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Sample records for growth hormone resistance

  1. Resistance to growth hormone releasing hormone and gonadotropins in Albright's hereditary osteodystrophy.

    PubMed

    Mantovani, Giovanna; Spada, Anna

    2006-05-01

    Heterozygous inactivating mutations in the Gs alpha gene cause Albright's hereditary osteo-dystrophy (AHO). Consistent with the observation that only maternally inherited mutations lead to resistance to hormone action (pseudohypoparathyroidism type Ia [PHP-Ia), recent studies have provided evidence for a predominant maternal origin of Gs alpha transcripts in endocrine organs, such as thyroid, gonad and pituitary. Accordingly, patients with PHP-Ia display variable degrees of resistance to parathyroid hormone (PTH), thyroid stimulating hormone (TSH), gonadotropins and growth hormone (GH) releasing hormone (GHRH). Although the incidence and the clinical and biochemical characteristics of PTH and TSH resistance have been widely investigated and described, the cause and significance of the reproductive dysfunction in AHO is still poorly understood. The clinical finding of alterations of GH secretion in these patients was described for the first time only 2 years ago. The present report briefly reviews the literature focusing on the actual knowledge about these last two subjects.

  2. Growth hormone resistance exacerbates cholestasis-induced murine liver fibrosis

    PubMed Central

    Stiedl, Patricia; McMahon, Robert; Blaas, Leander; Stanek, Victoria; Svinka, Jasmin; Grabner, Beatrice; Zollner, Gernot; Kessler, Sonja M.; Claudel, Thierry; Müller, Mathias; Mikulits, Wolfgang; Bilban, Martin; Esterbauer, Harald; Eferl, Robert; Haybaeck, Johannes; Trauner, Michael; Casanova, Emilio

    2016-01-01

    Growth hormone (GH) resistance has been associated with liver cirrhosis in humans but its contribution to the disease remains controversial. In order to elucidate whether GH resistance plays a causal role in the establishment and development of liver fibrosis, or rather represents a major consequence thereof, we challenged mice lacking the Growth hormone receptor gene (Ghr-/-, a model for GH resistance) by crossing them with Mdr2 knockout mice (Mdr2-/-), a mouse model of inflammatory cholestasis and liver fibrosis. Ghr-/-;Mdr2-/- mice showed elevated serum markers associated with liver damage and cholestasis, extensive bile duct proliferation and increased collagen deposition relative to Mdr2 -/- mice, thus suggesting a more severe liver fibrosis phenotype. Additionally, Ghr-/-;Mdr2-/- mice had a pronounced down-regulation of hepato-protective genes Hnf6, Egfr and Igf-1, and significantly increased levels of ROS and apoptosis in hepatocytes, compared to control mice. Moreover, single knockout mice (Ghr-/-) fed with a diet containing 1% cholic acid displayed an increase in hepatocyte ROS production, hepatocyte apoptosis and bile infarcts compared to their wildtype littermates, indicating that loss of Ghr renders hepatocytes more susceptible to toxic bile acid accumulation. Surprisingly, and despite their severe fibrotic phenotype, Ghr-/-;Mdr2-/- mice displayed a significant decrease in tumour incidence compared to Mdr2-/- mice, indicating that loss of Ghr signaling may slow the progression from fibrosis/cirrhosis to cancer in the liver. Conclusion Our findings suggest that GH resistance dramatically exacerbates liver fibrosis in a mouse model of inflammatory cholestasis, therefore suggesting that GH resistance plays a causal role in the disease and provides a novel target for the development of liver fibrosis treatments. PMID:25179284

  3. Myogenic expression of an injectable protease-resistant growth hormone-releasing hormone augments long-term growth in pigs

    NASA Technical Reports Server (NTRS)

    Draghia-Akli, R.; Fiorotto, M. L.; Hill, L. A.; Malone, P. B.; Deaver, D. R.; Schwartz, R. J.

    1999-01-01

    Ectopic expression of a new serum protease-resistant porcine growth hormone-releasing hormone, directed by an injectable muscle-specific synthetic promoter plasmid vector (pSP-HV-GHRH), elicits growth in pigs. A single 10 mg intramuscular injection of pSP-HV-GHRH DNA followed by electroporation in three-week-old piglets elevated serum GHRH levels by twofold to fourfold, enhanced growth hormone secretion, and increased serum insulin-like growth factor-I by threefold to sixfold over control pigs. After 65 days the average body weight of the pigs injected with pSP-HV-GHRH was approximately 37% greater than the placebo-injected controls and resulted in a significant reduction in serum urea concentration, indicating a decrease in amino acid catabolism. Evaluation of body composition indicated a uniform increase in mass, with no organomegaly or associated pathology.

  4. Myogenic expression of an injectable protease-resistant growth hormone-releasing hormone augments long-term growth in pigs

    NASA Technical Reports Server (NTRS)

    Draghia-Akli, R.; Fiorotto, M. L.; Hill, L. A.; Malone, P. B.; Deaver, D. R.; Schwartz, R. J.

    1999-01-01

    Ectopic expression of a new serum protease-resistant porcine growth hormone-releasing hormone, directed by an injectable muscle-specific synthetic promoter plasmid vector (pSP-HV-GHRH), elicits growth in pigs. A single 10 mg intramuscular injection of pSP-HV-GHRH DNA followed by electroporation in three-week-old piglets elevated serum GHRH levels by twofold to fourfold, enhanced growth hormone secretion, and increased serum insulin-like growth factor-I by threefold to sixfold over control pigs. After 65 days the average body weight of the pigs injected with pSP-HV-GHRH was approximately 37% greater than the placebo-injected controls and resulted in a significant reduction in serum urea concentration, indicating a decrease in amino acid catabolism. Evaluation of body composition indicated a uniform increase in mass, with no organomegaly or associated pathology.

  5. ACSL4 promotes prostate cancer growth, invasion and hormonal resistance.

    PubMed

    Wu, Xinyu; Deng, Fangming; Li, Yirong; Daniels, Garrett; Du, Xinxin; Ren, Qinghu; Wang, Jinhua; Wang, Ling Hang; Yang, Yang; Zhang, Valerio; Zhang, David; Ye, Fei; Melamed, Jonathan; Monaco, Marie E; Lee, Peng

    2015-12-29

    Increases in fatty acid metabolism have been demonstrated to promote the growth and survival of a variety of cancers, including prostate cancer (PCa). Here, we examine the expression and function of the fatty acid activating enzyme, long-chain fatty acyl-CoA synthetase 4 (ACSL4), in PCa. Ectopic expression of ACSL4 in ACSL4-negative PCa cells increases proliferation, migration and invasion, while ablation of ACSL4 in PCa cells expressing endogenous ACSL4 reduces cell proliferation, migration and invasion. The cell proliferative effects were observed both in vitro, as well as in vivo. Immunohistochemical analysis of human PCa tissue samples indicated ACSL4 expression is increased in malignant cells compared with adjacent benign epithelial cells, and particularly increased in castration-resistant PCa (CRPC) when compared with hormone naive PCa. In cell lines co-expressing both ACSL4 and AR, proliferation was independent of exogenous androgens, suggesting that ACSL4 expression may lead to CRPC. In support for this hypothesis, ectopic ACSL4 expression induced resistance to treatment with Casodex, via decrease in apoptosis. Our studies further indicate that ACSL4 upregulates distinct pathway proteins including p-AKT, LSD1 and β-catenin. These results suggest ACSL4 could serve as a biomarker and potential therapeutic target for CRPC.

  6. Growth and development in a child with resistance to thyroid hormone and ectopic thyroid gland.

    PubMed

    Heather, Natasha; Hall, Kate; Neas, Katherine; Potter, Howard; Wiltshire, Esko

    2012-03-01

    Resistance to thyroid hormone is an uncommon problem, which has rarely been associated with thyroid dysgenesis. We report a case with both thyroid gland ectopy and resistance to thyroid hormone and, thus, a reduced capacity to produce and respond to thyroid hormone. The patient presented at 2 years of age with developmental delay, dysmorphic features, and elevation in both thyroxine and thyrotropin. We document her response to therapy with thyroxine, with particular regard to her growth and development. Persistent elevation of thyrotropin is commonly recognized during treatment of congenital hypothyroidism. Resistance to thyroid hormone may be an important additional diagnosis to consider in cases where thyrotropin remains persistently elevated.

  7. Growth Hormone

    MedlinePlus

    ... to help diagnose and monitor the treatment of acromegaly and gigantism . Growth hormone is essential for normal ... signs and symptoms of GH excess ( gigantism and acromegaly ). Suppression testing may be done when a pituitary ...

  8. Effect of growth hormone and resistance exercise on muscle growth in young men.

    PubMed

    Yarasheski, K E; Campbell, J A; Smith, K; Rennie, M J; Holloszy, J O; Bier, D M

    1992-03-01

    The purpose of this study was to determine whether growth hormone (GH) administration enhances the muscle anabolism associated with heavy-resistance exercise. Sixteen men (21-34 yr) were assigned randomly to a resistance training plus GH group (n = 7) or to a resistance training plus placebo group (n = 9). For 12 wk, both groups trained all major muscle groups in an identical fashion while receiving 40 micrograms recombinant human GH.kg-1.day-1 or placebo. Fat-free mass (FFM) and total body water increased (P less than 0.05) in both groups but more (P less than 0.01) in the GH recipients. Whole body protein synthesis rate increased more (P less than 0.03), and whole body protein balance was greater (P = 0.01) in the GH-treated group, but quadriceps muscle protein synthesis rate, torso and limb circumferences, and muscle strength did not increase more in the GH-treated group. In the young men studied, resistance exercise with or without GH resulted in similar increments in muscle size, strength, and muscle protein synthesis, indicating that 1) the larger increase in FFM with GH treatment was probably due to an increase in lean tissue other than skeletal muscle and 2) resistance training supplemented with GH did not further enhance muscle anabolism and function.

  9. Disease resistance or growth: the role of plant hormones in balancing immune responses and fitness costs

    PubMed Central

    Denancé, Nicolas; Sánchez-Vallet, Andrea; Goffner, Deborah; Molina, Antonio

    2013-01-01

    Plant growth and response to environmental cues are largely governed by phytohormones. The plant hormones ethylene, jasmonic acid, and salicylic acid (SA) play a central role in the regulation of plant immune responses. In addition, other plant hormones, such as auxins, abscisic acid (ABA), cytokinins, gibberellins, and brassinosteroids, that have been thoroughly described to regulate plant development and growth, have recently emerged as key regulators of plant immunity. Plant hormones interact in complex networks to balance the response to developmental and environmental cues and thus limiting defense-associated fitness costs. The molecular mechanisms that govern these hormonal networks are largely unknown. Moreover, hormone signaling pathways are targeted by pathogens to disturb and evade plant defense responses. In this review, we address novel insights on the regulatory roles of the ABA, SA, and auxin in plant resistance to pathogens and we describe the complex interactions among their signal transduction pathways. The strategies developed by pathogens to evade hormone-mediated defensive responses are also described. Based on these data we discuss how hormone signaling could be manipulated to improve the resistance of crops to pathogens. PMID:23745126

  10. Recovery responses of testosterone, growth hormone, and IGF-1 after resistance exercise.

    PubMed

    Kraemer, William J; Ratamess, Nicholas A; Nindl, Bradley C

    2017-03-01

    The complexity and redundancy of the endocrine pathways during recovery related to anabolic function in the body belie an oversimplistic approach to its study. The purpose of this review is to examine the role of resistance exercise (RE) on the recovery responses of three major anabolic hormones, testosterone, growth hormone(s), and insulin-like growth factor 1. Each hormone has a complexity related to differential pathways of action as well as interactions with binding proteins and receptor interactions. Testosterone is the primary anabolic hormone, and its concentration changes during the recovery period depending on the upregulation or downregulation of the androgen receptor. Multiple tissues beyond skeletal muscle are targeted under hormonal control and play critical roles in metabolism and physiological function. Growth hormone (GH) demonstrates differential increases in recovery with RE based on the type of GH being assayed and workout being used. IGF-1 shows variable increases in recovery with RE and is intimately linked to a host of binding proteins that are essential to its integrative actions and mediating targeting effects. The RE stress is related to recruitment of muscle tissue with the glandular release of hormones as signals to target tissues to support homeostatic mechanisms for metabolism and tissue repair during the recovery process. Anabolic hormones play a crucial role in the body's response to metabolism, repair, and adaptive capabilities especially in response to anabolic-type RE. Changes of these hormones following RE during recovery in the circulatory biocompartment of blood are reflective of the many mechanisms of action that are in play in the repair and recovery process. Copyright © 2017 the American Physiological Society.

  11. Growth hormone deficiency - children

    MedlinePlus

    Growth hormone deficiency means the pituitary gland does not make enough growth hormone. ... The pituitary gland is located at the base of the brain. This gland controls the body's balance of hormones. It ...

  12. [Thyroid hormone resistance syndromes].

    PubMed

    Bernal, Juan

    2011-04-01

    Thyroid hormone resistance syndromes are a group of genetic conditions characterized by decreased tissue sensitivity to thyroid hormones. Three syndromes, in which resistance to hormone action is respectively due to mutations in the gene encoding for thyroid hormone receptor TRβ, impaired T4 and T3 transport, and impaired conversion of T4 to T3 mediated by deiodinases. An updated review of each of these forms of resistance is provided, and their pathogenetic mechanisms and clinical approaches are discussed.

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

    PubMed

    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.

  14. [Hormones and hair growth].

    PubMed

    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.

  15. Caffeine Attenuates Acute Growth Hormone Response to a Single Bout of Resistance Exercise

    PubMed Central

    Wu, Bo-Han; Lin, Jung-Chang

    2010-01-01

    The purpose of this study was to investigate the effects of caffeine consume on substrate metabolism and acute hormonal responses to a single bout of resistance exercise (RE). Ten resistance-trained men participated in this study. All subjects performed one repetition maximum (1RM) test and then performed two protocols: caffeine (CAF, 6 mg·kg-1) and control (CON) in counter balanced order. Subjects performed RE (8 exercises, 3 sets of 10 repetitions at 75% of 1RM) after caffeine or placebo ingestion one hour prior to RE. Blood samples collected prior to treatment ingestion (pre-60), immediately prior to RE (pre-exe), and 0, 15, 30 min post to RE (P0, P15, P30) for analysis of insulin, testosterone, cortisol, growth hormone, glucose, free fatty acid and lactic acid. Each experiment was separated by seven days. In this study, statistical analysis of a two-way analysis of variance (treatment by time) with repeated measures was applied. After ingesting caffeine, the concentrations of free fatty acid (pre- exe, P0, P15, P30) in CAF were significantly higher than CON (p < 0.05). Additionally, the responses of GH (P0, P15, P30) in CAF were significantly lower than CON (p < 0.05), whereas the concentrations of insulin, testosterone and cortisol were not different between CAF and CON (p < 0.05) after RE. The results of this study indicated that caffeine ingestion prior to RE might attenuate the response of GH. This effect might be caused by the elevation in blood FFA concentration at the beginning of RE. Key points Caffeine ingestion may attenuate the response of GH to a single bout of resistance exercise. The depression of GH response may be caused by the elevation in serum FFA concentration at the beginning of resistance exercise. Caffeine ingestion before resistance exercise may not alert the concentration of cortisol and testosterone. PMID:24149694

  16. [Growth hormone treatment update].

    PubMed

    2014-02-01

    Short stature in children is a common cause for referral to pediatric endocrinologists, corresponding most times to normal variants of growth. Initially growth hormone therapy was circumscribed to children presenting growth hormone deficiency. Since the production of recombinant human hormone its use had spread to other pathologies.

  17. Acute resistance exercise stimulates sex-specific dimeric immunoreactive growth hormone responses.

    PubMed

    Luk, Hui Ying; Kraemer, William J; Szivak, Tunde K; Flanagan, Shawn D; Hooper, David R; Kupchak, Brian R; Comstock, Brett A; Dunn-Lewis, Courtenay; Vingren, Jakob L; DuPont, William H; Hymer, Wesley C

    2015-06-01

    We sought to determine if an acute heavy resistance exercise test (AHRET) would elicit sex-specific responses in circulating growth hormone (GH), with untreated serum and serum treated with a reducing agent to break disulfide-bindings between GH dimers. 19 untrained participants (nine men and ten women) participated in an acute heavy resistance exercise test using the back squat. Blood samples were drawn before exercise (Pre), immediate post (IP), +15 min (+15), and +30 min (+30) afterwards. Serum samples were chemically reduced using glutathione (GSH). ELISAs were then used to compare immunoreactive GH concentrations in reduced (+GSH) and non-reduced (-GSH) samples. Data were analyzed using a three-way (2 sex × 2 treatment × 4 time) mixed methods ANOVA, with significance set at p ≤ 0.05. GSH reduction resulted in increased immunoreactive GH concentrations when compared to non-reduced samples at Pre (1.68 ± 0.33 μg/L vs 1.25 ± 0.25 μg/L), IP (7.69 ± 1.08 μg/L vs 5.76 ± 0.80 μg/L), +15 min (4.39 ± 0.58 μg/L vs 3.24 ± 0.43 μg/L), and +30 min (2.35 ± 0.49 μg/L vs 1.45 ± 0.23 μg/L). Also, women demonstrated greater GH responses compared to men, and this was not affected by reduction. Heavy resistance exercise increases immunoreactive GH dimer concentrations in men and women, with larger increases in women and more sustained response in men. The physiological significance of a sexually dimorphic GH response adds to the growing literature on aggregate GH and may be explained by differences in sex hormones and the structure of the GH cell network. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Impaired JAK-STAT signal transduction contributes to growth hormone resistance in chronic uremia

    PubMed Central

    Schaefer, Franz; Chen, Yu; Tsao, Tanny; Nouri, Pouneh; Rabkin, Ralph

    2001-01-01

    Chronic renal failure (CRF) is associated with resistance to the growth-promoting and anabolic actions of growth hormone (GH). In rats with CRF induced by partial renal ablation, 7 days of GH treatment had a diminished effect on weight gain and hepatic IGF-1 and IGFBP-1 mRNA levels, compared with sham-operated pair-fed controls. To assess whether GH resistance might be due to altered signal transduction, activation of the JAK-STAT pathway was studied 10 or 15 minutes after intravenous injection of 5 mg/kg GH or vehicle. Hepatic GH receptor (GHR) mRNA levels were significantly decreased in CRF, but GHR protein abundance and GH binding to microsomal and plasma membranes was unaltered. JAK2, STAT1, STAT3, and STAT5 protein abundance was also unchanged. However, GH-induced tyrosine phosphorylation of JAK2, STAT5, and STAT3 was 75% lower in the CRF animals. Phosphorylated STAT5 and STAT3 were also diminished in nuclear extracts. The expression of the suppressor of cytokine signaling-2 (SOCS-2) was increased twofold in GH-treated CRF animals, and SOCS-3 mRNA levels were elevated by 60% in CRF, independent of GH treatment. In conclusion, CRF causes a postreceptor defect in GH signal transduction characterized by impaired phosphorylation and nuclear translocation of GH-activated STAT proteins, which is possibly mediated, at least in part, by overexpression of SOCS proteins. PMID:11489940

  19. Stimulation of myofibrillar protein synthesis in hindlimb suspended rats by resistance exercise and growth hormone.

    PubMed

    Linderman, J K; Whittall, J B; Gosselink, K L; Wang, T J; Mukku, V R; Booth, F W; Grindeland, R E

    1995-01-01

    The objective of this study was to determine the ability of a single bout of resistance exercise alone or in combination with recombinant human growth hormone (rhGH) to stimulate myofibrillar protein synthesis (Ks) in hindlimb suspended (HLS) adult female rats. Plantar flexor muscles were stimulated with resistance exercise, consisting of 10 repetitions of ladder climbing on a 1 m grid (85 degrees), carrying an additional 50% of their body weight attached to their tails. Saline or rhGH (1 mg/kg) was administered 30' prior to exercise, and Ks was determined with a constant infusion of 3H-Leucine at 15', 60', 180', and 360' following exercise. Three days of HLS depressed Ks approximately 65% and 30-40% in the soleus and gastrocnemius muscles, respectively (p < or = 0.05). Exercise increased soleus Ks in saline-treated rats 149% 60' following exercise (p < or = 0.05), decaying to that of non-exercised animals during the next 5 hours. Relative to suspended, non-exercised rats rhGH+exercise increased soleus Ks 84%, 108%, and 72% at 15', 60' and 360' following exercise (p < or = 0.05). Gastrocnemius Ks was not significantly increased by exercise or the combination of rhGH and exercise up to 360' post-exercise. Results from this study indicate that resistance exercise stimulated Ks 60' post-exercise in the soleus of HLS rats, with no apparent effect of rhGH to enhance or prolong exercise-induced stimulation. Results suggests that exercise frequency may be important to maintenance of the slow-twitch soleus during non-weightbearing, but that the ability of resistance exercise to maintain myofibrillar protein content in the gastrocnemius of hindlimb suspended rats cannot be explained by acute stimulation of synthesis.

  20. Stimulation of Myofibrillar Protein Synthesis in Hindlimb Suspended Rats by Resistance Exercise and Growth Hormone

    NASA Technical Reports Server (NTRS)

    Linderman, Jon K.; Whittall, Justen B.; Gosselink, Kristin L.; Wang, Tommy J.; Mukku, Venkat R.; Booth, Frank W.; Grindeland, Richard E.

    1995-01-01

    The objective of this study was to determine the ability of a single bout of resistance exercise alone or in combination with recombinant human growth hormone (rhGH) to stimulate myofibrillar protein synthesis (Ks) in hindlimb suspended (HLS) adult female rats. Plantar flexor muscles were stimulated with resistance exercise, consisting of 10 repetitions of ladder climbing on a 1 m grid (85 deg.), carrying an additional 50% of their body weight attached to their tails. Saline or rhGH (1 mg/kg) was administered 30' prior to exercise, and Ks was determined with a constant infusion of H-3-Leucine at 15', 60', 180', and 360' following exercise. Three days of HLS depressed Ks is approx. equal to 65% and 30-40% in the soleus and gastrocnemius muscles, respectively (p is less than or equal to 0.05). Exercise increased soleus Ks in saline-treated rats 149% 60' following exercise (p less than or equal to 0.05), decaying to that of non-exercised animals during the next 5 hours. Relative to suspended, non-exercised rats rhGH + exercise increased soleus Ks 84%, 108%, and 72% at 15', 60' and 360' following exercise (p is less than or equal to 0.05). Gastrocnemius Ks was not significantly increased by exercise or the combination of rhGH and exercise up to 360' post-exercise. Results from this study indicate that resistance exercise stimulated Ks 60' post-exercise in the soleus of HLS rats, with no apparent effect of rhGH to enhance or prolong exercise-induced stimulation. Results suggests that exercise frequency may be important to maintenance of the slow-twitch soleus during non-weightbearing, but that the ability of resistance exercise to maintain myofibrillar protein content in the gastrocnemius of hindlimb suspended rats cannot be explained by acute stimulation of synthesis.

  1. Echocardiographic dimensions and function in adults with primary growth hormone resistance (Laron syndrome).

    PubMed

    Feinberg, M S; Scheinowitz, M; Laron, Z

    2000-01-15

    Patients with primary growth hormone (GH) resistance-Laron Syndrome (LS)-have no GH signal transmission, and thus, no generation of circulating insulin-like growth factor-I (IGF-I), and should serve as a unique model to explore the controversies concerning the longterm effect of GH/IGF-I deficiency on cardiac dimension and function. We assessed 8 patients with LS (4 men, 4 women) with a mean (+/- SD) age of 38+/-7 years (range 22 to 45), and 8 aged-matched controls (4 men, 4 women) with a mean age of 38+/-9 years (range 18 to 47) by echocardiography at rest, following exercise, and during dobutamine administration. Left ventricular (LV) septum, posterior wall, and end-diastolic diameter were significantly reduced in untreated patients with LS compared with the control group (p<0.05 for all). Systolic Doppler-derived parameters, including LV stroke volume, stroke index, cardiac output, and cardiac index, were significantly lower (p<0.05 for all) than in the control subjects, whereas LV diastolic Doppler parameters, including mitral valve waves E, A, E/A ratio, and E deceleration time, were similar in both groups. LV ejection fraction at rest as well as the stress-induced increment of the LV ejection fraction were similar in both groups. Our results show that untreated patients with long-term IGF-I deficiency have reduced cardiac dimensions and output but normal LV ejection fraction at rest and LV contractile reserve following stress.

  2. Growth hormone-releasing hormone resistance in pseudohypoparathyroidism type ia: new evidence for imprinting of the Gs alpha gene.

    PubMed

    Mantovani, Giovanna; Maghnie, Mohamad; Weber, Giovanna; De Menis, Ernesto; Brunelli, Valeria; Cappa, Marco; Loli, Paola; Beck-Peccoz, Paolo; Spada, Anna

    2003-09-01

    Heterozygous inactivating mutations in the Gs alpha gene cause Albright's hereditary osteodystrophy. Consistent with the observation that only maternally inherited mutations lead to resistance to hormone action [pseudohypoparathyroidism type Ia (PHP Ia)], recent studies provided evidence for a predominant maternal origin of Gs alpha transcripts in endocrine organs, such as thyroid, gonad, and pituitary. The aim of this study was to investigate the presence of pituitary resistance to hypothalamic hormones acting via Gs alpha-coupled receptors in patients with PHP Ia. Six of nine patients showed an impaired GH responsiveness to GHRH plus arginine, consistent with a complete GH deficiency (GH peak from 2.6-8.6 microg/liter, normal > 16.5), and partial (GH peak 13.9 and 13.6 microg/liter) and normal responses were found in two and one patient, respectively. Accordingly, IGF-I levels were below and in the low-normal range in seven and two patients. All patients had a normal cortisol response to 1 microg ACTH test, suggesting a normal corticotroph function that was confirmed by a normal ACTH and cortisol response to CRH test in three patients. In conclusion, we report that in addition to PTH and TSH resistance, patients with PHP Ia display variable degrees of GHRH resistance, consistent with Gs alpha imprinting in human pituitary.

  3. Growth hormone test

    MedlinePlus

    ... 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 ...

  4. Innate Dysfunction Promotes Linear Growth Failure in Pediatric Crohn Disease and Growth Hormone Resistance in Murine Ileitis

    PubMed Central

    D’Mello, Sharon; Trauernicht, Anna; Ryan, Anne; Bonkowski, Erin; Willson, Tara; Trapnell, Bruce C.; Frank, Stuart J.; Kugasathan, Subra; Denson, Lee A.

    2011-01-01

    Background Growth failure remains a common complication of pediatric Crohn Disease (CD), and has been associated with small bowel involvement and need for surgery. We have reported that patients with elevated (≥ 1.6 mcg/mL) Granulocyte Macrophage Colony Stimulating Factor auto-antibodies (GM-CSF Ab) are more likely to experience complicated ileal disease requiring surgery. We hypothesized that concurrent GM-CSF Ab and CARD15 risk allele carriage (C15+GMAb+) would be associated with growth failure in CD, and growth hormone (GH) resistance in murine ileitis. Methods We enrolled 229 pediatric CD patients at two sites and determined CARD15 genotype, serum GM-CSF Ab and GH binding protein (GHBP), and height (HTz) and weight (WTz) z scores at diagnosis. Ileitis was induced in card15 deficient mice by gm-csf neutralization and NSAID exposure. Hepatic GH receptor (Ghr) abundance and GH dependent Stat5 activation were determined by western blot, and Igf-I mRNA expression by real-time PCR. Results Mean[95th CI] HTz at diagnosis was reduced to −0.48[−4.2,2.3] in C15+GMAb+patients, compared to −0.07[−4.9,3.4] in disease controls, p≤0.05. Circulating GHBP, as a marker for tissue GHR abundance, was reduced in C15+GMAb+ patients. Hepatic Ghr abundance, GH induction of Stat5 tyrosine phosphorylation, and Igf-I mRNA expression were reduced in male card15 deficient mice with ileitis due to gm-csf neutralization and NSAID exposure. Conclusions Innate dysfunction due to concurrent genetic variation in CARD15 and neutralizing GM-CSF Ab is associated with linear growth failure in pediatric CD, and hepatic GH resistance in murine ileitis. PMID:21337672

  5. Suppression in growth hormone during overeating ameliorates the increase in insulin resistance and cardiovascular disease risk

    PubMed Central

    Cornford, Andrea S.; Barkan, Ariel L.; Hinko, Alexander

    2012-01-01

    Previously, we reported that overeating for only a few days markedly suppressed the secretion of growth hormone (GH). The purpose of the present study was to determine the role of this reduction in GH concentration on key metabolic adaptations that occur during 2 wk of overeating. Nine nonobese, healthy adults were admitted to the hospital for 2 wk, during which time they ate ∼4,000 kcal/day (70 kcal·kg fat-free mass−1·day−1; 50% carbohydrate, 35% fat, and 15% protein), and their plasma GH concentration was allowed to decline naturally (control). An additional eight subjects underwent the same overeating intervention and received exogenous GH treatment (GHT) administered in four daily injections to mimic physiological GH secretion throughout the 2-wk overeating period. We measured plasma insulin and glucose concentrations in the fasting and postprandial state as well as fasting lipolytic rate, proteolytic rate, and fractional synthetic rate (FSR) using stable-isotope tracer methods. GHT prevented the fall in plasma GH concentration, maintaining plasma GH concentration at baseline levels (1.2 ± 0.2 ng/ml), which increased fasting and postprandial assessments of insulin resistance (P < 0.05) and increased fasting lipidemia (all P < 0.05 vs. control). In addition, preventing the suppression in GH with overeating also blunted the increase in systemic proteolysis (P < 0.05 GHT vs. control). However, GHT did not alter lipolysis or FSR in response to overeating. In conclusion, our main findings suggest that the suppression in GH secretion that naturally occurs during the early stages of overeating may help attenuate the insulin resistance and hyperlipidemia that typically accompany overeating. PMID:23011065

  6. Growth hormone and growth?

    PubMed

    Harvey, Steve

    2013-09-01

    Pituitary GH is obligatory for normal growth in mammals, but the importance of pituitary GH in avian growth is less certain. In birds, pituitary GH is biologically active and has growth promoting actions in the tibia-test bioassay. Its importance in normal growth is indicated by the growth suppression following the surgical removal of the pituitary gland or after the immunoneutralization of endogenous pituitary GH. The partial restoration of growth in some studies with GH-treated hypophysectomized birds also suggests GH dependency in avian growth, as does the dwarfism that occurs in some strains with GHR dysfunctions. Circulating GH concentrations are also correlated with body weight gain, being high in young, rapidly growing birds and low in slower growing older birds. Nevertheless, despite these observations, there is an extensive literature that concludes pituitary GH is not important in avian growth. This is based on numerous studies with hypophysectomized and intact birds that show only slight, transitory or absent growth responses to exogenous GH-treatment. Moreover, while circulating GH levels correlate with weight gain in young birds, this may merely reflect changes in the control of pituitary GH secretion during aging, as numerous studies involving experimental alterations in growth rate fail to show positive correlations between plasma GH concentrations and the alterations in growth rate. Furthermore, growth is known to occur in the absence of pituitary GH, as most embryonic development occurs prior to the ontogenetic appearance of pituitary somatotrophs and the appearance of GH in embryonic circulation. Early embryonic growth is also independent of the endocrine actions of pituitary GH, since removal of the presumptive pituitary gland does not impair early growth. Embryonic growth does, however, occur in the presence of extrapituitary GH, which is produced by most tissues and has autocrine or paracrine roles that locally promote growth and development

  7. Cholesterol biosynthesis inhibitor RO 48-8071 suppresses growth of hormone-dependent and castration-resistant prostate cancer cells

    PubMed Central

    Liang, Yayun; Mafuvadze, Benford; Aebi, Johannes D; Hyder, Salman M

    2016-01-01

    Standard treatment for primary prostate cancer includes systemic exposure to chemotherapeutic drugs that target androgen receptor or antihormone therapy (chemical castration); however, drug-resistant cancer cells generally emerge during treatment, limiting the continued use of systemic chemotherapy. Patients are then treated with more toxic standard therapies. Therefore, there is an urgent need for novel and more effective treatments for prostate cancer. The cholesterol biosynthetic pathway is an attractive therapeutic target for treating endocrine-dependent cancers because cholesterol is an essential structural and functional component of cell membranes as well as the metabolic precursor of endogenous steroid hormones. In this study, we have examined the effects of RO 48-8071 (4′-[6-(allylmethylamino)hexyloxy]-4-bromo-2′-fluorobenzophenone fumarate; Roche Pharmaceuticals internal reference: RO0488071) (RO), which is an inhibitor of 2, 3-oxidosqualene cyclase (a key enzyme in the cholesterol biosynthetic pathway), on prostate cancer cells. Exposure of both hormone-dependent and castration-resistant human prostate cancer cells to RO reduced prostate cancer cell viability and induced apoptosis in vitro. RO treatment reduced androgen receptor protein expression in hormone-dependent prostate cancer cells and increased estrogen receptor β (ERβ) protein expression in both hormone-dependent and castration-resistant prostate cancer cell lines. Combining RO with an ERβ agonist increased its ability to reduce castration-resistant prostate cancer cell viability. In addition, RO effectively suppressed the growth of aggressive castration-resistant human prostate cancer cell xenografts in vivo without any signs of toxicity to experimental animals. Importantly, RO did not reduce the viability of normal prostate cells in vitro. Our study is the first to demonstrate that the cholesterol biosynthesis inhibitor RO effectively suppresses growth of human prostate cancer cells

  8. Cholesterol biosynthesis inhibitor RO 48-8071 suppresses growth of hormone-dependent and castration-resistant prostate cancer cells.

