with IGF-I; 9 boys with intrauterine growth retardation (IUGR) aged 6.3 +/- 1.25 years treated by hGH; and 22 boys with idiopathic short stature (ISS) aged 8.0 +/- 1.55 years treated by hGH. The dose of hGH was 33 microg/kg/day, that of IGF-I 180-200 microg/kg/day. the U/L body segment ratio in IGHD patients decreased from 2.3 +/- 0.7 to 1.1 +/- 0.7 (p <0.001), and the Ht SDS increased from -4.9 +/- 1.3 to 2.3 +/- 1 (p < 0.001) following treatment. In MPHD patients the U/L body segment decreased from 1.1 +/- 1.1 to -0.6 +/- 1.0 (p < 0.001), and the Ht SDS increased from -3.3 +/- 1.4 to -2.5 +/- 1.0 (p < 0.009). In the LS group the U/L body segment ratio did not change with IGF-I treatment but Ht improved from -6.1 +/- 1.3 to -4.6 +/- 1.2 (p < 0.001), The differential growth response of the children with IUGR and with ISS resembled that of the children with LS. hGH and IGF-I act differentially on the spine and limbs.

  10. Potent agonists of growth hormone-releasing hormone. Part I.

    Science.gov (United States)

    Zarandi, M; Serfozo, P; Zsigo, J; Bokser, L; Janaky, T; Olsen, D B; Bajusz, S; Schally, A V

    1992-03-01

    Analogs of the 29 amino acid sequence of growth hormone-releasing hormone (GH-RH) with agmatine (Agm) in position 29 have been synthesized by the solid phase method, purified, and tested in vitro and in vivo. The majority of the analogs contained desaminotyrosine (Dat) in position 1, but a few of them had Tyr1, or N-MeTyr1. Some peptides contained one or more additional L- or D-amino acid substitutions in positions 2, 12, 15, 21, 27, and/or 28. Compared to the natural sequence of GH-RH(1-29)NH2, [Dat1,Ala15]GH-RH(1-28)Agm (MZ-3-191) and [D-Ala2,Ala15]GH-RH(1-28)Agm (MZ-3-201) were 8.2 and 7.1 times more potent in vitro, respectively. These two peptides contained Met27. Their Nle27 analogs, [Dat1,Ala15,Nle27]GH-RH(1-28)Agm(MZ-2-51), prepared previously (9), and [D-Ala2,Ala15,Nle28]GH-RH(1-28)Agm(MZ-3-195) showed relative in vitro potencies of 10.5 and 2.4, respectively. These data indicate that replacement of Met27 by Nle27 enhanced the GH-releasing activity of the analog when the molecule contained Dat1-Ala2 residues at the N-terminus, but peptides containing Tyr1-D-Ala2 in addition to Nle27 showed decreased potencies. Replacement of Ser28 with Asp in multi-substituted analogs of GH-RH(1-28)Agm resulted in a decrease in in vitro potencies compared to the parent compound. Thus, the Ser28-containing MZ-2-51, and [Dat1,Ala15,D-Lys21,Nle27]GH-RH(1-28)Agm, its Asp28 homolog (MZ-3-149), possessed relative activities of 10.5 and 5.6, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Response to GH treatment in adult GH deficiency is predicted by gender, age, and IGF1 SDS but not by stimulated GH-peak

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, Ulla; Brabant, Georg; Maiter, Dominique

    2013-01-01

    We studied whether the severity of GH deficiency (GHD) defined as i) GH-peak on stimulation tests (insulin tolerance test (ITT), arginine, and glucagon), ii) number of additional pituitary deficits, or iii) baseline IGF1 SDS could impact the response to GH treatment. We further explored whether iv...

  12. Silent pituitary macroadenoma co-secreting growth hormone and thyroid stimulating hormone.

    Science.gov (United States)

    Sen, Orhan; Ertorer, M Eda; Aydin, M Volkan; Erdogan, Bulent; Altinors, Nur; Zorludemir, Suzan; Guvener, Nilgun

    2005-04-01

    Silent pituitary adenomas are a group of tumors showing heterogenous morphological features with no hormonal function observed clinically. To date no explanation has been provided as to why these tumors remain "silent". We report a case of a silent macroadenoma with both growth hormone (GH) and thyroid stimulating hormone (TSH) staining and secretion but with no clinical manifestations, in particular, the absence of features of acromegaly or hyperthyroidism. The relevant literature is reviewed.

  13. Phosphorylation of the adaptor protein SH2B1β regulates its ability to enhance growth hormone-dependent macrophage motility

    OpenAIRE

    Su, Hsiao-Wen; Lanning, Nathan J.; Morris, David L.; Argetsinger, Lawrence S.; Lumeng, Carey N.; Carter-Su, Christin

    2013-01-01

    Previous studies have shown that growth hormone (GH) recruits the adapter protein SH2B1β to the GH-activated, GH receptor-associated tyrosine kinase JAK2, implicating SH2B1β in GH-dependent actin cytoskeleton remodeling, and suggesting that phosphorylation at serines 161 and 165 in SH2B1β releases SH2B1β from the plasma membrane. Here, we examined the role of SH2B1β in GH regulation of macrophage migration. We show that GH stimulates migration of cultured RAW264.7 macrophages, and primary cul...

  14. Multi-Messenger Astronomy with Gravitational Waves

    Indian Academy of Sciences (India)

    Sound + images show Bailey was out in the India-Australia match on 12 Jan 2016. Image credit: Rediff / Fox news / Twitter. Page 10. Electromagnetic follow up: the Indian context. Page 11. Multi-Messenger Astronomy with Gravitational Waves | LIGO-G1601377-v2. Varun Bhalerao (IUCAA) | 1 July 2016. 11. 20 – 60 keV:.

  15. Messenger RNA surveillance: neutralizing natural nonsense

    DEFF Research Database (Denmark)

    Weischelfeldt, Joachim Lütken; Lykke-Andersen, Jens; Porse, Bo

    2005-01-01

    Messenger RNA transcripts that contain premature stop codons are degraded by a process termed nonsense-mediated mRNA decay (NMD). Although previously thought of as a pathway that rids the cell of non-functional mRNAs arising from mutations and processing errors, new research suggests a more general...

  16. Mobile MSN Messenger: Still a Complement?

    Directory of Open Access Journals (Sweden)

    Marcus Nyberg

    2008-10-01

    Full Text Available In order to understand how mobile instant messaging services can fit into the users’ current communication behavior, Ericsson Research performed a qualitative user study in Sweden in May 2007. The results showed that the respondents were positive towards (free of charge mobile MSN Messenger and perceived it as an ex¬tension of the computer-based version that could be used anywhere. However, although MSN Messenger on the com¬puter definitely was considered as a ‘must-have’ application, the mobile version was only perceived as a ‘nice-to-have’ application and a complement to text mes¬saging (SMS. Almost one year later, in April 2008, Ericsson Research performed a short qualita¬tive follow-up study with the same set of respondents to un¬derstand if and how the mobile MSN Messenger usage had changed. The results actually revealed that none of the re¬spondents used mobile MSN Messenger anymore as the application no longer was free of charge. On a general level, the study highlights important considera¬tions when intro¬ducing computer-based concepts and Internet services in a mo¬bile environment.

  17. 12 CFR 7.1012 - Messenger service.

    Science.gov (United States)

    2010-01-01

    ... service” means any service, such as a courier service or armored car service, used by a national bank and... service do not advertise, or otherwise represent, that the bank itself is providing the service, although the bank may advertise that its customers may use one or more third party messenger services to...

  18. Messenger RNA 3' end formation in plants.

    Science.gov (United States)

    Hunt, A G

    2008-01-01

    Messenger RNA 3' end formation is an integral step in the process that gives rise to mature, translated messenger RNAs in eukaryotes. With this step, a pre-messenger RNA is processed and polyadenylated, giving rise to a mature mRNA bearing the characteristic poly(A) tract. The poly(A) tract is a fundamental feature of mRNAs, participating in the process of translation initiation and being the focus of control mechanisms that define the lifetime of mRNAs. Thus messenger RNA 3' end formation impacts two steps in mRNA biogenesis and function. Moreover, mRNA 3' end formation is something of a bridge that integrates numerous other steps in mRNA biogenesis and function. While the process is essential for the expression of most genes, it is also one that is subject to various forms of regulation, such that both quantitative and qualitative aspects of gene expression may be modulated via the polyadenylation complex. In this review, the current status of understanding of mRNA 3' end formation in plants is discussed. In particular, the nature of mRNA 3' ends in plants is reviewed, as are recent studies that are beginning to yield insight into the functioning and regulation of plant polyadenylation factor subunits.

  19. Gigantism caused by growth hormone secreting pituitary adenoma.

    Science.gov (United States)

    Rhee, Noorisaem; Jeong, Kumi; Yang, Eun Mi; Kim, Chan Jong

    2014-06-01

    Gigantism indicates excessive secretion of growth hormones (GH) during childhood when open epiphyseal growth plates allow for excessive linear growth. Case one involved a 14.7-year-old boy presented with extreme tall stature. His random serum GH level was 38.4 ng/mL, and failure of GH suppression was noted during an oral glucose tolerance test (OGTT; nadir serum GH, 22.7 ng/mL). Magnetic resonance imaging (MRI) of the brain revealed a 12-mm-sized pituitary adenoma. Transsphenoidal surgery was performed and a pituitary adenoma displaying positive immunohistochemical staining for GH was reported. Pituitary MRI scan was performed 4 months after surgery and showed recurrence/residual tumor. Medical treatment with a long-acting somatostatin analogue for six months was unsuccessful. As a result, secondary surgery was performed. Three months after reoperation, the GH level was 0.2 ng/mL and insulin-like growth factor 1 was 205 ng/mL. Case two involved a 14.9-year-old boy, who was referred to our department for his tall stature. His basal GH level was 9.3 ng/mL, and failure of GH suppression was reported during OGTT (nadir GH, 9.0 ng/mL). Pituitary MRI showed a 6-mm-sized pituitary adenoma. Surgery was done and histopathological examination demonstrated a pituitary adenoma with positive staining for GH. Three months after surgery, the GH level was 0.2 ng/mL and nadir GH during OGTT was less than 0.1 ng/mL. Pituitary MRI scans showed no residual tumor. We present two cases of gigantism caused by a GH-secreting pituitary adenoma with clinical and microscopic findings.

  20. Gigantism caused by growth hormone secreting pituitary adenoma

    Directory of Open Access Journals (Sweden)

    Noorisaem Rhee

    2014-06-01

    Full Text Available Gigantism indicates excessive secretion of growth hormones (GH during childhood when open epiphyseal growth plates allow for excessive linear growth. Case one involved a 14.7-year-old boy presented with extreme tall stature. His random serum GH level was 38.4 ng/mL, and failure of GH suppression was noted during an oral glucose tolerance test (OGTT; nadir serum GH, 22.7 ng/mL. Magnetic resonance imaging (MRI of the brain revealed a 12-mm-sized pituitary adenoma. Transsphenoidal surgery was performed and a pituitary adenoma displaying positive immunohistochemical staining for GH was reported. Pituitary MRI scan was performed 4 months after surgery and showed recurrence/residual tumor. Medical treatment with a long-acting somatostatin analogue for six months was unsuccessful. As a result, secondary surgery was performed. Three months after reoperation, the GH level was 0.2 ng/mL and insulin-like growth factor 1 was 205 ng/mL. Case two involved a 14.9-year-old boy, who was referred to our department for his tall stature. His basal GH level was 9.3 ng/mL, and failure of GH suppression was reported during OGTT (nadir GH, 9.0 ng/mL. Pituitary MRI showed a 6-mm-sized pituitary adenoma. Surgery was done and histopathological examination demonstrated a pituitary adenoma with positive staining for GH. Three months after surgery, the GH level was 0.2 ng/mL and nadir GH during OGTT was less than 0.1 ng/mL. Pituitary MRI scans showed no residual tumor. We present two cases of gigantism caused by a GH-secreting pituitary adenoma with clinical and microscopic findings.

  1. Gigantism caused by growth hormone secreting pituitary adenoma

    Science.gov (United States)

    Rhee, Noorisaem; Jeong, Kumi; Yang, Eun Mi

    2014-01-01

    Gigantism indicates excessive secretion of growth hormones (GH) during childhood when open epiphyseal growth plates allow for excessive linear growth. Case one involved a 14.7-year-old boy presented with extreme tall stature. His random serum GH level was 38.4 ng/mL, and failure of GH suppression was noted during an oral glucose tolerance test (OGTT; nadir serum GH, 22.7 ng/mL). Magnetic resonance imaging (MRI) of the brain revealed a 12-mm-sized pituitary adenoma. Transsphenoidal surgery was performed and a pituitary adenoma displaying positive immunohistochemical staining for GH was reported. Pituitary MRI scan was performed 4 months after surgery and showed recurrence/residual tumor. Medical treatment with a long-acting somatostatin analogue for six months was unsuccessful. As a result, secondary surgery was performed. Three months after reoperation, the GH level was 0.2 ng/mL and insulin-like growth factor 1 was 205 ng/mL. Case two involved a 14.9-year-old boy, who was referred to our department for his tall stature. His basal GH level was 9.3 ng/mL, and failure of GH suppression was reported during OGTT (nadir GH, 9.0 ng/mL). Pituitary MRI showed a 6-mm-sized pituitary adenoma. Surgery was done and histopathological examination demonstrated a pituitary adenoma with positive staining for GH. Three months after surgery, the GH level was 0.2 ng/mL and nadir GH during OGTT was less than 0.1 ng/mL. Pituitary MRI scans showed no residual tumor. We present two cases of gigantism caused by a GH-secreting pituitary adenoma with clinical and microscopic findings. PMID:25077093

  2. Insulin and GH secretion in adolescent girls with irregular cycles: polycystic vs multifollicular ovaries.

    Science.gov (United States)

    Villa, P; Rossodivita, A; Fulghesu, A M; Cucinelli, F; Barini, A; Apa, R; Belosi, C; Lanzone, A

    2003-04-01

    In the present study insulin (I) and GH secretion was studied in a group of twenty-five young adolescent girls (mean age: 15 +/- 0.23 yr) with cycle irregularity associated to clinical signs of hyperandrogenism in comparison with that observed in eleven normal matched subjects with regular menses. All patients underwent basal hormone measurements and, on two consecutive days, an oral glucose tolerance test (OGTT) and a GHRH iv test. Therefore, all subjects had a transabdominal US scan for the measurement of ovarian volume and the characterization of ovarian morphology. On the basis of the US examination we found patients with polycystic ovaries (PCO-like group) and subjects with multifollicular ovaries (MFO group). PCO-like group exhibited T (pirregular menses showed plasma concentrations of AUC for I (AUC-I) significantly higher in respect to control group (7359.4 +/- 709 vs 5447 +/- 431 microIU/ml x 180 min, p<0.01) as well as both PCO-like group and MFO group did (p<0.001 and p<0.01) respectively. MFO group showed higher values of the AUC for GH (AUC-GH) (2809 +/- 432 ng/ml x 120 min) in respect to controls (1708 +/- 208 ng/ml x 120 min, p<0.05) and PCO-like subjects (p<0.001), who on the contrary showed the lowest AUC-GH values (618 +/- 119 ng/ml x 120 min). In conclusion, PCO-like patients associated hyperinsulinemia with a blunted GH secretion while MFO patients had higher GH secretion associated with higher AUC-I values in a way suggesting an immature and still developing reproductive system.

  3. A Natural Variant of Obestatin, Q90L, Inhibits Ghrelin's Action on Food Intake and GH Secretion and Targets NPY and GHRH Neurons in Mice

    OpenAIRE

    Hassouna, Rim; Zizzari, Philippe; Viltart, Odile; Yang, Seung-Kwon; Gardette, Robert; Videau, Catherine; Badoer, Emilio; Epelbaum, Jacques; Tolle, Virginie

    2012-01-01

    BACKGROUND: Ghrelin and obestatin are two gut-derived peptides originating from the same ghrelin/obestatin prepropeptide gene (GHRL). While ghrelin stimulates growth hormone (GH) secretion and food intake and inhibits γ-aminobutyric-acid synaptic transmission onto GHRH (Growth Hormone Releasing Hormone) neurons, obestatin blocks these effects. In Humans, GHRL gene polymorphisms have been associated with pathologies linked to an unbalanced energy homeostasis. We hypothesized that one polymorph...

  4. Growth hormone doping: a review

    Directory of Open Access Journals (Sweden)

    Erotokritou-Mulligan I

    2011-07-01

    Full Text Available Ioulietta Erotokritou-Mulligan, Richard IG Holt, Peter H SönksenDevelopmental Origins of Health and Disease Division, University of Southampton School of Medicine, The Institute of Developmental Science, Southampton General Hospital, Southampton, UKAbstract: The use of growth hormone (GH as a performance enhancing substance was first promoted in lay publications, long before scientists fully acknowledged its benefits. It is thought athletes currently use GH to enhance their athletic performance and to accelerate the healing of sporting injuries. Over recent years, a number of high profile athletes have admitted to using GH. To date, there is only limited and weak evidence for its beneficial effects on performance. Nevertheless the “hype” around its effectiveness and the lack of a foolproof detection methodology that will detect its abuse longer than 24 hours after the last injection has encouraged its widespread use. This article reviews the current evidence of the ergogenic effects of GH along with the risks associated with its use. The review also examines methodologies, both currently available and in development for detecting its abuse.Keywords: performance enhancing substance, GH, doping in sport, detection methods

  5. GH replacement therapy and second neoplasms in adult survivors of childhood cancer: a retrospective study from a single institution.

    Science.gov (United States)

    Brignardello, E; Felicetti, F; Castiglione, A; Fortunati, N; Matarazzo, P; Biasin, E; Sacerdote, C; Ricardi, U; Fagioli, F; Corrias, A; Arvat, E

    2015-02-01

    Growth hormone deficiency (GHD) is the most common endocrine late effect observed in childhood cancer survivors (CCS) previously submitted to cranial irradiation. Radiation therapy can also increase the risk of second neoplasms (SNs). Since in previous studies GH replacement therapy was associated with increased incidence of neoplasia, we explored the association between SNs and GH replacement therapy in a cohort of CCS with GHD. Within the clinical cohort of CCS referred to the Transition Unit for Childhood Cancer Survivors of Turin between November 2001 and December 2012, we considered all patients who developed GHD as a consequence of cancer therapies. GHD was always diagnosed in childhood. To evaluate the quality of data, our cohort was linked to the Childhood Cancer Registry of Piedmont. GHD was diagnosed in 49 out of 310 CCS included in our clinical cohort. At least one SN was diagnosed in 14 patients, meningioma and basal cell carcinoma being the most common SNs. The cumulative incidence of SNs was similar in GH-treated and -untreated patients (8 SNs out of 26 GH-treated and 6 out of 23 GH-untreated patients; p = 0.331). Age, sex and paediatric cancer type had no impact on SNs development. In our CCS, GH replacement therapy does not seem to increase the risk of SNs. Anyway, independently from replacement therapy, in these patients we observed an elevated risk of SNs, possibly related to previous radiation therapy, which suggests the need of a close long-term follow-up.

  6. Cirugía transesfenoidal: primera opción de tratamiento para adenomas hipofisarios secretores de GH Transsphenoidal surgery: first treatment option for GH secreting hypophyseal adenomas

    Directory of Open Access Journals (Sweden)

    Omar López Arbolay

    2004-12-01

    Full Text Available La elevación de los niveles de hormona del crecimiento (GH promueve el crecimiento grotesco de partes acras (acromegalia o incremento de la talla (gigantismo según la edad, así como trastornos metabólicos de relevancia biológica. La adenomectomía selectiva clasifica entre las modalidades de tratamiento. El objetivo del presente trabajo fue evaluar los resultados del tratamiento microquirúrgico por vía transeptoesfenoidal de los adenomas productores de GH en nuestro medio. Presentamos un estudio retrospectivo de pacientes intervenidos por vía transeptoesfenoidal, por esta variedad de adenomas, en el servicio de neurocirugía del Hospital "Hermanos Ameijeiras" desde 1996 al 2003. Se analizaron edad, sexo, síntomas cardinales, imaginología, niveles hormonales, complicaciones y evolución posoperatoria. Resultó que las complicaciones relacionadas con el proceder quirúrgico no fueron relevantes y ninguna persistió más allá del mes. La diabetes insípida fue la más frecuente. Los síntomas mejoraron y los títulos de GH descendieron por debajo de los niveles de curación en el 58,06 % de los operados. Se concluye que la adenomectomía transeptoesfenoidal es un proceder seguro y recomendable como tratamiento de elección en estos pacientes.The elevation of the growth hormone (GH levels enhances the grotesque growth of acral parts (acromegaly or the increase of height (gigantism according to age, as well as metabolic disorders of biological relevance. The selective adenotomy is among the treatment modalities. The objective of the present paper was to evaluate the results of the microsurgical transseptosphenoidal treatment of the GH producing adenomas in our setting. A retrospective study of patients that underwent transseptosphenoidal surgery for presenting this variety of adenomas at the neurosurgery service of "Hermanos Ameijeiras" Hospital from 1996 to 2003, was conducted. Age, cardinal symptoms, imaging, hormonal levels

  7. Human growth hormone. Its use and abuse.

    Science.gov (United States)

    Bradley, C A; Sodeman, T M

    1990-09-01

    The use of hGH may become a significant challenge to the sports world. Scientific and ethical questions regarding its use may become more pressing if synthetic hGH becomes available to the public. The potential appeal of hGH to athletic competitors is obvious, but at present no benefits of this hormone as an ergogenic aid have been clearly demonstrated. Indeed, clinical experience with acromegalics suggests that prolonged exposure to elevated doses of hGH produces detrimental neuromuscular responses. Perhaps an even more intense ethical issue concerns the use of hGH in children and adolescents. The use of hGH to increase height and thereby increase chances for athletic success may be tempting to both coaches and parents. Athletes, parents, coaches, and team physicians must be aware that hGH has not been shown to enhance athletic performance and that its potential long-term side effects are irreversible and even may be life threatening.

  8. Growth and maturational changes in dense fibrous connective tissue following 14 days of rhGH supplementation in the dwarf rat

    Science.gov (United States)

    Kyparos, Antonios; Orth, Michael W.; Vailas, Arthur C.; Martinez, Daniel A.

    2002-01-01

    The purpose of this study was to investigate the impact of recombinant human growth hormone (rhGH) on patella tendon (PT), medial collateral ligament (MCL), and lateral collateral ligament (LCL) on collagen growth and maturational changes in dwarf GH-deficient rats. Twenty male Lewis mutant dwarf rats, 37 days of age, were randomly assigned to Dwarf + rhGH (n = 10) and Dwarf + vehicle (n = 10) groups. The GH group received 1.25 mg rhGH/kg body wt twice daily for 14 days. rhGH administration stimulated dense fibrous connective tissue growth, as demonstrated by significant increases in hydroxyproline specific activity and significant decreases in the non-reducible hydroxylysylpyridinoline (HP) collagen cross-link contents. The increase in the accumulation of newly accreted collagen was 114, 67, and 117% for PT, MCL, and LCL, respectively, in 72 h. These findings suggest that a short course rhGH treatment can affect the rate of new collagen production. However, the maturation of the tendon and ligament tissues decreased 18-25% during the rapid accumulation of de novo collagen. We conclude that acute rhGH administration in a dwarf rat can up-regulate new collagen accretion in dense fibrous connective tissues, while causing a reduction in collagen maturation. Copyright 2002 Elsevier Science Ltd.

  9. Evaluation of the increase in GH and IGF-1 and effectiveness in the treatment on Zacatecas population; Evaluacion del aumento en GH e IGF-1 y eficacia en el tratamiento en poblacion zacatecana

    Energy Technology Data Exchange (ETDEWEB)

    Gallegos F, P. I.; Badillo A, V., E-mail: perla_gf17@hotmail.com [Universidad Autonoma de Zacatecas, Unidad Academica de Estudios Nucleares, Laboratorio de Radioinmunoanalisis y Quimioluminiscencia, Cipres No. 10, Fracc. La Penuela, 98060 Zacatecas (Mexico)

    2013-10-15

    The acromegaly and gigantism are dysfunctions that are caused by hyper-secretion of growth hormone (GH) and of production in liver of growth factor similar to the insulin type 1 (IGF-1) mediated by the GH secretion. The secretor pituitary adenomas of GH are the main cause of the hyper-secretion. The acromegaly and gigantism are manifested respectively by acral alterations and extremities increase, and an excessive growth of the bones. Although a world prevalence of 40-60 cases by inhabitants million is registered, very few formal studies exist that confirm this number. According to the program Epiacro in Mexico is considered a prevalence of 13 cases by inhabitants million. In the Zacatecas State official statistical numbers are not had for these pathologies. Due to the few registrations that exist, or to the cases reported in Mexico, is necessary to evaluate patients with suspicion and with hyper-secretion diagnostic of GH, to contribute and/or to reinforce the health state and national statistics. In this work the GH and IGF-1 concentrations were measured on Zacatecas population to estimate the age range and sex with more probability of suffering this illness, and to evaluate the patients that have received some treatment to check their effectiveness verifying the GH and IGF-1 decrease and being able to obtain normal values. We register 26 patient cases with suspicion of GH hyper-secretion, of these 9 were affected by the illness. The hyper-secretion cases were presented with more frequency in half age adults, being affected in a same way as much men as women. To the end of the study only an affected patient concludes with the pharmacological treatment for the GH hyper-secretion control of a group of 5. (Author)

  10. Ghrelin: ghrelin as a regulatory Peptide in growth hormone secretion.

    Science.gov (United States)

    Khatib, Nazli; Gaidhane, Shilpa; Gaidhane, Abhay M; Khatib, Mahanaaz; Simkhada, Padam; Gode, Dilip; Zahiruddin, Quazi Syed

    2014-08-01

    Ghrelin is a type of growth hormone (GH) secretagogue that stimulates the release of GH. It is a first hormone linking gastrointestinal-pituitary axis. This review highlights the interaction of ghrelin with GHRH and somatostatin to regulate the secretion of GH and intends to explore the possible physiological role of the ghrelin-pituitary-GH axis linkage system. Ghrelin is highly conserved among species and is classified into octanoylated (C8:0), decanoylated (C10:0), decenoylated (C10:1) and nonacylated,ghrelin. Acylated ghrelin is the major active form of human ghrelin. The primary production site of ghrelin is the stomach, and it interacts with stomach ghrelin as well as hypothalamic GHRH and somatostatin in the regulation of pituitary GH secretion. Ghrelin stimulate GH release through the GHS receptor to increase intracellular Ca2+ ([Ca2+] levels via IP3 signal transduction pathway. Ghrelin is a specific endogenous ligand for the GHS receptor and provides a definitive proof of the occurance of a GHS-GHS receptor signalling system in the regulation of GH secretion. Studies suggests that ghrelin is a powerful pharmacological agent that exerts a potent, time-dependent stimulation of pulsatile secretion of GH.