    PubMed

    Liang, Yayun; Mafuvadze, Benford; Aebi, Johannes D; Hyder, Salman M

    2016-01-01

    Standard treatment for primary prostate cancer includes systemic exposure to chemotherapeutic drugs that target androgen receptor or antihormone therapy (chemical castration); however, drug-resistant cancer cells generally emerge during treatment, limiting the continued use of systemic chemotherapy. Patients are then treated with more toxic standard therapies. Therefore, there is an urgent need for novel and more effective treatments for prostate cancer. The cholesterol biosynthetic pathway is an attractive therapeutic target for treating endocrine-dependent cancers because cholesterol is an essential structural and functional component of cell membranes as well as the metabolic precursor of endogenous steroid hormones. In this study, we have examined the effects of RO 48-8071 (4'-[6-(allylmethylamino)hexyloxy]-4-bromo-2'-fluorobenzophenone fumarate; Roche Pharmaceuticals internal reference: RO0488071) (RO), which is an inhibitor of 2, 3-oxidosqualene cyclase (a key enzyme in the cholesterol biosynthetic pathway), on prostate cancer cells. Exposure of both hormone-dependent and castration-resistant human prostate cancer cells to RO reduced prostate cancer cell viability and induced apoptosis in vitro. RO treatment reduced androgen receptor protein expression in hormone-dependent prostate cancer cells and increased estrogen receptor β (ERβ) protein expression in both hormone-dependent and castration-resistant prostate cancer cell lines. Combining RO with an ERβ agonist increased its ability to reduce castration-resistant prostate cancer cell viability. In addition, RO effectively suppressed the growth of aggressive castration-resistant human prostate cancer cell xenografts in vivo without any signs of toxicity to experimental animals. Importantly, RO did not reduce the viability of normal prostate cells in vitro. Our study is the first to demonstrate that the cholesterol biosynthesis inhibitor RO effectively suppresses growth of human prostate cancer cells. Our

  9. Effects of Growth Hormone on Cardiac Remodeling During Resistance Training in Rats

    PubMed Central

    Junqueira, Adriana; Cicogna, Antônio Carlos; Engel, Letícia Estevam; Aldá, Maiara Almeida; de Tomasi, Loreta Casquel; Giuffrida, Rogério; Giometti, Inês Cristina; Freire, Ana Paula Coelho Figueira; Aguiar, Andreo Fernando; Pacagnelli, Francis Lopes

    2016-01-01

    Background Although the beneficial effects of resistance training (RT) on the cardiovascular system are well established, few studies have investigated the effects of the chronic growth hormone (GH) administration on cardiac remodeling during an RT program. Objective To evaluate the effects of GH on the morphological features of cardiac remodeling and Ca2+ transport gene expression in rats submitted to RT. Methods Male Wistar rats were divided into 4 groups (n = 7 per group): control (CT), GH, RT and RT with GH (RTGH). The dose of GH was 0.2 IU/kg every other day for 30 days. The RT model used was the vertical jump in water (4 sets of 10 jumps, 3 bouts/wk) for 30 consecutive days. After the experimental period, the following variables were analyzed: final body weight (FBW), left ventricular weight (LVW), LVW/FBW ratio, cardiomyocyte cross-sectional area (CSA), collagen fraction, creatine kinase muscle-brain fraction (CK-MB) and gene expressions of SERCA2a, phospholamban (PLB) and ryanodine (RyR). Results There was no significant (p > 0.05) difference among groups for FBW, LVW, LVW/FBW ratio, cardiomyocyte CSA, and SERCA2a, PLB and RyR gene expressions. The RT group showed a significant (p < 0.05) increase in collagen fraction compared to the other groups. Additionally, the trained groups (RT and RTGH) had greater CK-MB levels compared to the untrained groups (CT and GH). Conclusion GH may attenuate the negative effects of RT on cardiac remodeling by counteracting the increased collagen synthesis, without affecting the gene expression that regulates cardiac Ca2+ transport. PMID:26647722

  10. Effects of Growth Hormone on Cardiac Remodeling During Resistance Training in Rats.

    PubMed

    Junqueira, Adriana; Cicogna, Antônio Carlos; Engel, Letícia Estevam; Aldá, Maiara Almeida; de Tomasi, Loreta Casquel; Giuffrida, Rogério; Giometti, Inês Cristina; Freire, Ana Paula Coelho Figueira; Aguiar, Andreo Fernando; Pacagnelli, Francis Lopes

    2016-01-01

    Although the beneficial effects of resistance training (RT) on the cardiovascular system are well established, few studies have investigated the effects of the chronic growth hormone (GH) administration on cardiac remodeling during an RT program. To evaluate the effects of GH on the morphological features of cardiac remodeling and Ca2+ transport gene expression in rats submitted to RT. Male Wistar rats were divided into 4 groups (n = 7 per group): control (CT), GH, RT and RT with GH (RTGH). The dose of GH was 0.2 IU/kg every other day for 30 days. The RT model used was the vertical jump in water (4 sets of 10 jumps, 3 bouts/wk) for 30 consecutive days. After the experimental period, the following variables were analyzed: final body weight (FBW), left ventricular weight (LVW), LVW/FBW ratio, cardiomyocyte cross-sectional area (CSA), collagen fraction, creatine kinase muscle-brain fraction (CK-MB) and gene expressions of SERCA2a, phospholamban (PLB) and ryanodine (RyR). There was no significant (p > 0.05) difference among groups for FBW, LVW, LVW/FBW ratio, cardiomyocyte CSA, and SERCA2a, PLB and RyR gene expressions. The RT group showed a significant (p < 0.05) increase in collagen fraction compared to the other groups. Additionally, the trained groups (RT and RTGH) had greater CK-MB levels compared to the untrained groups (CT and GH). GH may attenuate the negative effects of RT on cardiac remodeling by counteracting the increased collagen synthesis, without affecting the gene expression that regulates cardiac Ca2+ transport.

  11. [Growth hormone signaling pathways].

    PubMed

    Zych, Sławomir; Szatkowska, Iwona; Czerniawska-Piatkowska, Ewa

    2006-01-01

    The substantial improvement in the studies on a very complicated mechanism-- growth hormone signaling in a cell, has been noted in last decade. GH-induced signaling is characterized by activation of several pathways, including extracellular signal-regulated kinase (ERK), the signal transducer and activator of transcription and phosphatidylinositol-3 kinase (PI3) pathways. This review shows a current model of the growth hormone receptor dimerization, rotation of subunits and JAK2 kinase activation as the initial steps in the cascade of events. In the next stages of the signaling process, the GH-(GHR)2-(JAK2)2 complex may activate signaling molecules such as Stat, IRS-1 and IRS-2, and particularly all cascade proteins that activate MAP kinase. These pathways regulate basal cellular functions including target gene transcription, enzymatic activity and metabolite transport. Therefore growth hormone is considered as a major regulator of postnatal growth and metabolism, probably for mammary gland growth and development too.

  12. Resistance to juvenile hormone and an insect growth regulator in Drosophila is associated with an altered cytosolic juvenile hormone-binding protein

    SciTech Connect

    Shemshedini, L.; Wilson, T.G. )

    1990-03-01

    The Met mutant of Drosophila melanogaster is highly resistant to juvenile hormone III (JH III) or its chemical analog, methoprene, an insect growth regulator. Five major mechanisms of insecticide resistance were examined in Met and susceptible Met{sup +} flies. These two strains showed only minor differences when penetration, excretion, tissue sequestration, or metabolism of ({sup 3}H)JH III was measured. In contrast, when we examined JH III binding by a cytosolic binding protein from a JH target tissue, Met strains had a 10-fold lower binding affinity than did Met{sup +} strains. Studies using deficiency-bearing chromosomes provide strong evidence that the Met locus controls the binding protein characteristics and may encode the protein. These studies indicate that resistance in Met flies results from reduced binding affinity of a cytosolic binding protein for JH III.

  13. Immunoreactive and bioactive growth hormone responses to resistance exercise in men who are lean or obese.

    PubMed

    Thomas, Gwendolyn A; Kraemer, William J; Kennett, Mary J; Comstock, Brett A; Maresh, Carl M; Denegar, Craig R; Volek, Jeff S; Hymer, Wesley C

    2011-08-01

    It has been suggested that obese individuals have a blunted growth hormone (GH) response to spontaneous and stimulated GH secretion. The present study was designed to examine the effects of a high-volume, whole body acute resistance exercise (RE) protocol on immunoreactive GH (iGH), bioactive GH (bGH), and GH-binding protein (GHBP) in sedentary lean and obese men. Nine obese (mean ± SD: 20.8 ± 2.1 yr old, 177.0 ± 4.1 cm height, 108.7 ± 15.9 kg body mass, 37.6 ± 5.29% body fat) and nine lean (20.1 ± 2.1 yr old, 177.8 ± 8.7 cm height, 71.7 ± 5.8 kg body mass, 14.7 ± 3.54% body fat) men completed an acute RE protocol (6 exercises, 3 sets of 10 repetitions at 85-95% of 10 repetitions maximum with 120- and 90-s rest periods), and blood samples were collected before, at the midpoint, and immediately after exercise and during recovery (+50, +70, and +110). In contrast to prior studies, which examined acute responses to cardiovascular exercise protocols, groups did not differ in iGH response to the exercise stimulus. However, bGH concentrations overall were significantly lower in the obese than the lean participants (P < 0.001). Additionally, obese individuals had significantly higher GHBP concentrations (P < 0.001). Results suggest that obese and lean sedentary men performing a high-volume, whole body acute RE protocol demonstrate similar increases in iGH. Blunted bGH and elevated GHBP concentrations are indicative of altered GH activity associated with obesity. Prior research findings of blunted iGH response may be attributable to RE protocols not equated on relative intensity or volume. These results underscore the complexity of pituitary biology and its related mechanisms and may have implications for exercise prescription in the treatment of obesity.

  14. Arginine and ornithine supplementation increases growth hormone and insulin-like growth factor-1 serum levels after heavy-resistance exercise in strength-trained athletes.

    PubMed

    Zajac, Adam; Poprzecki, Stanisław; Zebrowska, Aleksandra; Chalimoniuk, Małgorzata; Langfort, Jozef

    2010-04-01

    This placebo-controlled double-blind study was designed to investigate the effect of arginine and ornithine (arg and orn) supplementation during 3-week heavy-resistance training on serum growth hormone/insulin-like growth factor-1/insulin-like growth factor-binding protein 3 (GH/IGF-1/IGFBP-3), testosterone, cortisol, and insulin levels in experienced strength-trained athletes. The subjects were randomly divided between a placebo group (n = 8) and the l-Arg/l-Orn-supplemented group (n = 9), and performed pre and posttraining standard exercise tests with the same absolute load, which consisted of the same exercise schedule as that applied in the training process. Fasting blood samples were obtained at rest, 2 minutes after the cessation of the strength exercise protocol, and after 1 hour of recovery. The resting concentrations of the investigated hormones and IGFBP-3 did not differ significantly between the study groups. In response to exercise test, all the hormones were elevated (p < 0.05) at both time points. Significant increases (p < 0.05) were observed in both GH and IGF-1 serum levels after arg and orn supplementation at both time points, whereas a significant decrease was seen in IGFBP-3 protein during the recovery period. Because there was no between-group difference in the remaining hormone levels, it appears that the GH/IGF-1/IGFBP-3 complex may be the major player in muscle tissue response to short-term resistance training after arg and orn supplementation.

  15. Growth hormone signaling pathways.

    PubMed

    Carter-Su, Christin; Schwartz, Jessica; Argetsinger, Lawrence S

    2016-06-01

    Over 20years ago, our laboratory showed that growth hormone (GH) signals through the GH receptor-associated tyrosine kinase JAK2. We showed that GH binding to its membrane-bound receptor enhances binding of JAK2 to the GHR, activates JAK2, and stimulates tyrosyl phosphorylation of both JAK2 and GHR. The activated JAK2/GHR complex recruits a variety of signaling proteins, thereby initiating multiple signaling pathways and cellular responses. These proteins and pathways include: 1) Stat transcription factors implicated in the expression of multiple genes, including the gene encoding insulin-like growth factor 1; 2) Shc adapter proteins that lead to activation of the grb2-SOS-Ras-Raf-MEK-ERK1,2 pathway; 3) insulin receptor substrate proteins implicated in the phosphatidylinositol-3-kinase and Akt pathway; 4) signal regulatory protein α, a transmembrane scaffold protein that recruits proteins including the tyrosine phosphatase SHP2; and 5) SH2B1, a scaffold protein that can activate JAK2 and enhance GH regulation of the actin cytoskeleton. Our recent work has focused on the function of SH2B1. We have shown that SH2B1β is recruited to and phosphorylated by JAK2 in response to GH. SH2B1 localizes to the plasma membrane, cytoplasm and focal adhesions; it also cycles through the nucleus. SH2B1 regulates the actin cytoskeleton and promotes GH-dependent motility of RAW264.7 macrophages. Mutations in SH2B1 have been found in humans exhibiting severe early-onset childhood obesity and insulin resistance. These mutations impair SH2B1 enhancement of GH-induced macrophage motility. As SH2B1 is expressed ubiquitously and is also recruited to a variety of receptor tyrosine kinases, our results raise the possibility that effects of SH2B1 on the actin cytoskeleton in various cell types, including neurons, may play a role in regulating body weight.

  16. Prismatic cases: Laron syndrome (primary growth hormone resistance) from patient to laboratory to patient.

    PubMed

    Laron, Z

    1995-05-01

    Clinical investigations started in 1958 of a group of children with characteristics resembling GH deficiency, but who had extremely high levels of plasma GH, led to the description of the syndrome of primary GH resistance or insensitivity (Laron syndrome), the discovery of its molecular defect, and the clinical application of biosynthetic insulin-like growth factor-I. This syndrome is a unique model that enables study of the GH receptor, its signal transduction, and the comparison between the effects of GH and insulin-like growth factor-I.

  17. Extrapituitary growth hormone and growth?

    PubMed

    Harvey, Steve; Baudet, Marie-Laure

    2014-09-01

    While growth hormone (GH) is obligatory for postnatal growth, it is not required for a number of growth-without-GH syndromes, such as early embryonic or fetal growth. Instead, these syndromes are thought to be dependent upon local growth factors, rather than pituitary GH. The GH gene is, however, also expressed in many extrapituitary tissues, particularly during early development and extrapituitary GH may be one of the local growth factors responsible for embryonic or fetal growth. Moreover, as the expression of the GH receptor (GHR) gene mirrors that of GH in extrapituitary tissues the actions of GH in early development are likely to be mediated by local autocrine or paracrine mechanisms, especially as extrapituitary GH expression occurs prior to the ontogeny of pituitary somatotrophs or the appearance of GH in the circulation. The extrapituitary expression of pituitary somatotrophs or the appearance of GH in the circulation. The extrapituitary expression of GH in embryos has also been shown to be of functional relevance in a number of species, since the immunoneutralization of endogenous GH or the blockade of GH production is accompanied by growth impairment or cellular apoptosis. The extrapituitary expression of the GH gene also persists in some central and peripheral tissues postnatally, which may reflect its continued functional importance and physiological or pathophysiological significance. The expression and functional relevance of extrapituitary GH, particularly during embryonic growth, is the focus of this brief review.

  18. Hormonal Control of Fetal Growth.

    ERIC Educational Resources Information Center

    Cooke, Paul S.; Nicoll, Charles S.

    1983-01-01

    Summarizes recent research on hormonal control of fetal growth, presenting data obtained using a new method for studying the area. Effects of endocrine ablations and congenital deficiencies, studies of hormone/receptor levels, in-vitro techniques, hormones implicated in promoting fetal growth, problems with existing methodologies, and growth of…

  19. Hormonal Control of Fetal Growth.

    ERIC Educational Resources Information Center

    Cooke, Paul S.; Nicoll, Charles S.

    1983-01-01

    Summarizes recent research on hormonal control of fetal growth, presenting data obtained using a new method for studying the area. Effects of endocrine ablations and congenital deficiencies, studies of hormone/receptor levels, in-vitro techniques, hormones implicated in promoting fetal growth, problems with existing methodologies, and growth of…

  20. Growth hormone/IGF-I and/or resistive exercise maintains myonuclear number in hindlimb unweighted muscles

    NASA Technical Reports Server (NTRS)

    Allen, D. L.; Linderman, J. K.; Roy, R. R.; Grindeland, R. E.; Mukku, V.; Edgerton, V. R.

    1997-01-01

    In the present study of rats, we examined the role, during 2 wk of hindlimb suspension, of growth hormone/insulin-like growth factor I (GH/IGF-I) administration and/or brief bouts of resistance exercise in ameliorating the loss of myonuclei in fibers of the soleus muscle that express type I myosin heavy chain. Hindlimb suspension resulted in a significant decrease in mean soleus wet weight that was attenuated either by exercise alone or by exercise plus GH/IGF-I treatment but was not attenuated by hormonal treatment alone. Both mean myonuclear number and mean fiber cross-sectional area (CSA) of fibers expressing type I myosin heavy chain decreased after 2 wk of suspension compared with control (134 vs. 162 myonuclei/mm and 917 vs. 2,076 micron2, respectively). Neither GH/IGF-I treatment nor exercise alone affected myonuclear number or fiber CSA, but the combination of exercise and growth-factor treatment attenuated the decrease in both variables. A significant correlation was found between mean myonuclear number and mean CSA across all groups. Thus GH/IGF-I administration and brief bouts of muscle loading had an interactive effect in attenuating the loss of myonuclei induced by chronic unloading.

  1. Growth hormone/IGF-I and/or resistive exercise maintains myonuclear number in hindlimb unweighted muscles

    NASA Technical Reports Server (NTRS)

    Allen, D. L.; Linderman, J. K.; Roy, R. R.; Grindeland, R. E.; Mukku, V.; Edgerton, V. R.

    1997-01-01

    In the present study of rats, we examined the role, during 2 wk of hindlimb suspension, of growth hormone/insulin-like growth factor I (GH/IGF-I) administration and/or brief bouts of resistance exercise in ameliorating the loss of myonuclei in fibers of the soleus muscle that express type I myosin heavy chain. Hindlimb suspension resulted in a significant decrease in mean soleus wet weight that was attenuated either by exercise alone or by exercise plus GH/IGF-I treatment but was not attenuated by hormonal treatment alone. Both mean myonuclear number and mean fiber cross-sectional area (CSA) of fibers expressing type I myosin heavy chain decreased after 2 wk of suspension compared with control (134 vs. 162 myonuclei/mm and 917 vs. 2,076 micron2, respectively). Neither GH/IGF-I treatment nor exercise alone affected myonuclear number or fiber CSA, but the combination of exercise and growth-factor treatment attenuated the decrease in both variables. A significant correlation was found between mean myonuclear number and mean CSA across all groups. Thus GH/IGF-I administration and brief bouts of muscle loading had an interactive effect in attenuating the loss of myonuclei induced by chronic unloading.

  2. Skeletal unloading induces selective resistance to the anabolic actions of growth hormone on bone

    NASA Technical Reports Server (NTRS)

    Halloran, B. P.; Bikle, D. D.; Harris, J.; Autry, C. P.; Currier, P. A.; Tanner, S.; Patterson-Buckendahl, P.; Morey-Holton, E.

    1995-01-01

    Loss of skeletal weight bearing or physical unloading of bone in the growing animal inhibits bone formation and induces a bone mineral deficit. To determine whether the inhibition of bone formation induced by skeletal unloading in the growing animal is a consequence of diminished sensitivity to growth hormone (GH) we studied the effects of skeletal unloading in young hypophysectomized rats treated with GH (0, 50, 500 micrograms/100 g body weight/day). Skeletal unloading reduced serum osteocalcin, impaired uptake of 3H-proline into bone, decreased proximal tibial mass, and diminished periosteal bone formation at the tibiofibular junction. When compared with animals receiving excipient alone, GH administration increased bone mass in all animals. The responses in serum osteocalcin, uptake of 3H-proline and 45Ca into the proximal tibia, and proximal tibial mass in non-weight bearing animals were equal to those in weight bearing animals. The responses in trabecular bone volume in the proximal tibia and bone formation at the tibiofibular junction to GH, however, were reduced significantly by skeletal unloading. Bone unloading prevented completely the increase in metaphyseal trabecular bone normally induced by GH and severely dampened the stimulatory effect (158% vs. 313%, p < 0.002) of GH on periosteal bone formation. These results suggest that while GH can stimulate the overall accumulation of bone mineral in both weight bearing and non-weight bearing animals, skeletal unloading selectively impairs the response of trabecular bone and periosteal bone formation to the anabolic actions of GH.

  3. Skeletal unloading induces selective resistance to the anabolic actions of growth hormone on bone

    NASA Technical Reports Server (NTRS)

    Halloran, B. P.; Bikle, D. D.; Harris, J.; Autry, C. P.; Currier, P. A.; Tanner, S.; Patterson-Buckendahl, P.; Morey-Holton, E.

    1995-01-01

    Loss of skeletal weight bearing or physical unloading of bone in the growing animal inhibits bone formation and induces a bone mineral deficit. To determine whether the inhibition of bone formation induced by skeletal unloading in the growing animal is a consequence of diminished sensitivity to growth hormone (GH) we studied the effects of skeletal unloading in young hypophysectomized rats treated with GH (0, 50, 500 micrograms/100 g body weight/day). Skeletal unloading reduced serum osteocalcin, impaired uptake of 3H-proline into bone, decreased proximal tibial mass, and diminished periosteal bone formation at the tibiofibular junction. When compared with animals receiving excipient alone, GH administration increased bone mass in all animals. The responses in serum osteocalcin, uptake of 3H-proline and 45Ca into the proximal tibia, and proximal tibial mass in non-weight bearing animals were equal to those in weight bearing animals. The responses in trabecular bone volume in the proximal tibia and bone formation at the tibiofibular junction to GH, however, were reduced significantly by skeletal unloading. Bone unloading prevented completely the increase in metaphyseal trabecular bone normally induced by GH and severely dampened the stimulatory effect (158% vs. 313%, p < 0.002) of GH on periosteal bone formation. These results suggest that while GH can stimulate the overall accumulation of bone mineral in both weight bearing and non-weight bearing animals, skeletal unloading selectively impairs the response of trabecular bone and periosteal bone formation to the anabolic actions of GH.

  4. Growth Hormone Plus Resistance Exercise Attenuate Structural Changes in Rat Myotendinous Junctions Resulting from Chronic Unloading

    PubMed Central

    Curzi, D.; Lattanzi, D.; Ciuffoli, S.; Burattini, S.; Grindeland, R.E.; Edgerton, V.R.; Roy, R.R.; Tidball, J.G.; Falcieri, E.

    2013-01-01

    Myotendinous junctions (MTJs) are specialized sites on the muscle surface where forces generated by myofibrils are transmitted across the sarcolemma to the extracellular matrix. At the ultrastructural level, the interface between the sarcolemma and extracellular matrix is highly folded and interdigitated at these junctions. In this study, the effect of exercise and growth hormone (GH) treatments on the changes in MTJ structure that occur during muscle unloading, has been analyzed. Twenty hypophysectomized rats were assigned randomly to one of five groups: ambulatory control, hindlimb unloaded, hindlimb unloaded plus exercise (3 daily bouts of 10 climbs up a ladder with 50% body wt attached to the tail), hindlimb unloaded plus GH (2 daily injections of 1 mg/kg body wt, i.p.), and hindlimb unloaded plus exercise plus GH. MTJs of the plantaris muscle were analyzed by electron microscopy and the contact between muscle and tendon was evaluated using an IL/B ratio, where B is the base and IL is the interface length of MTJ’s digit-like processes. After 10 days of unloading, the mean IL/B ratio was significantly lower in unloaded (3.92), unloaded plus exercise (4.18), and unloaded plus GH (5.25) groups than in the ambulatory control (6.39) group. On the opposite, the mean IL/B ratio in the group treated with both exercise and GH (7.3) was similar to control. These findings indicate that the interaction between exercise and GH treatments attenuates the changes in MTJ structure that result from chronic unloading and thus can be used as a countermeasure to these adaptations. PMID:24441190

  5. A nonpeptidyl growth hormone secretagogue.

    PubMed

    Smith, R G; Cheng, K; Schoen, W R; Pong, S S; Hickey, G; Jacks, T; Butler, B; Chan, W W; Chaung, L Y; Judith, F

    1993-06-11

    A nonpeptidyl secretagogue for growth hormone of the structure 3-amino-3-methyl-N-(2,3,4,5-tetrahydro-2-oxo-1-([2'-(1H-tetrazol-5 -yl) (1,1'-biphenyl)-4-yl]methyl)-1H-1-benzazepin-3(R)-yl)-butanamid e (L-692,429) has been identified. L-692,429 synergizes with the natural growth hormone secretagogue growth hormone-releasing hormone and acts through an alternative signal transduction pathway. The mechanism of action of L-692,429 and studies with peptidyl and nonpeptidyl antagonists suggest that this molecule is a mimic of the growth hormone-releasing hexapeptide His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP-6). L-692,429 is an example of a nonpeptidyl specific secretagogue for growth hormone.

  6. Lack of dietary carbohydrates induces hepatic growth hormone (GH) resistance in rats.

    PubMed

    Bielohuby, Maximilian; Sawitzky, Mandy; Stoehr, Barbara J M; Stock, Peggy; Menhofer, Dominik; Ebensing, Sabine; Bjerre, Mette; Frystyk, Jan; Binder, Gerhard; Strasburger, Christian; Wu, Zida; Christ, Bruno; Hoeflich, Andreas; Bidlingmaier, Martin

    2011-05-01

    GH is a well established regulator of growth, lipid, and glucose metabolism and therefore important for fuel utilization. However, little is known about the effects of macronutrients on the GH/IGF system. We used low-carbohydrate/high-fat diets (LC-HFD) as a model to study the impact of fat, protein, and carbohydrates on the GH/IGF-axis; 12-wk-old Wistar rats were fed either regular chow, a moderate, protein-matched LC-HFD, or a ketogenic LC-HFD (percentage of fat/protein/carbohydrates: chow, 16.7/19/64.3; LC-HF-1, 78.7/19.1/2.2; LC-HF-2, 92.8/5.5/1.7). After 4 wk, body and tibia length, lean body mass, and fat pad weights were measured. Furthermore, we investigated the effects of LC-HFD on 1) secretion of GH and GH-dependent factors, 2) expression and signaling of components of the GH/IGF system in liver and muscle, and 3) hypothalamic and pituitary regulation of GH release. Serum concentrations of IGF-I, IGF binding protein-1, and IGF binding protein-3 were lower with LC-HF-1 and LC-HF-2 (P < 0.01). Both LC-HFD-reduced hepatic GH receptor mRNA and protein expression, decreased basal levels of total and phosphorylated Janus kinase/signal transducers and activators of transcription signaling proteins and reduced hepatic IGF-I gene expression. Hypothalamic somatostatin expression was reduced only with LC-HF-1, leading to increased pituitary GH secretion, higher IGF-I gene expression, and activation of IGF-dependent signaling pathways in skeletal muscle. In contrast, despite severely reduced IGF-I concentrations, GH secretion did not increase with LC-HF-2 diet. In conclusion, lack of carbohydrates in LC-HFD induces hepatic GH resistance. Furthermore, central feedback mechanisms of the GH/IGF system are impaired with extreme, ketogenic LC-HFD.

  7. Androgen metabolite-dependent growth of hormone receptor-positive breast cancer as a possible aromatase inhibitor-resistance mechanism.