  11. Yearly stepwise increments of the growth hormone dose results in a better growth response after four years in girls with Turner syndrome. Dutch Working Group on Growth Hormone

    NARCIS (Netherlands)

    van Teunenbroek, A.; de Muinck Keizer-Schrama, S. M.; Stijnen, T.; Jansen, M.; Otten, B. J.; Delemarre-van de Waal, H. A.; Vulsma, T.; Wit, J. M.; Rouwé, C. W.; Reeser, H. M.; Gosen, J. J.; Rongen-Westerlaken, C.; Drop, S. L.

    1996-01-01

    To optimize the growth promoting effect of growth hormone (GH), 65 previously untreated girls with Turner syndrome (TS), chronological age (CA) 2-11 yr, were randomized into 3 dosage regimen groups: A, B, and C, with a daily recombinant-human GH dose during 4 study years of 4-4-4-4, 4-6-6-6, and

  12. Emerging options in growth hormone therapy: an update

    Directory of Open Access Journals (Sweden)

    Kemp SF

    2011-08-01

    Full Text Available Stephen F Kemp, J Paul FrindikUniversity of Arkansas for Medical Sciences, Arkansas Children's Hospital, Little Rock, AR, USAAbstract: Growth hormone (GH was first used to treat a patient in 1958. For the next 25 years it was available only from cadaver sources, which was of concern because of safety considerations and short supply. In 1985, GH produced by recombinant DNA techniques became available, expanding its possible uses. Since that time there have been three indications approved by the US Food and Drug Administration (FDA for GH-deficiency states and nine indications approved for non-GH-deficiency states. In 2003 the FDA approved GH for use in idiopathic short stature (ISS, which may indirectly cover other diagnoses that have short stature as a feature. However, coverage for GH therapy is usually more reliably obtainable for a specific indication, rather than the ISS indication. Possible future uses for GH therapy could include the treatment of syndromes such as Russell–Silver syndrome or chondrodystrophy. Other non-short-stature indications could include wound healing and burns. Other uses that have been poorly studied include aging and physical performance, in spite of the interest already shown by elite athletes in using GH. The safety profile of GH developed over the past 25 years has shown it to be a very safe hormone with few adverse events associated with it. The challenge for the future is to follow these patients into adulthood to determine whether GH therapy poses any long-term risks.Keywords: growth hormone, somatotropin, anabolic, short stature

  13. Skin manifestations of growth hormone-induced diseases.

    Science.gov (United States)

    Kanaka-Gantenbein, Christina; Kogia, Christina; Abdel-Naser, Mohamed Badawy; Chrousos, George P

    2016-09-01

    The human skin is a well-organized organ bearing different types of cells in a well-structured interference to each other including epidermal and follicular keratinocytes, sebocytes, melanocytes, dermal papilla cells and fibroblasts, endothelial cells, sweat gland cells as well as nerves. Several hormones act on different cell types of the skin, while it is also considered an endocrine organ secreting hormones that act at several sites of the organism. GH receptors are found in almost all cell types forming the skin, while IGF-1 receptors' expression is restricted to the epidermal keratinocytes. Both Growth Hormone (GH) excess, as in the case of Acromegaly in adults, or Gigantism in growing children, and GH deficiency states lead to skin manifestations. In case of GH excess the main dermatological findings are skin thickening, coarsening of facial features, acrochordons, puffy hands and feet, oily skin and hyperhidrosis, while GH deficiency, on the contrary, is characterized by thin, dry skin and disorder of normal sweating. Moreover, special disorders associated with GH excess may have specific characteristics, as is the case of café-au-lait spots in Neurofibromatosis, or big café-au-lait skin hyperpigmented regions with irregular margins, as is the case in McCune-Albright syndrome. Meticulous examination of the skin may therefore contribute to the final diagnosis in cases of GH-induced disorders.

  14. MESSENGER at Mercury: Early Orbital Operations

    Science.gov (United States)

    McNutt, Ralph L., Jr; Solomon, Sean C.; Bedini, Peter D.; Anderson, Brian J.; Blewett, David T.; Evans, Larry G.; Gold, Robert E.; Krimigis, Stamatios M.; Murchie, Scott L.; Nittler, Larry R.; hide

    2013-01-01

    The MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) spacecraft, launched in August 2004 under NASA's Discovery Program, was inserted into orbit about the planet Mercury in March 2011. MESSENGER's three flybys of Mercury in 2008-2009 marked the first spacecraft visits to the innermost planet since the Mariner 10 flybys in 1974-1975. The unprecedented orbital operations are yielding new insights into the nature and evolution of Mercury. The scientific questions that frame the MESSENGER mission led to the mission measurement objectives to be achieved by the seven payload instruments and the radio science experiment. Interweaving the full set of required orbital observations in a manner that maximizes the opportunity to satisfy all mission objectives and yet meet stringent spacecraft pointing and thermal constraints was a complex optimization problem that was solved with a software tool that simulates science observations and tracks progress toward meeting each objective. The final orbital observation plan, the outcome of that optimization process, meets all mission objectives. MESSENGER's Mercury Dual Imaging System is acquiring a global monochromatic image mosaic at better than 90% coverage and at least 250 m average resolution, a global color image mosaic at better than 90% coverage and at least 1 km average resolution, and global stereo imaging at better than 80% coverage and at least 250 m average resolution. Higher-resolution images are also being acquired of targeted areas. The elemental remote sensing instruments, including the Gamma-Ray and Neutron Spectrometer and the X-Ray Spectrometer, are being operated nearly continuously and will establish the average surface abundances of most major elements. The Visible and Infrared Spectrograph channel of MESSENGER's Mercury Atmospheric and Surface Composition Spectrometer is acquiring a global map of spectral reflectance from 300 to 1450 nm wavelength at a range of incidence and emission

  15. Growth hormone-specific induction of the nuclear localization of porcine growth hormone receptor in porcine hepatocytes.

    Science.gov (United States)

    Lan, H N; Hong, P; Li, R N; Shan, A S; Zheng, X

    2017-10-01

    The phenomenon of nuclear translocation of growth hormone receptor (GHR) in human, rat, and fish has been reported. To date, this phenomenon has not been described in a domestic animal (such as pig). In addition, the molecular mechanisms of GHR nuclear translocation have not been thoroughly elucidated. To this end, porcine hepatocytes were isolated and used as a cell model. We observed that porcine growth hormone (pGH) can induce porcine GHR's nuclear localization in porcine hepatocytes. Subsequently, the dynamics of pGH-induced pGHR's nuclear localization were analyzed and demonstrated that pGHR's nuclear localization occurs in a time-dependent manner. Next, we explored the mechanism of pGHR nuclear localization using different pGHR ligands, and we demonstrated that pGHR's nuclear translocation is GH(s)-dependent. We also observed that pGHR translocates into cell nuclei in a pGH dimerization-dependent fashion, whereas further experiments indicated that IMPα/β is involved in the nuclear translocation of the pGH-pGHR dimer. The pGH-pGHR dimer may form a pGH-GHR-JAK2 multiple complex in cell nuclei, which would suggest that similar to its function in the cell membrane, the nuclear-localized pGH-pGHR dimer might still have the ability to signal. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Synergistic effect of parathyroid hormone and growth hormone on trabecular and cortical bone formation in hypophysectomized rats.

    Science.gov (United States)

    Guevarra, Maria Sarah N; Yeh, James K; Castro Magana, Mariano; Aloia, John F

    2010-01-01

    Growth hormone (GH) deficiency in pediatric patients results in short stature and osteopenia. We postulated that the GH and parathyroid hormone (PTH) combination would result in improvement in bone growth and bone formation. Forty hypophysectomized female rats at age 8 weeks were divided into hypophysectomy (HX), HX + PTH (62.5 microg/kg, s.c. daily), HX + GH (3.33 mg/kg, s.c. daily), and HX + PTH + GH for a 4-week study. GH increased body weight, bone growth, bone mineral content (BMC) and bone mineral density (BMD), whereas PTH increased BMC and BMD without a significant effect on bone size. GH increased both periosteal and endocortical bone formation and cortical size, while PTH increased only endocortical bone formation. GH mitigated the trabecular bone loss by increasing bone formation, while PTH increased bone mass by increasing bone formation and suppressing osteoclast number per bone area. The result of combined intervention shows an increase in trabecular, periosteal and endocortical bone formation and suppression of bone resorption resulting in a synergistic effect on increasing trabecular and cortical bone volume and BMD. The combination treatment of PTH and GH increases bone growth, bone formation, decreases bone resorption and has a synergistic effect on increasing bone density and bone mass. Copyright (c) 2010 S. Karger AG, Basel.

  17. Evaluation of growth hormone release and human growth hormone treatment in children with cranial irradiation-associated short stature

    International Nuclear Information System (INIS)

    Romshe, C.A.; Zipf, W.B.; Miser, A.; Miser, J.; Sotos, J.F.; Newton, W.A.

    1984-01-01

    We studied nine children who had received cranial irradiation for various malignancies and subsequently experienced decreased growth velocity. Their response to standard growth hormone stimulation and release tests were compared with that in seven children with classic GH deficiency and in 24 short normal control subjects. With arginine and L-dopa stimulation, six of nine patients who received radiation had a normal GH response (greater than 7 ng/ml), whereas by design none of the GH deficient and all of the normal children had a positive response. Only two of nine patients had a normal response to insulin hypoglycemia, with no significant differences in the mean maximal response of the radiation and the GH-deficient groups. Pulsatile secretion was not significantly different in the radiation and GH-deficient groups, but was different in the radiation and normal groups. All subjects in the GH-deficient and radiation groups were given human growth hormone for 1 year. Growth velocity increased in all, with no significant difference in the response of the two groups when comparing the z scores for growth velocity of each subject's bone age. We recommend a 6-month trial of hGH in children who have had cranial radiation and are in prolonged remission with a decreased growth velocity, as there is no completely reliable combination of GH stimulation or release tests to determine their response

  18. Hepatic receptors for homologous growth hormone in the eel

    International Nuclear Information System (INIS)

    Hirano, T.

    1991-01-01

    The specific binding of 125I-labeled eel growth hormone (eGH) to liver membranes of the eel was examined. The specific binding to the 10,000g pellet was greater than that to the 600g pellet. The specific binding was linear up to about 100 mg fresh tissue, and was saturable with increasing amounts of membrane. The specific binding was pH-, temperature-, and time-dependent, with the optimum pH at 7.4, and greater specific binding was obtained at 15 and 25 degrees than at 35 degrees. Scatchard analysis of liver binding gave an association constant of 1.1 x 10(9) M-1 and a capacity of 105 fmol/mg protein. The receptor preparation was highly specific for GHs. Natural and recombinant eel GHs as well as recombinant salmon GH competed equally with 125I-eGH for the receptor sites of the 10,000g liver membrane. Ovine GH was more potent in displacing the labeled eGH than the homologous eel hormone. Tilapia GH and ovine prolactin (PRL) were needed in greater amounts (40 times) than eGH to displace the labeled eGH. Salmon and tilapia PRLs were still less potent (500 times) than eGH. There was no displacement with eel PRL. No significant change in the specific binding was seen 1 week after hypophysectomy, whereas injection of eGH into the hypophysectomized eel caused a significant reduction after 24 hr. The binding to the membrane fractions from gills, kidney, muscle, intestine, and brain was low and exclusively nonspecific, indicating the presence of specific GH receptors predominantly in the liver

  19. Evaluation of the increase in GH and IGF-1 and effectiveness in the treatment on Zacatecas population

    International Nuclear Information System (INIS)

    Gallegos F, P. I.; Badillo A, V.

    2013-10-01

    The acromegaly and gigantism are dysfunctions that are caused by hyper-secretion of growth hormone (GH) and of production in liver of growth factor similar to the insulin type 1 (IGF-1) mediated by the GH secretion. The secretor pituitary adenomas of GH are the main cause of the hyper-secretion. The acromegaly and gigantism are manifested respectively by acral alterations and extremities increase, and an excessive growth of the bones. Although a world prevalence of 40-60 cases by inhabitants million is registered, very few formal studies exist that confirm this number. According to the program Epiacro in Mexico is considered a prevalence of 13 cases by inhabitants million. In the Zacatecas State official statistical numbers are not had for these pathologies. Due to the few registrations that exist, or to the cases reported in Mexico, is necessary to evaluate patients with suspicion and with hyper-secretion diagnostic of GH, to contribute and/or to reinforce the health state and national statistics. In this work the GH and IGF-1 concentrations were measured on Zacatecas population to estimate the age range and sex with more probability of suffering this illness, and to evaluate the patients that have received some treatment to check their effectiveness verifying the GH and IGF-1 decrease and being able to obtain normal values. We register 26 patient cases with suspicion of GH hyper-secretion, of these 9 were affected by the illness. The hyper-secretion cases were presented with more frequency in half age adults, being affected in a same way as much men as women. To the end of the study only an affected patient concludes with the pharmacological treatment for the GH hyper-secretion control of a group of 5. (Author)

  20. Establishment and clinical application of immunoradiometric assay for human growth hormone in serum

    International Nuclear Information System (INIS)

    Ji Jinfeng; Wu Congyuan; Niu Zhanpo; Zhang Kui; Song Ailing; Deng Jieying; Shi Mifan

    1992-01-01

    An immunoradiometric assay (IRMA) for human growth hormone (hGH) in serum is developed based on two high specific monoclonal antibodies against hGh. It can specifically detect the levels of serum bioactive hGh and had no cross-reaction with human prolactin (hPRL) and hGh oligmeric forms. The sensitivity was 0.2 ng/ml and the recovery for different concentrations of hGh was 92.0% ∼ 103.2%. The coefficients of variation for intra and inter-assay were<9.1% and <14.2%, respectively. Integral analysis of the results of RIA and IRMA with the patients' clinical manifestations revealed that hGh IRMA is better than hGh RIA in reflecting the clinical states of different acromegalic patients

  1. A first-in-man phase 1 trial for long-acting TransCon Growth Hormone.

    Science.gov (United States)

    Gilfoyle, David; Mortensen, Eva; Christoffersen, Eva Dam; Leff, Jonathan A; Beckert, Michael

    2018-04-01

    TransCon growth hormone (GH) is a sustained-release inactive prodrug consisting of unmodified GH transiently bound to an inert carrier molecule designed to release fully active GH over a one-week period. This was a first-in-man phase 1 randomized trial was to evaluate the safety, tolerability, immunogenicity, pharmacokinetics (PK), and pharmacodynamics (PD) of a single dose of TransCon GH as compared to equivalent doses of daily GH (Omnitrope) or placebo in healthy adults. Forty-four healthy male adults were randomized to 4 cohorts of 11 subjects, distributed in a 7:2:2 ratio (TransCon GH: Omnitrope: placebo). A single injection of 4 possible TransCon GH doses (i.e., 0.04, 0.08, 0.16, or 0.24mg GH/kg/wk) or two different Omnitrope doses (i.e., 0.08 or 0.16mg GH/kg/wk divided into 7 equal daily doses) were administered with subjects evaluated for adverse events, immunogenicity, and GH and insulin-like growth factor-1 (IGF-1) levels. TransCon GH was well tolerated; no serious adverse events occurred, no injection site reaction differences between TransCon GH, Omnitrope, or placebo were identified, no nodules or lipoatrophy were reported, and no anti-GH binding antibodies or ECG changes were detected. Overall, the exposure of GH (C max ) and IGF-1 (AUC 0-168h ) following administration of equivalent doses of TransCon GH and Omnitrope were similar. GH and IGF-1 kinetics showed a dose-proportional increase following a single SC administration of TransCon GH and indicated that the prodrug is suitable for weekly administration. These results support advancement of TransCon GH to pediatric and adult GHD trials. Clinical trial registration numbers: NCT01010425 (clinicaltrials.gov). Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Ovarian morphology and function during growth hormone therapy of short girls born small for gestational age

    DEFF Research Database (Denmark)

    Tinggaard, Jeanette; Jensen, Rikke Beck; Sundberg, Karin

    2014-01-01

    OBJECTIVE: To study the effect of growth hormone (GH) treatment on ovarian and uterine morphology and function in short, prepubertal small-for-gestational-age (SGA) girls.DESIGN: A multinational, randomized controlled trial on safety and efficacy of GH therapy in short, prepubertal children born...... in SGA girls is prudent. Altogether, the findings are reassuring. However, long-term effects of GH treatment on adult reproductive function remain unknown.CLINICAL TRIAL REGISTRATION NUMBER: EudraCT 2005-001507-19....

  3. The production of nitric oxide in EL4 lymphoma cells overexpressing growth hormone.

    Science.gov (United States)

    Arnold, Robyn E; Weigent, Douglas A

    2003-01-01

    Growth hormone (GH) is produced by immunocompetent cells and has been implicated in the regulation of a multiplicity of functions in the immune system involved in growth and activation. However, the actions of endogenous or lymphocyte GH and its contribution to immune reactivity when compared with those of serum or exogenous GH are still unclear. In the present study, we overexpressed lymphocyte GH in EL4 lymphoma cells, which lack the GH receptor (GHR), to determine the role of endogenous GH in nitric oxide (NO) production and response to genotoxic stress. Western blot analysis demonstrated that the levels of GH increased approximately 40% in cells overexpressing GH (GHo) when compared with cells with vector alone. The results also show a substantial increase in NO production in cells overexpressing GH that could be blocked by N(G)-monomethyl-L-arginine (L-NMMA), an L-arginine analogue that competitively inhibits all three isoforms of nitric oxide synthase (NOS). No evidence was obtained to support an increase in peroxynitrite in cells overexpressing GH. Overexpression of GH increased NOS activity, inducible nitric oxide synthase (iNOS) promoter activity, and iNOS protein expression, whereas endothelial nitric oxide synthase and neuronal nitric oxide synthase protein levels were essentially unchanged. In addition, cells overexpressing GH showed increased arginine transport ability and intracellular arginase activity when compared with control cells. GH overexpression appeared to protect cells from the toxic effects of the DNA alkylating agent methyl methanesulfonate. This possibility was suggested by maintenance of the mitochondrial transmembrane potential in cells overexpressing GH when compared with control cells that could be blocked by L-NMMA. Taken together, the data support the notion that lymphocyte GH, independently of the GH receptor, may play a key role in the survival of lymphocytes exposed to stressful stimuli via the production of NO.

  4. NREM sleep architecture and relation to GH/IGF-1 axis in Laron syndrome.

    Science.gov (United States)

    Verrillo, Elisabetta; Bizzarri, Carla; Cappa, Marco; Bruni, Oliviero; Pavone, Martino; Cutrera, Renato

    2010-01-01

    Laron syndrome (LS), known as growth hormone (GH) receptor deficiency, is a rare form of inherited GH resistance. Sleep disorders were described as a common feature of adult LS patients, while no data are available in children. Bi-directional interactions between human sleep and the somatotropic system were previously described, mainly between slow wave sleep and the nocturnal GH surge. To analyze the sleep macro- and microstructure in LS and to evaluate the influence of substitutive insulin-like growth factor 1 (IGF-1) therapy on it. Two young LS females underwent polysomnography; the first study was performed during IGF-1 therapy, the second one after a 3-month wash-out period. In both patients, the sleep macrostructure showed that time in bed, sleep period time, total sleep time, sleep efficiency and rapid eye movement (REM) percentage were all increased during wash-out. The sleep microstructure (cyclic alternating pattern: CAP) showed significantly higher EEG slow oscillations (A1%) in NREM sleep, both during IGF-1 therapy and wash-out. Sleep macrostructure in LS children is slightly affected by substitutive IGF-1 therapy. Sleep microstructure shows an increase of A1%, probably related to abnormally high hypothalamic GHRH secretion, due to GH insensitivity. Copyright 2010 S. Karger AG, Basel.

  5. Growth Hormone's Effect on Adipose Tissue: Quality versus Quantity.

    Science.gov (United States)

    Berryman, Darlene E; List, Edward O

    2017-07-26

    Obesity is an excessive accumulation or expansion of adipose tissue (AT) due to an increase in either the size and/or number of its characteristic cell type, the adipocyte. As one of the most significant public health problems of our time, obesity and its associated metabolic complications have demanded that attention be given to finding effective therapeutic options aimed at reducing adiposity or the metabolic dysfunction associated with its accumulation. Growth hormone (GH) has therapeutic potential due to its potent lipolytic effect and resultant ability to reduce AT mass while preserving lean body mass. However, AT and its resident adipocytes are significantly more dynamic and elaborate than once thought and require one not to use the reduction in absolute mass as a readout of efficacy alone. Paradoxically, therapies that reduce GH action may ultimately prove to be healthier, in part because GH also possesses potent anti-insulin activities along with concerns that GH may promote the growth of certain cancers. This review will briefly summarize some of the newer complexities of AT relevant to GH action and describe the current understanding of how GH influences this tissue using data from both humans and mice. We will conclude by considering the therapeutic use of GH or GH antagonists in obesity, as well as important gaps in knowledge regarding GH and AT.

  6. Growth Hormone Research Society perspective on the development of long-acting growth hormone preparations

    DEFF Research Database (Denmark)

    Christiansen, Jens Sandahl; Backeljauw, Philippe F; Bidlingmaier, Martin

    2016-01-01

    OBJECTIVE: The Growth Hormone (GH) Research Society (GRS) convened a workshop to address important issues regarding trial design, efficacy, and safety of long-acting growth hormone preparations (LAGH). PARTICIPANTS: A closed meeting of 55 international scientists with expertise in GH, including...... and revised in an open forum on the concluding day. This was edited further and then circulated to attendees from academic institutions for review after the meeting. Participants from pharmaceutical companies did not participate in the planning, writing, or in the discussions and text revision on the final...

  7. Effects of recombinant human growth hormone in the treatment of dwarfism and relationship between IGF-1, IGFBP-3 and thyroid hormone.

    Science.gov (United States)

    Ren, Shanxiang; Nie, Yuxiang; Wang, Aihong

    2016-12-01

    The effects of recombinant human growth hormone (rhGH) in the treatment of dwarfism and the relationship between insulin-like growth factor (IGF)-1, IGF-binding protein (IGFBP)-3 and thyroid hormone were examined in the present study. For this purpose, 66 patients diagnosed with dwarfism were selected retrospectively, with 36 cases of growth hormone deficiency (GHD) and 30 cases of idiopathic short stature (ISS). The therapeutic dose of GHD 0.10 IU/kg·day and ISS 0.15 IU/kg·day were injected subcutaneously every night before sleep until adulthood. The average follow-up was 5 years, and the results were evaluated and measured every 3 months, including height, BA, secondary test of growth hormone (GH peak), IGF-1, IGFBP-3 and thyroid hormone (FT3, FT4 and TSH). After treatment, the height, BA, GH peak, IGF-A and IGFBP-3 of the GHD group were all increased, and the differences were statistically significant (P0.05). The results of the Pearson-related analysis suggested that GH peak of the GHD group, IGF-1 and IGFBP-3 were positively associated with height (P0.05). rhGH was effective for GHD and ISS, with the GHD effect being positively associated with the GH peak, IGF-1 and IGFBP-3. ISS had no obvious relationship with GH peak, IGF-1 and IGFBP-3 although other influencing factors may be involved.

  8. GH administration and discontinuation in healthy elderly men

    DEFF Research Database (Denmark)

    Lange, K H; Isaksson, F; Rasmussen, M H

    2001-01-01

    GH administration results in increased lean body mass (LBM), decreased fat mass (FM) and increased energy expenditure (EE). GH therapy may therefore have potential benefits, especially in the elderly, who are known to have decreased function of the GH/IGF-I axis. Several studies have focused...... discontinuation on body composition, resting oxygen uptake (VO2), resting heart rate (HR) and GH related serum markers in healthy elderly men....

  9. Effect of growth hormone replacement therapy on plasma lecithin:cholesterol acyltransferase and lipid transfer protein activities in growth hormone-deficient adults

    NARCIS (Netherlands)

    J.A. Beentjes; A. van Tol (Arie); W.J. Sluiter (Wim); R.P.F. Dullaart (Robin)

    2000-01-01

    textabstractThe effects of growth hormone (GH) replacement on plasma lecithin:cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP), and phospholipid transfer protein (PLTP), factors involved in high density lipoprotein (HDL) metabolism, are

  10. Influence of hyperthyroidism on growth hormone secretion.

    Science.gov (United States)

    Valcavi, R; Dieguez, C; Zini, M; Muruais, C; Casanueva, F; Portioli, I

    1993-05-01

    Hyperthyroidism is associated with altered GH secretion. Whether this is due to changes of somatotroph responsiveness or reflects an alteration in negative feedback signals at the hypothalamic level is unknown. We therefore performed a series of studies to shed some light onto this issue. Study 1: GHRH (1 microgram/kg b.w.) was injected i.v. in 38 hyperthyroid patients and in 30 normal subjects; in 11 of the patients the GHRH test was repeated following methimazole-induced remission of hyperthyroidism. Study 2: hGH (2 U i.v.) or saline were administered 3 hours prior to GHRH; six hyperthyroid patients and six normal subjects were studied. Study 3: ten normal subjects and ten hyperthyroid patients were given 75 g oral glucose or water 30 minutes before GHRH. Study 4: 11 normal subjects and eight hyperthyroid patients were studied. TRH or vehicle were dissolved in 250 ml of saline solution and infused at a rate of 400 micrograms/h for 150 minutes. Thirty minutes after the beginning of the infusions, L-arginine (30 g infused over 45 min i.v.) was administered. Hyperthyroid patients were compared to normal subjects. Growth hormone was measured by RIA at 15-minute intervals. GH responses to GHRH were subnormal in hyperthyroid patients. Following antithyroid drug treatment with methimazole, GH responses to GHRH increased in these patients in comparison to pretreatment values. Serum IGF-I levels, which were elevated before treatment, decreased after methimazole administration. Exogenous GH administration induced a clear decrease of GH responses to GHRH in both control and hyperthyroid subjects. On the other hand, oral glucose load decreased the GH responses to GHRH in normal but not in hyperthyroid subjects. TRH administration did not modify the GH responses to arginine in either normal subjects or hyperthyroid patients. Hyperthyroidism is associated with increased serum IGF-I levels and marked alterations in the neuroregulation of GH secretion. These changes involve

  11. Overall and cause-specific mortality in GH-deficient adults on GH replacement

    DEFF Research Database (Denmark)

    Gaillard, Rolf C; Mattsson, Anders F; Akerblad, Ann-Charlotte

    2012-01-01

    Hypopituitarism is associated with an increased mortality rate but the reasons underlying this have not been fully elucidated. The purpose of this study was to evaluate mortality and associated factors within a large GH-replaced population of hypopituitary patients.......Hypopituitarism is associated with an increased mortality rate but the reasons underlying this have not been fully elucidated. The purpose of this study was to evaluate mortality and associated factors within a large GH-replaced population of hypopituitary patients....