    PubMed

    Hanamura, Toru; Niwa, Toshifumi; Nishikawa, Sayo; Konno, Hiromi; Gohno, Tatsuyuki; Tazawa, Chika; Kobayashi, Yasuhito; Kurosumi, Masafumi; Takei, Hiroyuki; Yamaguchi, Yuri; Ito, Ken-Ichi; Hayashi, Shin-Ichi

    2013-06-01

    Aromatase inhibitors (AIs) have been reported to exert their antiproliferative effects in postmenopausal women with hormone receptor-positive breast cancer not only by reducing estrogen production but also by unmasking the inhibitory effects of androgens such as testosterone (TS) and dihydrotestosterone (DHT). However, the role of androgens in AI-resistance mechanisms is not sufficiently understood. 5α-Androstane-3β,17β-diol (3β-diol) generated from DHT by 3β-hydroxysteroid dehydrogenase type 1 (HSD3B1) shows androgenic and substantial estrogenic activities, representing a potential mechanism of AI resistance. Estrogen response element (ERE)-green fluorescent protein (GFP)-transfected MCF-7 breast cancer cells (E10 cells) were cultured for 3 months under steroid-depleted, TS-supplemented conditions. Among the surviving cells, two stable variants showing androgen metabolite-dependent ER activity were selected by monitoring GFP expression. We investigated the process of adaptation to androgen-abundant conditions and the role of androgens in AI-resistance mechanisms in these variant cell lines. The variant cell lines showed increased growth and induction of estrogen-responsive genes rather than androgen-responsive genes after stimulation with androgens or 3β-diol. Further analysis suggested that increased expression of HSD3B1 and reduced expression of androgen receptor (AR) promoted adaptation to androgen-abundant conditions, as indicated by the increased conversion of DHT into 3β-diol by HSD3B1 and AR signal reduction. Furthermore, in parental E10 cells, ectopic expression of HSD3B1 or inhibition of AR resulted in adaptation to androgen-abundant conditions. Coculture with stromal cells to mimic local estrogen production from androgens reduced cell sensitivity to AIs compared with parental E10 cells. These results suggest that increased expression of HSD3B1 and reduced expression of AR might reduce the sensitivity to AIs as demonstrated by enhanced androgen

  8. Growth hormone stimulation test (image)

    MedlinePlus

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

  9. Endogenous Hormonal and Growth Factor Responses to Heavy Resistance Exercise Protocols

    DTIC Science & Technology

    1989-03-20

    factors related to more anaerobic HREP stimulates serum hGH responses. Klimes et al. (17) had previously found little effect of changes in acid-base...periods and IORM load. All HREPs did not produce increases in serum hGH. The pattern of SM-C increases varied among HREPs and did not follow hGH changes ...rest period length). This design allowed for a more quantitative approach to examine responses to heavy resistance exercise due to specific changes in

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

    NASA Technical Reports Server (NTRS)

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

    1999-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1999-01-01

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

  12. Laron syndrome (primary growth hormone resistance or insensitivity): the personal experience 1958-2003.

    PubMed

    Laron, Zvi

    2004-03-01

    Clinical and laboratory investigations starting in 1958 of a group of dwarfed children resembling isolated GH deficiency but who had very high serum levels of GH led to the description of the syndrome of primary GH resistance or insensitivity (Laron syndrome) and subsequently to the discovery of its molecular defects residing in the GH receptor and leading to an inability of IGF-I generation. With the biosynthesis of IGF-I in 1986, therapeutic trials started. Continuously more and more patients are being diagnosed in many parts of the world with a variety of molecular defects. This syndrome proved to be a unique model that enables the study of the consequences of GH receptor defects, the physiopathology of GH-IGF-I disruption, and comparison of the GH-independent IGF-I effects. This review presents the personal experience gained from the study follow-up and treatment of the 60 patients followed up for many years in the Israeli cohort.

  13. Resistance to the Beneficial Metabolic Effects and Hepatic Antioxidant Defense Actions of Fibroblast Growth Factor 21 Treatment in Growth Hormone-Overexpressing Transgenic Mice

    PubMed Central

    Boparai, Ravneet K.; Arum, Oge; Miquet, Johanna G.; Masternak, Michal M.; Khardori, Romesh K.

    2015-01-01

    Fibroblast growth factor 21 (FGF21) modulates a diverse range of biological functions, including glucose and lipid metabolism, adaptive starvation response, and energy homeostasis, but with limited mechanistic insight. FGF21 treatment has been shown to inhibit hepatic growth hormone (GH) intracellular signaling. To evaluate GH axis involvement in FGF21 actions, transgenic mice overexpressing bovine GH were used. Expectedly, in response to FGF21 treatment control littermates showed metabolic improvements whereas GH transgenic mice resisted most of the beneficial effects of FGF21, except an attenuation of the innate hyperinsulinemia. Since FGF21 is believed to exert its effects mostly at the transcriptional level, we analyzed and observed significant upregulation in expression of various genes involved in carbohydrate and lipid metabolism, energy homeostasis, and antioxidant defense in FGF21-treated controls, but not in GH transgenics. The resistance of GH transgenic mice to FGF21-induced changes underlines the necessity of normal GH signaling for the beneficial effects of FGF21. PMID:26089880

  14. Growth Hormone-Releasing Hormone in Diabetes

    PubMed Central

    Fridlyand, Leonid E.; Tamarina, Natalia A.; Schally, Andrew V.; Philipson, Louis H.

    2016-01-01

    Growth hormone-releasing hormone (GHRH) is produced by the hypothalamus and stimulates growth hormone synthesis and release in the anterior pituitary gland. In addition, GHRH is an important regulator of cellular functions in many cells and organs. Expression of GHRH G-Protein Coupled Receptor (GHRHR) has been demonstrated in different peripheral tissues and cell types, including pancreatic islets. Among the peripheral activities, recent studies demonstrate a novel ability of GHRH analogs to increase and preserve insulin secretion by beta-cells in isolated pancreatic islets, which makes them potentially useful for diabetes treatment. This review considers the role of GHRHR in the beta-cell and addresses the unique engineered GHRH agonists and antagonists for treatment of type 2 diabetes mellitus. We discuss the similarity of signaling pathways activated by GHRHR in pituitary somatotrophs and in pancreatic beta-cells and possible ways as to how the GHRHR pathway can interact with glucose and other secretagogues to stimulate insulin secretion. We also consider the hypothesis that novel GHRHR agonists can improve glucose metabolism in Type 2 diabetes by preserving the function and survival of pancreatic beta-cells. Wound healing and cardioprotective action with new GHRH agonists suggest that they may prove useful in ameliorating certain diabetic complications. These findings highlight the future potential therapeutic effectiveness of modulators of GHRHR activity for the development of new therapeutic approaches in diabetes and its complications. PMID:27777568

  15. Treatment challenges for community oncologists treating postmenopausal women with endocrine-resistant, hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer

    PubMed Central

    Gradishar, William J

    2016-01-01

    Community-based oncologists are faced with challenges and opportunities when delivering quality patient care, including high patient volumes and diminished resources; however, there may be the potential to deliver increased patient education and subsequently improve outcomes. This review discusses the treatment of postmenopausal women with endocrine-resistant, hormone receptor-positive, human epidermal growth factor receptor 2- negative advanced breast cancer in order to illustrate considerations in the provision of pertinent quality education in the treatment of these patients and the management of therapy-related adverse events. An overview of endocrine-resistant breast cancer and subsequent treatment challenges is also provided. Approved treatment options for endocrine-resistant breast cancer include hormonal therapies and mammalian target of rapamycin inhibitors. Compounds under clinical investigation are also discussed. PMID:27468248

  16. Increased P85alpha is a potent negative regulator of skeletal muscle insulin signaling and induces in vivo insulin resistance associated with growth hormone excess.

    PubMed

    Barbour, Linda A; Mizanoor Rahman, Shaikh; Gurevich, Inga; Leitner, J Wayne; Fischer, Stephanie J; Roper, Michael D; Knotts, Trina A; Vo, Yen; McCurdy, Carrie E; Yakar, Shoshana; Leroith, Derek; Kahn, C Ronald; Cantley, Lewis C; Friedman, Jacob E; Draznin, Boris

    2005-11-11

    Insulin resistance is a cardinal feature of normal pregnancy and excess growth hormone (GH) states, but its underlying mechanism remains enigmatic. We previously found a significant increase in the p85 regulatory subunit of phosphatidylinositol kinase (PI 3-kinase) and striking decrease in IRS-1-associated PI 3-kinase activity in the skeletal muscle of transgenic animals overexpressing human placental growth hormone. Herein, using transgenic mice bearing deletions in p85alpha, p85beta, or insulin-like growth factor-1, we provide novel evidence suggesting that overexpression of p85alpha is a primary mechanism for skeletal muscle insulin resistance in response to GH. We found that the excess in total p85 was entirely accounted for by an increase in the free p85alpha-specific isoform. In mice with a liver-specific deletion in insulin-like growth factor-1, excess GH caused insulin resistance and an increase in skeletal muscle p85alpha, which was completely reversible using a GH-releasing hormone antagonist. To understand the role of p85alpha in GH-induced insulin resistance, we used mice bearing deletions of the genes coding for p85alpha or p85beta, respectively (p85alpha (+/-) and p85beta(-/-)). Wild type and p85beta(-/-) mice developed in vivo insulin resistance and demonstrated overexpression of p85alpha and reduced insulin-stimulated PI 3-kinase activity in skeletal muscle in response to GH. In contrast, p85alpha(+/-)mice retained global insulin sensitivity and PI 3-kinase activity associated with reduced p85alpha expression. These findings demonstrated the importance of increased p85alpha in mediating skeletal muscle insulin resistance in response to GH and suggested a potential role for reducing p85alpha as a therapeutic strategy for enhancing insulin sensitivity in skeletal muscle.

  17. Growth Hormone Deficiency in Children

    MedlinePlus

    ... brain. In children, GH is essential for normal growth, muscle and bone strength, and distribution of body fat. ... Delayed puberty What are the side effects of growth hormone therapy? Mild to moderate side ... Muscle or joint pain • Mildly underactive thyroid gland • Swelling ...

  18. Growth Hormone: Use and Abuse

    MedlinePlus

    ... GH helps children grow taller (also called linear growth), increases muscle mass, and decreases body fat. In both children ... syndrome In adults, GH is used to treat • Growth hormone deficiency • Muscle wasting (loss of muscle tissue) from HIV • Short ...

  19. Obesity, growth hormone and exercise.

    PubMed

    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.

  20. Hormonal regulation of fetal growth.

    PubMed

    Gicquel, C; Le Bouc, Y

    2006-01-01

    Fetal growth is a complex process depending on the genetics of the fetus, the availability of nutrients and oxygen to the fetus, maternal nutrition and various growth factors and hormones of maternal, fetal and placental origin. Hormones play a central role in regulating fetal growth and development. They act as maturational and nutritional signals in utero and control tissue development and differentiation according to the prevailing environmental conditions in the fetus. The insulin-like growth factor (IGF) system, and IGF-I and IGF-II in particular, plays a critical role in fetal and placental growth throughout gestation. Disruption of the IGF1, IGF2 or IGF1R gene retards fetal growth, whereas disruption of IGF2R or overexpression of IGF2 enhances fetal growth. IGF-I stimulates fetal growth when nutrients are available, thereby ensuring that fetal growth is appropriate for the nutrient supply. The production of IGF-I is particularly sensitive to undernutrition. IGF-II plays a key role in placental growth and nutrient transfer. Several key hormone genes involved in embryonic and fetal growth are imprinted. Disruption of this imprinting causes disorders involving growth defects, such as Beckwith-Wiedemann syndrome, which is associated with fetal overgrowth, or Silver-Russell syndrome, which is associated with intrauterine growth retardation. Optimal fetal growth is essential for perinatal survival and has long-term consequences extending into adulthood. Given the high incidence of intrauterine growth retardation and the high risk of metabolic and cardiovascular complications in later life, further clinical and basic research is needed to develop accurate early diagnosis of aberrant fetal growth and novel therapeutic strategies.

  1. Growth hormone can improve insulin resistance and differentiation in pancreas of senescence accelerated prone male mice (SAMP8).

    PubMed

    Cuesta, Sara; Kireev, Roman; Forman, Katherine; García, Cruz; Acuña, Darío; Vara, Elena; Tresguerres, Jesús A F

    2011-04-01

    The aim of the present study was to investigate the effect of aging on several parameters related to glucose metabolism, proliferation and differentiation in the pancreas and how GH administration to old SAMP8 mice could affect these parameters. Pancreas samples were obtained from two types of male mice models: senescence-accelerated prone (SAMP8) and senescence-accelerated-resistant (SAMR1) mice SAMP8 and SAMR1 mice and the influence of exogenous administration of GH (2mgs.c./kg/day) on SAMP8 mice. RNA was isolated from pancreas samples of male mice using the kit RNeasy total RNA kit Ref. 50974104 (Qiagen). Insulin was measured in plasma by RIA kit and glucose was measured in plasma by an assay kit. Aging decreases the expression of differentiation in the pancreas of Pdx-1, FoxO 1 and FoxO 3A but not of Sirt 1 or of the expression of the proliferative genes PCNA and Sei1. The expression of glucagon and GLUT2 were increased with aging and no differences were observed in somatostatin and insulin expressions. Insulin levels in plasma were increased with aging in SAMP8 mice. IGF-1 expression was reduced with aging. The treatment with GH was able to increase the expression of Sirt 1, Pdx-1, FoxO 3A and IGF-1. On the other hand, the treatment decreased the expression of glucagon, GLUT2, somatostatin and insulin, furthermore GH was able to decrease the plasma levels of insulin in old male SAMP8 mice (p<0.0004). The present study has shown that aging is associated with significant alterations in the relative expression of pancreatic genes involved in insulin secretion as well as in the differentiation and in the intra islet glucose metabolism. According to our results, GH administration to old SAMP8 mice was able to improve the pancreatic function of the old SAMP8 mice and to decrease insulin and glucagon expressions in the pancreas improving instead insulin levels and glucose metabolism. Copyright © 2010 Growth Hormone Research Society. Published by Elsevier Ltd. All

  2. Growth Hormone Deficiency in Adults

    MedlinePlus

    ... Center Pacientes y Cuidadores Hormones and Health The Endocrine System Hormones Endocrine Disrupting Chemicals (EDCs) Steroid and Hormone ... Learn About Clinical Trials Hormones and Health The Endocrine System Hormones Endocrine Disrupting Chemicals (EDCs) Steroid and Hormone ...

  3. Anabolic steroids and growth hormone.

    PubMed

    Haupt, H A

    1993-01-01

    Athletes are generally well educated regarding substances that they may use as ergogenic aids. This includes anabolic steroids and growth hormone. Fortunately, the abuse of growth hormone is limited by its cost and the fact that anabolic steroids are simply more enticing to the athlete. There are, however, significant potential adverse effects regarding its use that can be best understood by studying known growth hormone excess, as demonstrated in the acromegalic syndrome. Many athletes are unfamiliar with this syndrome and education of the potential consequences of growth hormone excess is important in counseling athletes considering its use. While athletes contemplating the use of anabolic steroids may correctly perceive their risks for significant physiologic effects to be small if they use the steroids for brief periods of time, many of these same athletes are unaware of the potential for habituation to the use of anabolic steroids. The result may be incessant use of steroids by an athlete who previously considered only short-term use. As we see athletes taking anabolic steroids for more prolonged periods, we are likely to see more severe medical consequences. Those who eventually do discontinue the steroids are dismayed to find that the improvements made with the steroids generally disappear and they have little to show for hours or even years of intense training beyond the psychological scars inherent with steroid use. Counseling of these athletes should focus on the potential adverse psychological consequences of anabolic steroid use and the significant risk for habituation.

  4. Growth hormone therapy in progeria.

    PubMed

    Sadeghi-Nejad, Ab; Demmer, Laurie

    2007-05-01

    Catabolic processes seen in Hutchinson-Gilford progeria resemble those of normal aging and, in the affected children, usually result in death at an early age. In addition to its growth promoting effects, growth hormone (GH) has potent anabolic properties. Administration of GH ameliorates some of the catabolic effects of normal aging. We report the results of GH treatment in a young child with progeria.

  5. Genetics Home Reference: isolated growth hormone deficiency

    MedlinePlus

    ... Genetic Testing (4 links) Genetic Testing Registry: Ateleiotic dwarfism Genetic Testing Registry: Autosomal dominant isolated somatotropin deficiency ... in my area? Other Names for This Condition dwarfism, growth hormone deficiency dwarfism, pituitary growth hormone deficiency ...

  6. Preweaning growth hormone treatment ameliorates adipose tissue insulin resistance and inflammation in adult male offspring following maternal undernutrition.

    PubMed

    Reynolds, C M; Li, M; Gray, C; Vickers, M H

    2013-08-01

    It is well established that early-life nutritional alterations lead to increased risk of obesity and metabolic disorders in adult life. Although it is clear that obesity gives rise to chronic low-grade inflammation, there is little evidence regarding the role of inflammation in the adipose tissue of undernourished (UN) offspring. GH reduces fat mass and has antiinflammatory properties. The present study examined the effect of maternal UN on adipose inflammation in adult offspring and whether GH treatment during a critical period of developmental plasticity could ameliorate metabolic dysfunction associated with a poor start to life. Sprague Dawley rats were assigned to chow (C) or UN (50% ad libitum; UN) diet throughout gestation. Male C and UN pups received saline (control saline [CS]/UN) or GH (2.5 μg/g/d; control growth hormone [CGH]/undernourished growth hormone [UNGH]) from days 3-21. Postweaning males were further randomized and fed either chow or high-fat diet until day 160. An ex vivo glucose uptake assay demonstrated adipose tissue from UN offspring displayed attenuated insulin-stimulated glucose uptake compared with CS, CGH, and UNGH. This was associated with increased insulin receptor, glucose transporter 4, and insulin receptor substrate 1 gene expression. Furthermore, UN demonstrated enhanced TNFα and IL-1β secretion from adipose explants and stromal vascular fraction cultures accompanied by increased adipose tissue gene expression of several key proinflammatory genes and markers of macrophage infiltration. Overall, UN offspring displayed a more potent immunophenotype, which correlated with decreased insulin sensitivity. Preweaning GH treatment negates these detrimental effects, indicating the potential for reversing metabolic dysfunction in UN adult offspring.

  7. A Simulated Growth Hormone Analysis

    NASA Astrophysics Data System (ADS)

    Harris, Mary

    1996-08-01

    Growth hormone is a drug that is sometimes abused by amateur or professional athletes for performance-enhancement. This laboratory is a semimicroscale simulation analysis of a sample of "urine" to detect proteins of two very different molecular weights. Gel filtration uses a 10 mL disposable pipette packed with Sephadex. Students analyze the fractions from the filtration by comparing colors of the Brilliant Blue Coomassie Dye as it interacts with the proteins in the sample to a standard set of known concentration of protein with the dye. The simulated analysis of growth hormone is intended to be included in a unit on organic chemistry or in the second year of high school chemistry.

  8. The influence of growth hormone on bone and adipose programming.

    PubMed

    Oberbauer, Anita M

    2014-01-01

    In utero growth hormone exposure is associated with distinct immediate growth responses and long term impacts on adult physiological parameters that include obesity, insulin resistance, and bone function. Growth hormone accelerates cellular proliferation in many tissues but is exemplified by increases in the number of cells within the cartilaginous growth plate of bone. In some cases growth hormone also potentiates differentiation as seen in the differentiation of adipocytes that rapidly fill upon withdrawal of growth hormone. Growth hormone provokes these changes either by direct action or through intermediaries such as insulin-like growth factor-I and other downstream effector molecules. The specific mechanism used by growth hormone in programming tissues is not yet fully characterized and likely represents a multipronged approach involving DNA modification, altered adult hormonal milieu, and the development of an augmented stem cell pool capable of future engagement as is seen in adipose accrual. This review summarizes findings of growth hormone's influence on in utero and neonatal cellular and metabolic profiles related to bone and adipose tissue.

  9. Epiphyseal growth plate growth hormone receptor signaling is decreased in chronic kidney disease-related growth retardation.

    PubMed

    Troib, Ariel; Landau, Daniel; Kachko, Leonid; Rabkin, Ralph; Segev, Yael

    2013-11-01

    Linear growth retardation in children with chronic kidney disease (CKD) has been ascribed to insensitivity to growth hormone. This resistance state has been attributed to impaired growth hormone signaling through the JAK2/STAT5 pathway in liver and skeletal muscle leading to reduced insulin-like growth factor-I (IGF-I). Here we determine whether systemic and growth plate alterations in growth hormone signaling contribute to CKD-induced linear growth retardation using partially nephrectomized and pair-fed control 20-day-old rats. Serum growth hormone did not change in rats with CKD, yet serum IGF-I levels were decreased and growth retarded. The tibial growth plate hypertrophic zone was wider and vascularization at the primary ossification center was reduced in CKD. This was associated with a decrease in growth plate vascular endothelial growth factor (VEGF) mRNA and immunostainable VEGF and IGF-I levels. Growth plate growth hormone receptor and STAT5 protein levels were unchanged, while JAK2 was reduced. Despite comparable growth hormone and growth hormone receptor levels in CKD and control rats, relative STAT5 phosphorylation was significantly depressed in CKD. Of note, the mRNA of SOCS2, an inhibitor of growth hormone signaling, was increased. Thus, linear growth impairment in CKD can in part be explained by impaired long bone growth plate growth hormone receptor signaling through the JAK2/STAT5 pathway, an abnormality that may be caused by an increase in SOCS2 expression.

  10. RENAL PRO-APOPTOTIC PROTEINS ARE REDUCED BY GROWTH HORMONE RESISTANCE BUT NOT BY VISCERAL FAT REMOVAL

    PubMed Central

    Gesing, Adam; Bartke, Andrzej; Wang, Feiya; Karbownik-Lewinska, Malgorzata; Masternak, Michal M.

    2013-01-01

    The growth hormone (GH) receptor knockout (GHRKO) mice are highly insulin sensitive and long-lived. Surgical visceral fat removal (VFR) improves insulin signaling in normal mice and rats and extends longevity in rats. We have previously demonstrated decreased expression of certain pro-apoptotic genes in kidneys of GHRKO mice, and suggested that this may contribute to the increased longevity of these animals. The aim of the present study was to examine the level of the following proteins: caspase-3, caspase-9, caspase-8, bax, bad, phospho-bad (p-bad), bcl-2, Smac/DIABLO, Apaf-1, phospho-p53 (pp53) and cytochrome c (cyc) in male GHRKO and normal (N) mice subjected to VFR or sham surgery, at approximately 6 months of age. The kidneys were collected 2 months after VFR. Results: Caspase-3, caspase-8, bax, bad, Smac/DIABLO, Apaf-1 and pp53 levels were decreased in GHRKO mice as compared to N animals. VFR did not change the level of any of the examined proteins. Conclusion: Decreased renal levels of pro-apoptotic proteins may contribute to extended lifespan due to targeted disruption of GH receptor (Ghr) gene but are apparently not involved in mediating the effects of VFR. PMID:21391871

  11. Growth and growth hormone: An overview.

    PubMed

    Teran, Enrique; Chesner, Jaclyn; Rapaport, Robert

    2016-06-01

    Growth is a good indicator of a child's health. Growth disturbances, including short stature or growth failure, could be indications of illnesses such as chronic disease, nutritional deficits, celiac disease or hormonal abnormalities. Therefore, a careful assessment of the various requirements for normal growth needs to be done by history, physical examination, and screening laboratory tests. More details will be reviewed about the GH-IGF axis, its abnormalities with special emphasis on GH deficiency, its diagnosis and treatment. GH treatment indications in the US will be reviewed and a few only will be highlighted. They will include GH deficiency, as well as the treatment of children born SGA, including the results of a US study using FDA approved dose of 0.48mg/kg/week. GH deficiency in adults will also be briefly reviewed. Treatment of patients with SHOX deficiency will also be discussed. Possible side effects of GH treatment and the importance of monitoring safety will be highlighted.

  12. Effect of insulin-like growth factor-I treatment on serum androgens and testicular and penile size in males with Laron syndrome (primary growth hormone resistance).

    PubMed

    Laron, Z; Klinger, B

    1998-02-01

    Serum gonadotrophins. androgens, insulin and insulin-like growth factor-I (IGF-I) were determined before and during long-term treatment with recombinant IGF-I of seven males with Laron syndrome, and the changes correlated with changes in testicular volume and penile size. The subjects were four boys below the age of 5, two boys aged 10 and 14 but prepubertal and one 28-year-old fully sexually developed adult. IGF-I was administered by a once daily subcutaneous injection of 150 microg/kg per day to the boys and 120 microg/kg per day to the adult patient. In the very young boys no change in serum gonadotrophins, androgens, gonads or genitals was registered. In the two older boys and the adult patient, there was a progressive rise in luteinizing hormone, follicle-stimulating hormone and testosterone. Concomitantly, there was an increase in size of the testes and penile length. The two boys started puberty. As very high serum IGF-I levels were registered in the adult patient, the daily dose was progressively decreased to 70 microg/kg per day. Stopping the IGF-I administration in this patient, according to the protocol, led to a return to pretreatment serum levels and testicular and penile size. This report shows for the first time a direct effect of IGF-I on sex hormones and sex organs in the male.

  13. Growth hormone regulation of follicular growth.

    PubMed

    Lucy, Matthew C

    2011-01-01

    The somatotropic axis-consisting of growth hormone (GH), the insulin-like growth factors 1 and 2 (IGF1 and IGF2), GH binding protein (GHBP), IGF binding proteins (IGFBPs) 1 to 6, and the cell-surface receptors for GH and the IGFs-has major effects on growth, lactation and reproduction. The primary target tissues for GH are involved in growth and metabolism. The functionality of the somatotropic axis depends in part on the expression of liver GH receptor (GHR), which determines the amount of IGF1 released from the liver in response to GH. The IGF1 acts as a pleiotropic growth factor and also serves as the endocrine negative feedback signal controlling pituitary GH secretion. Growth hormone and IGF1 undergo dynamic changes throughout the life cycle, particularly when animals are either growing, early post partum or lactating. Cells within the reproductive tract can respond directly to GH but to a lesser degree than the primary target tissues. The major impact that GH has on reproduction, therefore, may be secondary to its systemic effects on metabolism (including insulin sensitivity) or secondary to the capacity for GH to control IGF1 secretion. Insulin-like growth factor 1 and IGFBP are also synthesised within the ovary and this local synthesis is a component of the collective IGF1 action on the follicle. Future studies of GH should focus on its direct effects on the follicle as well as its indirect effects mediated by shifts in nutrient metabolism, insulin sensitivity, IGF1 and IGFBP.

  14. Growth hormone deficiency: an update.

    PubMed

    Audí, L; Fernández-Cancio, M; Camats, N; Carrascosa, A

    2013-03-01

    Growth hormone (GH) deficiency (GHD) in humans manifests differently according to the individual developmental stage (early after birth, during childhood, at puberty or in adulthood), the cause or mechanism (genetic, acquired or idiopathic), deficiency intensity and whether it is the only pituitary-affected hormone or is combined with that of other pituitary hormones or forms part of a complex syndrome. Growing knowledge of the genetic basis of GH deficiency continues to provide us with useful information to further characterise mutation types and mechanisms for previously described and new candidate genes. Despite these advances, a high proportion of GH deficiencies with no recognisable acquired basis continue to be labelled as idiopathic, although less frequently when they are congenital and/or familial. The clinical and biochemical diagnoses continue to be a conundrum despite efforts to harmonise biochemical assays for GH and IGF-1 analysis, probably because the diagnosis based on the so-called GH secretion stimulation tests will prove to be of limited usefulness for predicting therapy indications.

  15. Growth Hormone and Craniofacial Tissues. An update

    PubMed Central

    Litsas, George

    2015-01-01

    Growth hormone is an important regulator of bone homeostasis. In childhood, it determines the longitudinal bone growth, skeletal maturation, and acquisition of bone mass. In adulthood, it is necessary to maintain bone mass throughout life. Although an association between craniofacial and somatic development has been clearly established, craniofacial growth involves complex interactions of genes, hormones and environment. Moreover, as an anabolic hormone seems to have an important role in the regulation of bone remodeling, muscle enhancement and tooth development. In this paper the influence of growth hormone on oral tissues is reviewed. PMID:25674165

  16. Expression of growth hormone and growth hormone receptor in fibroadenomas of the breast.

    PubMed

    Lenicek, Tanja; Kasumović, Dino; Stajduhar, Emil; Dzombeta, Tihana; Jukić, Zoran; Kruslin, Bozo

    2013-06-01

    Fibroadenoma is the most prevalent benign breast tumor. It consists of epithelial and stromal components. In general, breast tumors are highly hormonally dependent and growth hormone by its physiology may have a possible oncogenic potential. Therefore, the aim of this study was to determine the expression of growth hormone and growth hormone receptor in epithelial and stromal components of fibroadenomas. Study group included 30 randomly chosen fibroadenomas from female patients aged between 18 and 69 years. The expression of growth hormone and growth hormone receptor was defined in both histologic components of fibroadenomas. Growth hormone was expressed in 96.7% of both epithelial and stromal components of fibroadenomas, with stronger expression in the stromal component. The same percentage of positive reaction (96.7%) was obtained in the epithelial component of fibroadenomas for growth hormone receptor expression. Only 6.7% of stromal components tested for growth hormone receptor were positive. The high expression of growth hormone and growth hormone receptor in fibroadenoma tissue indicates their possible role in the pathogenesis of this tumor. Follow up of patients with high expression of growth hormone and growth hormone receptor may be suggested.

  17. Growth hormone doping: a review

    PubMed Central

    Erotokritou-Mulligan, Ioulietta; Holt, Richard IG; Sönksen, Peter H

    2011-01-01

    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. PMID:24198576

  18. Growth hormone and physical performance.

    PubMed

    Birzniece, Vita; Nelson, Anne E; Ho, Ken K Y

    2011-05-01

    There has been limited research and evidence that GH enhances physical performance in healthy adults or in trained athletes. Even so, human growth hormone (GH) is widely abused by athletes. In healthy adults, GH increases lean body mass, although it is possible that fluid retention contributes to this effect. The most recent data indicate that GH does not enhance muscle strength, power, or aerobic exercise capacity, but improves anaerobic exercise capacity. In fact, there are adverse effects of long-term GH excess such that sustained abuse of GH can lead to a state mimicking acromegaly, a condition with increased morbidity and mortality. This review will examine GH effects on body composition and physical performance in health and disease.

  19. [Plant hormones, plant growth regulators].

    PubMed

    Végvári, György; Vidéki, Edina

    2014-06-29

    Plants seem to be rather defenceless, they are unable to do motion, have no nervous system or immune system unlike animals. Besides this, plants do have hormones, though these substances are produced not in glands. In view of their complexity they lagged behind animals, however, plant organisms show large scale integration in their structure and function. In higher plants, such as in animals, the intercellular communication is fulfilled through chemical messengers. These specific compounds in plants are called phytohormones, or in a wide sense, bioregulators. Even a small quantity of these endogenous organic compounds are able to regulate the operation, growth and development of higher plants, and keep the connection between cells, tissues and synergy between organs. Since they do not have nervous and immume systems, phytohormones play essential role in plants' life.

  20. Multiple hormonal resistances: Diagnosis, evaluation and therapy.

    PubMed

    Linglart, Agnès; Silve, Caroline; Rothenbuhler, Anya

    2015-05-01

    Molecular alterations of cAMP-mediated signaling affect primarily the signaling of the PTH/PTHrp receptor, and, with different severities the signaling of other hormones, including TSH. The identification of PTH and other hormonal resistances implies to look for the genetic disorder supporting the metabolic disorder. Copyright © 2015. Published by Elsevier Masson SAS.