  12. Binding properties of beetal recombinant caprine growth hormone to ...

    African Journals Online (AJOL)

    SAM

    2014-07-23

    Jul 23, 2014 ... The aim of the study was to illustrate the radio-receptor assay of beetal recombinant caprine growth hormone (rcGH) ... interaction with microsomal membrane that shall be beneficial to study hormone receptor interactions of other Bovidae .... adding 1 ml of ice cold assay buffer, followed by 1 ml of 25% (w/v).

  13. Messengers of the universe: Session IV Summary

    International Nuclear Information System (INIS)

    Bernardini, Elisa; Serpico, Pasquale Dario

    2013-01-01

    Being stable, light and neutral weakly interacting particles, neutrinos are ideal messengers of the deep universe and a channel of choice in particular to explore the very high energy Galactic and Extragalactic sky, playing a synergic role most notably with gamma-ray observations. Neutrino astronomy—long after the SN1987A detection in the MeV range—is mature enough for decisive tests of astrophysical paradigms. Its current status constitutes one of the two big pillars of the “Messengers of the universe” session of the Neutrino Oscillation Workshop 2012. Neutrinos may also play a role in some cosmological contexts, such as the early universe and the dark matter problem. We review both aspects in this session summary report

  14. Bacterial nucleotide-based second messengers.

    Science.gov (United States)

    Pesavento, Christina; Hengge, Regine

    2009-04-01

    In all domains of life nucleotide-based second messengers transduce signals originating from changes in the environment or in intracellular conditions into appropriate cellular responses. In prokaryotes cyclic di-GMP has emerged as an important and ubiquitous second messenger regulating bacterial life-style transitions relevant for biofilm formation, virulence, and many other bacterial functions. This review describes similarities and differences in the architecture of the cAMP, (p)ppGpp, and c-di-GMP signaling systems and their underlying signaling principles. Moreover, recent advances in c-di-GMP-mediated signaling will be presented and the integration of c-di-GMP signaling with other nucleotide-based signaling systems will be discussed.

  15. The Energy Messenger, Number 1, Volume 4

    International Nuclear Information System (INIS)

    Stancil, J.

    1995-01-01

    'The Energy Messenger' is a Department of Energy publication on energy activities of interest to American Indians. The first issue of 1995 (in a magazine format) includes articles on: tribes winning grants to develop energy resources, recruiting of internships for DOE, information about Title XXVI-Indian Energy Resources, American Indian Heritage Month, tribal perspective on DOE actions, joint ventures between tribes and the DOE, and brief description of recent DOE activities

  16. The Energy Messenger, Number 1, Volume 4

    Energy Technology Data Exchange (ETDEWEB)

    Stancil, J. [ed.

    1995-01-01

    `The Energy Messenger` is a Department of Energy publication on energy activities of interest to American Indians. The first issue of 1995 (in a magazine format) includes articles on: tribes winning grants to develop energy resources, recruiting of internships for DOE, information about Title XXVI-Indian Energy Resources, American Indian Heritage Month, tribal perspective on DOE actions, joint ventures between tribes and the DOE, and brief description of recent DOE activities.

  17. A half-century of studies of growth hormone insensitivity/Laron syndrome: A historical perspective.

    Science.gov (United States)

    Rosenbloom, Arlan L

    2016-06-01

    A growth hormone (GH) dependent substance responsible for sulfate uptake by costal cartilage of hypophysectomized rats, labeled sulfation factor, was reported in 1957. In 1962 the radioimmunoassay for GH was described. The clinical picture of severe GH deficiency but with high serum concentrations of GH was reported in 3 siblings in 1966 and followed by a 1968 report of 22 patients belonging to 14 consanguineous oriental Jewish families in Israel. Defective sulfation factor generation was demonstrated in 15 of these individuals and in a 1971 report; FFA response to IV GH and growth response to GH injections suggested competitive saturation of peripheral tissue receptors by an abnormal GH. However, studies published in 1973 demonstrated normal fractionation of their circulating GH, and normal binding of GH from 22 patients to various antisera used for radioimmunoassay. In 1976, the Israeli investigators reported that circulating GH from 7 patients reacted normally in the recently developed radioreceptor assay for GH. In 1984, using hepatic microsome pellets, they demonstrated that the defect was a failure of GH binding to receptors. Characterization of the human GH receptor (GHR) gene, reported in 1989, included the initial description of a genetic defect of the GHR in 2 of 9 Israeli patients. At about the same time began the identification in Ecuador of what was to become the largest population of GH insensitivity in the world, ~100 individuals, and the only substantial population with a common mutation of the GH receptor. Treatment studies with recombinant IGF-I began in 1990. Growth response was modest compared to that of GH treated GH deficient subjects. The spectrum of GH insensitivity has expanded beyond GH receptor deficiency to include postreceptor abnormalities: IGF-I gene mutation (1996); IGF-I receptor mutation (2003); signal transducer and activator of transcription 5b mutation (2003); and mutation of the GH-dependent acid labile subunit (2004). Rare

  18. Pituitary-hormone secretion by thyrotropinomas.

    Science.gov (United States)

    Roelfsema, Ferdinand; Kok, Simon; Kok, Petra; Pereira, Alberto M; Biermasz, Nienke R; Smit, Jan W; Frolich, Marijke; Keenan, Daniel M; Veldhuis, Johannes D; Romijn, Johannes A

    2009-01-01

    Hormone secretion by somatotropinomas, corticotropinomas and prolactinomas exhibits increased pulse frequency, basal and pulsatile secretion, accompanied by greater disorderliness. Increased concentrations of growth hormone (GH) or prolactin (PRL) are observed in about 30% of thyrotropinomas leading to acromegaly or disturbed sexual functions beyond thyrotropin (TSH)-induced hyperthyroidism. Regulation of non-TSH pituitary hormones in this context is not well understood. We there therefore evaluated TSH, GH and PRL secretion in 6 patients with up-to-date analytical and mathematical tools by 24-h blood sampling at 10-min intervals in a clinical research laboratory. The profiles were analyzed with a new deconvolution method, approximate entropy, cross-approximate entropy, cross-correlation and cosinor regression. TSH burst frequency and basal and pulsatile secretion were increased in patients compared with controls. TSH secretion patterns in patients were more irregular, but the diurnal rhythm was preserved at a higher mean with a 2.5 h phase delay. Although only one patient had clinical acromegaly, GH secretion and IGF-I levels were increased in two other patients and all three had a significant cross-correlation between the GH and TSH. PRL secretion was increased in one patient, but all patients had a significant cross-correlation with TSH and showed decreased PRL regularity. Cross-ApEn synchrony between TSH and GH did not differ between patients and controls, but TSH and PRL synchrony was reduced in patients. We conclude that TSH secretion by thyrotropinomas shares many characteristics of other pituitary hormone-secreting adenomas. In addition, abnormalities in GH and PRL secretion exist ranging from decreased (joint) regularity to overt hypersecretion, although not always clinically obvious, suggesting tumoral transformation of thyrotrope lineage cells.

  19. Changes in GH/IGF-1 axis in intrauterine growth retardation: consequences of fetal programming?

    Science.gov (United States)

    Setia, S; Sridhar, M G

    2009-11-01

    Fetal growth is a complex process that depends on the genotype and epigenotype of the fetus, maternal nutrition, the availability of nutrients and oxygen to the fetus, intrauterine insults, and a variety of growth factors and proteins of maternal and fetal/placental origin. In the fetus, growth hormone (GH) plays little or no role in regulating fetal growth, and insulin-like growth factors (IGFs) control growth directly independent of fetal GH secretion. Placental growth hormone (PGH) is the prime regulator of maternal serum IGF-1 during pregnancy. Total as well as free PGH and IGFs are significantly lower in pregnancies with intrauterine growth retardation (IUGR). The GH/IGF axis is significantly affected by intrauterine growth retardation and some of these alterations may lead to permanent pathological programming of the IGF axis. Alterations in the IGF axis may play a role in the future occurrence of insulin resistance and hypertension. In this review we focus on the regulation of fetal growth and the role of fetal programming in the late consequences of a poor fetal environment reflected in IUGR.

  20. Holographic gauge mediation via strongly coupled messengers

    International Nuclear Information System (INIS)

    McGuirk, Paul; Shiu, Gary; Sumitomo, Yoske

    2010-01-01

    We consider a relative of semidirect gauge mediation where the hidden sector exists at large 't Hooft coupling. Such scenarios can be difficult to describe using perturbative field theory methods but may fall into the class of holographic gauge mediation scenarios, meaning that they are amenable to the techniques of gauge/gravity duality. We use a recently found gravity solution to examine one such case, where the hidden sector is a cascading gauge theory resulting in a confinement scale not much smaller than the messenger mass. In the original construction of holographic gauge mediation, as in other examples of semidirect gauge mediation at strong coupling, the primary contributions to visible sector soft terms come from weakly coupled messenger mesons. In contrast to these examples, we describe the dual of a gauge theory where there are significant contributions from scales in which the strongly coupled messenger quarks are the effective degrees of freedom. In this regime, the visible sector gaugino mass can be calculated entirely from holography.

  1. Impact of Growth Hormone on Cystatin C

    Directory of Open Access Journals (Sweden)

    Lisa Sze

    2013-11-01

    Full Text Available Background: Cystatin C (CysC is an alternative marker to creatinine for estimation of the glomerular filtration rate (GFR. Hormones such as thyroid hormones and glucocorticoids are known to have an impact on CysC. In this study, we examined the effect of growth hormone (GH on CysC in patients with acromegaly undergoing transsphenoidal surgery. Methods: Creatinine, CysC, GH and insulin-like growth factor-1 (IGF-1 were determined in 24 patients with acromegaly before and following transsphenoidal surgery. Estimated GFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration formula. Results: In all patients, surgical debulking resulted in decreased clinical disease activity and declining GH/IGF-1 levels. Postoperatively, biochemical cure was documented in 20 out of 24 patients. Creatinine levels (mean ± SEM increased from 72 ± 3 to 80 ± 3 µmol/l (p = 0.0004 and concurrently, estimated GFR decreased from 99 ± 3 to 91 ± 3 ml/min (p = 0.0008. In contrast to creatinine, CysC levels decreased from 0.72 ± 0.02 to 0.68 ± 0.02 mg/l (p = 0.0008. Conclusions: Our study provides strong evidence for discordant effects of GH on creatinine and CysC in patients with acromegaly undergoing transsphenoidal surgery, thus identifying another hormone that influences CysC independent of renal function.

  2. Urinary growth hormone excretion in acromegaly

    DEFF Research Database (Denmark)

    Main, K M; Lindholm, J; Vandeweghe, M

    1993-01-01

    The biochemical assessment of disease activity in acromegaly still presents a problem, especially in treated patients with mild clinical symptoms. We therefore examined the diagnostic value of the measurement of urinary growth hormone (GH) excretion in seventy unselected patients with acromegaly...

  3. Growth hormone-induced insulin resistance in human subjects involves reduced pyruvate dehydrogenase activity

    DEFF Research Database (Denmark)

    Nellemann, B.; Vendelbo, M.H.; Nielsen, Thomas Svava

    2014-01-01

    Insulin resistance induced by growth hormone (GH) is linked to promotion of lipolysis by unknown mechanisms. We hypothesized that suppression of the activity of pyruvate dehydrogenase in the active form (PDHa) underlies GH-induced insulin resistance similar to what is observed during fasting....

  4. Cytoplasmic sequences of the growth hormone receptor necessary for signal transduction

    DEFF Research Database (Denmark)

    Goujon, L; Allevato, G; Simonin, G

    1994-01-01

    To study structure-function relationships of the growth hormone (GH) receptor (GHR), two functional systems have been developed. CHO cells were transiently cotransfected with the cDNA encoding the full-length rat GHR and with a construct consisting of the 5' flanking region of one of two GH...

  5. Expression of the growth hormone receptor gene in insulin producing cells

    DEFF Research Database (Denmark)

    Møldrup, Annette; Billestrup, N; Nielsen, Jens Høiriis

    1990-01-01

    Growth hormone (GH) plays a dual role in glucose homeostasis. On the one hand, it exerts an insulin antagonistic effect on the peripheral tissue, on the other hand, it stimulates insulin biosynthesis and beta-cell proliferation. The expression of GH-receptors on the rat insulinoma cell line RIN-5...

  6. Growth Hormone Receptor Signaling Pathways and its Negative Regulation by SOCS2

    DEFF Research Database (Denmark)

    Fernández Pérez, Leandro; Flores-Morales, Amilcar; Guerra, Borja

    2016-01-01

    Growth hormone (GH) is a critical regulator of linear body growth during childhood but continues to have important metabolic actions throughout life. The GH receptor (GHR) is ubiquitously expressed, and deficiency of GHR signaling causes a dramatic impact on normal physiology during somatic devel...

  7. An auxology-based growth hormone program : Update on the Australian experience

    NARCIS (Netherlands)

    Werther, GA; Cowell, CT

    In 1988, new guidelines for growth hormone (GH) usage emphasizing auxological criteria were adopted in Australia. Currently, 1,250 children with the following diagnoses are being treated: idiopathic GH deficiency (IGHD), 23.4%; malignancy-related GHD, 7.9%; Turner's syndrome, 12.1%; nonendogrine

  8. A Child with Local Lipohypertrophy following Recombinant Human Growth Hormone Administration

    NARCIS (Netherlands)

    Koppen, Ilan J. N.; Bakx, Roel; de Kruiff, Chris C.; van Trotsenburg, A. S. Paul

    2016-01-01

    Local lipohypertrophy due to recombinant human growth hormone (rhGH) administration is a rare phenomenon. Here, we report a case of an 11-year-old girl who presented with a paraumbilical swelling, approximately one year after the start of rhGH treatment for short stature due to the presumed

  9. Effects of previous growth hormone excess and current medical treatment for acromegaly on cognition

    NARCIS (Netherlands)

    Brummelman, Pauline; Koerts, Janneke; Dullaart, Robin P. F.; van den Berg, Gerrit; Tucha, Oliver; Wolffenbuttel, Bruce H. R.; van Beek, Andre P.

    2012-01-01

    Background In untreated acromegaly patients, decreased cognitive functioning is reported to be associated with the degree of growth hormone (GH) and IGF-1 excess. Whether previous GH excess or current medical treatment for acromegaly specifically affects cognition remains unclear. The aim of this

  10. The effect of oxandrolone on voice frequency in growth hormone-treated girls with Turner syndrome

    NARCIS (Netherlands)

    Menke, L.A.; Sas, T.C.J.; Koningsbrugge, S.H. van; Ridder, M.A. de; Zandwijken, G.R.; Boersma, B.; Dejonckere, P.H.; Muinck Keizer-Schrama, S.M.P.F. de; Otten, B.J.; Wit, J.M.

    2011-01-01

    OBJECTIVES/HYPOTHESIS: Oxandrolone (Ox) increases height gain but may also cause voice deepening in growth hormone (GH)-treated girls with Turner syndrome (TS). We assessed the effect of Ox on objective and subjective speaking voice frequency in GH-treated girls with TS. STUDY DESIGN: A multicenter,

  11. Bone Mineral Density and Body Composition in Adolescents with Childhood-Onset Growth Hormone Deficiency

    NARCIS (Netherlands)

    Boot, Annemieke M.; van der Sluis, Inge M.; Krenning, Eric P.; Keizer-Schrama, Sabine M. P. F. de Muinck

    2009-01-01

    Background/Aims: The aim of the present study was to evaluate bone mineral density (BMD) and body composition of patients with childhood-onset growth hormone (GH) deficiency (GHD) treated with GH during the transition period. Methods: BMD and body composition, measured by dual-energy X-ray

  12. Effects of growth hormone administration on the body composition and hormone levels of genetically fat sheep

    International Nuclear Information System (INIS)

    Francis, S.M.; Jopson, N.B.; Littlejohn, R.P.; Stuart, S.K.; Veenvliet, B.A.; Young, M.J.; Suttie, J.M.

    1998-01-01

    Coopworth sheep selected for low (lean) or high (fat) backfat have large differences in plasma GH profiles. Fat genotype ram lambs (5 months old) were treated with growth hormone (GH) to simulate the plasma GH profiles of lean sheep and investigate whether exogenous GH could modify carcass fatness. For 77 days, bovine GH was administered at 25mug/kg live weight per day either as a single, daily subcutaneous bolus (fat bolus) or via portable pulsatile infusion pumps (fat pump) which delivered GH solution at 90-min intervals into a jugular catheter. Measurements of body composition were made by computed tomography (CT) and ultrasonic scanning during the trial, with linear carcass measurements and proximate analysis undertaken at the end of the experiment. Before treatments began, mean plasma GH levels were lower (P < 0.01) in fat control (0.34 mug/l) than in lean lambs (1.1 mug/l). Several weeks after the start of the trial, mean plasma GH had increased in both fat bolus (1.2mug/l) and fat pump (0.45mug/l) treatment lambs with major changes in the pulsatility relative to the fat control lambs. Although these changes were maintained in the fat bolus lambs, by the end of the trial there was no significant difference in mean plasma GH between fat pump and fat control sheep. Throughout the trial, plasma IGF-1 levels were higher in fat bolus, fat pump and lean lambs than in fat control lambs. Analysis of body composition data over the GH treatment period revealed that the slope of the allometric equation for total fat relative to empty body weight was lower in the fat bolus lambs (1.07) than in the lean lambs (1.50) with fat control and fat pump treatment lambs intermediate (1.30 and 1.36, respectively). Subcutaneous fat was later maturing in lean lambs than in fat control and bolus treatment lambs when regressed against total fat, with the fat pump treatment lambs being intermediate. Linear carcass measurements revealed changes due to GH administration in the

  13. Growth without growth hormone in combined pituitary hormone deficiency caused by pituitary stalk interruption syndrome

    Directory of Open Access Journals (Sweden)

    Sang Soo Lee

    2017-03-01

    Full Text Available Growth hormone (GH is an essential element for normal growth. However, reports of normal growth without GH have been made in patients who have undergone brain surgery for craniopharyngioma. Normal growth without GH can be explained by hyperinsulinemia, hyperprolactinemia, elevated leptin levels, and GH variants; however, its exact mechanism has not been elucidated yet. We diagnosed a female patient aged 13 with combined pituitary hormone deficiency (CPHD caused by pituitary stalk interruption syndrome (PSIS. The patient has experienced recurrent hypoglycemic seizures since birth, but reached the height of 160 cm at the age of 13, showing normal growth. She grew another 8 cm for 3 years after the diagnosis, and she reached her final adult height of 168 cm which was greater than the midparental height, at the age of 16. The patient's blood GH and insulin-like growth factor-I levels were consistently subnormal, although her insulin levels were normal. Her physical examination conducted at the age of 15 showed truncal obesity, dyslipidemia, and osteoporosis, which are metabolic features of GH deficiency (GHD. Herein, we report a case in which a PSIS-induced CPHD patient attained her final height above mid parental height despite a severe GHD.

  14. Growth Hormone and Endocrinopathies

    Energy Technology Data Exchange (ETDEWEB)

    Kim, K W; Choe, K O; Park, C Y; Lee, H; Son, H Y; Huh, K B; Ryu, K J [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1979-03-15

    This is an analysis of 39 patients studied at the Yonsei Medical Center from January, 1976 to March 1979. Of these 35 patient were suspected of having hypothalamic insufficiency and subjected to the L-Dopa stimulation test to observe growth hormone secretary function while four acromegaly patient received the glucose loading test and L-Dopa stimulation test. The results are as follows: 1) The basal level of GH in the various disease was as follows: a) The basal level was lower than the control level but was not statistically significant b) In diabetes the mean value tended to higher than the control level but was not significant statistically c) In all four acromegaly patients the GH level was significantly higher than the control level 2) Of 13 patients with diabetes, nine had diabetic retinopathy, and of those nine, six showed increased L-Dopa response. However, of the four non retinopathic DM patients, only one showed increased response to L-Dopa. 3) Two patients out of ten with Sheehan's syndrome responded to L-Dopa stimulation. 4) One Patient of eight with pituitary chromophobe adenoma responded to L-Dopa stimulation. 5) Four acromegaly patients revealed 3 acidophilic adenoma and one chromophobe adenoma histologically. Of patients receiving the L-Dopa stimulation test. Two showed a paradoxical response. Two patients who received the glucose loading test showed suppressed response. 6) Of two craniopharyngioma patients, one showed increased GH response after L-Dopa stimulation. Increased response of GH after L-Dopa stimulation was seen in one two craniopharyngioma patients and also in one of two patients with short structure.

  15. Growth Hormone and Endocrinopathies

    Energy Technology Data Exchange (ETDEWEB)

    Kim, K. W.; Choe, K. O.; Park, C. Y.; Lee, H.; Son, H. Y.; Huh, K. B.; Ryu, K. J. [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1979-03-15

    This is an analysis of 39 patients studied at the Yonsei Medical Center from January, 1976 to March 1979. Of these 35 patient were suspected of having hypothalamic insufficiency and subjected to the L-Dopa stimulation test to observe growth hormone secretary function while four acromegaly patient received the glucose loading test and L-Dopa stimulation test. The results are as follows: 1) The basal level of GH in the various disease was as follows: a) The basal level was lower than the control level but was not statistically significant b) In diabetes the mean value tended to higher than the control level but was not significant statistically c) In all four acromegaly patients the GH level was significantly higher than the control level 2) Of 13 patients with diabetes, nine had diabetic retinopathy, and of those nine, six showed increased L-Dopa response. However, of the four non retinopathic DM patients, only one showed increased response to L-Dopa. 3) Two patients out of ten with Sheehan's syndrome responded to L-Dopa stimulation. 4) One Patient of eight with pituitary chromophobe adenoma responded to L-Dopa stimulation. 5) Four acromegaly patients revealed 3 acidophilic adenoma and one chromophobe adenoma histologically. Of patients receiving the L-Dopa stimulation test. Two showed a paradoxical response. Two patients who received the glucose loading test showed suppressed response. 6) Of two craniopharyngioma patients, one showed increased GH response after L-Dopa stimulation. Increased response of GH after L-Dopa stimulation was seen in one two craniopharyngioma patients and also in one of two patients with short structure.

  16. Growth Hormone and Endocrinopathies

    International Nuclear Information System (INIS)

    Kim, K. W.; Choe, K. O.; Park, C. Y.; Lee, H.; Son, H. Y.; Huh, K. B.; Ryu, K. J.

    1979-01-01

    This is an analysis of 39 patients studied at the Yonsei Medical Center from January, 1976 to March 1979. Of these 35 patient were suspected of having hypothalamic insufficiency and subjected to the L-Dopa stimulation test to observe growth hormone secretary function while four acromegaly patient received the glucose loading test and L-Dopa stimulation test. The results are as follows: 1) The basal level of GH in the various disease was as follows: a) The basal level was lower than the control level but was not statistically significant b) In diabetes the mean value tended to higher than the control level but was not significant statistically c) In all four acromegaly patients the GH level was significantly higher than the control level 2) Of 13 patients with diabetes, nine had diabetic retinopathy, and of those nine, six showed increased L-Dopa response. However, of the four non retinopathic DM patients, only one showed increased response to L-Dopa. 3) Two patients out of ten with Sheehan's syndrome responded to L-Dopa stimulation. 4) One Patient of eight with pituitary chromophobe adenoma responded to L-Dopa stimulation. 5) Four acromegaly patients revealed 3 acidophilic adenoma and one chromophobe adenoma histologically. Of patients receiving the L-Dopa stimulation test. Two showed a paradoxical response. Two patients who received the glucose loading test showed suppressed response. 6) Of two craniopharyngioma patients, one showed increased GH response after L-Dopa stimulation. Increased response of GH after L-Dopa stimulation was seen in one two craniopharyngioma patients and also in one of two patients with short structure.

  17. Fixed-functional appliance treatment combined with growth hormone therapy.

    Science.gov (United States)

    Jung, Min-Ho

    2017-09-01

    The purpose of this study was to illustrate the effects of growth hormone (GH) therapy and fixed functional appliance treatment in a 13-year-old Class II malocclusion patient without GH deficiency. GH has been shown to effectively increase endochondral growth and induce a more prognathic skeletal pattern. Although a major concern in Class II retrognathic patients is chin deficiency, long-term studies have shown that the mandibular growth enhancement effects of functional appliances are clinically insignificant. This case report demonstrates that the mandible grew significantly during fixed functional appliance treatment combined with GH therapy, with stable results during 2 years 11 months of retention. More studies are needed to evaluate GH therapy as a supplement in Class II treatment. Copyright © 2017 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

  18. Urinary growth hormone excretion in 657 healthy children and adults

    DEFF Research Database (Denmark)

    Main, K; Philips, M; Jørgensen, M

    1991-01-01

    .0001) with maximum values in Tanner stage 3 for girls and 4 for boys. This corresponded to a peak in u-GH excretion between 11.5-14.5 years in girls and 12.5-16 years in boys. Additionally, u-GH excretion in adults was significantly higher than in prepubertal children (p less than 0.001). The day/night ratio of u......Urinary growth hormone (u-GH) excretion was measured in 547 healthy children and 110 adults by ELISA with a detection limit of 1.1 ng/l u-GH after prior concentration of the urine samples (20- to 30-fold). u-GH excretion values were significantly dependent on the pubertal stage (p less than 0...

  19. Altered expression of estrogen receptor-α variant messenger RNAs between adjacent normal breast and breast tumor tissues

    International Nuclear Information System (INIS)

    Leygue, Etienne; Dotzlaw, Helmut; Watson, Peter H; Murphy, Leigh C

    2000-01-01

    reduction mammoplasty and breast tumor. Transfection experiments showed that the activation of the transcription of the pS2 gene by estrogen was drastically reduced in the presence of increased ERD3 expression. The authors hypothesized that the reduction in ERD3 expression could be a prerequisite for breast carcinogenesis to proceed. We observed a significantly higher relative expression of ERD5 messenger RNA in breast tumor components compared with matched adjacent normal breast tissue. These data confirm our previous observations performed on unmatched normal and neoplastic human breast tissues. Upregulated expression of this variant has already been reported in ER-negative/PR-positive tumors, as compared with ER-positive/PR-positive tumors, suggesting a possible correlation between ERD5 messenger RNA expression and breast tumor progression. Even though it has been suggested that ERD5 could be related to the acquisition of insensitivity to antiestrogen treatment (ie tamoxifen), accumulating data refute a general role for ERD5 in hormone-resistant tumors. Only ER-positive pS2-positive tamoxifen-resistant tumors have been shown to express significantly higher levels of ERD5 messenger RNA, as compared with control tumors. Taken together, these data suggest that the exact biologic significance of ERD5 variant expression during breast tumorigenesis and breast cancer progression, if any, remains unclear. In conclusion, we have shown that the relative expressions of ERC4 and ERD5 variant messenger RNAs were increased in human breast tumor tissue, as compared with normal adjacent tissue, whereas the expression of ERD3 variant messenger RNA was decreased in breast tumor tissues. These results suggest that the expressions of several ER-α variant messenger RNAs are deregulated during human breast tumorigenesis. Further studies are needed to determine whether these changes are transposed at the protein level. Furthermore, the putative role of ER-α variants in the mechanisms that

  20. Bartter syndrome and growth hormone deficiency: three cases.

    Science.gov (United States)

    Buyukcelik, Mithat; Keskin, Mehmet; Kilic, Beltinge Demircioglu; Kor, Yilmaz; Balat, Ayse

    2012-11-01

    Bartter syndrome is a rare autosomal recessive disorder characterized by hypokalemia, salt loss, and metabolic alkalosis. Short stature is one of the clinical manifestations in these children. Although polyuria, polydipsia, hypokalemia, and salt loss may be responsible for growth retardation, the exact pathogenesis of short stature in Bartter syndrome is not known. In this study, we present three children diagnosed as having Bartter syndrome with short stature and growth hormone (GH) deficiency. After recombinant human growth hormone therapy (rhGH), their growth velocities were improved. These results indicate that GH deficiency may contribute to short stature in children with Bartter syndrome, and rhGH therapy would be an excellent adjunctive treatment for short children with this syndrome whose condition is resistant to conventional therapies in terms of growth.

  1. Acetylcholine Modulates the Hormones of the Growth Hormone/Insulinlike Growth Factor-1 Axis During Development in Mice.

    Science.gov (United States)

    Lecomte, Marie-José; Bertolus, Chloé; Ramanantsoa, Nélina; Saurini, Françoise; Callebert, Jacques; Sénamaud-Beaufort, Catherine; Ringot, Maud; Bourgeois, Thomas; Matrot, Boris; Collet, Corinne; Nardelli, Jeannette; Mallet, Jacques; Vodjdani, Guilan; Gallego, Jorge; Launay, Jean-Marie; Berrard, Sylvie

    2018-04-01

    Pituitary growth hormone (GH) and insulinlike growth factor (IGF)-1 are anabolic hormones whose physiological roles are particularly important during development. The activity of the GH/IGF-1 axis is controlled by complex neuroendocrine systems including two hypothalamic neuropeptides, GH-releasing hormone (GHRH) and somatostatin (SRIF), and a gastrointestinal hormone, ghrelin. The neurotransmitter acetylcholine (ACh) is involved in tuning GH secretion, and its GH-stimulatory action has mainly been shown in adults but is not clearly documented during development. ACh, together with these hormones and their receptors, is expressed before birth, and somatotroph cells are already responsive to GHRH, SRIF, and ghrelin. We thus hypothesized that ACh could contribute to the modulation of the main components of the somatotropic axis during development. In this study, we generated a choline acetyltransferase knockout mouse line and showed that heterozygous mice display a transient deficit in ACh from embryonic day 18.5 to postnatal day 10, and they recover normal ACh levels from the second postnatal week. This developmental ACh deficiency had no major impact on weight gain and cardiorespiratory status of newborn mice. Using this mouse model, we found that endogenous ACh levels determined the concentrations of circulating GH and IGF-1 at embryonic and postnatal stages. In particular, serum GH level was correlated with brain ACh content. ACh also modulated the levels of GHRH and SRIF in the hypothalamus and ghrelin in the stomach, and it affected the levels of these hormones in the circulation. This study identifies ACh as a potential regulator of the somatotropic axis during the developmental period.

  2. Adenomas produtores de GH: Análise de 20 casos

    Directory of Open Access Journals (Sweden)

    Tella Jr Oswaldo Inácio de

    2002-01-01

    Full Text Available Os adenomas produtores de GH podem ser mono, bi ou pluri-hormonais. A associação mais frequente do GH é com a sub unidade alfa ou com a prolactina. Apresentam-se com as alterações clássicas de acromegalia, mas quando produzem mais que um hormônio podem apresentar sintomas visuais. Os mono-hormonais são geralmente microadenomas e os outros dois grupos tendem a ser macroadenomas. Analisamos nossa experiência com 20 casos deste tipo de adenomas e mostramos o resultado cirúrgico, que foi bastante satisfatório para o grupo mono-hormonal. A radioterapia deve ser considerada quando a ressecção não foi total.

  3. Valutazione di efficienza nella somministrazione dell’ormone della crescita (GH

    Directory of Open Access Journals (Sweden)

    Federico Spandonaro

    2013-03-01

    Full Text Available Treatment with growth hormone (somatropin is effective in six different medical conditions: growth hormone deficiency (GHD, Turner syndrome (TS, growth retardation in children born small for gestational age (SGA, Prader-Willi syndrome (PWS, growth retardation due to chronic renal insufficiency (CRI, growth retardation associated with a deficiency of the gene SHOX (Short Stature HOmeoboXContaining gene. The treatment proved to be also effective in adults who have an impaired growth hormone (acquired in adulthood or childhood.The growth hormone (GH is generally cost effective and, therefore, is usually reimbursed by public health services. In financial terms, GH is a major cost item for health systems. According to the Report OSMED 2010, GH ranks first in Italy between systemic hormonal preparations, excluding sex hormones, distributed by public system, with an annual value of approximately € 88 million (+ 12.7% compared to 2009.Considering the increasing need to control pharmaceutical expenditure, there is a strong interest for the efficient supply of the hormone by the regional health service. From this point of view, the comparison of the specialties on the market is normally carried out on the basis of the cost per mg; this approach, also used in the main studies of cost-effectiveness, is derived from a logic of cost minimization, but it may still be distorting, not taking into account the efficiency of devices used for the administration of the hormone.The proposed analysis verifies the efficiency of different available devices, evaluating the potential waste of product, depending both on the device used and on the characteristics of the population exposed to the treatment.Only in the case of single-dose and disposable formulations is theoretically possible to have zero waste and thus an equivalence between the actual cost of the treatment and the price charged. In other cases, the inefficiency causes a deviation between the actual cost and

  4. Spatial learning and memory in male mice with altered growth hormone action.

    Science.gov (United States)

    Basu, Amrita; McFarlane, Hewlet G; Kopchick, John J

    2017-07-01

    Growth hormone (GH) has a significant influence on cognitive performance in humans and other mammals. To understand the influence of altered GH action on cognition, we assessed spatial learning and memory using a Barnes maze (BM) comparing twelve-month old, male, bovine GH (bGH) and GH receptor antagonist (GHA) transgenic mice and their corresponding wild type (WT) littermates. During the acquisition training period in the BM, bGH mice showed increased latency, traveled longer path lengths and made more errors to reach the target than WT mice, indicating significantly poorer learning. Short-term memory (STM) and long-term memory (LTM) trials showed significantly suppressed memory retention in bGH mice when compared to the WT group. Conversely, GHA mice showed significantly better learning parameters (latency, path length and errors) and increased use of an efficient search strategy than WT mice. Our study indicates a negative impact of GH excess and a beneficial effect of the inhibition of GH action on spatial learning and memory and, therefore, cognitive performance in male mice. Further research to elucidate GH's role in brain function will facilitate identifying therapeutic applications of GH or GHA for neuropathological and neurodegenerative conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Ancient origin of placental expression in the growth hormone genes of anthropoid primates.

    Science.gov (United States)

    Papper, Zack; Jameson, Natalie M; Romero, Roberto; Weckle, Amy L; Mittal, Pooja; Benirschke, Kurt; Santolaya-Forgas, Joaquin; Uddin, Monica; Haig, David; Goodman, Morris; Wildman, Derek E

    2009-10-06

    In anthropoid primates, growth hormone (GH) genes have undergone at least 2 independent locus expansions, one in platyrrhines (New World monkeys) and another in catarrhines (Old World monkeys and apes). In catarrhines, the GH cluster has a pituitary-expressed gene called GH1; the remaining GH genes include placental GHs and placental lactogens. Here, we provide cDNA sequence evidence that the platyrrhine GH cluster also includes at least 3 placenta expressed genes and phylogenetic evidence that placenta expressed anthropoid GH genes have undergone strong adaptive evolution, whereas pituitary-expressed GH genes have faced strict functional constraint. Our phylogenetic evidence also points to lineage-specific gene gain and loss in early placental mammalian evolution, with at least three copies of the GH gene present at the time of the last common ancestor (LCA) of primates, rodents, and laurasiatherians. Anthropoid primates and laurasiatherians share gene descendants of one of these three copies, whereas rodents and strepsirrhine primates each maintain a separate copy. Eight of the amino-acid replacements that occurred on the lineage leading to the LCA of extant anthropoids have been implicated in GH signaling at the maternal-fetal interface. Thus, placental expression of GH may have preceded the separate series of GH gene duplications that occurred in catarrhines and platyrrhines (i.e., the roles played by placenta-expressed GHs in human pregnancy may have a longer evolutionary history than previously appreciated).

  6. Insulin and GH signaling in human skeletal muscle in vivo following exogenous GH exposure: impact of an oral glucose load.

    Directory of Open Access Journals (Sweden)

    Thomas Krusenstjerna-Hafstrøm

    2011-05-01

    Full Text Available GH induces acute insulin resistance in skeletal muscle in vivo, which in rodent models has been attributed to crosstalk between GH and insulin signaling pathways. Our objective was to characterize time course changes in signaling pathways for GH and insulin in human skeletal muscle in vivo following GH exposure in the presence and absence of an oral glucose load.Eight young men were studied in a single-blinded randomized crossover design on 3 occasions: 1 after an intravenous GH bolus 2 after an intravenous GH bolus plus an oral glucose load (OGTT, and 3 after intravenous saline plus OGTT. Muscle biopsies were taken at t = 0, 30, 60, and 120. Blood was sampled at frequent intervals for assessment of GH, insulin, glucose, and free fatty acids (FFA.GH increased AUC(glucose after an OGTT (p<0.05 without significant changes in serum insulin levels. GH induced phosphorylation of STAT5 independently of the OGTT. Conversely, the OGTT induced acute phosphorylation of the insulin signaling proteins Akt (ser(473 and thr(308, and AS160.The combination of OGTT and GH suppressed Akt activation, whereas the downstream expression of AS160 was amplified by GH. WE CONCLUDED THE FOLLOWING: 1 A physiological GH bolus activates STAT5 signaling pathways in skeletal muscle irrespective of ambient glucose and insulin levels 2 Insulin resistance induced by GH occurs without a distinct suppression of insulin signaling proteins 3 The accentuation of the glucose-stimulated activation of AS 160 by GH does however indicate a potential crosstalk between insulin and GH.ClinicalTrials.gov NCT00477997.

  7. Management of endocrine disease: GH excess: diagnosis and medical therapy

    DEFF Research Database (Denmark)

    Andersen, Marianne

    2014-01-01

    Acromegaly is predominantly caused by a pituitary adenoma, which secretes an excess of GH resulting in increased IGF-I levels. Most of the GH assays used currently measure only the 22 kDa form of GH. In theory, the diagnostic sensitivity may be lower compared to the previous assays, which used...... polyclonal antibodies. Many GH-secreting adenomas are plurihormonal and may co-secrete prolactin, TSH and α-subunit. Hyperprolactinemia is found in 30-40% of patients with acromegaly and hyperprolactinemia may occasionally be diagnosed before acromegaly is apparent.Although trans-sphenoidal surgery of a GH......-secreting adenoma remains the first treatment at most centres, the role of somatostatin analogues, octreotide LAR and lanreotide Autogel, as primary therapy is still the subject of some debate. While normalization of GH and IGF-I levels is the main objective in all patients with acromegaly, GH and IGF-I levels may...

  8. TRANSMISI GEN PhGH DAN PERFORMA PERTUMBUHAN IKAN LELE AFRIKA (Clarias gariepinus TRANSGENIK GENERASI KETIGA

    Directory of Open Access Journals (Sweden)

    Huria Marnis

    2017-01-01

    Full Text Available Penelitian ini bertujuan untuk mengevaluasi transmisi transgen PhGH dan performa ikan lele Afrika transgenik generasi ketiga (F3 yang meliputi pertumbuhan, rasio efisiensi konversi pakan, konsentrasi hormon pertumbuhan dan hormon IGF-I. Ikan lele transgenik F3 telah diproduksi dengan meyilangkan ikan lele transgenik F2 dengan non-transgenik. Deteksi transgen (PhGH dilakukan menggunakan metode PCR. Analisis hormon pertumbuhan dan hormon insuline-like growth factor (IGF-I menggunakan sampel serum darah dan metode enzyme linked immunosorbent assay (ELISA. Hasil penelitian menunjukkan bahwa ikan lele transgenik F3 yang digunakan pada pengujian ini terdeteksi positif membawa transgen dengan ukuran fragmen gen sebesar 1.500 bp. Transmisi transgen dari induk F2 ke F3 berkisar 0-75%. Pertumbuhan bobot populasi ikan lele transgenik F3 lebih tinggi 51,26% dibandingkan dengan ikan lele non-transgenik (P<0,05. Pertumbuhan bobot populasi ikan transgenik mencapai 484±60,3 g, sedangkan pertumbuhan bobot ikan non-transgenik 319,98±65,3 g. Nilai rasio konversi pakan ikan lele transgenik F3 sebesar 0,89 sedangkan non-transgenik 1,30. Hal ini menunjukkan bahwa efisiensi pakan ikan lele transgenik F3 lebih tinggi dibandingkan dengan ikan non-transgenik (P<0,05. Ikan lele transgenik mempunyai konsentrasi hormon pertumbuhan (5,67±2,65 ng/mL yang lebih tinggi (P<0,05 jika dibandingkan dengan ikan lele non-transgenik (3,00±1,41 ng/mL. Ikan lele transgenik juga memiliki kandungan hormon IGF-I (6,63±0,11 ng/mL lebih tinggi (P<0,05 dibandingkan dengan ikan lele non-transgenik (5,38±0,63 ng/mL. Tingginya konsentrasi hormon pertumbuhan dan hormon IGF-I dapat mewakili performa pertumbuhan dan efisiensi penggunaan pakan pada ikan lele transgenik. The aim of this study was to determine the transmission of a transgene (PhGH and to evaluate the performance of F3 transgenic African catfish, such as body weight, feed conversion ratio (FCR, growth hormone and IGF-I hormone

  9. Response to growth hormone treatment and final height after cranial or craniospinal irradiation

    International Nuclear Information System (INIS)

    Sulmont, V.; Brauner, R.; Fontoura, M.; Rappaport, R.

    1990-01-01

    Growth hormone (GH) deficiency (GHD) induced by cranial irradiation has become a frequent indication of hGH substitutive therapy. This study analyses the growth response to hGH therapy and the factors involved in the decrease in growth velocity observed after cranial irradiation. One hundred children given cranial radiation for pathology distant from the hypothalamo-pituitary area were studied. Fifty-six of them received hGH therapy for GHD resulting in decreased growth velocity. The initial annual height gain in the cranial-irradiated group was comparable to that of patients treated for idiopathic GHD; additional spinal irradiation significantly reduced the growth response. Twenty-eight hGH-treated patients reached final heights which were compared to those of 2 untreated irradiated groups, one with GHD (n=27) and the other with normal GH secretion (n=17). The height SD score changes observed in hGH therapy were +0.3 in the cranial (n=10) and -1.2 SD in the craniospinal (n=18) groups. GH deficiency had contributed to a mean height loss of 1 SD and spinal irradiation to a loss of 1.4SD. The small effect of hGH therapy on final height is probably linked to the small bone age retardation at onset of hGH therapy and to the fact that irradiated children entered puberty at a younger age in terms of chronological age and bone age than the idiopathic GHD patients. These data suggest that the results of gGH therapy in irradiated children might be improved with higher and more fractionated hGH doses and, in some patients, by delaying puberty using luteinizing hormone releasing hormone analogs

  10. Response to growth hormone treatment and final height after cranial or craniospinal irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Sulmont, V.; Brauner, R.; Fontoura, M.; Rappaport, R. (Hospital des Enfants Malades, Paris (France). Pediatric Endocrinology Unit and INSERM U30)

    1990-01-01

    Growth hormone (GH) deficiency (GHD) induced by cranial irradiation has become a frequent indication of hGH substitutive therapy. This study analyses the growth response to hGH therapy and the factors involved in the decrease in growth velocity observed after cranial irradiation. One hundred children given cranial radiation for pathology distant from the hypothalamo-pituitary area were studied. Fifty-six of them received hGH therapy for GHD resulting in decreased growth velocity. The initial annual height gain in the cranial-irradiated group was comparable to that of patients treated for idiopathic GHD; additional spinal irradiation significantly reduced the growth response. Twenty-eight hGH-treated patients reached final heights which were compared to those of 2 untreated irradiated groups, one with GHD (n=27) and the other with normal GH secretion (n=17). The height SD score changes observed in hGH therapy were +0.3 in the cranial (n=10) and -1.2 SD in the craniospinal (n=18) groups. GH deficiency had contributed to a mean height loss of 1 SD and spinal irradiation to a loss of 1.4SD. The small effect of hGH therapy on final height is probably linked to the small bone age retardation at onset of hGH therapy and to the fact that irradiated children entered puberty at a younger age in terms of chronological age and bone age than the idiopathic GHD patients. These data suggest that the results of gGH therapy in irradiated children might be improved with higher and more fractionated hGH doses and, in some patients, by delaying puberty using luteinizing hormone releasing hormone analogs.

  11. The effect of growth hormone replacement on the thyroid axis in patients with hypopituitarism: in vivo and ex vivo studies.

    Science.gov (United States)

    Glynn, Nigel; Kenny, Helena; Quisenberry, Leah; Halsall, David J; Cook, Paul; Kyaw Tun, Tommy; McDermott, John H; Smith, Diarmuid; Thompson, Christopher J; O'Gorman, Donal J; Boelen, Anita; Lado-Abeal, Joaquin; Agha, Amar

    2017-05-01

    Alterations in the hypothalamic-pituitary-thyroid axis have been reported following growth hormone (GH) replacement. The aim was to examine the relationship between changes in serum concentration of thyroid hormones and deiodinase activity in subcutaneous adipose tissue, before and after GH replacement. A prospective, observational study of patients receiving GH replacement as part of routine clinical care. Twenty adult hypopituitary men. Serum TSH, thyroid hormones - free and total thyroxine (T4) and triiodothyronine (T3) and reverse T3, thyroglobulin and thyroid-binding globulin (TBG) levels were measured before and after GH substitution. Changes in serum hormone levels were compared to the activity of deiodinase isoenzymes (DIO1, DIO2 and DIO3) in subcutaneous adipose tissue. The mean daily dose of growth hormone (GH) was 0·34 ± 0·11 mg (range 0·15-0·5 mg). Following GH replacement, mean free T4 levels declined (-1·09 ± 1·99 pmol/l, P = 0·02). Reverse T3 levels also fell (-3·44 ± 1·42 ng/dl, P = 0·03) and free T3 levels increased significantly (+0·34 ± 0·15 pmol/l, P = 0·03). In subcutaneous fat, DIO2 enzyme activity declined; DIO1 and DIO3 activities remained unchanged following GH substitution. Serum TSH, thyroglobulin and TBG levels were unaltered by GH therapy. In vitro analysis of subcutaneous adipose tissue from hypopituitary human subjects demonstrates that GH replacement is associated with significant changes in deiodinase isoenzyme activity. However, the observed variation in enzyme activity does not explain the changes in the circulating concentration of thyroid hormones induced by GH replacement. It is possible that deiodinase isoenzymes are differentially regulated by GH in other tissues including liver and muscle. © 2016 John Wiley & Sons Ltd.

  12. Detection and differentiation of 22kDa and 20kDa Growth Hormone proteoforms in human plasma by LC-MS/MS

    DEFF Research Database (Denmark)

    Sanmartín, Gerard Such; Bache, N.; Bosch, J.

    2015-01-01

    Human growth hormone (GH) is suspected to be widely and illegally used in sport to improve athletes' performance. For the detection of GH abuse, blood samples are screened for abnormal ratios between the 22 and 20kDa GH proteoforms that demonstrate the administration of the synthetic hormone....... Current detection methods are based on classical immunoassays as they provide sufficient sensitivity for the detection of GH proteoforms. These antibody based methods, however, suffer from unclear selectivity and potential cross-reactivity towards similar proteins. For unambiguous GH detection, we report...... a Mass Spectrometry ImmunoAssay (MSIA) that first enriches GH from plasma with an antibody of relatively low specificity, and subsequently quantifies the 22 and 20kDa proteoforms by Selected Reaction Monitoring (SRM) LC-MS/MS analysis. This method proved superior to an antibody-free strategy based on GH...

  13. Gladiolus hybridus ABSCISIC ACID INSENSITIVE 5 (GhABI5) is an important transcription factor in ABA signaling that can enhance Gladiolus corm dormancy and Arabidopsis seed dormancy.

    Science.gov (United States)

    Wu, Jian; Seng, Shanshan; Sui, Juanjuan; Vonapartis, Eliana; Luo, Xian; Gong, Benhe; Liu, Chen; Wu, Chenyu; Liu, Chao; Zhang, Fengqin; He, Junna; Yi, Mingfang

    2015-01-01

    The phytohormone abscisic acid (ABA) regulates plant development and is crucial for abiotic stress response. In this study, cold storage contributes to reducing endogenous ABA content, resulting in dormancy breaking of Gladiolus. The ABA inhibitor fluridone also promotes germination, suggesting that ABA is an important hormone that regulates corm dormancy. Here, we report the identification and functional characterization of the Gladiolus ABI5 homolog (GhABI5), which is a basic leucine zipper motif transcriptional factor (TF). GhABI5 is expressed in dormant vegetative organs (corm, cormel, and stolon) as well as in reproductive organs (stamen), and it is up-regulated by ABA or drought. Complementation analysis reveals that GhABI5 rescues the ABA insensitivity of abi5-3 during seed germination and induces the expression of downstream ABA response genes in Arabidopsis thaliana (EM1, EM6, and RD29B). Down-regulation of GhABI5 in dormant cormels via virus induced gene silence promotes sprouting and reduces the expression of downstream genes (GhLEA and GhRD29B). The results of this study reveal that GhABI5 regulates bud dormancy (vegetative organ) in Gladiolus in addition to its well-studied function in Arabidopsis seeds (reproductive organ).

  14. Gladiolus hybridus ABSCISIC ACID INSENSITIVE 5 (GhABI5 is an important transcription factor in ABA signaling that can enhance Gladiolus corm dormancy and Arabidopsis seed dormancy.

    Directory of Open Access Journals (Sweden)

    Jian eWu

    2015-11-01

    Full Text Available The phytohormone abscisic acid (ABA regulates plant development and is crucial for abiotic stress response. In this study, cold storage contributes to reducing endogenous ABA content, resulting in dormancy breaking of Gladiolus. The ABA inhibitor fluridone also promotes germination, suggesting that ABA is an important hormone that regulates corm dormancy. Here, we report the identification and functional characterization of the Gladiolus ABI5 homolog (GhABI5, which is a basic leucine zipper motif transcriptional factor (TF. GhABI5 is expressed in dormant vegetative organs (corm, cormel and stolon as well as in reproductive organs (stamen, and it is up-regulated by ABA or drought. Complementation analysis reveals that GhABI5 rescues the ABA insensitivity of abi5-3 during seed germination and induces the expression of downstream ABA response genes in Arabidopsis thaliana (EM1, EM6 and RD29B. Down-regulation of GhABI5 in dormant cormels via Virus Induced Gene Silence (VIGS promotes sprouting and reduces the expression of downstream genes (GhLEA and GhRD29B. The results of this study reveal that GhABI5 regulates bud dormancy (vegetative organ in Gladiolus in addition to its well-studied function in Arabidopsis seeds (reproductive organ.

  15. Growth hormone biases amygdala network activation after fear learning

    OpenAIRE

    Gisabella, Barbara; Farah, Shadia; Peng, Xiaoyu; Burgos-Robles, Anthony Noel; Lim, Seh Hong; Goosens, Ki Ann

    2016-01-01

    Prolonged stress exposure is a risk factor for developing posttraumatic stress disorder, a disorder characterized by the ?over-encoding' of a traumatic experience. A potential mechanism by which this occurs is through upregulation of growth hormone (GH) in the amygdala. Here we test the hypotheses that GH promotes the over-encoding of fearful memories by increasing the number of neurons activated during memory encoding and biasing the allocation of neuronal activation, one aspect of the proce...

  16. MRI of growth hormone-secreting pituitary adenomas: factors determining pretreatment hormone levels

    Energy Technology Data Exchange (ETDEWEB)

    Saeki, N.; Iuchi, T.; Eda, M.; Yamaura, A. [Dept. of Neurological Surgery, Chiba University School of Medicine (Japan); Isono, S. [Dept. of Neurological Surgery, Anesthesiology, Chiba University School of Medicine, Chiba (Japan)

    1999-10-01

    Preoperative serum growth hormone (GH) level is one of the most important determinants of outcome. Our aim was to assess MRI findings which may correlate with pretreatment GH levels in GH-secreting adenomas. We retrospectively studied 29 patients with acromegaly caused by a pituitary adenoma. Tumor size (height, width, thickness and volume), suprasellar extension, sphenoid or cavernous sinus invasion, signal intensity and contrast enhancement were studied. Linear regression analysis or Fisher's exact probability test was used for statistical analysis. Factors related to high GH levels were the maximum dimension of the tumour (r = 0.496, P < 0.01), its volume (r = 0.439, P < 0.05), spenoid sinus invasion (P < 0.01) and intracavernous carotid artery encasement (P < 0.01). The other items were not related to serum GH levels. Since we believe surgery is the first choice of treatment and the cavernous sinus is difficult of access with a conventional surgical approach, preoperative assessment of invasion into the cavernous sinus is critical for predicting the surgical outcome. Low GH levels (5-50 ng/ml) were found with tumours medial to the intercarotid line and high levels (more than 101 ng/ml) with invasive tumours with carotid artery encasement. Variable GH levels were noted with tumours extending beyond the intercarotid line. Because functioning adenomas invading the cavernous sinus tend to have markedly high hormone levels, and only patients with carotid artery encasement showed markedly elevated GH levels, we believe carotid artery encasement a reliable MRI indicator of cavernous sinus invasion. (orig.)