  1. Hormonal and nutritional drivers of intrauterine growth.

    PubMed

    Sferruzzi-Perri, Amanda N; Vaughan, Owen R; Forhead, Alison J; Fowden, Abigail L

    2013-05-01

    Size at birth is critical in determining life expectancy with both small and large neonates at risk of shortened life spans. This review examines the hormonal and nutritional drivers of intrauterine growth with emphasis on the role of foetal hormones as nutritional signals in utero. Nutrients drive intrauterine growth by providing substrate for tissue accretion, whereas hormones regulate nutrient distribution between foetal oxidative metabolism and mass accumulation. The main hormonal drivers of intrauterine growth are insulin, insulin-like growth factors and thyroid hormones. Together with leptin and cortisol, these hormones control cellular nutrient uptake and the balance between accretion and differentiation in regulating tissue growth. They also act indirectly via the placenta to alter the materno-foetal supply of nutrients and oxygen. By responding to nutrient and oxygen availability, foetal hormones optimize the survival and growth of the foetus with respect to its genetic potential, particularly during adverse conditions. However, changes in the intrauterine growth of individual tissues may alter their function permanently. In both normal and compromised pregnancies, intrauterine growth is determined by multiple hormonal and nutritional drivers which interact to produce a specific pattern of intrauterine development with potential lifelong consequences for health.

  2. [Hormones and hair growth in man].

    PubMed

    Moretti, G; Rampini, E; Rebora, A

    1977-12-01

    A literature review tries to diminish the ambiguity between hormones and hairs. Therefore the hormonal action in general (regulation of the protein synthesis indirectly by enzymatical regulation of the AMP-system or directly by hormones as active metabolites) and the methods to explore hormones-hair-interaction are discussed. Hormones pertaining to the pituitary-adrenal-gonadal axis are regarded as the paramount hormones; therefore the results of research in testosterone, 5-alpha-dihydrotestosterone, estrogens, progesterone, glucocorticoids, the hypophysis and its tropins are recapitulated. The main disorders of hair-growth, pattern baldness and "idiopathic" hirsutism, which would be dependent on a similar disturbance of androgen metabolism, are discussed. Pathology in hair-growth may arise in any point of the cascade of hormone action.

  3. Thyroid hormone and the growth plate.

    PubMed

    Shao, Yvonne Y; Wang, Lai; Ballock, R Tracy

    2006-12-01

    Thyroid hormone was first identified as a potent regulator of skeletal maturation at the growth plate more than forty years ago. Since that time, many in vitro and in vivo studies have confirmed that thyroid hormone regulates the critical transition between cell proliferation and terminal differentiation in the growth plate, specifically the maturation of growth plate chondrocytes into hypertrophic cells. However these studies have neither identified the molecular mechanisms involved in the regulation of skeletal maturation by thyroid hormone, nor demonstrated how the systemic actions of thyroid hormone interface with the local regulatory milieu of the growth plate. This article will review our current understanding of the role of thyroid hormone in regulating the process of endochondral ossification at the growth plate, as well as what is currently known about the molecular mechanisms involved in this regulation.

  4. Thyroid hormone resistance and its management

    PubMed Central

    Lado-Abeal, Joaquin

    2016-01-01

    The syndrome of impaired sensitivity to thyroid hormone, also known as syndrome of thyroid hormone resistance, is an inherited condition that occurs in 1 of 40,000 live births characterized by a reduced responsiveness of target tissues to thyroid hormone due to mutations on the thyroid hormone receptor. Patients can present with symptoms of hyperthyroidism or hypothyroidism. They usually have elevated thyroid hormones and a normal or elevated thyroid-stimulating hormone level. Due to their nonspecific symptomatic presentation, these patients can be misdiagnosed if the primary care physician is not familiar with the condition. This can result in frustration for the patient and sometimes unnecessary invasive treatment such as radioactive iodine ablation, as in the case presented herein. PMID:27034574

  5. Recombinant Bovine Growth Hormone Criticism Grows.

    ERIC Educational Resources Information Center

    Gaard, Greta

    1995-01-01

    Discusses concerns related to the use of recombinant bovine growth hormone in the United States and other countries. Analyses the issue from the perspectives of animal rights, human health, world hunger, concerns of small and organic farmers, costs to the taxpayer, and environmental questions. A sidebar discusses Canadian review of the hormone.…

  6. Recombinant Bovine Growth Hormone Criticism Grows.

    ERIC Educational Resources Information Center

    Gaard, Greta

    1995-01-01

    Discusses concerns related to the use of recombinant bovine growth hormone in the United States and other countries. Analyses the issue from the perspectives of animal rights, human health, world hunger, concerns of small and organic farmers, costs to the taxpayer, and environmental questions. A sidebar discusses Canadian review of the hormone.…

  7. Yucca schidigera can promote rabbit growth, fecundity, affect the release of hormones in vivo and in vitro, induce pathological changes in liver, and reduce ovarian resistance to benzene.

    PubMed

    Földešiová, Martina; Baláži, Andrej; Chrastinová, Ľubica; Pivko, Juraj; Kotwica, Jan; Harrath, Abdel Halim; Chrenek, Peter; Sirotkin, Alexander V

    2017-08-01

    This study evaluated the effect of Yucca schidigera (YS) extract on the physiological, reproductive, and endocrine indexes of New Zealand White rabbit does. Six-week-old rabbit does were fed a standard diet (control group) or a diet enriched with 5 or 20g of Y powder extract per 100-kg feed mixture for 350days. The does were artificially inseminated after induction of superovulation. Weight gain; conception and kindling rate; viability of pups and mothers; histopathological state of liver and muscle; plasma levels of progesterone (P4), oxytocin (OT), and prostaglandin F (PGF); and the release of P4, insulin-like growth factor I (IGF-I), OT, and PGF by isolated ovarian fragments and their response to the addition of benzene were analyzed. YS extract supplementation promoted weight gain and induced histopathological changes in the liver (creased vacuolization and occurrence of fuchsinophile inclusions in hepatocytes, liver fibrosis, hyperemia, occurrence of Kupffer cells, signs of necrosis and inflammation). YS consumption was not associated with changes in muscle (occurrence of fuchsinophile inclusions and signs of atrophy, interstitial edema, and inflammation), although Y2 increased muscle vascularization. YS supplementation increased conception and kindling rates but did not affect viability of pups or adult animals. Moreover, it enhanced plasma OT and PGF levels; plasma P4 concentration was increased by low-dose YS, but decreased by high-dose YS. Cultured ovarian fragments isolated from YS-fed does released more P4 and PGF and less IGF-I than ovarian fragments of control animals. However, YS supplementation did not affect ovarian OT release. Benzene alone did not influence the release of hormones by ovaries of control does. YS supplementation induced the inhibitory effect of benzene on the release of PGF, but not on other ovarian hormones. Collectively, these results suggest that dietary supplementation of YS extract can stimulate rabbit performance (growth and

  8. Oral manifestations in growth hormone disorders

    PubMed Central

    Atreja, Gaurav; Atreja, Shikha Handa; Jain, Nitul; Sukhija, Urvashi

    2012-01-01

    Growth hormone is of vital importance for normal growth and development. Individuals with growth hormone deficiency develop pituitary dwarfism with disproportionate delayed growth of skull and facial skeleton giving them a small facial appearance for their age. Both hyper and hypopituitarism have a marked effect on development of oro-facial structures including eruption and shedding patterns of teeth, thus giving an opportunity to treating dental professionals to first see the signs and symptoms of these growth disorders and correctly diagnose the serious underlying disease. PMID:22629503

  9. [Human growth hormone and Turner syndrome].

    PubMed

    Sánchez Marco, Silvia Beatriz; de Arriba Muñoz, Antonio; Ferrer Lozano, Marta; Labarta Aizpún, José Ignacio; Garagorri Otero, Jesús María

    2017-02-01

    The evaluation of clinical and analytical parameters as predictors of the final growth response in Turner syndrome patients treated with growth hormone. A retrospective study was performed on 25 girls with Turner syndrome (17 treated with growth hormone), followed-up until adult height. Auxological, analytical, genetic and pharmacological parameters were collected. A descriptive and analytical study was conducted to evaluate short (12 months) and long term response to treatment with growth hormone. A favourable treatment response was shown during the first year of treatment in terms of height velocity gain in 66.6% of cases (height-gain velocity >3cm/year). A favourable long-term treatment response was also observed in terms of adult height, which increased by 42.82±21.23cm (1.25±0.76 SDS), with an adult height gain of 9.59±5.39cm (1.68±1.51 SDS). Predictors of good response to growth hormone treatment are: A) initial growth hormone dose, B) time on growth hormone treatment until starting oestrogen therapy, C) increased IGF1 and IGFBP-3 levels in the first year of treatment, and D) height gain velocity in the first year of treatment. Copyright © 2015 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  10. Growth hormone replacement therapy in Costello syndrome.

    PubMed

    Triantafyllou, Panagiota; Christoforidis, Athanasios; Vargiami, Euthymia; Zafeiriou, Dimitrios I

    2014-12-01

    Costello syndrome (CS) is considered an overgrowth disorder given the macrosomia that is present at birth .However, shortly after birth the weight drops dramatically and the patients are usually referred for failure to thrive. Subsequently, affected patients develop the distinctive coarse facial appearance and are at risk for cardiac anomalies and solid tumor malignancies. Various endocrine disorders, although not very often, have been reported in patients with CS, including growth hormone deficiency, hypoglycemia, ACTH deficiency, cryptorchidism and hypothyroidism. We report a case of Costello syndrome with hypothyroidism, cryptorchidism and growth hormone deficiency and we evaluate the long-term safety and efficacy of growth hormone replacement therapy. The index patient is a paradigm of successful and safe treatment with growth hormone for almost 7 years. Since patients with CS are at increased risk for cardiac myopathy and tumor development they deserve close monitoring during treatment.

  11. Hormones and Human and Nonhuman Primate Growth.

    PubMed

    Bernstein, Robin Miriam

    2017-01-01

    The aim of this paper was to review information pertaining to the hormonal regulation of nonhuman primate growth, with specific focus on the growth hormone (GH)-insulin-like growth factor (IGF) axis and adrenal androgens. Hormones of the GH-IGF axis are consistently associated with measures of growth - linear, weight, or both - during the growth period; in adulthood, concentrations of IGF-I, IGF-binding protein-3, and GH-binding protein are not associated with any measures of size. Comparing patterns of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) may be especially relevant for understanding whether the childhood stage of growth and development is unique to humans and perhaps other apes. Genetic, hormonal, and morphological data on adrenarche in other nonhuman primate species suggest that this endocrine transition is delayed in humans, chimpanzees, and possibly gorillas, while present very early in postnatal life in macaques. This suggests that although perhaps permitted by an extension of the pre-adolescent growth period, childhood builds upon existing developmental substrates rather than having been inserted de novo into an ancestral growth trajectory. Hormones can provide insight regarding the evolution of the human growth trajectory. © 2017 S. Karger AG, Basel.

  12. Risk Assessment of Growth Hormones and Antimicrobial Residues in Meat

    PubMed Central

    Jeong, Sang-Hee; Kang, Daejin; Lim, Myung-Woon; Kang, Chang Soo

    2010-01-01

    Growth promoters including hormonal substances and antibiotics are used legally and illegally in food producing animals for the growth promotion of livestock animals. Hormonal substances still under debate in terms of their human health impacts are estradiol-17β, progesterone, testosterone, zeranol, trenbolone, and melengestrol acetate (MGA) . Many of the risk assessment results of natural steroid hormones have presented negligible impacts when they are used under good veterinary practices. For synthetic hormonelike substances, ADIs and MRLs have been established for food safety along with the approval of animal treatment. Small amounts of antibiotics added to feedstuff present growth promotion effects via the prevention of infectious diseases at doses lower than therapeutic dose. The induction of antimicrobial resistant bacteria and the disruption of normal human intestinal flora are major concerns in terms of human health impact. Regulatory guidance such as ADIs and MRLs fully reflect the impact on human gastrointestinal microflora. However, before deciding on any risk management options, risk assessments of antimicrobial resistance require large-scale evidence regarding the relationship between antimicrobial use in food-producing animals and the occurrence of antimicrobial resistance in human pathogens. In this article, the risk profiles of hormonal and antibacterial growth promoters are provided based on recent toxicity and human exposure information, and recommendations for risk management to prevent human health impacts by the use of growth promoters are also presented. PMID:24278538

  13. Risk assessment of growth hormones and antimicrobial residues in meat.

    PubMed

    Jeong, Sang-Hee; Kang, Daejin; Lim, Myung-Woon; Kang, Chang Soo; Sung, Ha Jung

    2010-12-01

    Growth promoters including hormonal substances and antibiotics are used legally and illegally in food producing animals for the growth promotion of livestock animals. Hormonal substances still under debate in terms of their human health impacts are estradiol-17β, progesterone, testosterone, zeranol, trenbolone, and melengestrol acetate (MGA) . Many of the risk assessment results of natural steroid hormones have presented negligible impacts when they are used under good veterinary practices. For synthetic hormonelike substances, ADIs and MRLs have been established for food safety along with the approval of animal treatment. Small amounts of antibiotics added to feedstuff present growth promotion effects via the prevention of infectious diseases at doses lower than therapeutic dose. The induction of antimicrobial resistant bacteria and the disruption of normal human intestinal flora are major concerns in terms of human health impact. Regulatory guidance such as ADIs and MRLs fully reflect the impact on human gastrointestinal microflora. However, before deciding on any risk management options, risk assessments of antimicrobial resistance require large-scale evidence regarding the relationship between antimicrobial use in food-producing animals and the occurrence of antimicrobial resistance in human pathogens. In this article, the risk profiles of hormonal and antibacterial growth promoters are provided based on recent toxicity and human exposure information, and recommendations for risk management to prevent human health impacts by the use of growth promoters are also presented.

  14. Hormone symphony during root growth and development.

    PubMed

    Garay-Arroyo, Adriana; De La Paz Sánchez, María; García-Ponce, Berenice; Azpeitia, Eugenio; Alvarez-Buylla, Elena R

    2012-12-01

    Hormones regulate plant growth and development in response to external environmental stimuli via complex signal transduction pathways, which in turn form complex networks of interaction. Several classes of hormones have been reported, and their activity depends on their biosynthesis, transport, conjugation, accumulation in the vacuole, and degradation. However, the activity of a given hormone is also dependent on its interaction with other hormones. Indeed, there is a complex crosstalk between hormones that regulates their biosynthesis, transport, and/or signaling functionality, although some hormones have overlapping or opposite functions. The plant root is a particularly useful system in which to study the complex role of plant hormones in the plastic control of plant development. Physiological, cellular, and molecular genetic approaches have been used to study the role of plant hormones in root meristem homeostasis. In this review, we discuss recent findings on the synthesis, signaling, transport of hormones and role during root development and examine the role of hormone crosstalk in maintaining homeostasis in the apical root meristem. Copyright © 2012 Wiley Periodicals, Inc.

  15. Obtaining growth hormone from calf blood

    NASA Technical Reports Server (NTRS)

    Kalchev, L. A.; Ralchev, K. K.; Nikolov, I. T.

    1979-01-01

    The preparation of a growth hormone from human serum was used for the isolation of the hormone from calf serum. The preparation was biologically active - it increased the quantity of the free fatty acids released in rat plasma by 36.4 percent. Electrophoresis in Veronal buffer, ph 8.6, showed the presence of a single fraction having mobility intermediate between that of alpha and beta globulins. Gel filtration through Sephadex G 100 showed an elutriation curve identical to that obtained by the growth hormone prepared from pituitary glands.

  16. Growth Hormone Response after Administration of L-dopa, Clonidine, and Growth Hormone Releasing Hormone in Children with Down Syndrome.

    ERIC Educational Resources Information Center

    Pueschel, Seigfried M.

    1993-01-01

    This study of eight growth-retarded children with Down's syndrome (aged 1 to 6.5 years) found that administration of growth hormone was more effective than either L-dopa or clonidine. Results suggest that children with Down's syndrome have both anatomical and biochemical hypothalamic derangements resulting in decreased growth hormone secretion and…

  17. Growth Hormone Response after Administration of L-dopa, Clonidine, and Growth Hormone Releasing Hormone in Children with Down Syndrome.

    ERIC Educational Resources Information Center

    Pueschel, Seigfried M.

    1993-01-01

    This study of eight growth-retarded children with Down's syndrome (aged 1 to 6.5 years) found that administration of growth hormone was more effective than either L-dopa or clonidine. Results suggest that children with Down's syndrome have both anatomical and biochemical hypothalamic derangements resulting in decreased growth hormone secretion and…

  18. Influence of glucocorticoids and growth hormone on insulin sensitivity in humans.

    PubMed

    Yuen, K C J; Chong, L E; Riddle, M C

    2013-06-01

    The seminal concept proposed by Sir Harold Himsworth more than 75 years ago that a large number of patients with diabetes were 'insulin insensitive', now termed insulin resistance, has now expanded to include several endocrine syndromes, namely those of glucocorticoid excess, and growth hormone excess and deficiency. Synthetic glucocorticoids are increasingly used to treat a wide variety of chronic diseases, whereas the beneficial effects of recombinant growth hormone replacement therapy in children and adults with growth hormone deficiency have now been well-recognized for over 25 years. However, clinical and experimental studies have established that increased circulating levels of glucocorticoids and growth hormone can also lead to worsening of insulin resistance, glucose intolerance, overt diabetes mellitus and cardiovascular disease. Improved understanding of the physiological 24-h rhythmicity of glucocorticoid and growth hormone secretion and its influence on the dawn phenomenon and the Staub-Trauggot effect has therefore led to renewed interest in studies on the mechanisms of insulin resistance induced by exogenous administration of glucocorticoids and growth hormone in humans. In this review, we describe the physiological events that result from the presence of resistance to insulin action at the level of skeletal muscle, adipose tissue, and liver, describe the known mechanisms of glucocorticoid- and growth hormone-mediated insulin resistance, and provide an update of the contributions of glucocorticoids and growth hormone to understanding the pathophysiology of insulin resistance and its effects on several endocrine syndromes. © 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.

  19. [Hormone replacement therapy--growth hormone, melatonin, DHEA and sex hormones].

    PubMed

    Fukai, Shiho; Akishita, Masahiro

    2009-07-01

    The ability to maintain active and independent living as long as possible is crucial for the healthy longevity. Hormones responsible for some of the manifestations associated with aging are growth hormone, insulin-like growth factor-1 (IGF-1), melatonin, dehydroepiandrosterone (DHEA), sex hormones and thyroid hormones. These hormonal changes are associated with changes in body composition, visceral obesity, muscle weakness, osteoporosis, urinary incontinence, loss of cognitive functioning, reduction in well being, depression, as well as sexual dysfunction. With the prolongation of life expectancy, both men and women today live the latter third life with endocrine deficiencies. Hormone replacement therapy may alleviate the debilitating conditions of secondary partial endocrine deficiencies by preventing or delaying some aspects of aging.

  20. Growth Hormone Research Society perspective on the development of long-acting growth hormone preparations

    USDA-ARS?s Scientific Manuscript database

    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). A closed meeting of 55 international scientists with expertise in GH, including pediatric and adult endocrino...

  1. New active series of growth hormone secretagogues.

    PubMed

    Guerlavais, Vincent; Boeglin, Damien; Mousseaux, Delphine; Oiry, Catherine; Heitz, Annie; Deghenghi, Romano; Locatelli, Vittorio; Torsello, Antonio; Ghé, Corrado; Catapano, Filomena; Muccioli, Giampiero; Galleyrand, Jean-Claude; Fehrentz, Jean-Alain; Martinez, Jean

    2003-03-27

    New growth hormone secretagogue (GHS) analogues were synthesized and evaluated for growth hormone releasing activity. This series derived from EP-51389 is based on a gem-diamino structure. Compounds that exhibited higher in vivo GH-releasing potency than hexarelin in rat (subcutaneous administration) were then tested per os in beagle dogs and for their binding affinity to human pituitary GHS receptors and to hGHS-R 1a. Compound 7 (JMV 1843, H-Aib-(d)-Trp-(d)-gTrp-formyl) showed high potency in these tests and was selected for clinical studies.(1)

  2. Sex steroids and growth hormone interactions.

    PubMed

    Fernández-Pérez, Leandro; de Mirecki-Garrido, Mercedes; Guerra, Borja; Díaz, Mario; Díaz-Chico, Juan Carlos

    2016-04-01

    GH and sex hormones are critical regulators of body growth and composition, somatic development, intermediate metabolism, and sexual dimorphism. Deficiencies in GH- or sex hormone-dependent signaling and the influence of sex hormones on GH biology may have a dramatic impact on liver physiology during somatic development and in adulthood. Effects of sex hormones on the liver may be direct, through hepatic receptors, or indirect by modulating endocrine, metabolic, and gender-differentiated functions of GH. Sex hormones can modulate GH actions by acting centrally, regulating pituitary GH secretion, and peripherally, by modulating GH signaling pathways. The endocrine and/or metabolic consequences of long-term exposure to sex hormone-related compounds and their influence on the GH-liver axis are largely unknown. A better understanding of these interactions in physiological and pathological states will contribute to preserve health and to improve clinical management of patients with growth, developmental, and metabolic disorders. Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

  3. Growth hormone in the aging male.

    PubMed

    Sattler, Fred R

    2013-08-01

    Secretion of growth hormone (GH) and IGF-1 levels decline during advancing years-of-life. These changes (somatopause) are associated with loss of vitality, muscle mass, physical function, together with the occurrence of frailty, central adiposity, cardiovascular complications, and deterioration of mental function. For GH treatment to be considered for anti-aging, improved longevity, organ-specific function, or quality of life should be demonstrable. A limited number of controlled studies suggest that GH supplementation in older men increases lean mass by ∼2 kg with similar reductions in fat mass. There is little evidence that GH treatment improves muscle strength and performance (e.g. walking speed or ability to climb stairs) or quality of life. The GHRH agonist (tesamorelin) restores normal GH pulsatility and amplitude, selectively reduces visceral fat, intima media thickness and triglycerides, and improves cognitive function in older persons. This report critically reviews the potential for GH augmentation during aging with emphasis on men since women appear more resistant to treatment.

  4. Recombinant Human Growth Hormone and Rosiglitazone for Abdominal Fat Accumulation in HIV-Infected Patients with Insulin Resistance: A Randomized, Double-Blind, Placebo-Controlled, Factorial Trial

    PubMed Central

    Glesby, Marshall J.; Albu, Jeanine; Chiu, Ya-Lin; Ham, Kirsis; Engelson, Ellen; He, Qing; Muthukrishnan, Varalakshmi; Ginsberg, Henry N.; Donovan, Daniel; Ernst, Jerry; Lesser, Martin; Kotler, Donald P.

    2013-01-01

    Background Recombinant human growth hormone (rhGH) reduces visceral adipose tissue (VAT) volume in HIV-infected patients but can worsen glucose homeostasis and lipoatrophy. We aimed to determine if adding rosiglitazone to rhGH would abrogate the adverse effects of rhGH on insulin sensitivity (SI) and subcutaneous adipose tissue (SAT) volume. Methodology/Principal Findings Randomized, double-blind, placebo-controlled, multicenter trial using a 2×2 factorial design in which HIV-infected subjects with abdominal obesity and insulin resistance were randomized to rhGH 3 mg daily, rosiglitazone 4 mg twice daily, combination rhGH + rosiglitazone, or double placebo (control) for 12 weeks. The primary endpoint was change in SI by frequently sampled intravenous glucose tolerance test from entry to week 12. Body composition was assessed by whole body magnetic resonance imaging (MRI) and dual Xray absorptiometry (DEXA). Seventy-seven subjects were randomized of whom 72 initiated study drugs. Change in SI from entry to week 12 differed across the 4 arms by 1-way ANCOVA (P = 0.02); by pair-wise comparisons, only rhGH (decreasing SI; P = 0.03) differed significantly from control. Changes from entry to week 12 in fasting glucose and glucose area under the curve on 2-hour oral glucose tolerance test differed across arms (1-way ANCOVA P = 0.004), increasing in the rhGH arm relative to control. VAT decreased significantly in the rhGH arms (−17.5% in rhGH/rosiglitazone and −22.7% in rhGH) but not in the rosiglitazone alone (−2.5%) or control arms (−1.9%). SAT did not change significantly in any arm. DEXA results were consistent with the MRI data. There was no significant rhGH x rosiglitazone interaction for any body composition parameter. Conclusions/Significance The addition of rosiglitazone abrogated the adverse effects of rhGH on insulin sensitivity and glucose tolerance while not significantly modifying the lowering effect of rhGH on VAT. Trial Registration

  5. Recombinant human growth hormone and rosiglitazone for abdominal fat accumulation in HIV-infected patients with insulin resistance: a randomized, double-blind, placebo-controlled, factorial trial.

    PubMed

    Glesby, Marshall J; Albu, Jeanine; Chiu, Ya-Lin; Ham, Kirsis; Engelson, Ellen; He, Qing; Muthukrishnan, Varalakshmi; Ginsberg, Henry N; Donovan, Daniel; Ernst, Jerry; Lesser, Martin; Kotler, Donald P

    2013-01-01

    Recombinant human growth hormone (rhGH) reduces visceral adipose tissue (VAT) volume in HIV-infected patients but can worsen glucose homeostasis and lipoatrophy. We aimed to determine if adding rosiglitazone to rhGH would abrogate the adverse effects of rhGH on insulin sensitivity (SI) and subcutaneous adipose tissue (SAT) volume. Randomized, double-blind, placebo-controlled, multicenter trial using a 2×2 factorial design in which HIV-infected subjects with abdominal obesity and insulin resistance were randomized to rhGH 3 mg daily, rosiglitazone 4 mg twice daily, combination rhGH + rosiglitazone, or double placebo (control) for 12 weeks. The primary endpoint was change in SI by frequently sampled intravenous glucose tolerance test from entry to week 12. Body composition was assessed by whole body magnetic resonance imaging (MRI) and dual Xray absorptiometry (DEXA). Seventy-seven subjects were randomized of whom 72 initiated study drugs. Change in SI from entry to week 12 differed across the 4 arms by 1-way ANCOVA (P = 0.02); by pair-wise comparisons, only rhGH (decreasing SI; P = 0.03) differed significantly from control. Changes from entry to week 12 in fasting glucose and glucose area under the curve on 2-hour oral glucose tolerance test differed across arms (1-way ANCOVA P = 0.004), increasing in the rhGH arm relative to control. VAT decreased significantly in the rhGH arms (-17.5% in rhGH/rosiglitazone and -22.7% in rhGH) but not in the rosiglitazone alone (-2.5%) or control arms (-1.9%). SAT did not change significantly in any arm. DEXA results were consistent with the MRI data. There was no significant rhGH x rosiglitazone interaction for any body composition parameter. The addition of rosiglitazone abrogated the adverse effects of rhGH on insulin sensitivity and glucose tolerance while not significantly modifying the lowering effect of rhGH on VAT. Clinicaltrials.gov NCT00130286.

  6. Peripheral activities of growth hormone-releasing hormone.

    PubMed

    Granata, R

    2016-07-01

    Growth hormone (GH)-releasing hormone (GHRH) is produced by the hypothalamus and stimulates GH synthesis and release in the anterior pituitary gland. In addition to its endocrine role, GHRH exerts a wide range of extrapituitary effects which include stimulation of cell proliferation, survival and differentiation, and inhibition of apoptosis. Accordingly, expression of GHRH, as well as the receptor GHRH-R and its splice variants, has been demonstrated in different peripheral tissues and cell types. Among the direct peripheral activities, GHRH regulates pancreatic islet and β-cell survival and function and endometrial cell proliferation, promotes cardioprotection and wound healing, influences the immune and reproductive systems, reduces inflammation, indirectly increases lifespan and adiposity and acts on skeletal muscle cells to inhibit cell death and atrophy. Therefore, it is becoming increasingly clear that GHRH exerts important extrapituitary functions, suggesting potential therapeutic use of the peptide and its analogs in a wide range of medical settings.

  7. Ghrelin and obestatin modulate growth hormone-releasing hormone release and synaptic inputs onto growth hormone-releasing hormone neurons.

    PubMed

    Feng, Dan D; Yang, Seung-Kwon; Loudes, Catherine; Simon, Axelle; Al-Sarraf, Tamara; Culler, Michael; Alvear-Perez, Rodrigo; Llorens-Cortes, Catherine; Chen, Chen; Epelbaum, Jacques; Gardette, Robert

    2011-09-01

    Ghrelin, a natural ligand of the growth hormone secretagogue receptor (GHS-R), is synthesized in the stomach but may also be expressed in lesser quantity in the hypothalamus where the GHS-R is located on growth hormone-releasing hormone (GHRH) neurons. Obestatin, a peptide derived from the same precursor as ghrelin, is able to antagonize the ghrelin-induced increase of growth hormone (GH) secretion in vivo but not from pituitary explants in vitro. Thus, the blockade of ghrelin-induced GH release by obestatin could be mediated at the hypothalamic level by the neuronal network that controls pituitary GH secretion. Ghrelin increased GHRH and decreased somatostatin (somatotropin-releasing inhibitory factor) release from hypothalamic explants, whereas obestatin only reduced the ghrelin-induced increase of GHRH release, thus indicating that the effect of ghrelin and obestatin is targeted to GHRH neurons. Patch-clamp recordings on mouse GHRH-enhanced green fluorescent protein neurons indicated that ghrelin and obestatin had no significant effects on glutamatergic synaptic transmission. Ghrelin decreased GABAergic synaptic transmission in 44% of the recorded neurons, an effect blocked in the presence of the GHS-R antagonist BIM28163, and stimulated the firing rate of 78% of GHRH neurons. Obestatin blocked the effects of ghrelin by acting on a receptor different from the GHS-R. These data suggest that: (i) ghrelin increases GHRH neuron excitability by increasing their action potential firing rate and decreasing the strength of GABA inhibitory inputs, thereby leading to an enhanced GHRH release; and (ii) obestatin counteracts ghrelin actions. Such interactions on GHRH neurons probably participate in the control of GH secretion.

  8. IGF-1 and insulin as growth hormones.

    PubMed

    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.

  9. [How corticoids, growth hormone and oestrogens influence lipids and atherosclerosis].