  17. Distribution and linkage disequilibrium analysis of polymorphisms of GH1 gene in different populations of pigs associated with body size.

    Science.gov (United States)

    Cheng, Yunyun; Liu, Songcai; Su, Dan; Lu, Chao; Zhang, Xin; Wu, Qingyan; Li, Siming; Fu, Haoyu; Yu, Hao; Hao, Linlin

    2016-03-01

    Growth hormone (GH) has been considered as a candidate gene for growth and body size in pigs. In this study, polymorphisms of the GH1 gene were evaluated for associations with body size traits in 190 pig individuals. Seventeen single-nucleotide polymorphisms (SNPs) were identified in GH1 gene of the large pig breeds and miniature pig breeds using direct sequencing and genotyped by allele-specific PCR approach. Notably, six (g.237A>G, g.283T>C, g.309A>G, g.318A>G, g.540A>G and g.544A>G) of them were significantly associated with body size, of which three loci (g.283T>C, g.309A>G, g.318A>G) located in the signal-peptide coding region of GH1 gene compose a CGG haplotype for large pigs and TAA haplotype for miniature pigs (P G and g.544A>G) located in the second intron of GH1 gene compose a GG haplotype for large pigs and AA haplotype for miniature pigs (P body size of pigs providing genetic basis for pig breeding with the improved economic benefits.

  18. Inflammation and linear bone growth: the inhibitory role of SOCS2 on GH/IGF-1 signaling.

    Science.gov (United States)

    Farquharson, Colin; Ahmed, S Faisal

    2013-04-01

    Linear bone growth is widely recognized to be adversely affected in children with chronic kidney disease (CKD) and other chronic inflammatory disorders. The growth hormone (GH)/insulin-like growth factor-1 (IGF-1) pathway is anabolic to the skeleton and inflammatory cytokines compromise bone growth through a number of different mechanisms, which include interference with the systemic as well as the tissue-level GH/IGF-1 axis. Despite attempts to promote growth and control disease, there are an increasing number of reports of the persistence of poor growth in a substantial proportion of patients receiving rhGH and/or drugs that block cytokine action. Thus, there is an urgent need to consider better and alternative forms of therapy that are directed specifically at the mechanism of the insult which leads to abnormal bone health. Suppressor of cytokine signaling 2 (SOCS2) expression is increased in inflammatory conditions including CKD, and is a recognized inhibitor of GH signaling. Therefore, in this review, we will focus on the premise that SOCS2 signaling represents a critical pathway in growth plate chondrocytes through which pro-inflammatory cytokines alter both GH/IGF-1 signaling and cellular function.

  19. Study on the relationship between SLE and the related serum hormone

    International Nuclear Information System (INIS)

    Lu Yun; Deng Shouzhen; Lin Xiangtong; Feng Shufang; Xu Jinhua; He Wanting; Zhang Guangming; Cheng Wei; Gao Quan

    1998-01-01

    To explore the relationship between PRL, GH(RIA), GH(RRA) serum levels changes and the onset and development of disease in patients with SLE, and to understand the hormonal changes in active and inactive phase of disease, 28 cases and 20 controls were studied. The results showed that anti-ds-DNA serum level in active and inactive phases was higher than those in controls (P 1 2 <0.05). This study indicated that the higher serum level of PRL, GH(RIA), GH(RRA) is correlated with some autoimmune characteristics of SLE, especially in its active phase. Therefore it gives some help for clinical study of SLE

  20. Mercury's Na Exosphere from MESSENGER Data

    Science.gov (United States)

    Killen, Rosemary M.; Burger, M. H.; Cassidy, T. A.; Sarantos, M.; Vervack, R. J.; McClintock, W. El; Merkel, A. W.; Sprague, A. L.; Solomon, S. C.

    2012-01-01

    MESSENGER entered orbit about Mercury on March 18, 2011. Since then, the Ultraviolet and Visible Spectrometer (UWS) channel of MESSENGER's Mercury Atmospheric and Surface Composition Spectrometer (MASCS) has been observing Mercury's exosphere nearly continuously. Daily measurements of Na brightness were fitted with non-uniform exospheric models. With Monte Carlo sampling we traced the trajectories of a representative number of test particles, generally one million per run per source process, until photoionization, escape from the gravitational well, or permanent sticking at the surface removed the atom from the simulation. Atoms were assumed to partially thermally accommodate on each encounter with the surface with accommodation coefficient 0.25. Runs for different assumed source processes are run separately, scaled and co-added. Once these model results were saved onto a 3D grid, we ran lines of sight from the MESSENGER spacecraft :0 infinity using the SPICE kernels and we computed brightness integrals. Note that only particles that contribute to the measurement can be constrained with our method. Atoms and molecules produced on the nightside must escape the shadow in order to scatter light if the excitation process is resonant-light scattering, as assumed here. The aggregate distribution of Na atoms fits a 1200 K gas, with a PSD distribution, along with a hotter component. Our models constrain the hot component, assumed to be impact vaporization, to be emitted with a 2500 K Maxwellian. Most orbits show a dawnside enhancement in the hot component broadly spread over the leading hemisphere. However, on some dates there is no dawn/dusk asymmetry. The portion of the hot/cold source appears to be highly variable.

  1. Selecting short-statured children needing growth hormone testing: Derivation and validation of a clinical decision rule

    Directory of Open Access Journals (Sweden)

    Bréart Gérard

    2008-07-01

    Full Text Available Abstract Background Numerous short-statured children are evaluated for growth hormone (GH deficiency (GHD. In most patients, GH provocative tests are normal and are thus in retrospect unnecessary. Methods A retrospective cohort study was conducted to identify predictors of growth hormone (GH deficiency (GHD in children seen for short stature, and to construct a very sensitive and fairly specific predictive tool to avoid unnecessary GH provocative tests. GHD was defined by the presence of 2 GH concentration peaks Results The initial study included 167 patients, 36 (22% of whom had GHD, including 5 (3% with certain GHD. Independent predictors of GHD were: growth rate Conclusion We have derived and performed an internal validation of a highly sensitive decision rule that could safely help to avoid more than 2/3 of the unnecessary GH tests. External validation of this rule is needed before any application.

  2. Exploiting Nanobodies in the Detection and Quantification of Human Growth Hormone via Phage-Sandwich Enzyme-Linked Immunosorbent Assay

    Directory of Open Access Journals (Sweden)

    Hossam Murad

    2017-05-01

    Full Text Available BackgroundMonitoring blood levels of human growth hormone (hGH in most children with short stature deficiencies is crucial for taking a decision of treatment with extended course of daily and expensive doses of recombinant hGH (rhGH or Somatropin®. Besides, misusing of rhGH by sportsmen is banned by the World Anti-Doping Agency and thus sensitive GH-detecting methods are highly welcome in this field. Nanobodies are the tiniest antigen-binding entity derived from camel heavy chain antibodies. They were successfully generated against numerous antigens including hormones.MethodsA fully nanobody-based sandwich ELISA method was developed in this work for direct measurement of GH in biological samples.ResultsTwo major characteristics of nanobody were exploited for this goal: the robust and stable structure of the nanobody (NbGH04 used to capture hGH from tested samples, and the great ability of tailoring, enabling the display of the anti-GH detector nanobody (NbGH07 on the tip of M13-phage. Such huge, stable, and easy-to-prepare phage-Nb was used in ELISA to provide an amplified signal. Previously, NbGH04 was retrieved on immobilized hGH by phage display from a wide “immune” cDNA library prepared from a hGH-immunized camel. Here, and in order to assure epitope heterogeneity, NbGH07 was isolated from the same library using NbGH04-captured hGH as bait. Interaction of both nanobodies with hGH was characterized and compared with different anti-GH nanobodies and antibodies. The sensitivity (~0.5 ng/ml and stability of the nanobody-base sandwich ELISA were assessed using rhGH before testing in the quantification of hGH in blood sera and cell culture supernatants.ConclusionIn regard to all advantages of nanobodies; stability, solubility, production affordability in Escherichia coli, and gene tailoring, nanobody-based phage sandwich ELISA developed here would provide a valuable method for hGH detection and quantification.

  3. Gravitational Waves and Multi-Messenger Astronomy

    Science.gov (United States)

    Centrella, Joan M.

    2010-01-01

    Gravitational waves are produced by a wide variety of sources throughout the cosmos, including the mergers of black hole and neutron star binaries/compact objects spiraling into central black holes in galactic nuclei, close compact binaries/and phase transitions and quantum fluctuations in the early universe. Observing these signals can bring new, and often very precise, information about their sources across vast stretches of cosmic time. In this talk we will focus on thee opening of this gravitational-wave window on the universe, highlighting new opportunities for discovery and multi-messenger astronomy.

  4. Evolutionary aspects of growth hormones and prolactins and their receptors

    International Nuclear Information System (INIS)

    Tarpey, J.F.

    1986-01-01

    The interactions of GH's, PRL's and PL's with receptors for GH and PRL were examined from a comparative and evolutionary viewpoint. The binding of 125 I-bGH to membrane preparations from liver of representatives of the major classes of non-mammalian vertebrates was also studied. Only hepatic membranes from sturgeon and Gillichthys had significant bGH binding and were further characterized and compared with male rabbit liver membranes in terms of time, temperature, pH, and membrane concentration to optimize binding conditions. The binding of several members of the GH, PRL, PL family of hormones to GH receptors from liver of sturgeon, Gillichthys, rabbit, mouse and rat was investigated. in terms of hormonal specificity, the mammalian receptors and the sturgeon binding sites were similar, while Gillichthys receptors had a different pattern of hormonal specificity. The binding of 125 I-oPRL to renal membranes of the turtle, Pseudemys scripta elegans, was characterized and compared to PRL binding sites of kidney membranes of the bullfrog, Rana catesbeiana, and the tiger salamander, Ambystoma tigrinum

  5. Human Growth Hormone Delivery with a Microneedle Transdermal System: Preclinical Formulation, Stability, Delivery and PK of Therapeutically Relevant Doses

    Directory of Open Access Journals (Sweden)

    Mahmoud Ameri

    2014-05-01

    Full Text Available This study evaluated the feasibility of coating formulated recombinant human growth hormone (rhGH on a titanium microneedle transdermal delivery system, Zosano Pharma (ZP-hGH, and assessed preclinical patch delivery performance. Formulation rheology and surface activity were assessed by viscometry and contact angle measurement. rhGH liquid formulation was coated onto titanium microneedles by dip-coating and drying. The stability of coated rhGH was determined by size exclusion chromatography-high performance liquid chromatography (SEC-HPLC. Preclinical delivery and pharmacokinetic studies were conducted in female hairless guinea pigs (HGP using rhGH coated microneedle patches at 0.5 and 1 mg doses and compared to Norditropin® a commercially approved rhGH subcutaneous injection. Studies demonstrated successful rhGH formulation development and coating on microneedle arrays. The ZP-hGH patches remained stable at 40 °C for six months with no significant change in % aggregates. Pharmacokinetic studies showed that the rhGH-coated microneedle patches, delivered with high efficiency and the doses delivered indicated linearity with average Tmax of 30 min. The absolute bioavailability of the microneedle rhGH patches was similar to subcutaneous Norditropin® injections. These results suggest that ZP-transdermal microneedle patch delivery of rhGH is feasible and may offer an effective and patient-friendly alternative to currently marketed rhGH injectables.

  6. Human Growth Hormone Delivery with a Microneedle Transdermal System: Preclinical Formulation, Stability, Delivery and PK of Therapeutically Relevant Doses.

    Science.gov (United States)

    Ameri, Mahmoud; Kadkhodayan, Miryam; Nguyen, Joe; Bravo, Joseph A; Su, Rebeca; Chan, Kenneth; Samiee, Ahmad; Daddona, Peter E

    2014-05-15

    This study evaluated the feasibility of coating formulated recombinant human growth hormone (rhGH) on a titanium microneedle transdermal delivery system, Zosano Pharma (ZP)-hGH, and assessed preclinical patch delivery performance. Formulation rheology and surface activity were assessed by viscometry and contact angle measurement. rhGH liquid formulation was coated onto titanium microneedles by dip-coating and drying. The stability of coated rhGH was determined by size exclusion chromatography-high performance liquid chromatography (SEC-HPLC). Preclinical delivery and pharmacokinetic studies were conducted in female hairless guinea pigs (HGP) using rhGH coated microneedle patches at 0.5 and 1 mg doses and compared to Norditropin® a commercially approved rhGH subcutaneous injection. Studies demonstrated successful rhGH formulation development and coating on microneedle arrays. The ZP-hGH patches remained stable at 40 °C for six months with no significant change in % aggregates. Pharmacokinetic studies showed that the rhGH-coated microneedle patches, delivered with high efficiency and the doses delivered indicated linearity with average Tmax of 30 min. The absolute bioavailability of the microneedle rhGH patches was similar to subcutaneous Norditropin® injections. These results suggest that ZP-transdermal microneedle patch delivery of rhGH is feasible and may offer an effective and patient-friendly alternative to currently marketed rhGH injectables.

  7. Cranial irradiation for cerebral and nasopharyngeal tumours in children: evidence for the production of a hypothalmic defect in growth hormone release

    International Nuclear Information System (INIS)

    Blacklay, A.; Grossman, A.; Ross, R.J.M.; Savage, M.O.; Davies, P.S.W.; Plowman, P.N.; Besser, G.M.; Coy, D.H.

    1986-01-01

    A synthetic 29-amino acid analogue of human pancreatic GH-releasing hormone (GHRH(1-29)NH 2 ) has recently been shown to stimulate the release of GH in normal subjects. The authors have studied the GH reponse to GHRH(1-29)NH 2 in nine children irradiated for brain and nasopharyngeal tumours, who were not growing and were deficient in GH as assessed by insulin-induced hypoglycaemia. Serum GH rose in response to GHRH(1-29)NH 2 in all the children, and in five the peak serum GH response was > 20 mu./1. The data suggest that when hypothalamo-pituitary irradiation results in GH deficiency, this is due to a failure of the synthesis or delivery of endogenous GHRH from the hypothalamus to the pituitary cells. It also suggests that it may be possible to treat such children using synthetic GHRH in place of exogenous GH. (author)

  8. Preliminary report: BGLIIA-BGLIIB haplotype of growth hormone cluster is associated with glucose intolerance in non-insulin-dependent diabetes mellitus and with growth hormone deficit in growth retardation.

    Science.gov (United States)

    Bottini, E; Lucarelli, P; Amante, A; Saccucci, P; Gloria-Bottini, F

    2002-01-01

    We studied 101 growth-retarded children from the population of Ancona (Italy). Plasma growth hormone (GH) levels at the end of insulin and clonidine tests were considered for classification of children into 3 categories according to severity of GH deficit: total deficit of GH (TD), partial deficit (PD, and familiar short stature (FSS; no deficit of GH). The BGLIIA*2/BGLIIB*1 haplotype of GH cluster that was previously found to be negatively associated with severe glucose intolerance in non-insulin-dependent diabetes mellitus (NIDDM) is negatively associated with GH deficit in growth-retarded children. The hypothesis that intrauterine growth retardation and glucose intolerance in adult life could be phenotypes of the same underlying genotype has been recently put forward. The present observation suggests that genes influencing both growth and glucose tolerance are encoded in the GH cluster. Copyright 2002 by W.B. Saunders Company

  9. Growth hormone biases amygdala network activation after fear learning.

    Science.gov (United States)

    Gisabella, B; Farah, S; Peng, X; Burgos-Robles, A; Lim, S H; Goosens, K A

    2016-11-29

    Prolonged stress exposure is a risk factor for developing posttraumatic stress disorder, a disorder characterized by the 'over-encoding' of a traumatic experience. A potential mechanism by which this occurs is through upregulation of growth hormone (GH) in the amygdala. Here we test the hypotheses that GH promotes the over-encoding of fearful memories by increasing the number of neurons activated during memory encoding and biasing the allocation of neuronal activation, one aspect of the process by which neurons compete to encode memories, to favor neurons that have stronger inputs. Viral overexpression of GH in the amygdala increased the number of amygdala cells activated by fear memory formation. GH-overexpressing cells were especially biased to express the immediate early gene c-Fos after fear conditioning, revealing strong autocrine actions of GH in the amygdala. In addition, we observed dramatically enhanced dendritic spine density in GH-overexpressing neurons. These data elucidate a previously unrecognized autocrine role for GH in the regulation of amygdala neuron function and identify specific mechanisms by which chronic stress, by enhancing GH in the amygdala, may predispose an individual to excessive fear memory formation.

  10. Developments in our understanding of the effects of growth hormone on white adipose tissue from mice: implications to the clinic.

    Science.gov (United States)

    Berryman, Darlene E; Henry, Brooke; Hjortebjerg, Rikke; List, Edward O; Kopchick, John J

    2016-01-01

    Adipose tissue (AT) is a well-established target of growth hormone (GH) and is altered in clinical conditions associated with excess, deficiency and absence of GH action. Due to the difficulty in collecting AT from clinical populations, genetically modified mice have been useful in better understanding how GH affects this tissue. Recent findings in mice would suggest that the impact of GH on AT is beyond alterations of lipolysis, lipogenesis or proliferation/ differentiation. AT depot-specific alterations in immune cells, extracellular matrix, adipokines, and senescence indicate an expanded role for GH in AT physiology. This mouse data will guide additional studies necessary to evaluate the therapeutic potential and safety of GH for conditions associated with altering AT, such as obesity. In this review, we introduce several relatively new intricacies of GH's effect on AT, focusing on recent studies in mice. Finally, we summarize the clinical implications of these findings.

  11. Estrogens regulate the hepatic effects of growth hormone, a hormonal interplay with multiple fates

    DEFF Research Database (Denmark)

    Fernández-Pérez, Leandro; Guerra, Borja; Díaz-Chico, Juan C

    2013-01-01

    The liver responds to estrogens and growth hormone (GH) which are critical regulators of body growth, gender-related hepatic functions, and intermediate metabolism. The effects of estrogens on liver can be direct, through the direct actions of hepatic ER, or indirect, which include the crosstalk...

  12. IGF-1 and insulin as growth hormones.

    Science.gov (United States)

    Laron, Zvi

    2004-01-01

    IGF-1 generated in the liver is the anabolic effector and linear growth promoting hormone of the pituitary growth hormone (GH). This is evidenced by dwarfism in states of congenital IGF-1 deficiency, Igf1 gene mutation/deletions or knockouts, and in Laron syndrome (LS), due to GH receptor gene mutations/deletions or IGF-1 receptor blocking. In a positive way, daily IGF-1 administration to stunted patients with LS or hGH gene deletion accelerates linear growth velocity. IGF-1 acts on the proliferative cells of the epiphyseal cartilage. IGF-1 also induces organ and tissue growth; its absence causing organomicria. Insulin shares a common ancestry with IGF-1 and with 45% amino acid homology, as well as very close relationships in the structure of its receptors and post-receptor cascade, also acts as a growth hormone. It has protein anabolic activity and stimulates IGF-1 synthesis. Pancreas agenesis causes short babies, and obese children with hyperinsulinism, with or without pituitary GH, have an accelerated growth rate and skeletal maturation; so do babies with macrosomia. Whether the insulin growth effect is direct, or mediated by IGF-1 or leptin is controversial.

  13. Urine metabonomic profiling of a female adolescent with PIT-1 mutation before and during growth hormone therapy: insights into the metabolic effects of growth hormone.

    Science.gov (United States)

    Abd Rahman, Shaffinaz; Schirra, Horst Joachim; Lichanska, Agnieszka M; Huynh, Tony; Leong, Gary M

    2013-01-01

    Growth hormone (GH) is a protein hormone with important roles in growth and metabolism. The objective of this study was to investigate the metabolism of a human subject with severe GH deficiency (GHD) due to a PIT-1 gene mutation and the metabolic effects of GH therapy using Nuclear Magnetic Resonance (NMR)-based metabonomics. NMR-based metabonomics is a platform that allows the metabolic profile of biological fluids such as urine to be recorded, and any alterations in the profile modulated by GH can potentially be detected. Urine samples were collected from a female subject with severe GHD before, during and after GH therapy, and from healthy age- and sex-matched controls and analysed with NMR-based metabonomics. The samples were collected at a hospital and the study was performed at a research facility. We studied a 17 year old female adolescent with severe GHD secondary to PIT-1 gene mutation who had reached final adult height and who had ceased GH therapy for over 3 years. The subject was subsequently followed for 5 years with and without GH therapy. Twelve healthy age-matched female subjects acted as control subjects. The GH-deficient subject re-commenced GH therapy at a dose of 1 mg/day to normalise serum IGF-1 levels. Urine metabolic profiles were recorded using NMR spectroscopy and analysed with multivariate statistics to distinguish the profiles at different time points and identify significant metabolites affected by GH therapy. NMR-based metabonomics revealed that the metabolic profile of the GH-deficient subject altered with GH therapy and that her profile was different from healthy controls before, and during withdrawal of GH therapy. This study illustrates the potential use of NMR-based metabonomics for monitoring the effects of GH therapy on metabolism by profiling the urine of GH-deficient subjects. Further controlled studies in larger numbers of GH-deficient subjects are required to determine the clinical benefits of NMR-based metabonomics in

  14. Lack of hormone binding in COS-7 cells expressing a mutated growth hormone receptor found in Laron dwarfism.

    Science.gov (United States)

    Edery, M; Rozakis-Adcock, M; Goujon, L; Finidori, J; Lévi-Meyrueis, C; Paly, J; Djiane, J; Postel-Vinay, M C; Kelly, P A

    1993-01-01

    A single point mutation in the growth hormone (GH) receptor gene generating a Phe-->Ser substitution in the extracellular binding domain of the receptor has been identified in one family with Laron type dwarfism. The mutation was introduced by site-directed mutagenesis into cDNAs encoding the full-length rabbit GH receptor and the extracellular domain or binding protein (BP) of the human and rabbit GH receptor, and also in cDNAs encoding the full length and the extracellular domain of the related rabbit prolactin (PRL) receptor. All constructs were transiently expressed in COS-7 cells. Both wild type and mutant full-length rabbit GH and PRL receptors, as well as GH and prolactin BPs (wild type and mutant), were detected by Western blot in cell membranes and concentrated culture media, respectively. Immunofluorescence studies showed that wild type and mutant full-length GH receptors had the same cell surface and intracellular distribution and were expressed with comparable intensities. In contrast, all mutant forms (full-length receptors or BPs), completely lost their modify the synthesis ligand. These results clearly demonstrate that this point mutation (patients with Laron syndrome) does not modify the synthesis or the intracellular pathway of receptor proteins, but rather abolishes ability of the receptor or BP to bind GH and is thus responsible for the extreme GH resistance in these patients. Images PMID:8450064

  15. A novel growth hormone receptor gene deletion mutation in a patient with primary growth hormone insensitivity syndrome (Laron syndrome).

    Science.gov (United States)

    Yamamoto, Hiroyasu; Kouhara, Haruhiko; Iida, Keiji; Chihara, Kazuo; Kasayama, Soji

    2008-04-01

    Growth hormone (GH) insensitivity syndrome (Laron syndrome) is known to be caused by genetic disorders of the GH-IGF-1 axis. Although many mutations in the GH receptor have been identified, there have been only a few reports of deletions of the GH receptor gene. A Japanese adult female patient with Laron syndrome was subjected to chromosome analysis with basic G-banding and also with a high accuracy technique. Each exon of the GH receptor gene was amplified by means of PCR. Since this patient was diagnosed with osteoporosis, the effects of alendronate on bone mineral density (BMD) were also examined. The chromosome analysis with the high accuracy technique demonstrated a large deletion of the short arm in one allele of chromosome 5 from p11 to p13.1 [46, XX, del (5) (p11-p13.1)]. PCR amplification of exons of the GH receptor gene showed that only exons 2 and 3 were amplified. Low-dose IGF-1 administration (30microg/kg body weight) failed to increase her BMD, whereas alendronate administration resulted in an increase associated with a decrease in urinary deoxypyridinoline (DPD) and serum osteocalcin concentrations. The GH receptor gene of the patient was shown to lack exons 4-10. To the best of our knowledge, this is the third case report of Laron syndrome with large GH receptor deletion. Alendronate was effective for the enhancement of BMD.

  16. Chronopharmacological effects of growth hormone on the executive function and oxidative stress response in rats

    Directory of Open Access Journals (Sweden)

    Carlos K B Ferrari

    2017-01-01

    Full Text Available Objective(s: to investigate the chronopharmacological effects of growth hormone on executive function and the oxidative stress response in rats. Materials and Methods: Fifty male Wistar rats (36-40 weeks old had ad libitum access to water and food and were separated into four groups: diurnal control, nocturnal control, diurnal GH-treated, and nocturnal GH-treated animals. Levels of Cu, Zn superoxide dismutase (Cu,Zn-SOD, and superoxide release by spleen macrophages were evaluated. For memory testing, adaptation and walking in an open field platform was used. GH-treated animals demonstrated better performance in exploratory and spatial open-field tests. Results: The latency time in both GH-treated groups was significantly lower compared with the latency time of the control groups. The diurnal GH treatment did not stimulate superoxide release but increased the CuZn-SOD enzyme levels. The nocturnal GH treatment did not influence the superoxide release and CuZn-SOD concentration. GH treatment also resulted in heart atrophy and lung hypertrophy. Conclusion: Growth hormone treatment improved the performance of executive functions at the cost of oxidative stress triggering, and this effect was dependent on the circadian period of hormone administration. However, GH treatment caused damaging effects such as lung hypertrophy and heart atrophy.

  17. Chronopharmacological effects of growth hormone on the executive function and oxidative stress response in rats.

    Science.gov (United States)

    Ferrari, Carlos K B; França, Eduardo L; Monteiro, Luciane A; Santos, Bruno L; Pereira-Junior, Alfredo; Honorio-França, Adenilda C

    2017-01-01

    To investigate the chronopharmacological effects of growth hormone on executive function and the oxidative stress response in rats. Fifty male Wistar rats (36-40 weeks old) had ad libitum access to water and food and were separated into four groups: diurnal control, nocturnal control, diurnal GH-treated, and nocturnal GH-treated animals. Levels of Cu, Zn superoxide dismutase (Cu, Zn-SOD), and superoxide release by spleen macrophages were evaluated. For memory testing, adaptation and walking in an open field platform was used. GH-treated animals demonstrated better performance in exploratory and spatial open-field tests. The latency time in both GH-treated groups was significantly lower compared with the latency time of the control groups. The diurnal GH treatment did not stimulate superoxide release but increased the CuZn-SOD enzyme levels. The nocturnal GH treatment did not influence the superoxide release and CuZn-SOD concentration. GH treatment also resulted in heart atrophy and lung hypertrophy. Growth hormone treatment improved the performance of executive functions at the cost of oxidative stress triggering, and this effect was dependent on the circadian period of hormone administration. However, GH treatment caused damaging effects such as lung hypertrophy and heart atrophy.

  18. Regulation of His-dTrp-Ala-Trp-dPhe-Lys-NH2 (GHRP-6)-induced GH secretion in the rat.

    Science.gov (United States)

    Mallo, F; Alvarez, C V; Benitez, L; Burguera, B; Coya, R; Casanueva, F F; Dieguez, C

    1993-01-01

    dexamethasone did not affect the GH responses to GHRH, highlighting a differential regulation of these hormones on somatotroph responsiveness to these peptides.

  19. Multi-Messenger Astronomy and Dark Matter

    Science.gov (United States)

    Bergström, Lars

    This chapter presents the elaborated lecture notes on Multi-Messenger Astronomy and Dark Matter given by Lars Bergström at the 40th Saas-Fee Advanced Course on "Astrophysics at Very High Energies". One of the main problems of astrophysics and astro-particle physics is that the nature of dark matter remains unsolved. There are basically three complementary approaches to try to solve this problem. One is the detection of new particles with accelerators, the second is the observation of various types of messengers from radio waves to gamma-ray photons and neutrinos, and the third is the use of ingenious experiments for direct detection of dark matter particles. After giving an introduction to the particle universe, the author discusses the relic density of particles, basic cross sections for neutrinos and gamma-rays, supersymmetric dark matter, detection methods for neutralino dark matter, particular dark matter candidates, the status of dark matter detection, a detailled calculation on an hypothetical "Saas-Fee Wimp", primordial black holes, and gravitational waves.

  20. Obesity alters gene expression for GH/IGF-I axis in mouse mammary fat pads: differential role of cortistatin and somatostatin.

    Directory of Open Access Journals (Sweden)

    Alicia Villa-Osaba

    Full Text Available Locally produced growth hormone (GH and IGF-I are key factors in the regulation of mammary gland (MG development and may be important in breast cancer development/progression. Somatostatin (SST and cortistatin (CORT regulate GH/IGF-I axis at various levels, but their role in regulating GH/IGF-I in MGs remains unknown. Since obesity alters the expression of these systems in different tissues and is associated to MG (patho physiology, we sought to investigate the role of SST/CORT in regulating GH/IGF-I system in the MGs of lean and obese mice. Therefore, we analyzed GH/IGF-I as well as SST/CORT and ghrelin systems expression in the mammary fat pads (MFPs of SST- or CORT-knockout (KO mice and their respective littermate-controls fed a low-fat (LF or a high-fat (HF diet for 16 wks. Our results demonstrate that the majority of the components of GH/IGF-I, SST/CORT and ghrelin systems are locally expressed in mouse MFP. Expression of elements of the GH/IGF-I axis was significantly increased in MFPs of HF-fed control mice while lack of endogenous SST partially suppressed, and lack of CORT completely blunted, the up-regulation observed in obese WT-controls. Since SST/CORT are known to exert an inhibitory role on the GH/IGFI axis, the increase in SST/CORT-receptor sst2 expression in MFPs of HF-fed CORT- and SST-KOs together with an elevation on circulating SST in CORT-KOs could explain the differences observed. These results offer new information on the factors (GH/IGF-I axis involved in the endocrine/metabolic dysregulation of MFPs in obesity, and suggest that CORT is not a mere SST sibling in regulating MG physiology.

  1. A robust test for growth hormone doping--present status and future prospects.

    Science.gov (United States)

    Nelson, Anne E; Ho, Ken K

    2008-05-01

    Although doping with growth hormone (GH) is banned, there is anecdotal evidence that it is widely abused. GH is reportedly used often in combination with anabolic steroids at high doses for several months. Development of a robust test for GH has been challenging because recombinant human 22 kDa (22K) GH used in doping is indistinguishable analytically from endogenous GH and there are wide physiological fluctuations in circulating GH concentrations. One approach to GH testing is based on measurement of different circulating GH isoforms using immunoassays that differentiate between 22K and other GH isoforms. Administration of 22K GH results in a change in its abundance relative to other endogenous pituitary GH isoforms. The differential isoform method has been implemented; however, its utility is limited because of the short window of opportunity of detection. The second approach, which will extend the window of opportunity of detection, is based on the detection of increased levels of circulating GH-responsive proteins, such as insulin-like growth factor (IGF) axis and collagen peptides. Age and gender are the major determinants of variability for IGF-I and the collagen markers; therefore, a test based on these markers must take age into account for men and women. Extensive data is now available that validates the GH-responsive marker approach and implementation is now largely dependent on establishing an assured supply of standardized assays. Future directions will include more widespread implementation of both approaches by the World Anti-Doping Agency, possible use of other platforms for measurement and an athlete's passport to establish individual reference levels for biological parameters such as GH-responsive markers. Novel approaches include gene expression and proteomic profiling. 2008, Asian Journal of Andrology, SIMM and SJTU. All rights reserved.

  2. Adipokine zinc-α2-glycoprotein regulated by growth hormone and linked to insulin sensitivity.

    Science.gov (United States)

    Balaz, Miroslav; Ukropcova, Barbara; Kurdiova, Timea; Gajdosechova, Lucia; Vlcek, Miroslav; Janakova, Zuzana; Fedeles, Jozef; Pura, Mikulas; Gasperikova, Daniela; Smith, Steven R; Tkacova, Ruzena; Klimes, Iwar; Payer, Juraj; Wolfrum, Christian; Ukropec, Jozef

    2015-02-01

    Hypertrophic obesity is associated with impaired insulin sensitivity and lipid-mobilizing activity of zinc-α2-glycoprotein. Adipose tissue (AT) of growth hormone (GH) -deficient patients is characterized by extreme adipocyte hypertrophy due to defects in AT lipid metabolism. It was hypothesized that zinc-α2-glycoprotein is regulated by GH and mediates some of its beneficial effects in AT. AT from patients with GH deficiency and individuals with obesity-related GH deficit was obtained before and after 5-year and 24-month GH supplementation therapy. GH action was tested in primary human adipocytes. Relationships of GH and zinc-α2-glycoprotein with adipocyte size and insulin sensitivity were evaluated in nondiabetic patients with noncancerous cachexia and hypertrophic obesity. AT in GH-deficient adults displayed a substantial reduction of zinc-α2-glycoprotein. GH therapy normalized AT zinc-α2-glycoprotein. Obesity-related relative GH deficit was associated with almost 80% reduction of zinc-α2-glycoprotein mRNA in AT. GH increased zinc-α2-glycoprotein mRNA in both AT of obese men and primary human adipocytes. Interdependence of GH and zinc-α2-glycoprotein in regulating AT morphology and metabolic phenotype was evident from their relationship with adipocyte size and AT-specific and whole-body insulin sensitivity. The results demonstrate that GH is involved in regulation of AT zinc-α2-glycoprotein; however, the molecular mechanism linking GH and zinc-α2-glycoprotein in AT is yet unknown. © 2014 The Obesity Society.

  3. Polysomnographic sleep, growth hormone insulin-like growth factor-I axis, leptin, and weight loss

    DEFF Research Database (Denmark)

    Rasmussen, Michael; Wildschiødtz, Gordon; Juul, Anders

    2008-01-01

    compared with nonobese subjects After diet-induced weight loss the differences in GH, free IGF-I, and leptin were no longer present between previously obese and nonobese subjects, whereas a significant difference in sleep duration and total IGF-I levels persisted. Rapid eye movement (REM) sleep, non-REM......Short sleep appears to be strongly associated with obesity and altered metabolic function, and sleep and growth hormone (GH) secretion seems interlinked. In obesity, both the GH-insulin-like-growth-factor-I (GH-IGF-I) axis and sleep have been reported to be abnormal, however, no studies have...... investigated sleep in relation to the GH-IGF-I axis and weight loss in obese subjects. In this study polygraphic sleep recordings, 24-h GH release, 24-h leptin levels, free-IGF-I, total-IGF-I, IGF-binding protein-3 (IGFBP-3), acid-labile subunit (ALS), cortisol and insulin sensitivity were determined in six...

  4. Restoration of hippocampal growth hormone reverses stress-induced hippocampal impairment

    Directory of Open Access Journals (Sweden)

    Caitlin M. Vander Weele

    2013-06-01

    Full Text Available Though growth hormone (GH is synthesized by hippocampal neurons, where its expression is influenced by stress exposure, its function is poorly characterized. Here, we show that a regimen of chronic stress that impairs hippocampal function in rats also leads to a profound decrease in hippocampal GH levels. Restoration of hippocampal GH in the dorsal hippocampus via viral-mediated gene transfer completely reversed stress-related impairment of two hippocampus-dependent behavioral tasks, auditory trace fear conditioning and contextual fear conditioning, without affecting hippocampal function in unstressed control rats. GH overexpression reversed stress-induced decrements in both fear acquisition and long-term fear memory. These results suggest that loss of hippocampal GH contributes to hippocampal dysfunction following prolonged stress and demonstrate that restoring hippocampal GH levels following stress can promote stress resilience.

  5. Environmental stress, TRH and lactation effects on plasma growth hormone of cattle

    International Nuclear Information System (INIS)

    Johnson, H.D.; DeDios, O.; Lippincott, A.C.

    1976-01-01

    Plasma growth hormone (GH) levels of cattle are influenced by numerous environmental and metabolic factors. Acute heat stress increases GH threefold with maximum value at 30 minutes post-exposure. TRH infusion also shows a threefold increase as early as 2 minutes post-infusion but with a continual elevation for approximately 20 minutes. Longer-term environmental heat stress exposure, as occurs in tropics and the summer season, lowers plasma GH of cattle. GH levels in high-producing, lactating cows are greater than in low producers. In summary, plasma increases in levels of GH immediately reflect the stressor effects on cattle, presumably through involvement of TRH release. Long-term heat stressors, such as seasonal or tropic acclimatization, lowers GH of lactating cattle. (author)

  6. Blends of synthetic and natural polymers as drug delivery systems for growth hormone.

    Science.gov (United States)

    Cascone, M G; Sim, B; Downes, S

    1995-05-01

    In order to overcome the biological deficiencies of synthetic polymers and to enhance the mechanical characteristics of natural polymers, two synthetic polymers, poly(vinyl alcohol) (PVA) and poly(acrylic acid) (PAA) were blended, in different ratios, with two biological polymers, collagen (C) and hyaluronic acid (HA). These blends were used to prepare films, sponges and hydrogels which were loaded with growth hormone (GH) to investigate their potential use as drug delivery systems. The GH release was monitored in vitro using a specific enzyme-linked immunosorbent assay. The results show that GH can be released from HA/PAA sponges and from HA/PVA and C/PVA hydrogels. The initial GH concentration used for sample loading affected the total quantity of GH released but not the pattern of release. The rate and quantity of GH released was significantly dependent on the HA or C content of the polymers.

  7. Differential effects on kidney and liver growth of a non-viral hGH-expression vector in hypophysectomized mice

    DEFF Research Database (Denmark)

    Khamaisi, Mogher; Søndergaard, Morten; Segev, Yael

    2007-01-01

    Non-viral gene transfer was investigated as a potential modality for the treatment of growth hormone deficiency (GHD) using hypophysectomized (Hx) mice as a model. Hx mice were injected with a control plasmid or a plasmid containing the human (h) GH gene driven by a ubiquitin promoter, or left...... and serum IGF-I levels, has differential effects on renal growth and glomerular volume. The potential effects of such excess glomerular growth induced by this intervention require further investigation....

  8. Taguchi Experimental Design for Optimization of Recombinant Human Growth Hormone Production in CHO Cell Lines and Comparing its Biological Activity with Prokaryotic Growth Hormone.

    Science.gov (United States)

    Aghili, Zahra Sadat; Zarkesh-Esfahani, Sayyed Hamid

    2018-02-01

    Growth hormone deficiency results in growth retardation in children and the GH deficiency syndrome in adults and they need to receive recombinant-GH in order to rectify the GH deficiency symptoms. Mammalian cells have become the favorite system for production of recombinant proteins for clinical application compared to prokaryotic systems because of their capability for appropriate protein folding, assembly, post-translational modification and proper signal. However, production level in mammalian cells is generally low compared to prokaryotic hosts. Taguchi has established orthogonal arrays to describe a large number of experimental situations mainly to reduce experimental errors and to enhance the efficiency and reproducibility of laboratory experiments.In the present study, rhGH was produced in CHO cells and production of rhGH was assessed using Dot blotting, western blotting and Elisa assay. For optimization of rhGH production in CHO cells using Taguchi method An M16 orthogonal experimental design was used to investigate four different culture components. The biological activity of rhGH was assessed using LHRE-TK-Luciferase reporter gene system in HEK-293 and compared to the biological activity of prokaryotic rhGH.A maximal productivity of rhGH was reached in the conditions of 1%DMSO, 1%glycerol, 25 µM ZnSO 4 and 0 mM NaBu. Our findings indicate that control of culture conditions such as the addition of chemical components helps to develop an efficient large-scale and industrial process for the production of rhGH in CHO cells. Results of bioassay indicated that rhGH produced by CHO cells is able to induce GH-mediated intracellular cell signaling and showed higher bioactivity when compared to prokaryotic GH at the same concentrations. © Georg Thieme Verlag KG Stuttgart · New York.

  9. 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.

  10. Morbidity and GH deficiency: a nationwide study

    DEFF Research Database (Denmark)

    Stochholm, K.; Laursen, T.; Green, A.

    2008-01-01

    identified in the National Patient Registry. Lag time until first admission was used as a measure of morbidity. Patients were divided into childhood onset (CO) and adult onset (AO), discriminated by an age cut-off of 18 years at onset of GHD. Method: Sex- and cause-specific hazard ratios (HRs) in CO and AO......Objective: To estimate morbidity in Denmark in all patients with GH deficiency (GHD). Design: Morbidity was analyzed in 1794 GHD patients and 8014 controls matched on age and gender. All records in the GHD patients were studied and additional morbidity noted. Diagnoses and dates of admissions were...

  11. GH62 arabinofuranosidases: Structure, function and applications

    DEFF Research Database (Denmark)

    Wilkens, Casper; Andersen, Susan; Dumon, Claire

    2017-01-01

    Motivated by industrial demands and ongoing scientific discoveries continuous efforts are made to identify and create improved biocatalysts dedicated to plant biomass conversion. α-1,2 and α-1,3 arabinofuranosyl specific α-l-arabinofuranosidases (EC 3.2.1.55) are debranching enzymes catalyzing...... exclusively α-l-arabinofuranosidases and these are of fungal and bacterial origin. Twenty-two GH62 enzymes out of 223 entries in the CAZy database have been characterized and very recently new knowledge was acquired with regard to crystal structures, substrate specificities, and phylogenetics, which overall...

  12. Changes in serum concentrations of growth hormone, insulin, insulin-like growth factor and insulin-like growth factor-binding proteins 1 and 3 and urinary growth hormone excretion during the menstrual cycle

    DEFF Research Database (Denmark)

    Juul, A; Scheike, Thomas Harder; Pedersen, A T

    1997-01-01

    Few studies exist on the physiological changes in the concentrations of growth hormone (GH), insulin-like growth factors (IGF) and IGF-binding proteins (IGFBP) within the menstrual cycle, and some controversy remains. We therefore decided to study the impact of endogenous sex steroids on the GH-I...

  13. A summary of the influence of exogenous estrogen administration across the lifespan on the GH/IGF-1 axis and implications for bone health.

    Science.gov (United States)

    Southmayd, Emily A; De Souza, Mary Jane

    2017-02-01

    Bone growth, development, and remodeling are modulated by numerous circulating hormones. Throughout the lifespan, the extent to which each of the hormones impacts bone differs. Understanding the independent and combined impact of these hormones on controlling bone remodeling allows for the development of more informed decision making regarding pharmacology, specifically the use of hormonal medication, at all ages. Endocrine control of bone health in women is largely dictated by the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis and the hypothalamic-pituitary-ovarian (HPO) axis. Growth hormone, secreted from the pituitary gland, stimulates cells in almost every tissue to secrete IGF-1, although the majority of circulating IGF-1 is produced hepatically. Indeed, systemic IGF-1 concentrations have been found to be correlated with bone mineral density (BMD) in both pre- and post-menopausal women and is often used as a marker of bone formation. Sex steroids produced by the ovaries, namely estradiol, mediate bone resorption through binding to estrogen receptors on osteoclasts and osteoblasts. Specifically, by increasing osteoclast apoptosis and decreasing osteoblast apoptosis, adequate estrogen levels prevent excessive bone resorption, which helps to explain the rapid decline in bone mass that occurs with the menopausal decrease in estrogen production. Though there are documented correlations between endogenous estrogen concentrations and GH/IGF-1 dynamics, this relationship changes across the lifespan as sex-steroid dynamics fluctuate and, possibly, as tissue responsiveness to GH stimulation decreases. Aside from the known role of endogenous sex steroids on bone health, the impact of exogenous estrogen administration is of interest, as exogenous formulations further modulate GH and IGF-1 production. However, the effect and extent of GH and IGF-1 modulation seems to be largely dependent on age at administration and route of administration. Specifically

  14. Cortical bone growth and maturational changes in dwarf rats induced by recombinant human growth hormone

    Science.gov (United States)

    Martinez, D. A.; Orth, M. W.; Carr, K. E.; Vanderby, R. Jr; Vailas, A. C.

    1996-01-01

    The growth hormone (GH)-deficient dwarf rat was used to investigate recombinant human (rh) GH-induced bone formation and to determine whether rhGH facilitates simultaneous increases in bone formation and bone maturation during rapid growth. Twenty dwarf rats, 37 days of age, were randomly assigned to dwarf plus rhGH (GH; n = 10) and dwarf plus vehicle (n = 10) groups. The GH group received 1.25 mg rhGH/kg body wt two times daily for 14 days. Biochemical, morphological, and X-ray diffraction measurements were performed on the femur middiaphysis. rhGH stimulated new bone growth in the GH group, as demonstrated by significant increases (P < 0.05) in longitudinal bone length (6%), middiaphyseal cross-sectional area (20%), and the amount of newly accreted bone collagen (28%) in the total pool of middiaphyseal bone collagen. Cortical bone density, mean hydroxyapatite crystal size, and the calcium and collagen contents (microgram/mm3) were significantly smaller in the GH group (P < 0.05). Our findings suggest that the processes regulating new collagen accretion, bone collagen maturation, and mean hydroxyapatite crystal size may be independently regulated during rapid growth.

  15. Clinical and molecuar characterization of Brazilian patients with growth hormone gene deletions

    Directory of Open Access Journals (Sweden)

    I.J.P. Arnhold

    1998-04-01

    Full Text Available Genomic DNA from 23 patients with isolated growth hormone (GH deficiency (12 males and 11 females: heights -4.9 ± 1.4 SDS was screened for GH gene deletions by restriction endonuclease analysis of polymerase chain reaction amplification products. Three unrelated patients had typical features of severe GH deficiency and deletions (6.7 kb in two and 7.6 kb in one of the GH gene. The two patients with 6.7-kb deletions developed growth-attenuating anti-GH antibodies whereas the patient with the 7.6-kb deletion continued to grow with GH replacement therapy. Our finding that 3/23 (~13% Brazilian subjects had GH gene deletions agrees with previous studies of severe isolated GH deficiency subjects in other populations. Two of three subjects (67% with deletions developed blocking antibodies despite administration of exogenous GH at low doses. Interestingly, only 1/10 of cases with affected relatives or parental consanguinity had GH-1 gene deletions

  16. Gene structure and functional characterization of growth hormone in dogfish, Squalus acanthias.

    Science.gov (United States)

    Moriyama, Shunsuke; Oda, Mayumi; Yamazaki, Tomohide; Yamaguchi, Kiyoko; Amiya, Noriko; Takahashi, Akiyoshi; Amano, Masafumi; Goto, Tomoaki; Nozaki, Masumi; Meguro, Hiroshi; Kawauchi, Hiroshi

    2008-06-01

    Dogfish (Squalus acanthias) growth hormone (GH) was identified by cDNA cloning and protein purification from the pituitary gland. Dogfish GH cDNA encoded a prehormone of 210 amino acids (aa). Sequence analysis of purified GH revealed that the prehormone is composed of a signal peptide of 27 aa and a mature protein of 183 aa. Dogfish GH showed 94% sequence identity with blue shark GH, and also showed 37-66%, 26%, and 48-67% sequence identity with GH from osteichtyes, an agnathan, and tetrapods. The site of production was identified through immunocytochemistry to be cells of the proximal pars distalis of the pituitary gland. Dogfish GH stimulates both insulin-like growth factor-I and II mRNA levels in dogfish liver in vitro. The dogfish GH gene consisted of five exons and four introns, the same as in lamprey, teleosts such as cypriniforms and siluriforms, and tetrapods. The 5'-flanking region within 1082 bp of the transcription start site contained consensus sequences for the TATA box, Pit-1/GHF-1, CRE, TRE, and ERE. These results show that the endocrine mechanism for growth stimulation by the GH-IGF axis was established at an early stage of vertebrate evolution, and that the 5-exon-type gene organization might reflect the structure of the ancestral gene for the GH gene family.

  17. Cortical bone growth and maturational changes in dwarf rats induced by recombinant human growth hormone

    Science.gov (United States)

    Martinez, D. A.; Orth, M. W.; Carr, K. E.; Vanderby, R. Jr; Vailas, A. C.

    1996-01-01

    The growth hormone (GH)-deficient dwarf rat was used to investigate recombinant human (rh) GH-induced bone formation and to determine whether rhGH facilitates simultaneous increases in bone formation and bone maturation during rapid growth. Twenty dwarf rats, 37 days of age, were randomly assigned to dwarf plus rhGH (GH; n = 10) and dwarf plus vehicle (n = 10) groups. The GH group received 1.25 mg rhGH/kg body wt two times daily for 14 days. Biochemical, morphological, and X-ray diffraction measurements were performed on the femur middiaphysis. rhGH stimulated new bone growth in the GH group, as demonstrated by significant increases (P bone length (6%), middiaphyseal cross-sectional area (20%), and the amount of newly accreted bone collagen (28%) in the total pool of middiaphyseal bone collagen. Cortical bone density, mean hydroxyapatite crystal size, and the calcium and collagen contents (microgram/mm3) were significantly smaller in the GH group (P bone collagen maturation, and mean hydroxyapatite crystal size may be independently regulated during rapid growth.

  18. Mercury's Interior from MESSENGER Radio Science Data

    Science.gov (United States)

    Genova, A.; Mazarico, E.; Goossens, S. J.; Lemoine, F. G.; Neumann, G. A.; Smith, D. E.; Zuber, M. T.

    2017-12-01

    The MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) spacecraft provided precise radio tracking data in orbit about Mercury for more than 4 years, from March 2011 to April 2015. These geodetic measurements enable us to investigate the interior structure of the planet from the inner core to the crust. The first three years of radio data allowed us to determine the gravity field of Mercury with a resolution of 150 km in the northern hemisphere (degree and order 50 in spherical harmonics) since the periapsis was located at higher latitudes (>65˚N) and 200-500 km altitudes. The comparison of this gravity solution with Mercury's topography, which was retrieved by using over 25 million individual measurements of the Mercury Laser Altimeter (MLA), resulted in a preliminary map of the crustal thickness of the planet. However, those results were limited by the resolution of the gravity field since the topography was defined in spherical harmonics up to degree and order 125. The last year of the MESSENGER extended mission was dedicated to a low-altitude campaign, where the spacecraft periapsis was maintained at altitudes between 25 and 100 km. The radio data collected during this mission phase allowed us to significantly improve the resolution of the gravity field locally in the northern hemisphere up to degree and order 100 in spherical harmonics. We present the gravity anomalies and crustal thickness maps that lead to a better understanding on the formation and evolution of specific regions. We present our estimated orientation model, which slightly differs from the solutions that were obtained by using Earth-based radar measurements and the co-registration of MESSENGER imaging and altimetry data. These previous estimates provide a direct measurement of the surface response, whereas the orientation model from gravity is more sensitive to the inner and outer core. A discrepancy between core and surface obliquities may provide fundamental

  19. The impact of idiopathic childhood-onset growth hormone deficiency (GHD) on bone mass in subjects without adult GHD

    DEFF Research Database (Denmark)

    Lange, Martin; Müller, Jørn; Svendsen, Ole Lander

    2005-01-01

    Despite seemingly adequate growth hormone (GH) treatment during childhood, children with GH deficiency (GHD) have reduced bone mineral density (BMD) at final height. The aim was to evaluate BMD and bone mineral content (BMC) in adults treated for idiopathic childhood-onset (CO) GHD, 18 years after...