    PubMed

    Marek, J; Hána, V; Krsek, M

    2007-04-01

    The hormones with a strong influence on the lipid spectrum and the development of atherosclerosis include cortisol, growth hormone and oestrogens. Cortisol accelerates atherosclerosis both through dyslipidemia and through an increase in visceral fat, hypertension, increased insulin resistance and the development of reduced glucose tolerance which may result in diabetes mellitus. Even when a cortisol excess disappears, as is the case of patients cured of Cushing syndrome, arterial walls remain permanently vulnerable to the atherosclerotic process. In conditions involving a lack of growth hormone, dyslipidemia develops and increases the burden on the cardiovascular system if not treated in a timely manner by the substitution of growth hormone. Oestrogens have a double effect: they have an anti-atherogenic effect on artery walls that are not yet damaged by an atherosclerotic process, but where atherosclerosis has already developed they have a prothrombotic effect and destabilise the atheromatous plaques. If oestrogen is to be used as protection against the onset of atherogenesis, it is necessary to start in a period when the atherosclerotic process has not yet begun to damage the woman's arterial walls and it is best to use natural hormones (estradiol) and to prevent endometriosis it should be combined with crystalline progesterone applied locally--inravaginally. Oestrogens should be given in small doses, preferably parenterally. Even this will not prevent genetic oestrogen effects though.

  10. History of growth hormone therapy.

    PubMed

    Blizzard, Robert M

    2012-01-01

    The first human to receive GH therapy was in 1956; it was of bovine origin and was given for 3 wk for metabolic balance studies revealing no effects. By 1958, three separate laboratories utilizing different extraction methods retrieved hGH from human pituitaries, purified it and used for clinical investigation. By 1959 presumed GHD patients were being given native hGH collected and extracted by various methods. Since 1 mg of hGH was needed to treat one patient per day, >360 human pituitaries were needed per patient per year. Thus, the availability of hGH was limited and was awarded on the basis of clinical research protocols approved by the National Pituitary Agency (NPA) established in 1961. hGH was dispensed and injected on a milligram weight basis with varied concentrations between batches from 0.5 units/mg to 2.0 units/mg of hGH. By 1977 a centralized laboratory was established to extract all human pituitaries in the US, this markedly improved the yield of hGH obtained and most remarkably, hGH of this laboratory was never associated with Creutzfeld-Jacob disease (CJD) resulting from the injection of apparently prior- contaminated hGH produced years earlier. However, widespread rhGH use was not possible even if a pituitary from each autopsy performed in the US was collected, this would only permit therapy for about 4,000 patients. Thus, the mass production of rhGH required the identification of the gene structure of the hormone, methodology that began in 1976 to make insulin by recombinant technology. Serendipity was manifest in 1985 when patients who had received hGH years previously were reported to have died of CJD. This led to the discontinuation of the distribution and use of hGH, at a time when a synthetic rhGH became available for clinical use. The creation of a synthetic rhGH was accompanied by unlimited supplies of hGH for investigation and therapy. However, the appropriate use and the potential abuse of this hormone are to be dealt with. The

  11. Nutrient Sensing Overrides Somatostatin and Growth Hormone-Releasing Hormone to Control Pulsatile Growth Hormone Release.

    PubMed

    Steyn, F J

    2015-07-01

    Pharmacological studies reveal that interactions between hypothalamic inhibitory somatostatin and stimulatory growth hormone-releasing hormone (GHRH) govern pulsatile GH release. However, in vivo analysis of somatostatin and GHRH release into the pituitary portal vasculature and peripheral GH output demonstrates that the withdrawal of somatostatin or the appearance of GHRH into pituitary portal blood does not reliably dictate GH release. Consequently, additional intermediates acting at the level of the hypothalamus and within the anterior pituitary gland are likely to contribute to the release of GH, entraining GH secretory patterns to meet physiological demand. The identification and validation of the actions of such intermediates is particularly important, given that the pattern of GH release defines several of the physiological actions of GH. This review highlights the actions of neuropeptide Y in regulating GH release. It is acknowledged that pulsatile GH release may not occur selectively in response to hypothalamic control of pituitary function. As such, interactions between somatotroph networks, the median eminence and pituitary microvasculature and blood flow, and the emerging role of tanycytes and pericytes as critical regulators of pulsatility are considered. It is argued that collective interactions between the hypothalamus, the median eminence and pituitary vasculature, and structural components within the pituitary gland dictate somatotroph function and thereby pulsatile GH release. These interactions may override hypothalamic somatostatin and GHRH-mediated GH release, and modify pulsatile GH release relative to the peripheral glucose supply, and thereby physiological demand.

  12. Growth Hormone Deficiency, Brain Development, and Intelligence

    ERIC Educational Resources Information Center

    Meyer-Bahlburg, Heino F. L.; And Others

    1978-01-01

    Available from: American Medical Association, 535 N. Dearborn Street, Chicago, Illinois 60610. In order to determine what effect, if any, growth hormone (GH) has on human brain development, 29 patients (mean age 11.7 years) with GH deficiency were selected according to the following criteria: no evidence of reversible GH deficiency, onset of…

  13. Human Growth Hormone: The Latest Ergogenic Aid?

    ERIC Educational Resources Information Center

    Cowart, Virginia S.

    1988-01-01

    Believing that synthetic human growth hormone (hGH) will lead to athletic prowess and fortune, some parents and young athletes wish to use the drug to enhance sports performance. Should hGH become widely available, its abuse could present many problems, from potential health risks to the ethics of drug-enhanced athletic performance. (JL)

  14. Growth hormone: health considerations beyond height gain

    USDA-ARS?s Scientific Manuscript database

    The therapeutic benefit of growth hormone (GH) therapy in improving height in short children is widely recognized; however, GH therapy is associated with other metabolic actions that may be of benefit in these children. Beneficial effects of GH on body composition have been documented in several dif...

  15. Growth Hormone Deficiency, Brain Development, and Intelligence

    ERIC Educational Resources Information Center

    Meyer-Bahlburg, Heino F. L.; And Others

    1978-01-01

    Available from: American Medical Association, 535 N. Dearborn Street, Chicago, Illinois 60610. In order to determine what effect, if any, growth hormone (GH) has on human brain development, 29 patients (mean age 11.7 years) with GH deficiency were selected according to the following criteria: no evidence of reversible GH deficiency, onset of…

  16. Human Growth Hormone: The Latest Ergogenic Aid?

    ERIC Educational Resources Information Center

    Cowart, Virginia S.

    1988-01-01

    Believing that synthetic human growth hormone (hGH) will lead to athletic prowess and fortune, some parents and young athletes wish to use the drug to enhance sports performance. Should hGH become widely available, its abuse could present many problems, from potential health risks to the ethics of drug-enhanced athletic performance. (JL)

  17. Growth hormone, growth factors, and acromegaly

    SciTech Connect

    Ludecke, D.K.; Tolis, G.T.

    1987-01-01

    This book contains five sections, each consisting of several papers. The section headings are: Biochemistry and Physiology of GH and Growth Factors, Pathology of Acromegaly, Clinical Endocrinology of Acromegaly, Nonsurgical Therapy of Acromegaly, and Surgical Therapy of Acromegaly.

  18. Growth hormone-releasing hormone is produced by adipocytes and regulates lipolysis through growth hormone receptor.

    PubMed

    Rodríguez-Pacheco, F; Gutierrez-Repiso, C; García-Serrano, S; Ho-Plagaro, A; Gómez-Zumaquero, J M; Valdes, S; Gonzalo, M; Rivas-Becerra, J; Montiel-Casado, C; Rojo-Martínez, G; García-Escobar, E; García-Fuentes, E

    2017-10-01

    Growth hormone-releasing hormone (GHRH) has a crucial role in growth hormone (GH) secretion, but little is known about its production by adipocytes and its involvement in adipocyte metabolism. To determine whether GHRH and its receptor (GHRH-R) are present in human adipocytes and to study their levels in obesity. Also, to analyze the effects of GHRH on human adipocyte differentiation and lipolysis. GHRH/GHRH-R and GH/GH-R mRNA expression levels were analyzed in human mature adipocytes from non-obese and morbidly obese subjects. Human mesenchymal stem cells (HMSC) were differentiated to adipocytes with GHRH (10(-14)-10(-8) M). Adipocyte differentiation, lipolysis and gene expression were measured and the effect of GH-R silencing was determined. Mature adipocytes from morbidly obese subjects showed a higher expression of GHRH and GH-R, and a lower expression of GHRH-R and GH than non-obese subjects (P<0.05). A total of 10(-14)-10(-10) M GHRH induced an inhibition of lipid accumulation and PPAR-γ expression (P<0.05), and an increase in glycerol release and HSL expression (P<0.05) in human differentiated adipocytes. A total of 10(-12)-10(-8) M GHRH decreased GHRH-R expression in human differentiated adipocytes (P<0.05). A total of 10(-10)-10(-8) M GHRH increased GH and GH-R expression in human differentiated adipocytes (P<0.05). The effects of GHRH at 10(-10) M on adipocyte differentiation and lipolysis were blocked when GH-R expression was silenced. GHRH and GHRH-R are expressed in human adipocytes and are negatively associated. GHRH at low doses may exert an anti-obesity effect by inhibiting HMSC differentiation in adipocytes and by increasing adipocyte lipolysis in an autocrine or paracrine pathway. These effects are mediated by GH and GH-R.

  19. Climacteric in untreated isolated growth hormone deficiency

    PubMed Central

    Menezes, Menilson; Salvatori, Roberto; Oliveira, Carla R.P.; Pereira, Rossana M.C.; Souza, Anita H.O.; Nobrega, Luciana M.A.; Cruz, Edla do A.C.; Menezes, Marcos; Alves, Érica O.; Aguiar-Oliveira, Manuel H.

    2008-01-01

    Objective To study the time, intensity of symptoms, hormonal profile, and related morbidity of climacteric in women with untreated isolated growth hormone (GH) deficiency (IGHD). Design Women belonging to a large Brazilian kindred with IGHD due to a homozygous mutation in the GH-releasing hormone receptor gene were studied. None of them had ever received GH replacement therapy. A two-step protocol was performed. In the first case-control experiment, aimed to determine the age at climacteric, we compared eight women with IGHD and 32 normal women between 37 and 55 years of age. In the second cross-sectional experiment, aimed to determine the severity of climacteric symptoms, seven women with IGHD (aged 47-65 y) were compared with 13 controls (aged 44-65 y). The Kupperman Index scores, serum follicle-stimulating hormone, luteinizing hormone, prolactin, and estradiol levels were determined, and pelvic and mammary ultrasonography, mammography, and colpocytology were performed. Results The number of women with follicle-stimulating hormone above 20 mIU/mL was higher in women with IGHD than controls. Kupperman’s Index was not different between the two groups. Menarche had been delayed and parity was lower in women with IGHD. Hormonal profile was similar, but prolactin was lower in women with IGHD. Uterine volume was smaller in women with IGHD, and endometrial thickness and ovarian volume were similar in the two groups. No difference in breast images or in colpocytology was observed between the two groups. Conclusions Menarche was delayed and the beginning of climacteric is anticipated in untreated lifetime IGHD, but menopausal symptoms and hormonal profile resemble the normal climacteric. PMID:18223507

  20. Specific involvement of gonadal hormones in the functional maturation of growth hormone releasing hormone (GHRH) neurons.

    PubMed

    Gouty-Colomer, Laurie-Anne; Méry, Pierre-François; Storme, Emilie; Gavois, Elodie; Robinson, Iain C; Guérineau, Nathalie C; Mollard, Patrice; Desarménien, Michel G

    2010-12-01

    Growth hormone (GH) is the key hormone involved in the regulation of growth and metabolism, two functions that are highly modulated during infancy. GH secretion, controlled mainly by GH releasing hormone (GHRH), has a characteristic pattern during postnatal development that results in peaks of blood concentration at birth and puberty. A detailed knowledge of the electrophysiology of the GHRH neurons is necessary to understand the mechanisms regulating postnatal GH secretion. Here, we describe the unique postnatal development of the electrophysiological properties of GHRH neurons and their regulation by gonadal hormones. Using GHRH-eGFP mice, we demonstrate that already at birth, GHRH neurons receive numerous synaptic inputs and fire large and fast action potentials (APs), consistent with effective GH secretion. Concomitant with the GH secretion peak occurring at puberty, these neurons display modifications of synaptic input properties, decrease in AP duration, and increase in a transient voltage-dependant potassium current. Furthermore, the modulation of both the AP duration and voltage-dependent potassium current are specifically controlled by gonadal hormones because gonadectomy prevented the maturation of these active properties and hormonal treatment restored it. Thus, GHRH neurons undergo specific developmental modulations of their electrical properties over the first six postnatal weeks, in accordance with hormonal demand. Our results highlight the importance of the interaction between the somatotrope and gonadotrope axes during the establishment of adapted neuroendocrine functions.

  1. Developmental programming: the role of growth hormone.

    PubMed

    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.

  2. Hypopituitarism: growth hormone and corticotropin deficiency.

    PubMed

    Capatina, Cristina; Wass, John A H

    2015-03-01

    This article presents an overview of adult growth hormone deficiency (AGHD) and corticotropin deficiency (central adrenal failure, CAI). Both conditions can result from various ailments affecting the hypothalamus or pituitary gland (most frequently a tumor in the area or its treatment). Clinical manifestations are subtle in AGHD but potentially life-threatening in CAI. The diagnosis needs dynamic testing in most cases. Treatment of AGHD is recommended in patients with documented severe deficiency, and treatment of CAI is mandatory in all cases. Despite significant progress in replacement hormonal therapy, more physiologic treatments and more reliable indicators of treatment adequacy are still needed.

  3. Prolactin and growth hormone in fish osmoregulation

    USGS Publications Warehouse

    Sakamoto, T.; McCormick, S.D.

    2006-01-01

    Prolactin is an important regulator of multiple biological functions in vertebrates, and has been viewed as essential to ion uptake as well as reduction in ion and water permeability of osmoregulatory surfaces in freshwater and euryhaline fish. Prolactin-releasing peptide seems to stimulate prolactin expression in the pituitary and peripheral organs during freshwater adaptation. Growth hormone, a member of the same family of hormones as prolactin, promotes acclimation to seawater in several teleost fish, at least in part through the action of insulin-like growth factor I. In branchial epithelia, development and differentiation of the seawater-type chloride cell (and their underlying biochemistry) is regulated by GH, IGF-I, and cortisol, whereas the freshwater-type chloride cell is regulated by prolactin and cortisol. In the epithelia of gastrointestinal tract, prolactin induces cell proliferation during freshwater adaptation, whereas cortisol stimulates both cell proliferation and apoptosis. We propose that control of salinity acclimation in teleosts by prolactin and growth hormone primarily involves regulation of cell proliferation, apoptosis, and differentiation (the latter including upregulation of specific ion transporters), and that there is an important interaction of these hormones with corticosteroids. ?? 2005 Elsevier Inc. All rights reserved.

  4. Obesity, growth hormone and weight loss.

    PubMed

    Rasmussen, Michael Højby

    2010-03-25

    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 profile and bone mineral density. It is well established that adult GHD usually is accompanied by an increase in fat accumulation and GH replacement in adult patients with GHD results in reduction of fat mass and abdominal fat mass in particular. It is also recognized that obesity and abdominal obesity in particular results in a secondary reduction in GH secretion and subnormal insulin-like growth factor-I (IGF-I) levels. The recovery of the GH IGF-I axis after weight loss suggest an acquired defect, however, the pathophysiologic role of GH in obesity is yet to be fully understood. In clinical studies examining the efficacy of GH in obese subjects very little or no effect are observed with respect to weight loss, whereas GH seems to reduce total and abdominal fat mass in obese subjects. The observed reductions in abdominal fat mass are modest and similar to what can be achieved by diet or exercise interventions.

  5. Enzyme immunoassay for rat growth hormone: applications to the study of growth hormone variants

    SciTech Connect

    Farrington, M.A.; Hymer, W.C.

    1987-06-29

    A sensitive and specific competitive enzyme immunoassay (EIA) for rat growth hormone was developed. In this assay soluble growth hormone and growth hormone adsorbed to a solid-phase support compete for monkey anti-growth hormone antibody binding sites. The immobilized antibody-growth hormone complex is detected and quantified using goat anti-monkey immunoglobin G covalently conjugated to horse radish peroxidase. Therefore, a high concentration of soluble growth hormone in the sample will result in low absorbance detection from the colored products of the enzyme reaction. Assay parameters were optimized by investigating the concentration of reagents and the reaction kinetics in each of the assay steps. The assay can be performed in 27 hours. A sensitivity range of 0.19 ng to 25 ng in the region of 10 to 90% binding was obtained. Near 50% binding (3 ng) the intraassay coefficient of variation (CV) was 5.54% and the interassay CV was 5.33%. The correlation coefficient (r/sup 2/) between radioimmunoassay and EIA was 0.956 and followed the curve Y = 0.78X + 1.0. 9 references, 6 figures.

  6. Preventing Growth Hormone Abuse: An Emerging Health Concern.

    ERIC Educational Resources Information Center

    White, George L.; And Others

    1989-01-01

    Facts about growth hormone abuse should be incorporated into substance abuse components of health education curriculums. Sources, uses, and dangers associated with human growth hormones are discussed. A sample lesson plan is included. (IAH)

  7. Gravitational effects on plant growth hormone concentration

    NASA Technical Reports Server (NTRS)

    Bandurski, R. S.; Schulze, A.

    1983-01-01

    Dolk's (1936) finding that more growth hormone diffuses from the lower side of a gravity-stimulated plant shoot than from the upper side is presently confirmed by means of both an isotope dilution assay and selected ion monitoring-gas chromatography-mass spectrometry, and it is established that the asymmetrically distributed hormone is indole-3-acetic acid (IAA). This is the first physicochemical demonstration that there is more IAA on the lower sides of a geostimulated plant shoot. It is also found that free IAA primarily occurs in the conductive vascular tissues of the shoot, while IAA esters predominate in the growing cortical cells. A highly sensitive gas chromatographic isotope dilution assay shows that the hormone asymmetry also occurs in the nonvascular tissue.

  8. [Synthesis and regulation of growth hormone secretion].

    PubMed

    Miyachi, Y; Yakushiji, F; Terazono, T

    1993-10-01

    Human growth hormone (hGH) is a single chain, 22 kd-protein with two intramolecular disulfide bonds. The hGH gene is located on chromosome 17 at band q22-q24 and has four introns separating five coding exons. The expression of hGH is restricted to the pituitary and regulated by GHF-1 which binds to the hGH promoter acting in concert with several other more ubiquitous DNA binding proteins. The secretion of hGH is regulated by GH releasing hormone (GRH) and somatostatin. GRH controls GH synthesis by stimulating transcription of GH mRNA while somatostatin determines the timing and amplitude of GH pulses. Pulsatile GH secretion is influenced by a number of neurogenic, metabolic and hormonal factors.

  9. Gravitational effects on plant growth hormone concentration

    NASA Technical Reports Server (NTRS)

    Bandurski, R. S.; Schulze, A.

    1983-01-01

    Dolk's (1936) finding that more growth hormone diffuses from the lower side of a gravity-stimulated plant shoot than from the upper side is presently confirmed by means of both an isotope dilution assay and selected ion monitoring-gas chromatography-mass spectrometry, and it is established that the asymmetrically distributed hormone is indole-3-acetic acid (IAA). This is the first physicochemical demonstration that there is more IAA on the lower sides of a geostimulated plant shoot. It is also found that free IAA primarily occurs in the conductive vascular tissues of the shoot, while IAA esters predominate in the growing cortical cells. A highly sensitive gas chromatographic isotope dilution assay shows that the hormone asymmetry also occurs in the nonvascular tissue.

  10. Genetics and epigenetics of parathyroid hormone resistance.

    PubMed

    Bastepe, Murat

    2013-01-01

    End-organ resistance to the actions of parathyroid hormone (PTH) is defined as pseudohypoparathyroidism (PHP). Described originally by Fuller Albright and his colleagues in early 1940s, this rare genetic disease is subclassified into two types according to the nephrogenous response to the administration of biologically active PTH. In type I, the PTH-induced urinary excretion of both phosphate and cyclic AMP (cAMP) is blunted. In type II, only the PTH-induced urinary excretion of phosphate is blunted, while the cAMP response is unimpaired. Different subtypes of PHP type I have been described based on the existence of additional clinical features, such as resistance to other hormones and Albright's hereditary osteodystrophy, and underlying molecular defects. Genetic mutations responsible for the different subtypes of PHP type I involve the GNAS complex locus, an imprinted gene encoding the α-subunit of the stimulatory G protein (Gsα) and several other transcripts that are expressed in a parent-of-origin specific manner. Mutations in Gsα-coding GNAS exons cause PHP-Ia and, in some cases, PHP-Ic, while mutations that disrupt the imprinting of GNAS lead to PHP-Ib. PHP type II is less well characterized with respect to its molecular cause. Recently, however, mutations in PRKAR1A, a regulatory subunit of the cAMP-dependent protein kinase, have been identified in several cases of PTH and other hormone resistance and skeletal dysplasia that are considered to be affected by PHP type II due to unimpaired urinary excretion of cAMP following PTH administration. Copyright © 2013 S. Karger AG, Basel.

  11. Antagonists of growth hormone-releasing hormone suppress in vivo tumor growth and gene expression in triple negative breast cancers.

    PubMed

    Perez, Roberto; Schally, Andrew V; Vidaurre, Irving; Rincon, Ricardo; Block, Norman L; Rick, Ferenc G

    2012-09-01

    This study evaluated the effects of a modern antagonistic analog of GHRH on tumor growth and on expression of inflammatory cytokine genes in two models of human triple negative breast cancers (TNBC). The TNBC subtype is refractory to the treatment options available for other hormone-independent breast cancers. Inflammatory cytokines play a major role in the cellular signaling associated with breast cancer pathogenesis and enhance epithelial-mesenchymal transitions (EMT), drug resistance, and metastatic potential. Growth hormone-releasing hormone (GHRH) is a hypothalamic neuropeptide which regulates the synthesis and release of growth hormone by the pituitary and is an autocrine/paracrine growth factor for multiple human cancers. The effects of analogs of GHRH on tumoral cytokine expression have not been previously investigated. Animals bearing xenografts of the human TNBC cell lines, HCC1806 and MX-1, were treated with MIA-602, an antagonistic analog of GHRH. Treatment with MIA-602 significantly reduced tumor growth. We quantified transcript levels of the genes for several inflammatory cytokines. Expression of INFγ, IL-1α, IL-4, IL-6, IL-8, IL-10, and TNFα, was significantly reduced by treatment with MIA-602. We conclude that treatment of TNBC with GHRH antagonists reduces tumor growth through an action mediated by tumoral GHRH receptors and produces a suppression of inflammatory cytokine signaling. Silencing of GHRH receptors in vitro with siRNA inhibited the expression of GHRH-R genes and inflammatory cytokine genes in HCC1806 and MX-1 cells. Further studies on GHRH antagonists may facilitate the development of new strategies for the treatment of resistant cancers.

  12. 21 CFR 862.1370 - Human growth hormone test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Human growth hormone test system. 862.1370 Section 862.1370 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Systems § 862.1370 Human growth hormone test system. (a) Identification. A human growth hormone test...

  13. 21 CFR 862.1370 - Human growth hormone test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Human growth hormone test system. 862.1370 Section 862.1370 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Systems § 862.1370 Human growth hormone test system. (a) Identification. A human growth hormone test...

  14. 21 CFR 862.1370 - Human growth hormone test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Human growth hormone test system. 862.1370 Section 862.1370 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Systems § 862.1370 Human growth hormone test system. (a) Identification. A human growth hormone test...

  15. Cortistatin vaccination--a solution to growth hormone deficiency.

    PubMed

    Moaeen-ud-Din, M; Malik, Nosheen; Guo, Yang Li; Ali, Ahmad; Babar, Masroor Ellahi

    2009-12-01

    Cortistatin and somatostatin are neuropeptides which have inhibitory effects on growth hormone through common five receptors. Although, both have inhibitory effects but, only cortistatin has direct inhibitory effects on growth hormone secretagogue and is more potent inhibitor of growth hormone than somatostatin. This control of growth hormone can be manipulated through immunoneutralization of cortistatin through cortistatin DNA vaccine rather than antibodies application. A DNA vaccine of cortistatin can be produced using recombinant DNA technology in a eukaryotic expression system and will serve as a tool not to only alleviate the growth hormone deficiency problems in human but, can also be used to improve growth rate in farm animals.

  16. Growth Hormone Therapy in Children with Chronic Renal Failure

    PubMed Central

    Cayir, Atilla; Kosan, Celalettin

    2015-01-01

    Growth is impaired in a chronic renal failure. Anemia, acidosis, reduced intake of calories and protein, decreased synthesis of vitamin D and increased parathyroid hormone levels, hyperphosphatemia, renal osteodystrophy and changes in growth hormone-insulin-like growth factor and the gonadotropin-gonadal axis are implicated in this study. Growth is adversely affected by immunosuppressives and corticosteroids after kidney transplantation. Treating metabolic disorders using the recombinant human growth hormone is an effective option for patients with inadequate growth rates. PMID:25745347

  17. Growth hormone therapy in children with chronic renal failure.

    PubMed

    Cayir, Atilla; Kosan, Celalettin

    2015-02-01

    Growth is impaired in a chronic renal failure. Anemia, acidosis, reduced intake of calories and protein, decreased synthesis of vitamin D and increased parathyroid hormone levels, hyperphosphatemia, renal osteodystrophy and changes in growth hormone-insulin-like growth factor and the gonadotropin-gonadal axis are implicated in this study. Growth is adversely affected by immunosuppressives and corticosteroids after kidney transplantation. Treating metabolic disorders using the recombinant human growth hormone is an effective option for patients with inadequate growth rates.

  18. Growth hormone in chronic renal disease.

    PubMed

    Gupta, Vishal; Lee, Marilyn

    2012-03-01

    Severe growth retardation (below the third percentile for height) is seen in up to one-third children with chronic kidney disease. It is thought to be multifactorial and despite optimal medical therapy most children are unable to reach their normal height. Under-nutrition, anemia, vitamin D deficiency with secondary hyperparathyroidism, metabolic acidosis, hyperphosphatemia, renal osteodystrophy; abnormalities in the growth hormone/insulin like growth factor system and sex steroids, all have been implicated in the pathogenesis of growth failure. Therapy includes optimization of nutritional and metabolic abnormalities. Failure to achieve adequate height despite 3-6 months of optimal medical measures mandates the use of recombinant GH (rGH) therapy, which has shown to result in catch-up growth, anywhere from 2 cm to 10 cm with satisfactory liner, somatic and psychological development.

  19. Growth hormone in chronic renal disease

    PubMed Central

    Gupta, Vishal; Lee, Marilyn

    2012-01-01

    Severe growth retardation (below the third percentile for height) is seen in up to one-third children with chronic kidney disease. It is thought to be multifactorial and despite optimal medical therapy most children are unable to reach their normal height. Under-nutrition, anemia, vitamin D deficiency with secondary hyperparathyroidism, metabolic acidosis, hyperphosphatemia, renal osteodystrophy; abnormalities in the growth hormone/insulin like growth factor system and sex steroids, all have been implicated in the pathogenesis of growth failure. Therapy includes optimization of nutritional and metabolic abnormalities. Failure to achieve adequate height despite 3–6 months of optimal medical measures mandates the use of recombinant GH (rGH) therapy, which has shown to result in catch-up growth, anywhere from 2 cm to 10 cm with satisfactory liner, somatic and psychological development. PMID:22470855

  20. Growth hormone therapy for people with thalassaemia.

    PubMed

    Ngim, Chin Fang; Lai, Nai Ming; Hong, Janet Yh; Tan, Shir Ley; Ramadas, Amutha; Muthukumarasamy, Premala; Thong, Meow-Keong

    2017-09-18

    Thalassaemia is a recessively-inherited blood disorder that leads to anaemia of varying severity. In those affected by the more severe forms, regular blood transfusions are required which may lead to iron overload. Accumulated iron from blood transfusions may be deposited in vital organs including the heart, liver and endocrine organs such as the pituitary glands which can affect growth hormone production. Growth hormone deficiency is one of the factors that can lead to short stature, a common complication in people with thalassaemia. Growth hormone replacement therapy has been used in children with thalassaemia who have short stature and growth hormone deficiency. To assess the benefits and safety of growth hormone therapy in people with thalassaemia. We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles, reviews and clinical trial registries. Our database and trial registry searches are current to 10 August 2017 and 08 August 2017, respectively. Randomised and quasi-randomised controlled trials comparing the use of growth hormone therapy to placebo or standard care in people with thalassaemia of any type or severity. Two authors independently selected trials for inclusion. Data extraction and assessment of risk of bias were also conducted independently by two authors. The quality of the evidence was assessed using GRADE criteria. One parallel trial conducted in Turkey was included. The trial recruited 20 children with homozygous beta thalassaemia who had short stature; 10 children received growth hormone therapy administered subcutaneously on a daily basis at a dose of 0.7 IU/kg per week and 10 children received standard care. The overall risk of bias in this trial was low except for the selection criteria and attrition bias which were unclear. The quality of the evidence for all major outcomes

  1. Multiple Effects of Growth Hormone in the Body: Is it Really the Hormone for Growth?

    PubMed Central

    Devesa, Jesús; Almengló, Cristina; Devesa, Pablo

    2016-01-01

    In this review, we analyze the effects of growth hormone on a number of tissues and organs and its putative role in the longitudinal growth of an organism. We conclude that the hormone plays a very important role in maintaining the homogeneity of tissues and organs during the normal development of the human body or after an injury. Its effects on growth do not seem to take place during the fetal period or during the early infancy and are mediated by insulin-like growth factor I (IGF-I) during childhood and puberty. In turn, IGF-I transcription is dependent on an adequate GH secretion, and in many tissues, it occurs independent of GH. We propose that GH may be a prohormone, rather than a hormone, since in many tissues and organs, it is proteolytically cleaved in a tissue-specific manner giving origin to shorter GH forms whose activity is still unknown. PMID:27773998

  2. Thyroid hormone receptors bind to defined regions of the growth hormone and placental lactogen genes.

    PubMed Central

    Barlow, J W; Voz, M L; Eliard, P H; Mathy-Harter, M; De Nayer, P; Economidis, I V; Belayew, A; Martial, J A; Rousseau, G G

    1986-01-01

    The intracellular receptor for thyroid hormone is a protein found in chromatin. Since thyroid hormone stimulates transcription of the growth hormone gene through an unknown mechanism, the hypothesis that the thyroid hormone-receptor complex interacts with defined regions of this gene has been investigated in a cell-free system. Nuclear extracts from human lymphoblastoid IM-9 cells containing thyroid hormone receptors were incubated with L-3,5,3'-tri[125I]iodothyronine and calf thymus DNA-cellulose. Restriction fragments of the human growth hormone gene were added to determine their ability to inhibit labeled receptor binding to DNA-cellulose. These fragments encompassed nucleotide sequences from about three kilobase pairs upstream to about four kilobase pairs downstream from the transcription initiation site. The thyroid hormone-receptor complex bound preferentially to the 5'-flanking sequences of the growth hormone gene in a region between nucleotide coordinates -290 and -129. The receptor also bound to an analogous promoter region in the human placental lactogen gene, which has 92% nucleotide sequence homology with the growth hormone gene. These binding regions appear to be distinct from those that are recognized by the receptor for glucocorticoids, which stimulate growth hormone gene expression synergistically with thyroid hormone. The presence of thyroid hormone was required for binding of its receptor to the growth hormone gene promoter, suggesting that thyroid hormone renders the receptor capable of recognizing specific gene regions. PMID:3466175

  3. Thyroid hormone receptors bind to defined regions of the growth hormone and placental lactogen genes.

    PubMed

    Barlow, J W; Voz, M L; Eliard, P H; Mathy-Harter, M; De Nayer, P; Economidis, I V; Belayew, A; Martial, J A; Rousseau, G G

    1986-12-01

    The intracellular receptor for thyroid hormone is a protein found in chromatin. Since thyroid hormone stimulates transcription of the growth hormone gene through an unknown mechanism, the hypothesis that the thyroid hormone-receptor complex interacts with defined regions of this gene has been investigated in a cell-free system. Nuclear extracts from human lymphoblastoid IM-9 cells containing thyroid hormone receptors were incubated with L-3,5,3'-tri[125I]iodothyronine and calf thymus DNA-cellulose. Restriction fragments of the human growth hormone gene were added to determine their ability to inhibit labeled receptor binding to DNA-cellulose. These fragments encompassed nucleotide sequences from about three kilobase pairs upstream to about four kilobase pairs downstream from the transcription initiation site. The thyroid hormone-receptor complex bound preferentially to the 5'-flanking sequences of the growth hormone gene in a region between nucleotide coordinates -290 and -129. The receptor also bound to an analogous promoter region in the human placental lactogen gene, which has 92% nucleotide sequence homology with the growth hormone gene. These binding regions appear to be distinct from those that are recognized by the receptor for glucocorticoids, which stimulate growth hormone gene expression synergistically with thyroid hormone. The presence of thyroid hormone was required for binding of its receptor to the growth hormone gene promoter, suggesting that thyroid hormone renders the receptor capable of recognizing specific gene regions.