  20. Treatment of growth failure in the absence of GH signaling: The Ecuadorian experience.

    Science.gov (United States)

    Guevara-Aguirre, Jaime; Guevara, Alexandra; Guevara, Carolina

    2018-02-01

    Recombinant human insulin-like growth factor-1 (rhIGF-1) treatment studies of growth failure in absence of growth hormone (GH) signaling (GH insensitivity -GHI, Laron syndrome -LS, GH Receptor deficiency -GHRD) have taken place in many locations around the globe. Results from these trials are comparable, and slight differences reported can be attributed to specific circumstances at different research sites. rhIGF-I treatment studies of GHI in Ecuador included various trials performed on children belonging to the largest and only homogeneous cohort of subjects with this condition in the world. All trials were performed by the same team of investigators and, during study periods, subjects received similar nutritional, physical activity and medical advice. Combination of these inherent conditions most likely creates less sources of variability during the research process. Indeed, diagnosis, selection and inclusion of research subjects; methodology used; transport, storage and delivery of study drug; data collection, monitoring and auditing; data analysis, discussion of results, conclusion inferences and reporting, etc., were submitted to the same sources of error. For the above-mentioned reasons, we are hereby mainly covering conclusions derived from rhIGF-I treatment studies of Ecuadorian children whit GHRD due to homozygosity of a splice site mutation occurring at GHR gene, whose unaffected parents were both heterozygous for the same mutation. We also describe studies of rhIGF-I administration in adolescent and adult subjects with GHRD, from the same cohort and with the same genetic anomaly. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. An application of CART algorithm in genetics: IGFs and cGH polymorphisms in Japanese quail

    Science.gov (United States)

    Kaplan, Selçuk

    2017-04-01

    The avian insulin-like growth factor-1 (IGFs) and avian growth hormone (cGH) genes are the most important genes that can affect bird performance traits because of its important function in growth and metabolism. Understanding the molecular genetic basis of variation in growth-related traits is of importance for continued improvement and increased rates of genetic gain. The objective of the present study was to identify polymorphisms of cGH and IGFs genes in Japanese quail using conventional least square method (LSM) and CART algorithm. Therefore, this study was aimed to demonstrate at determining the polymorphisms of two genes related growth characteristics via CART algorithm. A simulated data set was generated to analyze by adhering the results of some poultry genetic studies which it includes live weights at 5 weeks of age, 3 alleles and 6 genotypes of cGH and 2 alleles and 3 genotypes of IGFs. As a result, it has been determined that the CART algorithm has some advantages as for that LSM.

  2. Homozygous and heterozygous GH transgenesis alters fatty acid composition and content in the liver of Amago salmon (Oncorhynchus masou ishikawae

    Directory of Open Access Journals (Sweden)

    Manabu Sugiyama

    2012-08-01

    Growth hormone (GH transgenic Amago (Oncorhynchus masou ishikawae, containing the sockeye GH1 gene fused with metallothionein-B promoter from the same species, were generated and the physiological condition through lipid metabolism compared among homozygous (Tg/Tg and heterozygous GH transgenic (Tg/+ Amago and the wild type control (+/+. Previously, we have reported that the adipose tissue was generally smaller in GH transgenic fish compared to the control, and that the Δ-6 fatty acyl desaturase gene was down-regulated in the Tg/+ fish. However, fatty acid (FA compositions have not been measured previously in these fish. In this study we compared the FAs composition and content in the liver using gas chromatography. Eleven kinds of FA were detected. The composition of saturated and monounsaturated fatty acids (SFA and MUFA such as myristic acid (14:0, palmitoleic acid (16:1n-7, and cis-vaccenic acid (cis-18:1n-7 was significantly (P<0.05 decreased in GH transgenic Amago. On the other hand, the composition of polyunsaturated fatty acids (PUFAs such as linoleic acid (18:2n-6, arachidonic acid (20:4n-6, and docosapentaenoic acid (22:5n-3 was significantly (P<0.05 increased. Levels of serum glucose and triacylglycerol were significantly (P<0.05 decreased in the GH transgenics compared with +/+ fish. Furthermore, 3′-tag digital gene expression profiling was performed using liver tissues from Tg/Tg and +/+ fish, and showed that Mid1 interacting protein 1 (Mid1ip1, which is an important factor to activate Acetyl-CoA carboxylase (ACC, was down-regulated in Tg/Tg fish, while genes involved in FA catabolism were up-regulated, including long-chain-fatty-acid–CoA ligase 1 (ACSL1 and acyl-coenzyme A oxidase 3 (ACOX3. These data suggest that liver tissue from GH transgenic Amago showed starvation by alteration in glucose and lipid metabolism due to GH overexpression. The decrease of serum glucose suppressed Mid1ip1, and caused a decrease of de novo FA synthesis, resulting

  3. Purification and cultivation of human pituitary growth hormone secreting cells

    Science.gov (United States)

    Hymer, W. C.

    1979-01-01

    Efforts were directed towards maintenance of actively secreting human pituitary growth hormone cells (somatotrophs) in vitro. The production of human growth hormone (hGH) by this means would be of benefit for the treatment of certain human hypopituitary diseases such as dwarfism. One of the primary approaches was the testing of agents which may logically be expected to increase hGH release. The progress towards this goal is summarized. Results from preliminary experiments dealing with electrophoresis of pituitary cell for the purpose of somatotroph separation are described.

  4. Growth hormone and bone health.

    Science.gov (United States)

    Bex, Marie; Bouillon, Roger

    2003-01-01

    Growth hormone (GH) and insulin-like growth factor-I have major effects on growth plate chondrocytes and all bone cells. Untreated childhood-onset GH deficiency (GHD) markedly impairs linear growth as well as three-dimensional bone size. Adult peak bone mass is therefore about 50% that of adults with normal height. This is mainly an effect on bone volume, whereas true bone mineral density (BMD; g/cm(3)) is virtually normal, as demonstrated in a large cohort of untreated Russian adults with childhood-onset GHD. The prevalence of fractures in these untreated childhood-onset GHD adults was, however, markedly and significantly increased in comparison with normal Russian adults. This clearly indicates that bone mass and bone size matter more than true bone density. Adequate treatment with GH can largely correct bone size and in several studies also bone mass, but it usually requires more than 5 years of continuous treatment. Adult-onset GHD decreases bone turnover and results in a mild deficit, generally between -0.5 and -1.0 z-score, in bone mineral content and BMD of the lumbar spine, radius and femoral neck. Cross-sectional surveys and the KIMS data suggest an increased incidence of fractures. GH replacement therapy increases bone turnover. The three controlled studies with follow-up periods of 18 and 24 months demonstrated a modest increase in BMD of the lumbar spine and femoral neck in male adults with adult-onset GHD, whereas no significant changes in BMD were observed in women. GHD, whether childhood- or adult-onset, impairs bone mass and strength. Appropriate substitution therapy can largely correct these deficiencies if given over a prolonged period. GH therapy for other bone disorders not associated with primary GHD needs further study but may well be beneficial because of its positive effects on the bone remodelling cycle. Copyright 2003 S. Karger AG, Basel

  5. Autodecomposition of radiolabeled human growth hormone

    International Nuclear Information System (INIS)

    Baumann, G.; Amburn, K.

    1986-01-01

    Human growth hormone (hGH) was radiolabeled with 125 I, using a gentle lactoperoxidase technique. The stability and decomposition products of this tracer were studied by frequent periodic analysis by Sephadex G-100 chromatography on a long column. Monomeric 125 I-hGH showed an exponential decline, with a half-life of 61 days. The main radioactive degradation product was iodide, which appeared with a fractional appearance rate of 0.01136 per day. Secondary degradation products were a series of radioactive oligomers of hGH, which appeared with an overall fractional rate of 0.00525 per day. The kinetic data obtained should provide guidelines for the shelf-life and repurification schedule of radioiodinated polypeptides

  6. Role of the GH/IGF-1 axis in lifespan and healthspan: lessons from animal models.

    Science.gov (United States)

    Berryman, Darlene E; Christiansen, Jens Sandahl; Johannsson, Gudmundur; Thorner, Michael O; Kopchick, John J

    2008-12-01

    Animal models are fundamentally important in our quest to understand the genetic, epigenetic, and environmental factors that contribute to human aging. In comparison to humans, relatively short-lived mammals are useful models as they allow for rapid assessment of both genetic manipulation and environmental intervention as related to longevity. These models also allow for the study of clinically relevant pathologies as a function of aging. Data associated with more distant species offers additional insight and critical consideration of the basic physiological processes and molecular mechanisms that influence lifespan. Consistently, two interventions, caloric restriction and repression of the growth hormone (GH)/insulin-like growth factor-1/insulin axis, have been shown to increase lifespan in both invertebrates and vertebrate animal model systems. Caloric restriction (CR) is a nutrition intervention that robustly extends lifespan whether it is started early or later in life. Likewise, genes involved in the GH/IGF-1 signaling pathways can lengthen lifespan in vertebrates and invertebrates, implying evolutionary conservation of the molecular mechanisms. Specifically, insulin and insulin-like growth factor-1 (IGF-1)-like signaling and its downstream intracellular signaling molecules have been shown to be associated with lifespan in fruit flies and nematodes. More recently, mammalian models with reduced growth hormone (GH) and/or IGF-1 signaling have also been shown to have extended lifespans as compared to control siblings. Importantly, this research has also shown that these genetic alterations can keep the animals healthy and disease-free for longer periods and can alleviate specific age-related pathologies similar to what is observed for CR individuals. Thus, these mutations may not only extend lifespan but may also improve healthspan, the general health and quality of life of an organism as it ages. In this review, we will provide an overview of how the

  7. Small-scale extraction and radioiodination of human hormones for the substitution of imported radioimmunoassay reagents

    International Nuclear Information System (INIS)

    Gimbo, E.K.; Ribela, M.T.C.P.; Borghi, V.C.; Schwarz, I.; Morganti, L.; Araujo, E.A.; Bartolini, P.

    1988-01-01

    The methods for national production of radioimmunoassay reagents to substitute imported kits of: highly purified unlabelled hormones for radioiodination; 125 I-labelled hormones; and specific high titre antisera are presented. The extraction and purification of human growth hormone (hGH) and human luteinizing hormone (hGH) were done from human pituitaries. The 125 I-labelled hormones are obtained by stoichiometric methods. The 125 I-hGH, 125 I-hLH, I-hTSH and 125 I- h calcitonin were prepared and tested in internal and external quality control, in comparison with imported products. The parameters such as: maximum binding to specific antiserum (Bo), nonspecific binding (NSB), mean effective dose (ED 50), sensitivity and accuracy were evaluated. (M.C.K.) [pt

  8. CLINICAL AND HORMONAL MILIEU OF 9 PATIENTS WITH PRIMARY GROWTH HORMONE INSENSITIVITY SYNDROME AND THEIR RESPONSE TO IGF-I GENERATION TEST

    Directory of Open Access Journals (Sweden)

    M. Razzaghy-Azar

    2006-05-01

    Full Text Available Primary growth hormone insensitivity syndrome (GHIS is a rare entity which can be due to defects in growth hormone (GH receptor that is called type 1 Laron syndrome (T1LS or post receptor defects (type 2 Laron syndrome . The aim of study was determining the clinical and hormonal milieu of the patients with primary GHIS and their response to IGF-I (insulin like growth factor-I generation test (IGT. GH, IGF-I, IGF-II, IGF binding protein 1 and 3 (BP-1 and BP-3, GH binding protein (GHBP and anti-GH antibody were detected by ELISA and RIA methods. IGF-I and BP-3 were measured before and after IGT. Nine patients (8 males, 1 female (mean age ± SD, 6.4 ± 5 years with severe short stature and high GH level were studied. Height SDS was - 8.5 ± 2.6. In 7 patients GHBP was zero, IGF-I and BP-3 were low and did not increase after IGT, so they had T1LS. Two brothers did not show the hormonal milieu of GH receptor defect, and were called non Laron syndrome (NLS. Birth weight in patients with T1LS and NLS was 3.65 ± 0.2 Kg and 1.65 ± 0.2 Kg, respectively (P = 0.001. All of the patients had typical clinical feature of GH-deficiency, but nasal bridge depression and microphallus were not seen in NLS. GH treatment of NLS, normalized their growth velocity, but without catch up growth. In conclusion IGT can differentiate Laron syndrome from other types of short stature. GH and IGF-I of fetus have no role in intrauterine growth.

  9. A Child with Local Lipohypertrophy following Recombinant Human Growth Hormone Administration

    Directory of Open Access Journals (Sweden)

    Ilan J. N. Koppen

    2016-01-01

    Full Text Available Local lipohypertrophy due to recombinant human growth hormone (rhGH administration is a rare phenomenon. Here, we report a case of an 11-year-old girl who presented with a paraumbilical swelling, approximately one year after the start of rhGH treatment for short stature due to the presumed diagnosis of partial growth hormone insensitivity. Ultrasound imaging revealed an asymmetric distribution of subcutaneous fat tissue at the rhGH administration site, indicating local lipohypertrophy. After sparing her routine injection site and alternating other sites, the swelling disappeared within 6 months. Although the precise cause of local lipohypertrophy resulting from rhGH administration is still unclear, it might be related to the presumed diagnosis of partial growth hormone insensitivity.

  10. Pathophysiological implications of the chemical messengers; Implicaciones fisiopatologicas de los mensajeros quimicos

    Energy Technology Data Exchange (ETDEWEB)

    Blazquez Fernandez, E.

    2009-07-01

    To maintain a physical organization and a different composition of its surroundings environment, living beings use a great part of the energy that they produce. Vital processes require an elevated number of reactions which are regulated and integrated by chemical messengers. They use autocrine, paracrine, endocrine and synaptic signals through receptors of cell surface, nuclear or associated with ionic channels, enzymes, trim eric G proteins and to intracellular kinases. Through these mechanisms pheromones play an important role in the relationships between different individuals, and hormones are able to regulate the integrative functions of our organism. In the nervous system, neurotransmitters, neuromodulators, sensors and receptors between other messengers, play functions of great relevance, while growth factors stimulate cell proliferation and cytokines have many effects but the most important is the ones related with the control of the immflamatory process. Alterations of these messengers permit us a better understanding of the diseases and possibly of its treatments in a near future. Modifications of the expression of genes from the nuclear and mitochondrial genomes are responsible of monogenic, polygenic and mitochondrial diseases, while alterations in the activities of dopamine and serotonin neurotransmitters are related with schizophrenia, Parkinson disease and depression, respectively. Other example is the hyperthyroidism of the Graves-Bassedow disease due to the competitive interference of the LATS immunoglobulin with TSH at the level of the follicular cells producing thyroid hormones Twenty five years ago in the reviews on the mechanisms of insulin action, there was presentations in which the insulin receptor was located in the plasma membrane of the target cells while in the cytoplasm only a big interrogative was observed, that at present is replaced by chemical mediators cascades responsible of the multiple effects of insulin. This finding is similar

  11. Neurocognitive function in acromegaly after surgical resection of GH-secreting adenoma versus naïve acromegaly.

    Directory of Open Access Journals (Sweden)

    Juan Francisco Martín-Rodríguez

    Full Text Available Patients with active untreated acromegaly show mild to moderate neurocognitive disorders that are associated to chronic exposure to growth hormone (GH and insulin-like growth factor (IGF-I hypersecretion. However, it is unknown whether these disorders improve after controlling GH/IGF-I hypersecretion. The aim of this study was to compare neurocognitive functions of patients who successfully underwent GH-secreting adenoma transsphenoidal surgery (cured patients with patients with naive acromegaly. In addition, we wanted to determine the impact of different clinical and biochemical variables on neurocognitive status in patients with active disease and after long-term cure. A battery of six standardized neuropsychological tests assessed attention, memory and executive functioning. In addition, a quantitative electroencephalography with Low-Resolution Electromagnetic Tomography (LORETA solution was performed to obtain information about the neurophysiological state of the patients. Neurocognitive data was compared to that of a healthy control group. Multiple linear regression analysis was also conducted using clinical and hormonal parameters to obtain a set of independent predictors of neurocognitive state before and after cure. Both groups of patients scored significantly poorer than the healthy controls on memory tests, especially those assessing visual and verbal recall. Patients with cured acromegaly did not obtain better cognitive measures than naïve patients. Furthermore memory deficits were associated with decreased beta activity in left medial temporal cortex in both groups of patients. Regression analysis showed longer duration of untreated acromegaly was associated with more severe neurocognitive complications, regardless of the diagnostic group, whereas GH levels at the time of assessment was related to neurocognitive outcome only in naïve patients. Longer duration of post-operative biochemical remission of acromegaly was associated with

  12. Neurocognitive Function in Acromegaly after Surgical Resection of GH-Secreting Adenoma versus Naïve Acromegaly

    Science.gov (United States)

    Martín-Rodríguez, Juan Francisco; Madrazo-Atutxa, Ainara; Venegas-Moreno, Eva; Benito-López, Pedro; Gálvez, María Ángeles; Cano, David A.; Tinahones, Francisco J.; Torres-Vela, Elena; Soto-Moreno, Alfonso; Leal-Cerro, Alfonso

    2013-01-01

    Patients with active untreated acromegaly show mild to moderate neurocognitive disorders that are associated to chronic exposure to growth hormone (GH) and insulin-like growth factor (IGF-I) hypersecretion. However, it is unknown whether these disorders improve after controlling GH/IGF-I hypersecretion. The aim of this study was to compare neurocognitive functions of patients who successfully underwent GH-secreting adenoma transsphenoidal surgery (cured patients) with patients with naive acromegaly. In addition, we wanted to determine the impact of different clinical and biochemical variables on neurocognitive status in patients with active disease and after long-term cure. A battery of six standardized neuropsychological tests assessed attention, memory and executive functioning. In addition, a quantitative electroencephalography with Low-Resolution Electromagnetic Tomography (LORETA) solution was performed to obtain information about the neurophysiological state of the patients. Neurocognitive data was compared to that of a healthy control group. Multiple linear regression analysis was also conducted using clinical and hormonal parameters to obtain a set of independent predictors of neurocognitive state before and after cure. Both groups of patients scored significantly poorer than the healthy controls on memory tests, especially those assessing visual and verbal recall. Patients with cured acromegaly did not obtain better cognitive measures than naïve patients. Furthermore memory deficits were associated with decreased beta activity in left medial temporal cortex in both groups of patients. Regression analysis showed longer duration of untreated acromegaly was associated with more severe neurocognitive complications, regardless of the diagnostic group, whereas GH levels at the time of assessment was related to neurocognitive outcome only in naïve patients. Longer duration of post-operative biochemical remission of acromegaly was associated with better

  13. Optimizing Patient Management and Adherence for Children Receiving Growth Hormone.

    Science.gov (United States)

    Acerini, Carlo L; Wac, Katarzyna; Bang, Peter; Lehwalder, Dagmar

    2017-01-01

    Poor adherence with growth hormone (GH) therapy has been associated with worse clinical outcomes, which in children relates specifically to their linear growth and loss of quality of life. The "360° GH in Europe" meeting, held in Lisbon, Portugal, in June 2016 and funded by Merck KGaA (Germany), examined many aspects of GH diseases. The three sessions, entitled " Short Stature Diagnosis and Referral ," " Optimizing Patient Management ," and " Managing Transition ," each benefited from three guest speaker presentations, followed by an open discussion and are reported as a manuscript, authored by the speakers. Reported here is a summary of the proceedings of the second session, which reviewed the determinants of GH therapy response, factors affecting GH therapy adherence and the development of innovative technologies to improve GH treatment in children. Response to GH therapy varies widely, particularly in regard to the underlying diagnosis, although there is little consensus on the definition of a poor response. If the growth response is seen to be less than expected, the possible reasons should be discussed with patients and their parents, including compliance with the therapy regimen. Understanding and addressing the multiple factors that influence adherence, in order to optimize GH therapy, requires a multi-disciplinary approach. Because therapy continues over many years, various healthcare professionals will be involved at different periods of the patient's journey. The role of the injection device for GH therapy, frequent monitoring of response, and patient support are all important for maintaining adherence. New injection devices are incorporating electronic technologies for automated monitoring and recording of clinically relevant information on injections. Study results are indicating that such devices can at least maintain GH adherence; however, acceptance of novel devices needs to be assessed and there remains an on-going need for innovations.

  14. Optimizing Patient Management and Adherence for Children Receiving Growth Hormone

    Directory of Open Access Journals (Sweden)

    Carlo L. Acerini

    2017-11-01

    Full Text Available Poor adherence with growth hormone (GH therapy has been associated with worse clinical outcomes, which in children relates specifically to their linear growth and loss of quality of life. The “360° GH in Europe” meeting, held in Lisbon, Portugal, in June 2016 and funded by Merck KGaA (Germany, examined many aspects of GH diseases. The three sessions, entitled “Short Stature Diagnosis and Referral,” “Optimizing Patient Management,” and “Managing Transition,” each benefited from three guest speaker presentations, followed by an open discussion and are reported as a manuscript, authored by the speakers. Reported here is a summary of the proceedings of the second session, which reviewed the determinants of GH therapy response, factors affecting GH therapy adherence and the development of innovative technologies to improve GH treatment in children. Response to GH therapy varies widely, particularly in regard to the underlying diagnosis, although there is little consensus on the definition of a poor response. If the growth response is seen to be less than expected, the possible reasons should be discussed with patients and their parents, including compliance with the therapy regimen. Understanding and addressing the multiple factors that influence adherence, in order to optimize GH therapy, requires a multi-disciplinary approach. Because therapy continues over many years, various healthcare professionals will be involved at different periods of the patient’s journey. The role of the injection device for GH therapy, frequent monitoring of response, and patient support are all important for maintaining adherence. New injection devices are incorporating electronic technologies for automated monitoring and recording of clinically relevant information on injections. Study results are indicating that such devices can at least maintain GH adherence; however, acceptance of novel devices needs to be assessed and there remains an on

  15. USE OF MOLECULAR BIOLOGICAL TECHNIQUES TO EVALUATE EFFECT OF ENDOGENOUS HORMONES AND A XENOBIOTIC PESTICIDE ON GROWTH OF SHEEPSHEAD MINNOW

    Science.gov (United States)

    We have developed a teleost model to screen physiological effects of endocrine disrupting chemicals (EDCs) on somatic growth. Growth is largely controlled by the endocrine system via the growth-hormone releasing hormone (GRF) - growth hormone (GH) - insulin-like growth factor (IG...

  16. GH Therapy and first final height data in Noonan-like syndrome with loose anagen hair (Mazzanti syndrome).

    Science.gov (United States)

    Mazzanti, Laura; Tamburrino, Federica; Scarano, Emanuela; Perri, Annamaria; Vestrucci, Benedetta; Guidetti, Monica; Rossi, Cesare; Tartaglia, Marco

    2013-11-01

    Noonan-like syndrome with loose anagen hair (NS/LAH or Mazzanti Syndrome) is caused by a single missense mutation in SHOC2 promoting tN-myristoylation of the encoded protein. Cardinal features include facial features resembling NS, short stature often associated with proven growth hormone deficiency (GHD), typical ectodermal anomalies, and distinctive behavior. Overall, the clinical features are more severe than those generally observed in NS, even though the phenotype improves with age. We report on growth and pubertal trend in seven patients heterozygous for a mutated SHOC2 allele, treated with long-term GH-therapy, and final height (FH) in three of them. They were approximately -3 SDS below the Italian general population standards, they had very low IGF1 levels at baseline and GHD at pharmacological tests. All patients were treated with GH (0.035 mg/kg/day) for a mean period of 8.49 ± 5.72 years. After the 1st year of GH-therapy, IGF1 level and height velocity had increased. Three of 7 patients reached the FH (-2.34 ± 0.12 SDS) at 18.25 ± 0.73 years, after GH administration for 12.39 ± 2.12 years. Pubertal development was variable, showing a prolonged and delayed puberty or rapid pubertal progression that could impair the FH. Overall, our data in this small cohort suggest that NS/LAH patients benefit from long-term GH-therapy, although they do not show the characteristic catch-up growth of isolated GHD. While the observed growth and pubertal behavior is consistent with a dysfunction of the hypothalamic-pituitary-gonadal axis, the functional link between SHOC2 and the GH/IGF signaling pathways remains to be clarified. © 2013 Wiley Periodicals, Inc.

  17. The Impact of Growth Hormone Therapy on the Apoptosis Assessment in CD34+ Hematopoietic Cells from Children with Growth Hormone Deficiency

    Directory of Open Access Journals (Sweden)

    Miłosz Piotr Kawa

    2017-01-01

    Full Text Available Growth hormone (GH modulates hematopoietic cell homeostasis and is associated with apoptosis control, but with limited mechanistic insights. Aim of the study was to determine whether GH therapeutic supplementation (GH-TS could affect apoptosis of CD34+ cells enriched in hematopoietic progenitor cells of GH deficient (GHD children. CD34+ cells from peripheral blood of 40 GHD children were collected before and in 3rd and 6th month of GH-TS and compared to 60 controls adjusted for bone age, sex, and pubertal development. Next, apoptosis assessment via different molecular techniques was performed. Finally, to comprehensively characterize apoptosis process, global gene expression profile was determined using genome-wide RNA microarray technology. Results showed that GH-TS significantly reduced spontaneous apoptosis in CD34+ cells (p < 0.01 and results obtained using different methods to detect early and late apoptosis in analyzed cells population were consistent. GH-TS was also associated with significant downregulation of several members of TNF-alpha superfamily and other genes associated with apoptosis and stress response. Moreover, the significant overexpression of cyto-protective and cell cycle-associated genes was detected. These findings suggest that recombinant human GH has a direct anti-apoptotic activity in hematopoietic CD34+ cells derived from GHD subjects in course of GH-TS.

  18. Galanin does not affect the growth hormone-releasing hormone-stimulated growth hormone secretion in patients with hyperthyroidism.

    Science.gov (United States)

    Giustina, A; Bussi, A R; Legati, F; Bossoni, S; Licini, M; Schettino, M; Zuccato, F; Wehrenberg, W B

    1992-12-01

    Patients with hyperthyroidism have reduced spontaneous and stimulated growth hormone (GH) secretion. The aim of our study was to evaluate the effects of galanin, a novel neuropeptide which stimulates GH secretion in man, on the GH response to GHRH in patients with hyperthyroidism. Eight untreated hyperthyroid patients with Graves' disease (6F, 2M, aged 25-50 years) and six healthy volunteers (3F, 3M, aged 27-76 years) underwent from -10 to 30 min in random order: (i) porcine galanin, iv, 500 micrograms in 100 ml saline; or (ii) saline, iv, 100 ml. A bolus of human GHRH(1-29)NH2, 100 micrograms, was injected iv at 0 min. Hyperthyroid patients showed blunted GH peaks after GHRH+saline (10.2 +/- 2.5 micrograms/l) compared to normal subjects (20.7 +/- 4.8 micrograms/l, p hyperthyroid subjects (12.5 +/- 3 micrograms/l) compared to normal subjects (43.8 +/- 6 micrograms/l, p hyperthyroidism suggests that hyperthyroxinemia may either increase the somatostatin release by the hypothalamus or directly affect the pituitary GH secretory capacity.