  4. Growth Hormone-Insulin-Like Growth Factor Axis, Thyroid Axis, Prolactin, and Exercise.

    PubMed

    Hackney, Anthony C; Davis, Hope C; Lane, Amy R

    2016-01-01

    This chapter addresses what is known about the endocrine system components growth hormone (GH)-insulin-like growth factor (IGF) axis, thyroid axis, and prolactin relative to exercise and exercise training. Each one of these hormone axes contributes to the maintenance of homeostasis in the body through impact on a multitude of physiological systems. The homeostatic disruption of exercise causes differing responses in each hormone axis. GH levels increase with sufficient stimulation, and IGFs are released in response to GH from the anterior pituitary providing multiple roles including anabolic properties. Changes in the thyroid hormones T3 and T4 vary greatly with exercise, from increases/decreases to no change in levels across different exercise types, intensities and durations. These ambiguous findings could be due to numerous confounding factors (e.g. nutrition status) within the research. Prolactin increases proportionally to the intensity of the exercise. The magnitude may be augmented with extended durations; conflicting findings have been reported with resistance training. While the responses to exercise vary, it appears there may be overall adaptive and regenerative impacts on the body into recovery by these hormones through immune and tissue inflammatory responses/mediations. Nonetheless, well-designed exercise research studies are still needed on each of these hormones, especially thyroid hormones and prolactin.

  5. Growth hormone-releasing hormone disruption extends lifespan and regulates response to caloric restriction in mice

    PubMed Central

    Sun, Liou Y; Spong, Adam; Swindell, William R; Fang, Yimin; Hill, Cristal; Huber, Joshua A; Boehm, Jacob D; Westbrook, Reyhan; Salvatori, Roberto; Bartke, Andrzej

    2013-01-01

    We examine the impact of targeted disruption of growth hormone-releasing hormone (GHRH) in mice on longevity and the putative mechanisms of delayed aging. GHRH knockout mice are remarkably long-lived, exhibiting major shifts in the expression of genes related to xenobiotic detoxification, stress resistance, and insulin signaling. These mutant mice also have increased adiponectin levels and alterations in glucose homeostasis consistent with the removal of the counter-insulin effects of growth hormone. While these effects overlap with those of caloric restriction, we show that the effects of caloric restriction (CR) and the GHRH mutation are additive, with lifespan of GHRH-KO mutants further increased by CR. We conclude that GHRH-KO mice feature perturbations in a network of signaling pathways related to stress resistance, metabolic control and inflammation, and therefore provide a new model that can be used to explore links between GHRH repression, downregulation of the somatotropic axis, and extended longevity. DOI: http://dx.doi.org/10.7554/eLife.01098.001 PMID:24175087

  6. Growth of hormone-dependent MCF-7 breast cancer cells is promoted by constitutive caveolin-1 whose expression is lost in an EGF-R-mediated manner during development of tamoxifen resistance.

    PubMed

    Thomas, Nicholas B P; Hutcheson, Iain R; Campbell, Lee; Gee, Julia; Taylor, Kathryn M; Nicholson, Robert I; Gumbleton, Mark

    2010-02-01

    Caveolin-1 displays both tumour-suppressor and tumour-promoter properties in breast cancer. Using characterised preclinical cell models for the transition of oestrogen-sensitive (WT-MCF-7 cells) to a tamoxifen-resistant (TAM-R cells) phenotype we examined the role caveolin-1 in the development of hormone-resistant breast cancer. The WT-MCF-7 cells showed abundant expression of caveolin-1 which potentiated oestrogen-receptor (ERalpha) signalling and promoted cell growth despite caveolin-1 mediating inhibition of ERK signalling. In TAM-R cells caveolin-1 expression was negligible, repressed by EGF-R/ERK signalling. Pharmacological inhibition of EGFR/ERK in TAM-R cells restored caveolin-1 and also resulted in the emergence of pools of phosphorylated caveolin-1. WT-MCF-7 cells exposed to tamoxifen for upto 12 weeks displayed increased caveolin-1 (peaking by week 2) followed (after week 8) by a marked decrease as the cells progress to develop a stable tamoxifen-resistant phenotype. The targeted down-regulation (siRNA) of caveolin-1 in WT-MCF-7 cells reduced growth but did not affect their sensitivity to tamoxifen, suggesting loss of caveolin-1 alone is not sufficient to confer tamoxifen-resistance. Hyperactivation of EGFR/ERK is a feature of tamoxifen-resistant breast cancer cells, a principal driver of cell growth. Recombinant expression of caveolin-1 in TAM-R cells did not affect EGFR/ERK activity, potentially due to mislocalisation of caveolin-1 through hyperactivation of the mTOR pathway or altered caveolin-1 phosphorylation. This work defines a novel role for caveolin-1 with implications for the clinical course of breast cancer and identifies caveolin-1 as a potential drug target for the treatment of early oestrogen-dependent breast cancers. Further, the loss of caveolin-1 may have benefit as a molecular signature for tamoxifen resistance.

  7. The pituitary growth hormone cell in space

    NASA Technical Reports Server (NTRS)

    Hymer, Wesley C.; Grindeland, R.

    1989-01-01

    Growth hormone (GH), produced and secreted from specialized cells in the pituitary gland, controls the metabolism of protein, fat, and carbohydrate. It is also probably involved in the regulation of proper function of bone, muscle and immune systems. The behavior of the GH cell system was studied by flying either isolated pituitary cells or live rats. In the latter case, pituitary GH cells are prepared on return to earth and then either transplanted into hypophysectomized rats or placed into cell culture so that function of GH cells in-vivo vs. in-vitro can be compared. The results from three flights to date (STS-8, 1983; SL-3, 1985; Cosmos 1887, 1987) established that the ability of GH cells to release hormone, on return to earth, is compromised. The mechanism(s) responsible for this attenuation response is unknown. However, the data are sufficiently positive to indicate that the nature of the secretory defect resides directly within the GH cells.

  8. Dimerization of Human Growth Hormone by Zinc

    NASA Astrophysics Data System (ADS)

    Cunningham, Brian C.; Mulkerrin, Michael G.; Wells, James A.

    1991-08-01

    Size-exclusion chromatography and sedimentation equilibrium studies demonstrated that zinc ion (Zn2+) induced the dimerization of human growth hormone (hGH). Scatchard analysis of 65Zn2+ binding to hGH showed that two Zn2+ ions associate per dimer of hGH in a cooperative fashion. Cobalt (II) can substitute for Zn2+ in the hormone dimer and gives a visible spectrum characteristic of cobalt coordinated in a tetrahedral fashion by oxygen- and nitrogen-containing ligands. Replacement of potential Zn2+ ligands (His18, His21, and Glu174) in hGH with alanine weakened both Zn2+ binding and hGH dimer formation. The Zn2+-hGH dimer was more stable than monomeric hGH to denaturation in guanidine-HCl. Formation of a Zn2+-hGH dimeric complex may be important for storage of hGH in secretory granules.

  9. Regulation of bone mass by growth hormone.

    PubMed

    Olney, Robert C

    2003-09-01

    Growth hormone (GH) is a peptide hormone secreted from the pituitary gland under the control of the hypothalamus. It has a many actions in the body, including regulating a number of metabolic pathways. Some, but not all, of its effects are mediated through insulin-like growth factor-I (IGF-I). Both GH and IGF-I play significant roles in the regulation of growth and bone metabolism and hence are regulators of bone mass. Bone mass increases steadily through childhood, peaking in the mid 20s. Subsequently, there is a slow decline that accelerates in late life. During childhood, the accumulation in bone mass is a combination of bone growth and bone remodeling. Bone remodeling is the process of new bone formation by osteoblasts and bone resorption by osteoclasts. GH directly and through IGF-I stimulates osteoblast proliferation and activity, promoting bone formation. It also stimulates osteoclast differentiation and activity, promoting bone resorption. The result is an increase in the overall rate of bone remodeling, with a net effect of bone accumulation. The absence of GH results in a reduced rate of bone remodeling and a gradual loss of bone mineral density. Bone growth primarily occurs at the epiphyseal growth plates and is the result of the proliferation and differentiation of chondrocytes. GH has direct effects on these chondrocytes, but primarily regulates this function through IGF-I, which stimulates the proliferation of and matrix production by these cells. GH deficiency severely limits bone growth and hence the accumulation of bone mass. GH deficiency is not an uncommon complication in oncology and has long-term effects on bone health.

  10. Human Growth Hormone (HGH): Does It Slow Aging?

    MedlinePlus

    ... hormone can: Increase exercise capacity Increase bone density Increase muscle mass Decrease body fat Human growth hormone is also approved to treat ... Although it appears that human growth hormone can increase muscle mass and ... the amount of body fat in healthy older adults, the increase in muscle ...

  11. Psychomotor retardation in a girl with complete growth hormone deficiency.

    PubMed

    Dayal, Devi; Malhi, Prabhjot; Kumar Bhalla, Anil; Sachdeva, Naresh; Kumar, Rakesh

    2013-01-01

    Infants with complete growth hormone deficiency may suffer from psychomotor retardation in addition to severe growth failure. Without replacement therapy, they may have a compromised intellectual potential manifesting as learning disabilities and attention-deficit disorders in later life. In this communication, we discuss an infant who showed improvement in physical growth after growth hormone therapy but her psychomotor skills did not improve probably due to late start of treatment. There is a need to start growth hormone therapy as early as possible in infants with complete growth hormone deficiency to avoid adverse effects on psychomotor and brain development.

  12. Effects of ghrelin, growth hormone-releasing peptide-6, and growth hormone-releasing hormone on growth hormone, adrenocorticotropic hormone, and cortisol release in type 1 diabetes mellitus.

    PubMed

    de Sá, Larissa Bianca Paiva Cunha; Nascif, Sergio Oliva; Correa-Silva, Silvia Regina; Molica, Patricia; Vieira, José Gilberto Henriques; Dib, Sergio Atala; Lengyel, Ana-Maria Judith

    2010-10-01

    In type 1 diabetes mellitus (T1DM), growth hormone (GH) responses to provocative stimuli are normal or exaggerated, whereas the hypothalamic-pituitary-adrenal axis has been less studied. Ghrelin is a GH secretagogue that also increases adrenocorticotropic hormone (ACTH) and cortisol levels, similarly to GH-releasing peptide-6 (GHRP-6). Ghrelin's effects in patients with T1DM have not been evaluated. We therefore studied GH, ACTH, and cortisol responses to ghrelin and GHRP-6 in 9 patients with T1DM and 9 control subjects. The GH-releasing hormone (GHRH)-induced GH release was also evaluated. Mean fasting GH levels (micrograms per liter) were higher in T1DM (3.5 ± 1.2) than in controls (0.6 ± 0.3). In both groups, ghrelin-induced GH release was higher than that after GHRP-6 and GHRH. When analyzing Δ area under the curve (ΔAUC) GH values after ghrelin, GHRP-6, and GHRH, no significant differences were observed in T1DM compared with controls. There was a trend (P = .055) to higher mean basal cortisol values (micrograms per deciliter) in T1DM (11.7 ± 1.5) compared with controls (8.2 ± 0.8). No significant differences were seen in ΔAUC cortisol values in both groups after ghrelin and GHRP-6. Mean fasting ACTH values were similar in T1DM and controls. No differences were seen in ΔAUC ACTH levels in both groups after ghrelin and GHRP-6. In summary, patients with T1DM have normal GH responsiveness to ghrelin, GHRP-6, and GHRH. The ACTH and cortisol release after ghrelin and GHRP-6 is also similar to controls. Our results suggest that chronic hyperglycemia of T1DM does not interfere with GH-, ACTH-, and cortisol-releasing mechanisms stimulated by these peptides.

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

    PubMed

    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.

  14. Effects of retinoic acid on growth hormone-releasing hormone receptor, growth hormone secretagogue receptor gene expression and growth hormone secretion in rat anterior pituitary cells.

    PubMed

    Maliza, Rita; Fujiwara, Ken; Tsukada, Takehiro; Azuma, Morio; Kikuchi, Motoshi; Yashiro, Takashi

    2016-06-30

    Retinoic acid (RA) is an important signaling molecule in embryonic development and adult tissue. The actions of RA are mediated by the nuclear receptors retinoic acid receptor (RAR) and retinoid X receptor (RXR), which regulate gene expression. RAR and RXR are widely expressed in the anterior pituitary gland. RA was reported to stimulate growth hormone (GH) gene expression in the anterior pituitary cells. However, current evidence is unclear on the role of RA in gene expression of growth hormone-releasing hormone receptor (Ghrh-r), growth hormone secretagogue receptor (Ghs-r) and somatostatin receptors (Sst-rs). Using isolated anterior pituitary cells of rats, we examined the effects of RA on gene expression of these receptors and GH release. Quantitative real-time PCR revealed that treatment with all-trans retinoic acid (ATRA; 10(-6) M) for 24 h increased gene expression levels of Ghrh-r and Ghs-r; however, expressions of Sst-r2 and Sst-r5 were unchanged. Combination treatment with the RAR-agonist Am80 and RXR-agonist PA024 mimicked the effects of ATRA on Ghrh-r and Ghs-r gene expressions. Exposure of isolated pituitary cells to ATRA had no effect on basal GH release. In contrast, ATRA increased growth hormone-releasing hormone (GHRH)- and ghrelin-stimulated GH release from cultured anterior pituitary cells. Our results suggest that expressions of Ghrh-r and Ghs-r are regulated by RA through the RAR-RXR receptor complex and that RA enhances the effects of GHRH and ghrelin on GH release from the anterior pituitary gland.

  15. Random Secretion of Growth Hormone in Humans

    NASA Astrophysics Data System (ADS)

    Prank, Klaus; Kloppstech, Mirko; Nowlan, Steven J.; Sejnowski, Terrence J.; Brabant, Georg

    1996-08-01

    In normal humans, growth hormone (GH) is secreted from a gland located adjacent to the brain (pituitary) into the blood in distinct pulses, but in patients bearing a tumor within the pituitary (acromegaly) GH is excessively secreted in an irregular manner. It has been hypothesized that GH secretion in the diseased state becomes random. This hypothesis is supported by demonstrating that GH secretion in patients with acromegaly cannot be distinguished from a variety of linear stochastic processes based on the predictability of the fluctuations of GH concentration in the bloodstream.

  16. Gravitational effects on plant growth hormone concentration

    NASA Astrophysics Data System (ADS)

    Bandurski, Robert S.; Schulze, Aga

    Numerous studies, particularly those of H. Dolk in the 1930's, established by means of bio-assay, that more growth hormone diffused from the lower, than from the upper side of a gravity-stimulated plant shoot. Now, using an isotope dilution assay, with 4,5,6,7 tetradeutero indole-3-acetic acid as internal standard, and selected ion monitoring-gas chromatography-mass spectrometry as the method of determination, we have confirmed Dolk's finding and established that the asymmetrically distributed hormone is, in fact, indole-3-acetic acid (IAA). This is the first physico-chemical demonstration that there is more free IAA on the lower sides of a geo-stimulated plant shoot. We have also shown that free IAA occurs primarily in the conductive vascular tissues of the shoot, whereas IAA esters predominate in the growing cortical cells. Now, using an especially sensitive gas chromatographic isotope dilution assay we have found that the hormone asymmetry also occurs in the non-vascular tissue. Currently, efforts are directed to developing isotope dilution assays, with picogram sensitivity, to determine how this asymmetry of IAA distribution is attained so as to better understand how the plant perceives the geo-stimulus.

  17. Thyroid Hormones and Growth in Health and Disease

    PubMed Central

    Tarım, Ömer

    2011-01-01

    Thyroid hormones regulate growth by several mechanisms. In addition to their negative feedback effect on the stimulatory hormones thyrotropin-releasing hormone (TRH) and thyrotropin (TSH), thyroid hormones also regulate their receptors in various physiological and pathological conditions. Up-regulation and down-regulation of the thyroid receptors fine-tune the biological effects exerted by the thyroid hormones. Interestingly, the deiodinase enzyme system is another intrinsic regulator of thyroid physiology that adjusts the availability of thyroid hormones to the tissues, which is essential for normal growth and development. Almost all chronic diseases of childhood impair growth and development. Every disease may have a unique mechanism to halt linear growth, but reduced serum concentration or diminished local availability of thyroid hormones seems to be a common pathway. Therefore, the effects of systemic diseases on thyroid physiology must be taken into consideration in the evaluation of growth retardation in affected children. Conflict of interest:None declared. PMID:21750631

  18. Thyroid hormones and growth in health and disease.

    PubMed

    Tarım, Ömer

    2011-01-01

    Thyroid hormones regulate growth by several mechanisms. In addition to their negative feedback effect on the stimulatory hormones thyrotropin-releasing hormone (TRH) and thyrotropin (TSH), thyroid hormones also regulate their receptors in various physiological and pathological conditions. Up-regulation and down-regulation of the thyroid receptors fine-tune the biological effects exerted by the thyroid hormones. Interestingly, the deiodinase enzyme system is another intrinsic regulator of thyroid physiology that adjusts the availability of thyroid hormones to the tissues, which is essential for normal growth and development. Almost all chronic diseases of childhood impair growth and development. Every disease may have a unique mechanism to halt linear growth, but reduced serum concentration or diminished local availability of thyroid hormones seems to be a common pathway. Therefore, the effects of systemic diseases on thyroid physiology must be taken into consideration in the evaluation of growth retardation in affected children.

  19. [Acral acanthosis nigricans associated with taking growth hormone].

    PubMed

    Peña Irún, A

    2014-01-01

    Acanthosis nigricans is a skin lesion characterized by the presence of a hyperpigmented, velvety cutaneous thickening that usually appears in flexural areas. Less frequently, it can occur in other locations, such as the dorsum of hands and feet. In this case it is called acral acanthosis nigricans. It is a dermatological manifestation of systemic disease. It is often associated with insulin resistance-mediated endocrine diseases. A case is presented on a patient with acanthosis nigricans secondary to the use of growth hormone. Copyright © 2013 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

  20. Growth in children with chronic kidney disease: role of nutrition, growth hormone, dialysis, and steroids.

    PubMed

    Ingulli, Elizabeth G; Mak, Robert H

    2014-04-01

    Children with chronic kidney disease (CKD) have impaired growth that leads to short stature in adulthood. The problem persists even with successful transplantation and steroid withdrawal protocols. The aim of this review is to provide an overview of the pressing issues related to growth failure in children with CKD both before and after transplantation. Although great strides have been made in dialysis and transplantation, the incidence of abnormal adult height in children growing up with CKD remains as high as 45-60%. The lack of catch-up growth and resultant short stature is a critical issue for self-esteem and quality of life in many children with CKD. Aggressive daily dialysis, improved nutrition, treatment of metabolic bone disease, and the use of recombinant human growth hormone provide some hope for catch-up growth in select patients. The causes of growth failure in the setting of CKD are multifactorial. Attention to all the details by optimizing nutritional, bone and mineral metabolism, correcting metabolic acidosis and anemia, achieving excellent blood pressure control, reversing cardiovascular complications such as left ventricular hypertrophy, and minimizing the use of corticosteroids is the current standard of care. Aggressive daily dialysis can reverse many of the uremic derangements. For patients not yet on dialysis or for those after renal transplant, early institution of recombinant human growth hormone can promote growth. Improved understanding of the mechanisms of hormone resistance may offer novel targets or measurements of treatment effectiveness.

  1. Effects of fasting on growth hormone, growth hormone receptor, and insulin-like growth factor-I axis in seawater-acclimated tilapia, Oreochromis mossambicus.

    PubMed

    Fox, B K; Riley, L G; Hirano, T; Grau, E G

    2006-09-15

    Effects of fasting on the growth hormone (GH)--growth hormone receptor (GHR)-insulin-like growth factor-I (IGF-I) axis were characterized in seawater-acclimated tilapia (Oreochromis mossambicus). Fasting for 4 weeks resulted in significant reductions in body weight and specific growth rate. Plasma GH and pituitary GH mRNA levels were significantly elevated in fasted fish, whereas significant reductions were observed in plasma IGF-I and hepatic IGF-I mRNA levels. There was a significant negative correlation between plasma levels of GH and IGF-I in the fasted fish. No effect of fasting was observed on hepatic GHR mRNA levels. Plasma glucose levels were reduced significantly in fasted fish. The fact that fasting elicited increases in GH and decreases in IGF-I production without affecting GHR expression indicates a possible development of GH resistance.

  2. Metastatic Pancreatic Neuroendocrine Tumor that Progressed to Ectopic Adrenocorticotropic Hormone (ACTH) Syndrome with Growth Hormone-releasing Hormone (GHRH) Production

    PubMed Central

    Tadokoro, Rie; Sato, Shotaro; Otsuka, Fumiko; Ueno, Makoto; Ohkawa, Shinichi; Katakami, Hideki; Taniyama, Matsuo; Nagasaka, Shoichiro

    2016-01-01

    The patient was a 61-year-old woman who had a well-differentiated pancreatic neuroendocrine tumor (PNET) with lymph node metastasis. After 15 months of octreotide treatment, glucose control deteriorated and pigmentation of the tongue and moon face developed, leading to the diagnosis of ectopic adrenocorticotropic hormone (ACTH) syndrome. An abnormal secretion of growth hormone (GH) was identified, and the plasma growth hormone-releasing hormone (GHRH) level was elevated. A tumor biopsy specimen positively immunostained for ACTH and GHRH. Ectopic hormone secretion seems to have evolved along with the progression of the PNET. PMID:27746436

  3. Metastatic Pancreatic Neuroendocrine Tumor that Progressed to Ectopic Adrenocorticotropic Hormone (ACTH) Syndrome with Growth Hormone-releasing Hormone (GHRH) Production.

    PubMed

    Tadokoro, Rie; Sato, Shotaro; Otsuka, Fumiko; Ueno, Makoto; Ohkawa, Shinichi; Katakami, Hideki; Taniyama, Matsuo; Nagasaka, Shoichiro

    The patient was a 61-year-old woman who had a well-differentiated pancreatic neuroendocrine tumor (PNET) with lymph node metastasis. After 15 months of octreotide treatment, glucose control deteriorated and pigmentation of the tongue and moon face developed, leading to the diagnosis of ectopic adrenocorticotropic hormone (ACTH) syndrome. An abnormal secretion of growth hormone (GH) was identified, and the plasma growth hormone-releasing hormone (GHRH) level was elevated. A tumor biopsy specimen positively immunostained for ACTH and GHRH. Ectopic hormone secretion seems to have evolved along with the progression of the PNET.

  4. Detecting growth hormone misuse in athletes

    PubMed Central

    Holt, Richard I. G.

    2013-01-01

    Athletes have been misusing growth hormone (GH) for its anabolic and metabolic effects since the early 1980s, at least a decade before endocrinologists began to treat adults with GH deficiency. Although there is an ongoing debate about whether GH is performance enhancing, recent studies suggest that GH improves strength and sprint capacity, particularly when combined with anabolic steroids. The detection of GH misuse is challenging because it is an endogenous hormone. Two approaches have been developed to detect GH misuse; the first is based on the measurement of pituitary GH isoforms and the ratio of 22-kDa isoform to total GH. The second is based on the measurement of insulin like growth factor-I (IGF-I) and N-terminal propeptide of type III procollagen (P-III-NP) which increase in a dose-dependent manner in response to GH administration. Both methodologies have been approved by the World Anti-Doping Agency (WADA) and have led to the detection of a number of athletes misusing GH. PMID:24251151

  5. Effects of growth hormone reduction in a patient with polycystic ovary syndrome complicated with acromegaly.

    PubMed

    Goto, Junko; Otsuka, Fumio; Inagaki, Kenichi; Tsukamoto, Naoko; Suzuki, Jiro; Miyoshi, Tomoko; Ogura, Toshio; Kamada, Yasuhiko; Makino, Hirofumi

    2009-01-01

    We report a rare case of polycystic ovary syndrome (PCOS) complicated with acromegaly due to a growth hormone (GH)-producing pituitary adenoma. Complete removal of the pituitary adenoma successfully reduced circulating levels of GH and insulin-like growth factor (IGF)-1, which, in turn, resulted in the amelioration of gonadal dysfunction, hyperandrogenism, lutenizing hormone hypersecretion, and severe insulin resistance. This clinical complication suggests that activation of systemic GH-IGF-1 axis is potentially involved in the development of PCOS.

  6. Effect of Growth Hormone Deficiency on Brain Structure, Motor Function and Cognition

    ERIC Educational Resources Information Center

    Webb, Emma A.; O'Reilly, Michelle A.; Clayden, Jonathan D.; Seunarine, Kiran K.; Chong, Wui K.; Dale, Naomi; Salt, Alison; Clark, Chris A.; Dattani, Mehul T.

    2012-01-01

    The growth hormone-insulin-like growth factor-1 axis plays a role in normal brain growth but little is known of the effect of growth hormone deficiency on brain structure. Children with isolated growth hormone deficiency (peak growth hormone less than 6.7 [micro]g/l) and idiopathic short stature (peak growth hormone greater than 10 [micro]g/l)…

  7. Effect of Growth Hormone Deficiency on Brain Structure, Motor Function and Cognition

    ERIC Educational Resources Information Center

    Webb, Emma A.; O'Reilly, Michelle A.; Clayden, Jonathan D.; Seunarine, Kiran K.; Chong, Wui K.; Dale, Naomi; Salt, Alison; Clark, Chris A.; Dattani, Mehul T.

    2012-01-01

    The growth hormone-insulin-like growth factor-1 axis plays a role in normal brain growth but little is known of the effect of growth hormone deficiency on brain structure. Children with isolated growth hormone deficiency (peak growth hormone less than 6.7 [micro]g/l) and idiopathic short stature (peak growth hormone greater than 10 [micro]g/l)…

  8. Hormonal and lactational responses to growth hormone-releasing hormone treatment in lactating Japanese Black cows.

    PubMed

    Shingu, H; Hodate, K; Kushibiki, S; Ueda, Y; Touno, E; Shinoda, M; Ohashi, S

    2004-06-01

    Ten multiparous lactating Japanese Black cows (beef breed) were used to evaluate the effects of bovine growth hormone-releasing hormone (GHRH) analog on milk yield and profiles of plasma hormones and metabolites. The cows received 2 consecutive 21-d treatments (a daily s.c. injection of 3-mg GHRH analog or saline) in a 2 (group) x 2 (period) Latin square crossover design. The 5 cows in group A received GHRH analog during period 1 (from d 22 to 42 postpartum) and saline during period 2 (from d 57 to 77 postpartum), and those in group B received saline and GHRH analog during periods 1 and 2, respectively. Mean milk yield decreased in saline treated compared with that during the 1-wk period before treatment 7.4 and 19.1% during periods 1 (group B) and 2 (group A), respectively. Treatment with GHRH analog increased milk yield 17.4% (period 1, group A) and 6.3% (period 2, group B). Treatment with GHRH analog induced higher basal plasma concentrations of growth hormone (GH), insulin-like growth factor-1 (IGF-1), insulin, and glucose compared with saline-treated cows. In glucose challenge, the GHRH analog-treated beef cows had greater insulin secretion than the saline-treated beef cows. In insulin challenge, however, there were no significant differences in the areas surrounded by hypothetical lines of basal glucose concentrations and glucose response curves between GHRH analog- and saline-treated cows. These results demonstrate that GHRH analog treatment facilitates endogenous GH secretion in lactating Japanese Black cows, leading to increases in milk yield and plasma concentrations of IGF-1, insulin, and glucose.

  9. Effects of Growth Hormone on Bone.

    PubMed

    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.

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

    SciTech Connect

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

    1985-08-01

    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.

  11. Purification and properties of reptilian and amphibian growth hormones.

    PubMed

    Farmer, S W; Papkoff, H; Hayashida, T

    1976-09-01

    Highly purified growth hormone was isolated from the pituitaries of two reptilian species, the snapping turtle and the sea turtle, and two amphibian species, the bullfrog and the leopard frog. Characterization studies were performed with these growth hormones in comparison with mammalian and avian growth hormones. Great similarities among these species were found in chromatographic behavior, Ve/Vo ratios (2.0) on gel filtration, disc electrophoretic patterns, terminal amino acid residues and immunochemical reactivity with snapping turtle growth hormone antiserum. Species differences were noted in amino acid composition and immunoactivity measured by rat growth hormone antiserum, and these appeared to reflect the phylogenetic relationships among the four tetrapod species. The turtle and frog growth hormones gave parallel dose responses in the rat tibia assay. All were less potent than the bovine growth hormone standard except the bullfrog growth hormone which was equipotent if not more active. The data indicate that many elements of growth hormone structure have been strongly conserved during evolution.

  12. Growth hormone signaling is necessary for lifespan extension by dietary methionine.

    PubMed

    Brown-Borg, Holly M; Rakoczy, Sharlene G; Wonderlich, Joseph A; Rojanathammanee, Lalida; Kopchick, John J; Armstrong, Vanessa; Raasakka, Debbie

    2014-12-01

    Growth hormone significantly impacts lifespan in mammals. Mouse longevity is extended when growth hormone (GH) signaling is interrupted but markedly shortened with high-plasma hormone levels. Methionine metabolism is enhanced in growth hormone deficiency, for example, in the Ames dwarf, but suppressed in GH transgenic mice. Methionine intake affects also lifespan, and thus, GH mutant mice and respective wild-type littermates were fed 0.16%, 0.43%, or 1.3% methionine to evaluate the interaction between hormone status and methionine. All wild-type and GH transgenic mice lived longer when fed 0.16% methionine but not when fed higher levels. In contrast, animals without growth hormone signaling due to hormone deficiency or resistance did not respond to altered levels of methionine in terms of lifespan, body weight, or food consumption. Taken together, our results suggest that the presence of growth hormone is necessary to sense dietary methionine changes, thus strongly linking growth and lifespan to amino acid availability.

  13. Growth hormone deficiency in treated acromegaly.

    PubMed

    Mazziotti, Gherardo; Marzullo, Paolo; Doga, Mauro; Aimaretti, Gianluca; Giustina, Andrea

    2015-01-01

    Growth hormone deficiency (GHD) of the adult is characterized by reduced quality of life (QoL) and physical fitness, skeletal fragility, and increased weight and cardiovascular risk. Hypopituitarism may develop in patients after definitive treatment of acromegaly, but an exact prevalence of GHD in this population is still uncertain owing to limited awareness and the scarce and conflicting data available on this topic. Because acromegaly and GHD may yield adverse consequences on similar target systems, the final outcomes of some complications of acromegaly may be further affected by the occurrence of GHD. However, it is still largely unknown whether patients with post-acromegaly GHD may benefit from GH replacement. We review the diagnostic, clinical, and therapeutic aspects of GHD in adult patients treated for acromegaly.

  14. Fasting growth hormone levels in diabetes mellitus.

    PubMed

    Nazaimoon, W M; Ng, M L; Khalid, B A

    1993-11-01

    Fasting serum growth hormone (GH) levels of different groups of diabetic patients were measured and compared to age-matched normal subjects. Insulin-dependent diabetes mellitus (IDDM) children (aged 12-17 years) were found to have significantly lower fasting GH levels than age-matched normal children (p < 0.001). In the adult age groups of 18-44 and 45-76 years, the IDDM patients showed increased fasting GH levels compared to age-matched normal subjects (p < 0.06 and p < 0.001 respectively) and non-insulin-dependent diabetes mellitus (NIDDM) patients (p < 0.05 and p < 0.001 respectively). The fasting GH levels of IDDM patients of the age group 18-44 years also showed significant correlations with glycated haemoglobin (r = 0.510, p = 0.002) and fasting blood sugar levels (r = 0.571, p = 0.01).

  15. Pituitary resistance to thyroid hormones: pathophysiology and therapeutic options.

    PubMed

    Suzuki, Satoru; Shigematsu, Satoshi; Inaba, Hidefumi; Takei, Masahiro; Takeda, Teiji; Komatsu, Mitsuhisa

    2011-12-01

    Thyroid hormone secretion suppresses the expression of thyroid stimulating hormone (TSH), both of which are strictly controlled by a negative feedback loop between the hypothalamus-pituitary and thyroid. Pituitary resistance to thyroid hormone (PRTH) is defined as resistance to the action of thyroid hormone that is more severe in the pituitary than at the peripheral tissue level. Although the molecular basis of PRTH is not well understood, the clinical issue mainly involves imbalance between the hypothalamus-pituitary and peripheral thyroid hormone responsivity, which may induce peripheral thyrotoxic phenomena. Here, we review the pathogenesis and molecular aspects of PRTH, present a single case with inappropriate TSH secretion suffering from thyrotoxicosis treated with PTU, and discuss the possible choice of therapeutic options to correct the imbalance of thyroid hormone responsivity in both the hypothalamus-pituitary and peripheral tissues.

  16. Thyroid hormone resistance: a novel mutation in thyroid hormone receptor beta (THRB) gene - case report.

    PubMed

    Işık, Emregül; Beck Peccoz, Paolo; Campi, Irene; Özön, Alev; Alikaşifoğlu, Ayfer; Gönç, Nazlı; Kandemir, Nurgün

    2013-01-01

    Thyroid hormone resistance (THR) is a dominantly inherited syndrome characterized by reduced sensitivity to thyroid hormones. It is usually caused by mutations in the thyroid hormone receptor beta (THRB) gene. In the present report, we describe the clinical and laboratory characteristics and genetic analysis of patients with a novel THRB gene mutation. The index patient had been misdiagnosed as hyperthyroidism and treated with antithyroid drugs since eight days of age. Thyroid hormone results showed that thyrotropin (thyroid-stimulating hormone, TSH) was never suppressed despite elevated thyroid hormone levels, and there was no symptom suggesting hyperthyroidism. A heterozygous mutation at codon 350 located in exon 9 of the THRB gene was detected in all the affected members of the family. It is important to consider thyroid hormone levels in association with TSH levels to prevent inappropriate treatment and the potential complications, such as clinical hypothyroidism or an increase in goiter size.

  17. Resistance to thyroid hormone due to defective thyroid receptor alpha

    PubMed Central

    Moran, Carla; Chatterjee, Krishna

    2015-01-01

    Thyroid hormones act via nuclear receptors (TRα1, TRβ1, TRβ2) with differing tissue distribution; the role of α2 protein, derived from the same gene locus as TRα1, is unclear. Resistance to thyroid hormone alpha (RTHα) is characterised by tissue-specific hypothyroidism associated with near-normal thyroid function tests. Clinical features include dysmorphic facies, skeletal dysplasia (macrocephaly, epiphyseal dysgenesis), growth retardation, constipation, dyspraxia and intellectual deficit. Biochemical abnormalities include low/low-normal T4 and high/high-normal T3 concentrations, a subnormal T4/T3 ratio, variably reduced reverse T3, raised muscle creatine kinase and mild anaemia. The disorder is mediated by heterozygous, loss-of-function, mutations involving either TRα1 alone or both TRα1 and α2, with no discernible phenotype attributable to defective α2. Whole exome sequencing and diagnostic biomarkers may enable greater ascertainment of RTHα, which is important as thyroxine therapy reverses some metabolic abnormalities and improves growth, constipation, dyspraxia and wellbeing. The genetic and phenotypic heterogeneity of RTHα and its optimal management remain to be elucidated. PMID:26303090

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

    PubMed

    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.

  19. Hypoglycemia associated with clonidine testing for growth hormone deficiency.

    PubMed

    Huang, C; Banerjee, K; Sochett, E; Perlman, K; Wherrett, D; Daneman, D

    2001-08-01

    We have observed 4 cases of hypoglycemia associated with clonidine stimulation of growth hormone secretion; only one patient had growth hormone deficiency. Significant drowsiness after administration of clonidine may prolong the period of fasting in these children and mask early signs and symptoms, leading to severe hypoglycemia.

  20. Bovine growth hormone: human food safety evaluation.

    PubMed

    Juskevich, J C; Guyer, C G

    1990-08-24

    Scientists in the Food and Drug Administration (FDA), after reviewing the scientific literature and evaluating studies conducted by pharmaceutical companies, have concluded that the use of recombinant bovine growth hormone (rbGH) in dairy cattle presents no increased health risk to consumers. Bovine GH is not biologically active in humans, and oral toxicity studies have demonstrated that rbGH is not orally active in rats, a species responsive to parenterally administered bGH. Recombinant bGH treatment produces an increase in the concentration of insulin-like growth factor-I (IGF-I) in cow's milk. However, oral toxicity studies have shown that bovine IGF-I lacks oral activity in rats. Additionally, the concentration of IGF-I in milk of rbGH-treated cows is within the normal physiological range found in human breast milk, and IGF-I is denatured under conditions used to process cow's milk for infant formula. On the basis of estimates of the amount of protein absorbed intact in humans and the concentration of IGF-I in cow's milk during rbGH treatment, biologically significant levels of intact IGF-I would not be absorbed.

  1. Extrapituitary growth hormone synthesis in humans.

    PubMed

    Pérez-Ibave, Diana Cristina; Rodríguez-Sánchez, Iram Pablo; Garza-Rodríguez, María de Lourdes; Barrera-Saldaña, Hugo Alberto

    2014-01-01

    The gene for pituitary growth hormone (GH-N) in man belongs to a multigene locus located at chromosome 17q24.2, which also harbors four additional genes: one for a placental variant of GH-N (named GH-V) and three of chorionic somatommamotropin (CSH) type. Their tandem arrangement from 5' to 3' is: GH-N, CSH-L, CSH-1, GH-V and CSH-2. GH-N is mainly expressed in the pituitary from birth throughout life, while the remaining genes are expressed in the placenta of pregnant women. Pituitary somatotrophs secrete GH into the bloodstream to act at receptor sites in most tissues. GH participates in the regulation of several complex physiological processes, including growth and metabolism. Recently, the presence of GH has been described in several extrapituitary sites, such as neural, ocular, reproductive, immune, cardiovascular, muscular, dermal and skeletal tissues. It has been proposed that GH has an autocrine action in these tissues. While the body of evidence for its presence is constantly growing, research of its possible function and implications lag behind. In this review we highlight the evidence of extrapituitary synthesis of GH in humans.

  2. Studies on the nature of plasma growth hormone

    NASA Technical Reports Server (NTRS)

    Ellis, S.; Grindeland, R. E.; Reilly, T. J.; Yang, S. H.

    1976-01-01

    The paper presents further evidence for the existence of two discrete forms of growth hormone in human plasma, one which is detectable by both radioimmunoassay and bioassay and is immunoreactive, and the other, termed 'bioactive', which is detected by tibial bioassay but shows little reactivity with currently available antisera to pituitary growth hormone. The same division of immunoactive and bioactive growth hormone occurs in rats, though with less disparity. Tests on rats indicated that the bioactive hormone is preferentially released into jugular vein plasma and that plasma concentrations of the bioactive hormone can be enhanced by insulin administration. The bioactive hormone was detectable by tibial assays in Cohn fractions IV, IV-1, and IV-4, and could be concentrated about 40-fold by fractionation with (NaPO3)6 and (NH4)2SO4.

  3. Microbiome impact on metabolism and function of sex, thyroid, growth and parathyroid hormones.

    PubMed

    Kunc, Michał; Gabrych, Anna; Witkowski, Jacek M

    2016-01-01

    Commensal bacteria and their genes associated with host are known as microbiome. In recent years, microbial influence on host endocrine system has been under detailed investigation. The role of microbiome in the pathogenesis of insulin resistance and obesity, the function of hypothalamic-pituitary-adrenal axis and secretion of hormones regulating appetite is well described in world literature. In this article we discuss poorly reviewed issues: the microbiome role in modulation of non-peptide (sex and thyroid) and peptide (growth hormone and parathyroid hormone) functions. Understanding complex bidirectional relations between host endocrine system and bacteria is of fundamental importance to understanding microbial impact on host reproduction, risk of endocrine-related cancers, pathogenesis of non-thyroidal illness syndrome, growth failure in children and hormonal changes during chronic kidney disease. This article also highlights effects of dietary compounds on microbiome composition and bacterial enzymes activity, and thus host hormonal status.

  4. MENTAL RETARDATION AND ACCELERATED GROWTH: INAPPROPRIATE SECRETION OF HUMAN GROWTH HORMONE,

    DTIC Science & Technology

    he had periodic elevations of the fasting plasma growth hormone levels and regularly had a paradoxical fall in the hormone level associated with...insulin-induced hypoglycemia. The human growth hormone response to arginine infusion was perfectly normal. It is suggested that the occasional elevations...in human growth hormone under fasting conditions and the paradoxical response to insulin are compatible with the hypothesis that this patient

  5. Anthropometric measurements in patients with growth hormone deficiency before treatment with human growth hormone.

    PubMed

    Zachmann, M; Fernandez, F; Tassinari, D; Thakker, R; Prader, A

    1980-05-01

    In 74 children (52 males, 22 females) with growth hormone (GH) deficiency (30 cases with isolated GH-deficiency, two of them familial; 4 familial and one isolated case with tendency for formation of antibodies against hGH; 29 with other pituitary hormone defects; 10 craniopharyngiomas), various anthropometric measurements were analyzed before treatment with hGH. In all groups, standing height, sitting height, and subischial leg height were equally retarded, and bihumeral width was more retarded than biiliac width; the head was relatively large; fat tissue was increased with subscapular skinfolds being greater than triceps skinfolds, indicating relative obestiy of the trunk; muscle and/or bone mass was reduced. In isolated GH-deficiency, head shape was slightly scaphoid; in combined defects, it was round, and in craniopharyngioma cases, it was brachycephalic. It is concluded that antrhopometric measurements may help in differentiating the type of GH-deficiency.

  6. Justified and unjustified use of growth hormone

    PubMed Central

    van der Lely, A J

    2004-01-01

    Growth 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, morbid obesity, cardiac failure, and various catabolic conditions. However, the available placebo controlled studies have not reported many significant beneficial effects, and it might even be dangerous to use excessive GH dosages in conditions in which the body has just decided to decrease GH actions. GH can indeed induce changes in body composition that are considered to be advantageous to GH deficient and non-GH deficient subjects. In contrast to GH replacement therapy in GH deficient subjects, however, excessive GH action due to GH misuse seems to be ineffective in improving muscle power. Moreover, there are no available study data to indicate that the use of GH for non-GH deficient subjects should be advocated, especially as animal data suggest that lower GH levels are positively correlated with longevity. PMID:15466991

  7. Human growth hormone doping in sport

    PubMed Central

    Saugy, M; Robinson, N; Saudan, C; Baume, N; Avois, L; Mangin, P

    2006-01-01

    Background and objectives Recombinant human growth hormone (rhGH) has been on the list of forbidden substances since availability of its recombinant form improved in the early 1990s. Although its effectiveness in enhancing physical performance is still unproved, the compound is likely used for its potential anabolic effect on the muscle growth, and also in combination with other products (androgens, erythropoietin, etc.). The degree of similarity between the endogenous and the recombinant forms, the pulsatile secretion and marked interindividual variability makes detection of doping difficult. Two approaches proposed to overcome this problem are: the indirect method, which measures a combination of several factors in the biological cascade affected by administration of GH; and the direct method, which measures the difference between the circulating and the recombinant (represented by the unique 22 kD molecule) forms of GH. This article gives an overview of what is presently known about hGH in relation to sport. The available methods of detection are also evaluated. Methods Review of the literature on GH in relation to exercise, and its adverse effects and methods of detection when used for doping. Results and conclusion The main effects of exercise on hGH production and the use and effects of rhGH in athletes are discussed. Difficulties encountered by laboratories to prove misuse of this substance by both indirect and direct analyses are emphasised. The direct method currently seems to have the best reliability, even though the time window of detection is too short. hGH doping is a major challenge in the fight against doping. The effect of exercise on hGH and its short half‐life are still presenting difficulties during doping analysis. To date the most promising method appears to be the direct approach utilising immunoassays. PMID:16799101

  8. Ontogeny of pituitary growth hormone and growth hormone mRNA in the chicken.

    PubMed

    McCann-Levorse, L M; Radecki, S V; Donoghue, D J; Malamed, S; Foster, D N; Scanes, C G

    1993-01-01

    The changes in pituitary growth hormone (GH) mRNA levels have been determined by Northern blot analysis and laser densitometry during embryonic development and posthatch growth of white Leghorn cockerels. Pituitary GH mRNA levels were observed to progressively increase between 18 days of embryonic development to a maximum at 4 weeks of age (posthatch). Subsequently, pituitary GH mRNA levels declined between 4 and 8 weeks of age, and between 12 weeks of age and adulthood. Pituitary GH contents showed increases during embryonic development and posthatch growth that paralleled the rise in GH mRNA. The decline in pituitary GH mRNA levels between 4 weeks of age and adulthood occurs when GH secretion has been observed previously to decline.

  9. Effectiveness of Recombinant Human Growth Hormone for Pharyngocutaneous Fistula Closure

    PubMed Central

    Sari, Murat; Midi, Ahmet; Yumusakhuylu, Ali Cemal; Findik, Ozan; Binnetoglu, Adem

    2015-01-01

    Objectives In laryngeal cancer, which comprises 25% of head and neck cancer, chemotherapy has come into prominence with the increase in organ-protective treatments. With such treatment, salvage surgery has increased following recurrence; the incidence of pharyngocutaneous fistula has also increased in both respiratory and digestive system surgery. We investigated the effects of recombinant human growth hormone on pharyngocutaneous fistula closure in Sprague-Dawley rats, based on an increase in amino acid uptake and protein synthesis for wound healing, an increase in mitogenesis, and enhancement of collagen formation by recombinant human growth hormone. Methods This study was experimental animal study. Forty Sprague-Dawley rats were separated into two groups, and pharyngoesophagotomy was performed. The pharyngoesophagotomy was sutured with vicryl in both groups. Rats in group 1 (control group) received no treatment, while those in group 2 were administered a subcutaneous injection of recombinant human growth hormone daily. On day 14, the pharynx, larynx, and upper oesophagus were excised and examined microscopically. Results Pharyngocutaneous fistula exhibited better closure macroscopically in the recombinant human growth hormone group. There was a significant difference in collagen formation and epithelisation in the recombinant human growth hormone group compared to the control group. Conclusion This study is believed to be the first in which the effect of recombinant human growth hormone on pharyngocutaneous fistula closure was evaluated, and the findings suggest the potential of use of growth hormone for treatment of pharyngocutaneous fistula. PMID:26622960

  10. Continuous elevation of blood growth hormone concentrations by beeswax implant.

    PubMed

    Davis, S L; Dodson, M V; Ohlson, D L

    1983-09-01

    We examined constancy of release of purified ovine growth hormone from an implant containing soybean oil and beeswax. Implants contained an amount of growth hormone that was sufficient to increase concentrations in blood plasma by 20 and 40 ng/ml and to maintain those concentrations over 1 wk. Growth hormone in plasma increased to approximately 65 ng/ml in lambs receiving low dose implants the 1st day after implantation, returned to 31 ng/ml on day 2, and remained near this concentration for the remainder of the week. Pulse release of growth hormone was not similiar in the high dose lambs where growth hormone concentration in plasma averaged 45 ng/ml 1 day after implantation, then gradually increased to 60 ng/ml on day 6. Unimplanted control lambs had mean growth hormone concentrations of 2.9 to 3.9 ng/ml throughout the 6-day observation. This approach should interest investigators studying the chronic influence of purified or synthetic growth hormone on dairy cows, beef steers, or lambs.

  11. A framework integrating plant growth with hormones and nutrients.

    PubMed

    Krouk, Gabriel; Ruffel, Sandrine; Gutiérrez, Rodrigo A; Gojon, Alain; Crawford, Nigel M; Coruzzi, Gloria M; Lacombe, Benoît

    2011-04-01

    It is well known that nutrient availability controls plant development. Moreover, plant development is finely tuned by a myriad of hormonal signals. Thus, it is not surprising to see increasing evidence of coordination between nutritional and hormonal signaling. In this opinion article, we discuss how nitrogen signals control the hormonal status of plants and how hormonal signals interplay with nitrogen nutrition. We further expand the discussion to include other nutrient-hormone pairs. We propose that nutrition and growth are linked by a multi-level, feed-forward cycle that regulates plant growth, development and metabolism via dedicated signaling pathways that mediate nutrient and hormonal regulation. We believe this model will provide a useful concept for past and future research in this field. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

    PubMed Central

    Carta, Luisanna; Ibba, Anastasia; Guzzetti, Chiara

    2014-01-01

    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. PMID:24926456

  13. Ghrelin and the growth hormone secretagogue receptor in growth and development.

    PubMed

    Chanoine, J-P; De Waele, K; Walia, P

    2009-04-01

    The pancreas is a major source of ghrelin in the perinatal period, whereas gastric production progressively increases after birth. Loss of function of the genes for ghrelin or for the constitutively activated growth hormone secretagogue receptor (GHSR) does not affect birth weight and early postnatal growth. However, ghrl(-/-) or ghsr(-/-) mice fed a high fat diet starting soon after weaning are resistant to diet-induced obesity, suggesting that ghrelin affects the maturation of the metabolic axes involved in energy balance. In addition, animal and human studies suggest that GHSR plays a physiological role in linear growth. In mice, absence of the GHSR gene is associated with lower insulin-like growth factor 1 concentrations and lower body mass in adult animals, independently of food intake. In humans, a mutation of the GHSR gene that impairs the constitutive activity of the receptor was found in two families with short stature. Administration of acylated ghrelin to rat pups directly does not affect weight gain. In contrast, administration of ghrelin to pregnant or lactating rats results in greater fetal weight and postnatal weight gain, respectively, suggesting that maternal ghrelin may stimulate perinatal growth. These data point toward a physiological role for ghrelin and GHSR in growth and/or in the maturation of hormonal systems involved in the regulation of energy balance.

  14. Growth hormone (GH-1) gene deletions in children with isolated growth hormone deficiency (IGHD).

    PubMed

    Desai, Meena P; Mithbawkar, Shilpa M; Upadhye, Pradnya S; Shalia, Kavita K

    2012-07-01

    To detect growth hormone GH-1 gene deletions (6.7 kb, 7.6 kb, 7 kb) in familial/nonfamilial isolated growth hormone deficiency (IGHD) and note their clinical and investigative profile. Thirty (M16,F14) prepubertal IGHD patients aged 0.25 to 14 y, from 25 families were screened. Duration of growth failure, relevant history, clinical phenotype, and height SDS were recorded. Peak GH response to Clonidine (0.15 mg/m(2)), IGF-1, IGFBP-3 and pituitary/target gland hormones were studied. Genomic DNA of patients and family was analysed by PCR and DNA fragments were visualized on agarose gel electrophoresis. This series was divided into deletion +ve, Group I (n=12,40%) inclusive of six familial/six nonfamilial patients, and deletion -ve Group II (n=18,60%), 5 familial/13 nonfamilial cases; in total 11/30 were familial. Onset of growth failure was earlier in Group I (p<0.001) mean 1.1 vs 4.7 y. Mean height SDS was -7 vs. -4.5 in Groups I/II (p<0.01), age at presentation 5.1 vs 8.6 y. Overhanging forehead, prominent eyes, hypoplastic facies characterized Group I with FBS <50 mg/dl in 50% and very low peak GH <0.04 vs 2.04 ng/ml (p<0.001) in Group II. In both groups IGF-1 and IGFBP3 were low, other hormones were normal and MRI showed hypoplastic adenohypophysis. 40% had GH-1 gene deletion (6.7 kb deletion in 83%, 7.6 kb and a compound heterozygote in 8% each). In this series of 30 IGHD patients, frequency of GH-1 gene deletions (12/30) was 40%, and 54% among familial patients, and 31% with height SDS>-4. 83% had 6.7 kb deletion. Height SDS>-4, clinical phenotype, peak GH<1 ng/ml and hypoglycemia characterised IGHD Type IA.

  15. Regulation of growth hormone secretion by the growth hormone releasing hexapeptide (GHRP-6).

    PubMed

    Micic, D; Mallo, F; Peino, R; Cordido, F; Leal-Cerro, A; Garcia-Mayor, R V; Casanueva, F F

    1993-01-01

    Growth hormone (GH) secretion is regulated by a complex system of central and peripheral signals. Recently, a new GH-releasing hexapeptide (His-D-Trp-Ala-Trp-D-Phe-Lys-NH2) called GHRP-6 which specifically releases GH has been studied. In the present work the mechanism of action of GHRP-6 has been addressed in experimental animal models as well as in obese subjects. GHRP-6 releases GH independently of the hypothalamic factors GHRH and somatostatin and is a powerful GH releaser in obesity.

  16. An enzyme immunoassay for rat growth hormone - Applications to the study of growth hormone variants

    NASA Technical Reports Server (NTRS)

    Farrington, Marianne A.; Hymer, W. C.

    1987-01-01

    A sensitive and specific competitive enzyme immunoassay for rat growth hormone (GH) is described and its use in the detection of GH variants is demonstrated. In the present assay, soluble GH and GH adsorbed to a solid-phase support compete for monkey anti-GH antibody binding sites. The immobilized antibody-GH complex is detected and quantified using goat antimonkey immunoglobin G covalently conjugated to horseradish peroxidase. It is noted that the assay can be performed in 27 hours and that sensitivities in the range of 0.19 to 25 ng can be obtained in the region of 10 to 90 percent binding.

  17. An enzyme immunoassay for rat growth hormone - Applications to the study of growth hormone variants

    NASA Technical Reports Server (NTRS)

    Farrington, Marianne A.; Hymer, W. C.

    1987-01-01

    A sensitive and specific competitive enzyme immunoassay for rat growth hormone (GH) is described and its use in the detection of GH variants is demonstrated. In the present assay, soluble GH and GH adsorbed to a solid-phase support compete for monkey anti-GH antibody binding sites. The immobilized antibody-GH complex is detected and quantified using goat antimonkey immunoglobin G covalently conjugated to horseradish peroxidase. It is noted that the assay can be performed in 27 hours and that sensitivities in the range of 0.19 to 25 ng can be obtained in the region of 10 to 90 percent binding.

  18. The role of nitric oxide in the coronary vasoconstriction caused by growth hormone in anaesthetized pigs.

    PubMed

    Molinari, C; Battaglia, A; Bona, G; Grossini, E; Mary, D A; Vacca, G

    2000-03-01

    Intravenous injection of growth hormone in anaesthetized pigs has been shown to cause coronary vasoconstriction by antagonizing the vasodilatory effects of 2-adrenergic receptors. Because nitric oxide is believed to modulate or mediate 2-adrenergic effects, the present study was undertaken in the same experimental model to determine the role of nitric oxide in the above response to growth hormone. In fourteen pigs anaesthetized with sodium pentobarbitone, changes in left circumflex or anterior descending coronary blood flow caused by intravenous injection of 0.05 i.u. kg-1 of growth hormone at constant heart rate and arterial blood pressure were assessed using electromagnetic flowmeters. In a first control group of six pigs, growth hormone caused a decrease in coronary blood flow which averaged 13.1 % of the baseline values. In a second group of eight pigs, intravenous administration of N-nitro-L-arginine methyl ester (L-NAME) was used to block the endothelial release of nitric oxide. In these pigs, the subsequent injection of growth hormone did not cause any significant changes in coronary blood flow, even when performed after reversing the increase in arterial blood pressure and coronary vascular resistance caused by L-NAME with continuous intravenous infusion of papaverine. These results indicated that the coronary vasoconstricting effect of growth hormone, known to involve antagonism of 2-adrenergic vasodilatory effect, was mediated by inhibition of nitric oxide release.

  19. Effect of a pre-exercise energy supplement on the acute hormonal response to resistance exercise.

    PubMed

    Hoffman, Jay R; Ratamess, Nicholas A; Ross, Ryan; Shanklin, Miles; Kang, Jie; Faigenbaum, Avery D

    2008-05-01

    The effect of a pre-exercise energy sport drink on the acute hormonal response to resistance exercise was examined in eight experienced resistance trained men. Subjects were randomly provided either a placebo (P: maltodextrin) or the supplement (S: combination of branched chain amino acids, creatine, taurine, caffeine, and glucuronolactone). Subjects performed 6 sets of no more than 10 repetitions of the squat exercise at 75% of their 1 repetition maximum (1RM) with 2 minutes of rest between sets. Blood draws occurred at baseline pre-exercise, immediately post- (IP), 15 minutes post- (15P), and 30-minutes post (30P) exercise for measurement of serum growth hormone, total and free testosterone, cortisol, and insulin concentrations. Although significant differences were seen only at set 5, the total number of repetitions and training volume tended (p = 0.08) to be higher with S compared to P. Serum growth hormone and insulin concentrations were significantly higher at 15P and IP, respectively, in S compared to P. Results suggest that a pre-exercise energy S consumed 10 minutes before resistance exercise can enhance acute exercise performance by increasing the number of repetitions performed and the total volume of exercise. The enhanced exercise performance resulted in a significantly greater increase in both growth hormone and insulin concentrations, indicating an augmented anabolic hormone response to this pre-exercise S.

  20. Liquid growth hormone: preservatives and buffers.

    PubMed

    Kappelgaard, Anne-Marie; Bojesen, Anders; Skydsgaard, Karsten; Sjögren, Ingrid; Laursen, Torben

    2004-01-01

    Growth hormone (GH) treatment is a successful medical therapy for children and adults with GH deficiency as well as for growth retardation due to chronic renal disease, Turner syndrome and in children born small for gestational age. For all of these conditions, treatment is long term and patients receive daily subcutaneous injections of GH for many years. Patient compliance is therefore of critical importance to ensure treatment benefit. One of the major factors influencing compliance is injection pain. Besides the injection device used, pain perception and local tissue reaction following injection are dependent on the preservative used in the formulation and the concentration of GH. Injection pain may also be related to the buffer substance and injection volume. A liquid formulation of GH, Norditropi SimpleXx, has been developed that dispenses with the need for reconstitution before administration. The formulation uses phenol (3 mg/ml) as a preservative (to protect product from microbial degradation or contamination) and histidine as a buffer. Alternative preservatives used in other GH formulations include m-cresol (9 mg/ml) and benzyl alcohol (3-9 mg/ml). Buffering agents include citrate and phosphate. Phenol has been successfully used as a preservative in drug formulations for more than 50 years and is considered a safe and effective agent which complies with strict international requirements for preservatives in drug formulations. In toxicological studies, no or only mild local reactions have been observed following subcutaneous administration of phenol (7.5 mg/ml), m-cresol (3-4 mg/ml) and benzyl alcohol (9 mg/ml). No general toxicity reactions were observed after subcutaneous administration of these agents. Clinical evaluation of the preservatives and buffers used in Norditropin SimpleXx showed that pain perception was similar between formulations containing phenol and benzyl alcohol, whereas m-cresol was associated with more painful injections than benzyl

  1. Improved response of growth hormone to growth hormone-releasing hormone and reversible chronic thyroiditis after hydrocortisone replacement in isolated adrenocorticotropic hormone deficiency.

    PubMed

    Inagaki, Miho; Sato, Haruhiro; Miyamoto, Yoshiyasu; Hirukawa, Takashi; Sawaya, Asako; Miyakogawa, Takayo; Tatsumi, Ryoko; Kakuta, Takatoshi

    2009-07-20

    We report a 44-year-old Japanese man who showed a reversible blunted response of growth hormone (GH) to GH-releasing hormone (GRH) stimulation test and reversible chronic thyroiditis accompanied by isolated ACTH deficiency. He was admitted to our hospital because of severe general malaise, hypotension, and hypoglycemia. He showed repeated attacks of hypoglycemia, and his serum sodium level gradually decreased. Finally, he was referred to the endocrinology division, where his adrenocorticotropic hormone (ACTH) and cortisol values were found to be low, and his GH level was slightly elevated. An increased value of thyroid stimulating hormone (TSH) and decreased values of free triidothyronine and free thyroxine were observed along with anti-thyroglobulin antibody, suggesting chronic thyroiditis. Pituitary stimulation tests revealed a blunted response of ACTH and cortisol to corticotropin-releasing hormone, and a blunted response of GH to GRH. Hydrocortisone replacement was then started, and this improved the patient's general condition. His hypothyroid state gradually ameliorated and his titer of anti-thyroglobulin antibody decreased to the normal range. Pituitary function was re-evaluated with GRH stimulation test under a maintenance dose of 20 mg/day hydrocortisone and showed a normal response of GH to GRH. It is suggested that re-evaluation of pituitary and thyroid function is useful for diagnosing isolated ACTH deficiency after starting a maintenance dose of hydrocortisone in order to avoid unnecessary replacement of thyroid hormone.