  19. McCune-Albright syndrome: growth hormone and prolactin hypersecretion.

    Science.gov (United States)

    Christoforidis, Athanasios; Maniadaki, Ilianna; Stanhope, Richard

    2006-05-01

    McCune-Albright syndrome (MAS) has a special interest for endocrinologists as its pathogenesis results in hypersecretion of hormones in peripheral endocrine tissues. This can be expressed as precocious puberty, mainly in girls, primary hyperthyroidism, growth hormone (GH) and/or prolactin excess, hyperparathyroidism and hypercortisolism. The incidence of GH excess among patients with MAS has been assessed as up to 21%. The pathogenesis of GH hypersecretion in MAS is not completely understood, whereas it seems to be different from the aetiology of acromegaly/gigantism in non-MAS patients. The clinical expression of GH excess can be masked because of precocious puberty or craniofacial fibrous dysplasia, indicating the necessity for screening. Medical treatment is usually the only option in MAS patients with GH excess, as transsphenoidal surgery is usually restricted due to massive thickening of the skull base, whereas radiotherapy is contraindicated due to probable higher predisposition to sarcomatous transformation. The use of bromocriptine, cabergoline and octreotide, or the combination of these, has shown variable results, whereas pegvisomant, a GH receptor antagonist, is a new promising option, although not yet used in patients with MAS.

  20. Pituitary tumour causing gigantism. Morphology and in vitro hormone secretion.

    Science.gov (United States)

    Anniko, M; Ritzén, E M

    1986-01-01

    True gigantism with overproduction of growth hormone (GH) and prolactin (PRL) was diagnosed in a 13-year-old boy. The clinical history indicated that the tumour had caused an oversecretion of GH since the age of 4-5 years. At diagnosis, the sella turcica was markedly enlarged. No infiltrative growth was noted at surgery. Endocrine investigations showed elevated GH and PRL secretion. Light and electron microscopy of tumour tissue revealed densely packed pleomorphic cells of both GH and PRL type. In addition, oncocyte-like cells were observed. Organ culture of pieces of tumour tissue demonstrated continued secretion of GH and PRL into the medium for more than 5 days in vitro. Addition of bromocriptine to the medium caused a rapid decline in PRL secretion while GH secretion remained the same. X-ray irradiation in vitro also caused a decrease in PRL secretion. These effects of bromocriptine and X-ray on hormone secretion in vitro mirrored the corresponding effect of treatment, when the patient showed signs of tumour recurrence after pituitary surgery. It is concluded that also in childhood, the in vitro response of tumour tissue to various treatments may be explored as a possible way to predict the efficacy of pharmacological or irradiation treatment of pituitary tumours.

  1. Investigation of the immunological and receptor activity of human growth hormone in patients with acromegaly

    International Nuclear Information System (INIS)

    Dietz, A.

    1982-01-01

    Human growth hormone (hGH) was measured by means of the radioimmunoassay (RIA) and the radioreceptor assay (RRA). The receptors were liver plasma membranes (LPM) of pregnant rabbits. In the RIA, no cross-reaction was found with hPRL, whereas in the RRA the cross-reaction was 3 p.c. The Scatchard analysis revealed two binding sites for hGH at the receptor. Pre-treatment with hGH and Cortisol brought about an enhanced affinity without change of the specific bonding, whereas pre-treatment with bromocriptin showed no significant effect. Hypophyseal hGH was separated by means of gel chromatography into big-big and big-little hGH and a reduced receptor activity of the higher molecular hGH fraction was shown. The Scatchard analysis indicated a more unspecific bonding characteristic of the big hGH. Stimulation of hGH secretion by insulin hypoglycemia provoked an overproportional increase in big hGH in healthy persons, whereas in patients with acromegaly the secretion of little hGH was enhanced. The suppression of hGH secretion by long-term bromocriptin treatment led to a significant rise of the RIA/RRA quotient in patients with post-operative florid acromegaly. Acute administration of BC was shown to induce a stronger hGH drop in the RRA of responders than in their RIA, as compared to non-responders. By chromatographic separation it was found that in responders the secretion of little hGH is selectively inhibited, but no in non-responders. (orig.) [de

  2. Diseases associated with growth hormone-releasing hormone receptor (GHRHR) mutations.

    Science.gov (United States)

    Martari, Marco; Salvatori, Roberto

    2009-01-01

    The growth hormone (GH)-releasing hormone (GHRH) receptor (GHRHR) belongs to the G protein-coupled receptors family. It is expressed almost exclusively in the anterior pituitary, where it is necessary for somatotroph cells proliferation and for GH synthesis and secretion. Mutations in the human GHRHR gene (GHRHR) can impair ligand binding and signal transduction, and have been estimated to cause about 10% of autosomal recessive familial isolated growth hormone deficiency (IGHD). Mutations reported to date include five splice donor site mutations, two microdeletions, two nonsense mutations, seven missense mutations, and one mutation in the promoter. These mutations have an autosomal recessive mode of inheritance, and heterozygous individuals do not show signs of IGHD, although the presence of an intermediate phenotype has been hypothesized. Conversely, patients with biallelic mutations have low serum insulin-like growth factor-1 and GH levels (with absent or reduced GH response to exogenous stimuli), resulting--if not treated--in proportionate dwarfism. This chapter reviews the biology of the GHRHR, the mutations that affect its gene and their effects in homozygous and heterozygous individuals. Copyright © 2009 Elsevier Inc. All rights reserved.

  3. Alström syndrome is associated with short stature and reduced GH reserve.

    Science.gov (United States)

    Romano, S; Maffei, P; Bettini, V; Milan, G; Favaretto, F; Gardiman, M; Marshall, J D; Greggio, N A; Pozzan, G B; Collin, G B; Naggert, J K; Bronson, R; Vettor, R

    2013-10-01

    Alström syndrome (ALMS) is a rare autosomal recessive monogenic disease included in an emerging class of genetic disorders called 'ciliopathies' and is likely to impact the central nervous system as well as metabolic and endocrine function. Individuals with ALMS present clinical features resembling a growth hormone deficiency (GHD) condition, but thus far no study has specifically investigated this aspect in a large population. Twenty-three patients with ALMS (age, 1-52 years; 11 males, 12 females) were evaluated for anthropometric parameters (growth charts and standard deviation score (SDS) of height, weight, BMI), GH secretion by growth hormone-releasing hormone + arginine test (GHRH-arg), bone age, and hypothalamic-pituitary magnetic resonance imaging (MRI). A group of 17 healthy subjects served as controls in the GH secretion study. Longitudinal retrospective and prospective data were utilized. The length-for-age measurements from birth to 36 months showed normal growth with most values falling within -0·67 SDS to +1·28 SDS. A progressive decrease in stature-for-age was observed after 10 years of age, with a low final height in almost all ALMS subjects (>16-20 years; mean SDS, -2·22 ± 1·16). The subset of 12 patients with ALMS tested for GHRH-arg showed a significantly shorter stature than age-matched controls (154·7 ± 10·6 cm vs 162·9 ± 4·8 cm, P = 0·009) and a mild increase in BMI (Kg/m(2) ) (27·8 ± 4·8 vs 24·1 ± 2·5, P = 0·007). Peak GH after GHRH-arg was significantly lower in patients with ALMS in comparison with controls (11·9 ± 6·9 μg/l vs 86·1 ± 33·2 μg/l, P short stature reported in ALMS may be at least partially influenced by impairment of GH secretion. © 2013 John Wiley & Sons Ltd.

  4. Increased serum and bone matrix levels of transforming growth factor {beta}1 in patients with GH deficiency in response to GH treatment

    DEFF Research Database (Denmark)

    Ueland, Thor; Lekva, Tove; Otterdal, Kari

    2011-01-01

    Patients with adult onset GH deficiency (aoGHD) have secondary osteoporosis, which is reversed by long-term GH substitution. Transforming growth factor β1 (TGFβ1 or TGFB1) is abundant in bone tissue and could mediate some effects of GH/IGFs on bone. We investigated its regulation by GH/IGF1 in vivo...

  5. MESSENGER MERCURY RSS/MLA LEVEL 5 DERIVED DATA V1.0

    Data.gov (United States)

    National Aeronautics and Space Administration — This data set contains archival results from radio science investigations conducted during the MESSENGER mission. Radio measurements were made using the MESSENGER...

  6. Growth Hormone Receptor Mutations Related to Individual Dwarfism

    Science.gov (United States)

    Li, Charles; Zhang, Xiquan

    2018-01-01

    Growth hormone (GH) promotes body growth by binding with two GH receptors (GHRs) at the cell surface. GHRs interact with Janus kinase, signal transducers, and transcription activators to stimulate metabolic effects and insulin-like growth factor (IGF) synthesis. However, process dysfunctions in the GH–GHR–IGF-1 axis cause animal dwarfism. If, during the GH process, GHR is not successfully recognized and/or bound, or GHR fails to transmit the GH signal to IGF-1, the GH dysfunction occurs. The goal of this review was to focus on the GHR mutations that lead to failures in the GH–GHR–IGF-1 signal transaction process in the dwarf phenotype. Until now, more than 90 GHR mutations relevant to human short stature (Laron syndrome and idiopathic short stature), including deletions, missense, nonsense, frameshift, and splice site mutations, and four GHR defects associated with chicken dwarfism, have been described. Among the 93 identified mutations of human GHR, 68 occur extracellularly, 13 occur in GHR introns, 10 occur intracellularly, and two occur in the transmembrane. These mutations interfere with the interaction between GH and GHRs, GHR dimerization, downstream signaling, and the expression of GHR. These mutations cause aberrant functioning in the GH-GHR-IGF-1 axis, resulting in defects in the number and diameter of muscle fibers as well as bone development. PMID:29748515

  7. Growth Hormone Receptor Mutations Related to Individual Dwarfism

    Directory of Open Access Journals (Sweden)

    Shudai Lin

    2018-05-01

    Full Text Available Growth hormone (GH promotes body growth by binding with two GH receptors (GHRs at the cell surface. GHRs interact with Janus kinase, signal transducers, and transcription activators to stimulate metabolic effects and insulin‐like growth factor (IGF synthesis. However, process dysfunctions in the GH–GHR–IGF-1 axis cause animal dwarfism. If, during the GH process, GHR is not successfully recognized and/or bound, or GHR fails to transmit the GH signal to IGF-1, the GH dysfunction occurs. The goal of this review was to focus on the GHR mutations that lead to failures in the GH–GHR–IGF-1 signal transaction process in the dwarf phenotype. Until now, more than 90 GHR mutations relevant to human short stature (Laron syndrome and idiopathic short stature, including deletions, missense, nonsense, frameshift, and splice site mutations, and four GHR defects associated with chicken dwarfism, have been described. Among the 93 identified mutations of human GHR, 68 occur extracellularly, 13 occur in GHR introns, 10 occur intracellularly, and two occur in the transmembrane. These mutations interfere with the interaction between GH and GHRs, GHR dimerization, downstream signaling, and the expression of GHR. These mutations cause aberrant functioning in the GH-GHR-IGF-1 axis, resulting in defects in the number and diameter of muscle fibers as well as bone development.

  8. Growth hormone treatment in Turner's syndrome: A real world experience

    Directory of Open Access Journals (Sweden)

    Vijay Sheker Reddy Danda

    2017-01-01

    Full Text Available Objective: Short stature is a universal clinical feature of Turner's syndrome (TS. Growth failure begins in fetal life, and adults with TS are on an average 20 cm shorter than the normal female population. Since there is a paucity of data from India regarding the effect of growth hormone (GH on TS patients, we retrospectively analyzed the data of TS patients who are on GH treatment. Methods: This hospital-based observational retrospective study was conducted in a tertiary care hospital of Hyderabad. The data such as height, weight, and bone age of 16 patients who are diagnosed with TS on GH therapy for at least 6 months were included in the study. All the patients were treated with human recombinant GH at the dose of 0.3 mg/kg/week administered as daily subcutaneous injections. Results: The mean age at diagnosis was 12.7 years. The mean height at the start of GH therapy was 1.26 m, and mean height standard deviation score (HSDS was-0.61 when compared to Turner's specific reference data. With a mean duration of GH therapy of 25 months, the mean height at the end of therapy was 1.37 m and the mean height as per HSDS was + 0.37 resulting in a mean height gain of + 0.99 HSDS. Conclusion: Our observation shows that girls with TS benefit from early diagnosis and initiation of treatment with GH.

  9. Growth hormone, interferon-gamma, and leukemia inhibitory factor utilize insulin receptor substrate-2 in intracellular signaling

    DEFF Research Database (Denmark)

    Argetsinger, L S; Norstedt, G; Billestrup, Nils

    1996-01-01

    In this report, we demonstrate that insulin receptor substrate-2 (IRS-2) is tyrosyl-phosphorylated following stimulation of 3T3-F442A fibroblasts with growth hormone (GH), leukemia inhibitory factor and interferon-gamma. In response to GH and leukemia inhibitory factor, IRS-2 is immediately...... for GH is further demonstrated by the finding that GH stimulates association of IRS-2 with the 85-kDa regulatory subunit of phosphatidylinositol 3'-kinase and with the protein-tyrosine phosphatase SHP2. These results are consistent with the possibility that IRS-2 is a downstream signaling partner...

  10. Probing the Conformational and Functional Consequences of Disulfide Bond Engineering in Growth Hormone by Hydrogen-Deuterium Exchange Mass Spectrometry Coupled to Electron Transfer Dissociation

    DEFF Research Database (Denmark)

    Seger, Signe T; Breinholt, Jens; Faber, Johan H

    2015-01-01

    Human growth hormone (hGH), and its receptor interaction, is essential for cell growth. To stabilize a flexible loop between helices 3 and 4, while retaining affinity for the hGH receptor, we have engineered a new hGH variant (Q84C/Y143C). Here, we employ hydrogen-deuterium exchange mass spectrom......Human growth hormone (hGH), and its receptor interaction, is essential for cell growth. To stabilize a flexible loop between helices 3 and 4, while retaining affinity for the hGH receptor, we have engineered a new hGH variant (Q84C/Y143C). Here, we employ hydrogen-deuterium exchange mass...

  11. Growth hormone and adipose tissue: beyond the adipocyte.

    Science.gov (United States)

    Berryman, Darlene E; List, Edward O; Sackmann-Sala, Lucila; Lubbers, Ellen; Munn, Rachel; Kopchick, John J

    2011-06-01

    The last two decades have seen resurgence in research focused on adipose tissue. In part, the enhanced interest stems from an alarming increase in obesity rates worldwide. However, an understanding that this once simple tissue is significantly more intricate and interactive than previously realized has fostered additional attention. While few would argue that growth hormone (GH) radically alters fat mass, newer findings revealing the complexity of adipose tissue requires that GH's influence on this tissue be reexamined. Therefore, the objective of this review is to describe the more recent understanding of adipose tissue and to summarize our current knowledge of how GH may influence and contribute to these newer complexities of this tissue with special focus on the available data from mice with altered GH action. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Role of the new growth hormone-releasing secretagogues in the diagnosis of some hypothalamopituitary pathologies.

    Science.gov (United States)

    Casanueva, F F; Micic, D; Pombo, M; Leal, A; Bokser, L; Zugaza, J L; Dieguez, C

    1996-08-01

    Growth hormone (GH)-releasing hormone (GHRH) and somatostatin have a dominant role in regulating GH secretion. However, results of studies using the new class of GH secretogogues, particularly GHRP-6, indicate that there may also be other, as yet undefined, hypothalamic mechanisms involved. Studies in adults with hypothalamopituitary disconnection (functional pituitary stalk transection), show GHRP-6-mediated GH release to be completely blocked, indicating a main action at the hypothalamic rather than the pituitary level. The synergistic effect of GHRH plus GHRP-6 administration on GH release seen in normal adults (and virtually unaffected by age, obesity, or sex) is also absent in these patients, providing further support for this conclusion. Studies of the effects of GHRP-6 in children with GH deficiency due to perinatal pituitary stalk transection have produced similar findings. It is suggested that the combined GHRH plus GHRH-6 test should be a promising tool for diagnosing GH deficiency states in both children and adults, and may identify a subgroup of patients with GH deficiency caused by interruption of the hypothalamopituitary connection.

  13. Vitellogenin messenger rna in rooster liver

    NARCIS (Netherlands)

    Bos, Ebo Sijbren

    1975-01-01

    The investigations described in this thesis were carried out as a part of the studies in our laboratory on the control of gene expression in animal cells. They represent an example of the hormonal regulation of protein synthesis, viz. the induction of vitellogenin synthesis in rooster liver by the

  14. Calcium in Mercury's Exosphere: Modeling MESSENGER Data

    Science.gov (United States)

    Burger, Matthew H.; Killen, Rosemary M.; McClintock, William E.; Merkel, Aimee; Vervack, Ronald J.; Sarantos, Menelaos; Sprague, Ann L.

    2011-01-01

    Mercury is surrounded by a surface-bounded exosphere comprised of atomic species including hydrogen, sodium, potassium, calcium, magnesium, and likely oxygen. Because it is collisionless. the exosphere's composition represents a balance of the active source and loss processes. The Mercury Atmospheric and Surface Composition Spectrometer (MASCS) on the MErcury Surface. Space ENvironment. GEochemistry. and Ranging (MESSENGER) spacecraft has made high spatial-resolution observations of sodium, calcium, and magnesium near Mercury's surface and in the extended, anti-sunward direction. The most striking feature of these data has been the substantial differences in the spatial distribution of each species, Our modeling demonstrates that these differences cannot be due to post-ejection dynamics such as differences in photo-ionization rate and radiation pressure. but instead point to differences in the source mechanisms and regions on the surface from which each is ejected. The observations of calcium have revealed a strong dawn/dusk asymmetry. with the abundance over the dawn hemisphere significantly greater than over the dusk. To understand this asymmetry, we use a Monte Carlo model of Mercury's exosphere that we developed to track the motions of exospheric neutrals under the influence of gravity and radiation pressure. Ca atoms can be ejected directly from the surface or produced in a molecular exosphere (e.g., one consisting of CaO). Particles are removed from the system if they stick to the surface or escape from the model region of interest (within 15 Mercury radii). Photoionization reduces the final weighting given to each particle when simulating the Ca radiance. Preliminary results suggest a high temperature ( I-2x 10(exp 4) K) source of atomic Ca concentrated over the dawn hemisphere. The high temperature is consistent with the dissociation of CaO in a near-surface exosphere with scale height <= 100 km, which imparts 2 eV to the freshly produced Ca atom. This

  15. Experimental Modification of Rat Pituitary Growth Hormone Cell Function During and After Spaceflight

    Science.gov (United States)

    Hymer, W. C.; Salada, T.; Nye, P.; Grossman, E. J.; Lane, P. K.; Grindeland, R. E.

    1996-01-01

    Space-flown rats show a number of flight-induced changes in the structure and function of pituitary Growth Hormone (GH) cells after in vitro postflight testing. To evaluate the possible effects of microgravity on GH cells themselves, freshly dispersed rat anterior pituitary gland cells were seeded into vials containing serum +/- 1 micron HydroCortisone (HC) before flight. Five different cell preparations were used: the entire mixed-cell population of various hormone-producing cell types, cells of density less than 1.071 g/sq cm (band 1), cells of density greater than 1.071 g/sq cm (band 2), and cells prepared from either the dorsal or ventral part of the gland. Relative to ground control samples, bioactive GH released from dense cells during flight was reduced in HC-free medium but was increased in HC-containing medium. Band I and mixed cells usually showed opposite HC-dependent responses. Release of bioactive GH from ventral flight cells was lower; postflight responses to GH-releasing hormone challenge were reduced, and the cytoplasmic area occupied by GH in the dense cells was greater. Collectively, the data show that the chemistry and cellular makeup of the culture system modifies the response of GH cells to microgravity. As such, these cells offer a system to identify gravisensing mechanisms in secretory cells in future microgravity research.

  16. The Influence of Estrogens on the Biological and Therapeutic Actions of Growth Hormone in the Liver

    Directory of Open Access Journals (Sweden)

    Leandro Fernández-Pérez

    2012-07-01

    Full Text Available GH is main regulator of body growth and composition, somatic development, intermediate metabolism and gender-dependent dimorphism in mammals. The liver is a direct target of estrogens because it expresses estrogen receptors which are connected with development, lipid metabolism and insulin sensitivity, hepatic carcinogenesis, protection from drug-induced toxicity and fertility. In addition, estrogens can modulate GH actions in liver by acting centrally, regulating pituitary GH secretion, and, peripherally, by modulating GHR-JAK2-STAT5 signalling pathway. Therefore, the interactions of estrogens with GH actions in liver are biologically and clinically relevant because disruption of GH signaling may cause alterations of its endocrine, metabolic, and gender differentiated functions and it could be linked to dramatic impact in liver physiology during development as well as in adulthood. Finally, the interplay of estrogens with GH is relevant because physiological roles these hormones have in human, and the widespread exposition of estrogen or estrogen-related compounds in human. This review highlights the importance of these hormones in liver physiology as well as how estrogens modulate GH actions in liver which will help to improve the clinical use of these hormones.

  17. Study on GH receptors and PRL receptors on peripheral blood lymphocytes in patients of systemic lupus erythematosus

    International Nuclear Information System (INIS)

    Li Feng; Rao Junchang; Feng Shufang; Lu Yun; Deng Shouzhen

    2002-01-01

    Objective: To study the association of growth hormone (GH) and prolactin (PRL) and their receptors in patients with systemic lupus erythematosus. Methods: The authors measured serum PRL and GH level with radioimmunoassay (RIA) in 25 untreated patients of active SLE, 20 patients of inactive SLE and in 20 gender-age-paired control subjects. The authors also measured peripheral blood lymphocytes (PBMC) GH receptors (GHR) and PRL receptors (PRLR) with radioactive binding ligand assay (RLBA). Results: The specific binding (SB) ratio of PRLR was 6.7 ± 2.3%, the total binding ratio was 10.5 ± 4.6% in active patients of SLE. The SB of PRLR in active patients was higher than that of inactive patients (SB 2.5 ± 0.8%, TB 8.5 ± 4.3%) and that of 20 control subjects (SB 1.9 ± 1.2%, TB 9.3 ± 6.4%) (P 0.05). The serum GH and PRL level was also significantly increased in active patients of SLE (P<0.05). Conclusion: The increase of GHR and PRLR in the PBMCs of SLE was certainly associated with pathogenesis of SLE

  18. Low prevalence of hypopituitarism after subarachnoid haemorrhage using confirmatory testing and with BMI-specific GH cut-off levels.

    Science.gov (United States)

    Gardner, Chris J; Javadpour, Mohsen; Stoneley, Catherine; Purthuran, Mani; Biswas, Shubhabrata; Daousi, Christina; MacFarlane, Ian A; Cuthbertson, Daniel J

    2013-04-01

    Hypopituitarism following subarachnoid haemorrhage (SAH) has been reported to be a frequent occurrence. However, there is considerable heterogeneity between studies with differing patient populations and treatment modalities and most importantly employing differing endocrine protocols and (normal) reference ranges of GH. We aimed to examine prospectively a cohort of SAH survivors for development of hypopituitarism post-SAH using rigorous endocrine testing and compare GH response to glucagon stimulation with a cohort of healthy controls of a similar BMI. Sixty-four patients were investigated for evidence of hypopituitarism 3 months post-SAH with 50 patients tested again at 12 months. Glucagon stimulation testing (GST), with confirmation of deficiencies by GHRH/arginine testing for GH deficiency (GHD) and short synacthen testing for ACTH deficiency, was used. Basal testing of other hormonal axes was undertaken. Mean age of patients was 53±11.7 years and mean BMI was 27.5±5.7 kg/m(2). After confirmatory testing, the prevalence of hypopituitarism was 12% (GHD 10%, asymptomatic hypocortisolaemia 2%). There was no association between hypopituitarism and post-SAH vasospasm, presence of cerebral infarction, Fisher grade, or clinical grading at presentation. There was a significant correlation between BMI and peak GH to glucagon stimulation in both patients and controls. Identification of 'true' GHD after SAH requires confirmatory testing with an alternative stimulation test and application of BMI-specific cut-offs. Using such stringent criteria, we found a prevalence of hypopituitarism of 12% in our population.

  19. Clinical features of GH deficiency and effects of 3 years of GH replacement in adults with controlled Cushing's disease

    DEFF Research Database (Denmark)

    Höybye, Charlotte; Ragnarsson, Oskar; Jönsson, Peter J

    2010-01-01

    Patients in remission from Cushing's disease (CD) have many clinical features that are difficult to distinguish from those of concomitant GH deficiency (GHD). In this study, we evaluated the features of GHD in a large cohort of controlled CD patients, and assessed the effect of GH treatment....

  20. Growth hormone modulates hypothalamic inflammation in long-lived pituitary dwarf mice.

    Science.gov (United States)

    Sadagurski, Marianna; Landeryou, Taylor; Cady, Gillian; Kopchick, John J; List, Edward O; Berryman, Darlene E; Bartke, Andrzej; Miller, Richard A

    2015-12-01

    Mice in which the genes for growth hormone (GH) or GH receptor (GHR(-/-) ) are disrupted from conception are dwarfs, possess low levels of IGF-1 and insulin, have low rates of cancer and diabetes, and are extremely long-lived. Median longevity is also increased in mice with deletion of hypothalamic GH-releasing hormone (GHRH), which leads to isolated GH deficiency. The remarkable extension of longevity in hypopituitary Ames dwarf mice can be reversed by a 6-week course of GH injections started at the age of 2 weeks. Here, we demonstrate that mutations that interfere with GH production or response, in the Snell dwarf, Ames dwarf, or GHR(-/-) mice lead to reduced formation of both orexigenic agouti-related peptide (AgRP) and anorexigenic proopiomelanocortin (POMC) projections to the main hypothalamic projection areas: the arcuate nucleus (ARH), paraventricular nucleus (PVH), and dorsomedial nucleus (DMH). These mutations also reduce hypothalamic inflammation in 18-month-old mice. GH injections, between 2 and 8 weeks of age, reversed both effects in Ames dwarf mice. Disruption of GHR specifically in liver (LiGHRKO), a mutation that reduces circulating IGF-1 but does not lead to lifespan extension, had no effect on hypothalamic projections or inflammation, suggesting an effect of GH, rather than peripheral IGF-1, on hypothalamic development. Hypothalamic leptin signaling, as monitored by induction of pStat3, is not impaired by GHR deficiency. Together, these results suggest that early-life disruption of GH signaling produces long-term hypothalamic changes that may contribute to the longevity of GH-deficient and GH-resistant mice. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.