  2. Growth Hormone Inhibits Hepatic De Novo Lipogenesis in Adult Mice

    PubMed Central

    Cordoba-Chacon, Jose; Majumdar, Neena; List, Edward O.; Diaz-Ruiz, Alberto; Frank, Stuart J.; Manzano, Anna; Bartrons, Ramon; Puchowicz, Michelle; Kopchick, John J.

    2015-01-01

    Patients with nonalcoholic fatty liver disease (NAFLD) are reported to have low growth hormone (GH) production and/or hepatic GH resistance. GH replacement can resolve the fatty liver condition in diet-induced obese rodents and in GH-deficient patients. However, it remains to be determined whether this inhibitory action of GH is due to direct regulation of hepatic lipid metabolism. Therefore, an adult-onset, hepatocyte-specific, GH receptor (GHR) knockdown (aLivGHRkd) mouse was developed to model hepatic GH resistance in humans that may occur after sexual maturation. Just 7 days after aLivGHRkd, hepatic de novo lipogenesis (DNL) was increased in male and female chow-fed mice, compared with GHR-intact littermate controls. However, hepatosteatosis developed only in male and ovariectomized female aLivGHRkd mice. The increase in DNL observed in aLivGHRkd mice was not associated with hyperactivation of the pathway by which insulin is classically considered to regulate DNL. However, glucokinase mRNA and protein levels as well as fructose-2,6-bisphosphate levels were increased in aLivGHRkd mice, suggesting that enhanced glycolysis drives DNL in the GH-resistant liver. These results demonstrate that hepatic GH actions normally serve to inhibit DNL, where loss of this inhibitory signal may explain, in part, the inappropriate increase in hepatic DNL observed in NAFLD patients. PMID:26015548

  3. Concomitant occurrence of Turner syndrome and growth hormone deficiency.

    PubMed

    Yu, Jung; Shin, Ha Young; Lee, Chong Guk; Kim, Jae Hyun

    2016-11-01

    Turner syndrome (TS) is a genetic disorder in phenotypic females that has characteristic physical features and presents as partial or complete absence of the second sex chromosome. Growth hormone deficiency (GHD) is a condition caused by insufficient release of growth hormone from the pituitary gland. The concomitant occurrence of TS and GHD is rare and has not yet been reported in Korea. Here we report 2 cases of TS and GHD. In case 1, GHD was initially diagnosed. Karyotyping was performed because of the presence of the typical phenotype and poor response to growth hormone therapy, which revealed 45,X/45,X+mar. The patient showed increased growth velocity after the growth hormone dose was increased. In case 2, a growth hormone provocation test and chromosomal analysis were performed simultaneously because of decreased growth velocity and the typical TS phenotype, which showed GHD and a mosaic karyotype of 45,X/46,XX. The patient showed spontaneous pubertal development. In female patients with short stature, it is important to perform a throughout physical examination and test for hormonal and chromosomal abnormalities because diagnostic accuracy is important for treatment and prognosis.

  4. Concomitant occurrence of Turner syndrome and growth hormone deficiency

    PubMed Central

    Yu, Jung; Shin, Ha Young; Lee, Chong Guk

    2016-01-01

    Turner syndrome (TS) is a genetic disorder in phenotypic females that has characteristic physical features and presents as partial or complete absence of the second sex chromosome. Growth hormone deficiency (GHD) is a condition caused by insufficient release of growth hormone from the pituitary gland. The concomitant occurrence of TS and GHD is rare and has not yet been reported in Korea. Here we report 2 cases of TS and GHD. In case 1, GHD was initially diagnosed. Karyotyping was performed because of the presence of the typical phenotype and poor response to growth hormone therapy, which revealed 45,X/45,X+mar. The patient showed increased growth velocity after the growth hormone dose was increased. In case 2, a growth hormone provocation test and chromosomal analysis were performed simultaneously because of decreased growth velocity and the typical TS phenotype, which showed GHD and a mosaic karyotype of 45,X/46,XX. The patient showed spontaneous pubertal development. In female patients with short stature, it is important to perform a throughout physical examination and test for hormonal and chromosomal abnormalities because diagnostic accuracy is important for treatment and prognosis. PMID:28018463

  5. Growth hormone receptor polymorphisms and growth hormone response to stimulation test: a pilot study.

    PubMed

    Pagani, Sara; DE Filippo, Gianpaolo; Genoni, Giulia; Rendina, Domenico; Meazza, Cristina; Bozzola, Elena; Bona, Gianni; Bozzola, Mauro

    2016-06-29

    No gold standard pharmacological stimulation test exists for the diagnosis of growth hormone deficiency (GHD). In addition, the genetic factors that influence growth hormone (GH) responses remain unclear. This study aimed to determine whether polymorphisms in exon 6 of the GH receptor gene influence responses to the L-arginine GH stimulation test. This study included 27 prepubertal patients with confirmed GHD. GHD was defined as a peak GH level <8 ng/ml in response to pharmacological stimulation. The mean GH peak after L-arginine stimulation was 2.9 ± 2.9 ng/ml. The included patients had the following genotypes at the third position of codon 168: AA (n=1), AG (n=15) and GG (n=11). Patients carrying the AA and AG genotypes exhibited stronger responses to arginine than patients with the GG genotype (3.1 ± 2.7 vs. 1.5 ± 1.3 ng/ml, p = 0.01). The approach employed in this study could elucidate GH profiles under physiological and pathological conditions, facilitating improved interpretation of pharmacological stimulation tests.

  6. Episodic patterns of growth hormone secretion and growth hormone status of normal and tibial dyschondroplastic chickens.

    PubMed

    Vasilatos-Younken, R; Leach, R M

    1986-01-01

    Growth hormone status of normal and tibial dyschondroplastic (TD) birds was determined in 25 d old male chicks genetically selected for high and low incidence of TD. Birds were surgically prepared with indwelling venous catheters and blood samples remotely removed at 20 min intervals for 6 h to establish secretory patterns. Birds were maintained under a 16L:8D cycle, with free access to feed and water at all times. In a second experiment, secretory capacity was evaluated by administering a 10 micrograms/kg body weight dose of thyrotrophin releasing hormone (TRH). Blood samples were removed at 0, 5, 10, 20, 30, 60 and 120 min post-infusion of either TRH or saline (control). All birds displayed pulsatile patterns of GH secretion, with an average peak duration of 60 min and a 90 min inter-peak interval. Dyschondroplastic birds exhibited 50% higher mean peak amplitudes than normal birds (P less than .06), however, this difference was not translated into overall mean or total (curve area) differences. The magnitude of response to a TRH challenge was greater (P less than .10) for TD than for normal birds. In view of the relationships observed in other species between secretory pattern characteristics such as peak amplitude, and growth characteristics, it is suggested that differences in GH status of dyschondroplastic relative to normal birds may be related to initiation of the TD lesion.

  7. Growth Hormone Research Society perspective on the development of long-acting growth hormone preparations.

    PubMed

    Christiansen, Jens Sandahl; Backeljauw, Philippe F; Bidlingmaier, Martin; Biller, Beverly M K; Boguszewski, Margaret C S; Casanueva, Felipe F; Chanson, Philippe; Chatelain, Pierre; Choong, Catherine S; Clemmons, David R; Cohen, Laurie E; Cohen, Pinchas; Frystyk, Jan; Grimberg, Adda; Hasegawa, Yukihiro; Haymond, Morey W; Ho, Ken; Hoffman, Andrew R; Holly, Jeff M P; Horikawa, Reiko; Höybye, Charlotte; Jorgensen, Jens Otto L; Johannsson, Gudmundur; Juul, Anders; Katznelson, Laurence; Kopchick, John J; Lee, K O; Lee, Kuk-Wha; Luo, Xiaoping; Melmed, Shlomo; Miller, Bradley S; Misra, Madhusmita; Popovic, Vera; Rosenfeld, Ron G; Ross, Judith; Ross, Richard J; Saenger, Paul; Strasburger, Christian J; Thorner, Michael O; Werner, Haim; Yuen, Kevin

    2016-06-01

    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). A closed meeting of 55 international scientists with expertise in GH, including pediatric and adult endocrinologists, basic scientists, regulatory scientists, and participants from the pharmaceutical industry. Current literature was reviewed for gaps in knowledge. Expert opinion was used to suggest studies required to address potential safety and efficacy issues. Following plenary presentations summarizing the literature, breakout groups discussed questions framed by the planning committee. Attendees reconvened after each breakout session to share group reports. A writing team compiled the breakout session reports into a draft document that was discussed 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 day of the workshop. Scientists from industry and regulatory agencies reviewed the manuscript to identify any factual errors. LAGH compounds may represent an advance over daily GH injections because of increased convenience and differing phamacodynamic properties, providing the potential for improved adherence and outcomes. Better methods to assess adherence must be developed and validated. Long-term surveillance registries that include assessment of efficacy, cost-benefit, disease burden, quality of life, and safety are essential for understanding the impact of sustained exposure to LAGH preparations. © 2016 The authors.

  8. Toward gene therapy for growth hormone deficiency via salivary gland expression of growth hormone.

    PubMed

    Racz, G Z; Zheng, C; Goldsmith, C M; Baum, B J; Cawley, N X

    2015-03-01

    Salivary glands are useful targets for gene therapeutics. After gene transfer into salivary glands, regulated secretory pathway proteins, such as human growth hormone, are secreted into saliva, whereas constitutive secretory pathway proteins, such as erythropoietin, are secreted into the bloodstream. Secretion of human growth hormone (hGH) into the saliva is not therapeutically useful. In this study, we attempted to redirect the secretion of transgenic hGH from the saliva to the serum by site-directed mutagenesis. We tested hGH mutants first in vitro with AtT20 cells, a model endocrine cell line that exhibits polarized secretion of regulated secretory pathway proteins. Selected mutants were further studied in vivo using adenoviral-mediated gene transfer to rat submandibular glands. We identified two mutants with differences in secretion behavior compared to wild-type hGH. One mutant, ΔN1-6 , was detected in the serum of transduced rats, demonstrating that expression of this mutant in the salivary gland resulted in its secretion through the constitutive secretory pathway. This study demonstrates that mutagenesis of therapeutic proteins normally destined for the regulated secretory pathway may result in their secretion via the constitutive secretory pathway into the circulation for potential therapeutic benefit. © Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

  9. Growth hormone positive effects on craniofacial complex in Turner syndrome.

    PubMed

    Juloski, Jovana; Dumančić, Jelena; Šćepan, Ivana; Lauc, Tomislav; Milašin, Jelena; Kaić, Zvonimir; Dumić, Miroslav; Babić, Marko

    2016-11-01

    Turner syndrome occurs in phenotypic females with complete or partial absence of X chromosome. The leading symptom is short stature, while numerous but mild stigmata manifest in the craniofacial region. These patients are commonly treated with growth hormone to improve their final height. The aim of this study was to assess the influence of long-term growth hormone therapy on craniofacial morphology in Turner syndrome patients. In this cross-sectional study cephalometric analysis was performed on 13 lateral cephalograms of patients with 45,X karyotype and the average age of 17.3 years, who have received growth hormone for at least two years. The control group consisted of 13 Turner syndrome patients naive to growth hormone treatment, matched to study group by age and karyotype. Sixteen linear and angular measurements were obtained from standard lateral cephalograms. Standard deviation scores were calculated in order to evaluate influence of growth hormone therapy on craniofacial components. In Turner syndrome patients treated with growth hormone most of linear measurements were significantly larger compared to untreated patients. Growth hormone therapy mainly influenced posterior face height, mandibular ramus height, total mandibular length, anterior face height and maxillary length. While the increase in linear measurements was evident, angular measurements and facial height ratio did not show statistically significant difference. Acromegalic features were not found. Long-term growth hormone therapy has positive influence on craniofacial development in Turner syndrome patients, with the greatest impact on posterior facial height and mandibular ramus. However, it could not compensate X chromosome deficiency and normalize craniofacial features. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Neuroprotective Actions of Ghrelin and Growth Hormone Secretagogues

    PubMed Central

    Frago, Laura M.; Baquedano, Eva; Argente, Jesús; Chowen, Julie A.

    2011-01-01

    The brain incorporates and coordinates information based on the hormonal environment, receiving information from peripheral tissues through the circulation. Although it was initially thought that hormones only acted on the hypothalamus to perform endocrine functions, it is now known that they in fact exert diverse actions on many different brain regions including the hypothalamus. Ghrelin is a gastric hormone that stimulates growth hormone secretion and food intake to regulate energy homeostasis and body weight by binding to its receptor, growth hormone secretagogues–GH secretagogue-receptor, which is most highly expressed in the pituitary and hypothalamus. In addition, ghrelin has effects on learning and memory, reward and motivation, anxiety, and depression, and could be a potential therapeutic agent in neurodegenerative disorders where excitotoxic neuronal cell death and inflammatory processes are involved. PMID:21994488

  11. Growth hormone is permissive for neoplastic colon growth

    PubMed Central

    Chesnokova, Vera; Zonis, Svetlana; Zhou, Cuiqi; Recouvreux, Maria Victoria; Ben-Shlomo, Anat; Araki, Takako; Barrett, Robert; Workman, Michael; Wawrowsky, Kolja; Ljubimov, Vladimir A.; Uhart, Magdalena; Melmed, Shlomo

    2016-01-01

    Growth hormone (GH) excess in acromegaly is associated with increased precancerous colon polyps and soft tissue adenomas, whereas short-stature humans harboring an inactivating GH receptor mutation do not develop cancer. We show that locally expressed colon GH is abundant in conditions predisposing to colon cancer and in colon adenocarcinoma-associated stromal fibroblasts. Administration of a GH receptor (GHR) blocker in acromegaly patients induced colon p53 and adenomatous polyposis coli (APC), reversing progrowth GH signals. p53 was also induced in skin fibroblasts derived from short-statured humans with mutant GHR. GH-deficient prophet of pituitary-specific positive transcription factor 1 (Prop1)−/− mice exhibited induced colon p53 levels, and cross-breeding them with Apcmin+/− mice that normally develop intestinal and colon tumors resulted in GH-deficient double mutants with markedly decreased tumor number and size. We also demonstrate that GH suppresses p53 and reduces apoptosis in human colon cell lines as well as in induced human pluripotent stem cell-derived intestinal organoids, and confirm in vivo that GH suppresses colon mucosal p53/p21. GH excess leads to decreased colon cell phosphatase and tensin homolog deleted on chromosome 10 (PTEN), increased cell survival with down-regulated APC, nuclear β-catenin accumulation, and increased epithelial–mesenchymal transition factors and colon cell motility. We propose that GH is a molecular component of the “field change” milieu permissive for neoplastic colon growth. PMID:27226307

  12. Growth hormone is permissive for neoplastic colon growth.

    PubMed

    Chesnokova, Vera; Zonis, Svetlana; Zhou, Cuiqi; Recouvreux, Maria Victoria; Ben-Shlomo, Anat; Araki, Takako; Barrett, Robert; Workman, Michael; Wawrowsky, Kolja; Ljubimov, Vladimir A; Uhart, Magdalena; Melmed, Shlomo

    2016-06-07

    Growth hormone (GH) excess in acromegaly is associated with increased precancerous colon polyps and soft tissue adenomas, whereas short-stature humans harboring an inactivating GH receptor mutation do not develop cancer. We show that locally expressed colon GH is abundant in conditions predisposing to colon cancer and in colon adenocarcinoma-associated stromal fibroblasts. Administration of a GH receptor (GHR) blocker in acromegaly patients induced colon p53 and adenomatous polyposis coli (APC), reversing progrowth GH signals. p53 was also induced in skin fibroblasts derived from short-statured humans with mutant GHR. GH-deficient prophet of pituitary-specific positive transcription factor 1 (Prop1)(-/-) mice exhibited induced colon p53 levels, and cross-breeding them with Apc(min+/-) mice that normally develop intestinal and colon tumors resulted in GH-deficient double mutants with markedly decreased tumor number and size. We also demonstrate that GH suppresses p53 and reduces apoptosis in human colon cell lines as well as in induced human pluripotent stem cell-derived intestinal organoids, and confirm in vivo that GH suppresses colon mucosal p53/p21. GH excess leads to decreased colon cell phosphatase and tensin homolog deleted on chromosome 10 (PTEN), increased cell survival with down-regulated APC, nuclear β-catenin accumulation, and increased epithelial-mesenchymal transition factors and colon cell motility. We propose that GH is a molecular component of the "field change" milieu permissive for neoplastic colon growth.

  13. Adrenergic receptor control mechanism for growth hormone secretion.

    PubMed

    Blackard, W G; Heidingsfelder, S A

    1968-06-01

    The influence of catecholamines on growth hormone secretion has been difficult to establish previously, possibly because of the suppressive effect of the induced hyperglycemia on growth hormone concentrations. In this study, an adrenergic receptor control mechanism for human growth hormone (HGH) secretion was uncovered by studying the effects of alpha and beta receptor blockade on insulin-induced growth hormone elevations in volunteer subjects. Alpha adrenergic blockade with phentolamine during insulin hypoglycemia, 0.1 U/kg, inhibited growth hormon elevations to 30-50% of values in the same subjects during insulin hypoglycemia without adrenergic blockade. More complete inhibition by phentolamine could not be demonstrated at a lower dose of insulin (0.05 U/kg). Beta adrenergic blockade with propranolol during insulin hypoglycemia significantly enhanced HGH concentrations in paired experiments. The inhibiting effect of alpha adrenergic receptor blockade on HGH concentrations could not be attributed to differences in blood glucose or free fatty acid values; however, more prolonged hypoglycemia and lower plasma free fatty acid values may have been a factor in the greater HGH concentrations observed during beta blockade. In the absence of insulin induced hypoglycemia, neither alpha nor beta adrenergic receptor blockade had a detectable effect on HGH concentrations. Theophylline, an inhibitor of cyclic 3'5'-AMP phosphodiesterase activity, also failed to alter plasma HGH concentrations. These studies demonstrate a stimulatory effect of alpha receptors and a possible inhibitory effect of beta receptors on growth hormone secretion.

  14. Analysis of Paired Primary-Metastatic Hormone-Receptor Positive Breast Tumors (HRPBC) Uncovers Potential Novel Drivers of Hormonal Resistance

    PubMed Central

    Manso, Luis; Mourón, Silvana; Tress, Michael; Gómez-López, Gonzalo; Morente, Manuel; Ciruelos, Eva; Rubio-Camarillo, Miriam; Rodriguez-Peralto, Jose Luis; Pujana, Miguel A.; Pisano, David G.; Quintela-Fandino, Miguel

    2016-01-01

    We sought to identify genetic variants associated with disease relapse and failure to hormonal treatment in hormone-receptor positive breast cancer (HRPBC). We analyzed a series of HRPBC with distant relapse, by sequencing pairs (n = 11) of tumors (primary and metastases) at >800X. Comparative genomic hybridization was performed as well. Top hits, based on the frequency of alteration and severity of the changes, were tested in the TCGA series. Genes determining the most parsimonious prognostic signature were studied for their functional role in vitro, by performing cell growth assays in hormonal-deprivation conditions, a setting that mimics treatment with aromatase inhibitors. Severe alterations were recurrently found in 18 genes in the pairs. However, only MYC, DNAH5, CSFR1, EPHA7, ARID1B, and KMT2C preserved an independent prognosis impact and/or showed a significantly different incidence of alterations between relapsed and non-relapsed cases in the TCGA series. The signature composed of MYC, KMT2C, and EPHA7 best discriminated the clinical course, (overall survival 90,7 vs. 144,5 months; p = 0.0001). Having an alteration in any of the genes of the signature implied a hazard ratio of death of 3.25 (p<0.0001), and early relapse during the adjuvant hormonal treatment. The presence of the D348N mutation in KMT2C and/or the T666I mutation in the kinase domain of EPHA7 conferred hormonal resistance in vitro. Novel inactivating mutations in KMT2C and EPHA7, which confer hormonal resistance, are linked to adverse clinical course in HRPBC. PMID:27195705

  15. [Successful maintenance hemodialysis therapy with supplemented growth hormone in a diabetic patient with growth hormone insufficiency].

    PubMed

    Tanaka, Tomomi; Yoshida, Sayaka; Nishigaki, Keisuke; Kuyama, Tamaki; Maeda, Yoshitaka

    2013-01-01

    Growth hormone (GH) insufficiency is difficult to identify especially in adults, because its clinical manifestations overlap with metabolic syndrome and diabetes mellitus. We experienced a case of a 38-year-old woman who abruptly gained weight from the age of five, and was diagnosed as type 2 diabetes mellitus (DM) during her 20s. When the patient visited JA Toride Medical Center at age 38, her renal function had been severely damaged, and caused congestive heart failure. Hemodialysis (HD) therapy was introduced, and GH insufficiency was identified, based on her obesity profile since her childhood and hormone surveillance. GH supplementation was initially avoided, because of her concurrent problems of DM and advanced renal failure. However, because of her restricted activities in daily living (ADL) and frequent hypotension episodes, a decision was taken to start supplementary administration of GH, which consequently succeeded in stabilizing blood pressure and extended her ADL. Although GH supplementation has recently been reported to be effective in improving protein energy malnutrition in dialysis patients without GH insufficiency, there is no report concerning GH insufficiency in dialysis patients. This is the first case report of GH insufficiency, in which GH supplementation enabled the patient to continue HD.

  16. Growth hormone replacement therapy reduces risk of cancer in adult with growth hormone deficiency: A meta-analysis

    PubMed Central

    Li, Zhanzhan; Zhou, Qin; Li, Yanyan; Fu, Jun; Huang, Xinqiong; Shen, Liangfang

    2016-01-01

    The risk of growth hormone on cancer in adult with growth hormone deficiency remains unclear. We carried out a meta-analysis to evaluate the risk of cancer in adult with and without growth hormone replacement therapy. We searched PubMed, Web of Science, China National Knowledge Infrastructure, and WanFang databases up to 31 July 2016 for eligible studies. Pooled risk ratio (RR) with 95% confidence interval (CI) was calculated using fixed-or random-effects models if appropriate. The Newcastle-Ottawa Scale was used to assess the study quality. Two retrospective and seven prospective studies with a total of 11191 participants were included in the final analysis. The results from fixed-effects model showed this therapy was associated with the deceased risk of cancer in adult with growth hormone deficiency (RR=0.69, 95%CI: 0.59-0.82), with low heterogeneity within studies (I2=39.0%, P=0.108). We performed sensitivity analyses by sequentially omitting one study each time, and the pooled RRs did not materially change, indicating that our results were statistically stable. Begger's and Egger's tests suggested that there was no publication bias (Z=-0.63, P=0.520; t=0.16, P=0.874). Our study suggests that growth hormone replacement therapy could reduce risk of cancer in adult with growth hormone deficiency. PMID:27835910

  17. Adult Growth Hormone Deficiency – Benefits, Side Effects, and Risks of Growth Hormone Replacement

    PubMed Central

    Reed, Mary L.; Merriam, George R.; Kargi, Atil Y.

    2013-01-01

    Deficiency of growth hormone (GH) in adults results in a syndrome characterized by decreased muscle mass and exercise capacity, increased visceral fat, impaired quality of life, unfavorable alterations in lipid profile and markers of cardiovascular risk, decrease in bone mass and integrity, and increased mortality. When dosed appropriately, GH replacement therapy (GHRT) is well tolerated, with a low incidence of side effects, and improves most of the alterations observed in GH deficiency (GHD); beneficial effects on mortality, cardiovascular events, and fracture rates, however, remain to be conclusively demonstrated. The potential of GH to act as a mitogen has resulted in concern over the possibility of increased de novo tumors or recurrence of pre-existing malignancies in individuals treated with GH. Though studies of adults who received GHRT in childhood have produced conflicting reports in this regard, long-term surveillance of adult GHRT has not demonstrated increased cancer risk or mortality. PMID:23761782

  18. Vibrational spectroscopic studies of solid recombinant bovine growth hormone and related growth hormone analogs

    NASA Astrophysics Data System (ADS)

    Thamann, Thomas J.; Chao, Robert S.

    1999-09-01

    Infrared and Raman spectra have been obtained for lyophilized recombinant bovine growth hormone (r-bGH), partially reduced, and completely reduced r-bGH, plus a tryptic digest fragment of r-bGH. Amide I and II data indicate r-bGH to have substantial helical character. Partially reduced r-bGH, in which the carboxyl terminal disulfide bridge (residues 181, 189) has been cleaved, has slightly less helical content than r-bGH. The spectral data indicate that breaking the carboxyl terminal cystine link produces only localized structural alterations. The additional cleavage of the second disulfide bridge (residues 53 164) leads to a further decrease in helix content, accompanied by increases in β-sheet and disordered structures. A tryptic digest r-bGH fragment (residues 96-133), which contains a small amount of biological activity (≈10%), has predominantly helical structure.

  19. Thyroid hormones in fetal growth and prepartum maturation.

    PubMed

    Forhead, A J; Fowden, A L

    2014-06-01

    The thyroid hormones, thyroxine (T4) and triiodothyronine (T3), are essential for normal growth and development of the fetus. Their bioavailability in utero depends on development of the fetal hypothalamic-pituitary-thyroid gland axis and the abundance of thyroid hormone transporters and deiodinases that influence tissue levels of bioactive hormone. Fetal T4 and T3 concentrations are also affected by gestational age, nutritional and endocrine conditions in utero, and placental permeability to maternal thyroid hormones, which varies among species with placental morphology. Thyroid hormones are required for the general accretion of fetal mass and to trigger discrete developmental events in the fetal brain and somatic tissues from early in gestation. They also promote terminal differentiation of fetal tissues closer to term and are important in mediating the prepartum maturational effects of the glucocorticoids that ensure neonatal viability. Thyroid hormones act directly through anabolic effects on fetal metabolism and the stimulation of fetal oxygen consumption. They also act indirectly by controlling the bioavailability and effectiveness of other hormones and growth factors that influence fetal development such as the catecholamines and insulin-like growth factors (IGFs). By regulating tissue accretion and differentiation near term, fetal thyroid hormones ensure activation of physiological processes essential for survival at birth such as pulmonary gas exchange, thermogenesis, hepatic glucogenesis, and cardiac adaptations. This review examines the developmental control of fetal T4 and T3 bioavailability and discusses the role of these hormones in fetal growth and development with particular emphasis on maturation of somatic tissues critical for survival immediately at birth.

  20. Effects of treatment with recombinant human growth hormone on insulin sensitivity and glucose metabolism in adults with growth hormone deficiency.

    PubMed

    Fowelin, J; Attvall, S; Lager, I; Bengtsson, B A

    1993-11-01

    In a double-blind, cross-over, placebo-controlled trial, the effect of 26 weeks of replacement therapy with recombinant human growth hormone (rhGH) on insulin sensitivity and glucose metabolism in nine patients with adult-onset growth hormone deficiency was studied with a euglycemic clamp. Glucose production and utilization were studied with D-(3-3H)-glucose infusions. Comparisons were made with placebo treatment for 6 and 26 weeks, respectively. GH therapy for 6 weeks increased fasting plasma concentrations of glucose and insulin. However, after 26 weeks of GH treatment, no significant changes in glucose or insulin concentrations were recorded. GH treatment induced a marked change in insulin action evident after 6 weeks of therapy as shown by lower glucose infusion rates (GIRs) during the clamp compared with placebo treatment (2.6 +/- 0.4 v 4.1 +/- 0.7 mg.kg-1.min-1). This change in insulin action was due to a decreased insulin effect on glucose utilization. After 26 weeks of GH therapy, there was no significant difference in GIRs. During placebo treatment, insulin sensitivity and insulin, glucose, and nonesterified fatty acid (NEFA) concentrations were unchanged compared with concentrations measured before the study. Thus GH replacement therapy induces a change in insulin action in GH-deficient individuals. Whether this change represents a decrease in insulin action (ie, insulin resistance) or a restoration of action to normal is presently unclear, since a healthy control group was not included in the study. During long-term treatment, the present study suggests that the change in insulin action can be reversed, probably secondarily to changes in body composition.

  1. Mechanisms of hormonal therapy resistance in breast cancer.

    PubMed

    Hayashi, Shin-ichi; Kimura, Mariko

    2015-04-01

    Whilst estrogen receptor (ER)-positive breast cancers are preferentially treated with hormone therapy, approximately one-third of them relapse. The mechanisms of refractoriness have been investigated by numerous studies but have not been fully clarified. Hormonal therapy resistance, particularly aromatase inhibitor (AI) resistance, may be related to the acquisition of alternative intracellular ER signaling. We have been investing the mechanisms using cancer specimens and cell lines by monitoring the transcription activity of ERs. AI refractory specimens showed diverse ER activity in the adenovirus estrogen receptor element-green fluorescent protein (ERE-GFP) assay and varied sensitivity to anti-estrogens, indicating the existence of multiple resistant mechanisms. We established six different types of cell lines mimicking AI resistance from ERE-GFP-introduced ER-positive cell lines. They revealed that multiple and alternative ER activating pathways were involved in the resistance, such as phosphorylation-dependent or androgen metabolite-dependent mechanisms. The response to fulvestrant and mammalian target of rapamycin inhibitor also varied among individual resistant cell lines. These results indicate that further subclassification of ER-positive breast cancer is extremely important to decide the therapeutic management of not only hormonal therapy but also new molecular target therapy.

  2. Growth hormone and the transition from puberty into adulthood.

    PubMed

    Attanasio, Andrea F; Shalet, Stephen M

    2007-03-01

    With modern growth hormone (GH) replacement algorithms, children with a diagnosis of growth hormone deficiency achieve at the end of pediatric GH treatment an adult height that is on the average in the normal range. Recent experience with GH replacement in young adults with childhood-onset growth hormone deficiency, however, has shown that these patients present with variable degrees of somatic immaturity. As childhood GH treatment is discontinued when final height is attained, attention moves to the phase of somatic development that follows the end of longitudinal growth, called ''transition'', which had been excluded previously from consideration for either pediatric or adult GH replacement. This article reviews the changes taking place during this phase of development and their relevance for the attainment of adult body maturation. The critical role of GH in this process is described.

  3. Ethylene and Hormonal Cross Talk in Vegetative Growth and Development.

    PubMed

    Van de Poel, Bram; Smet, Dajo; Van Der Straeten, Dominique

    2015-09-01

    Ethylene is a gaseous plant hormone that most likely became a functional hormone during the evolution of charophyte green algae, prior to land colonization. From this ancient origin, ethylene evolved into an important growth regulator that is essential for myriad plant developmental processes. In vegetative growth, ethylene appears to have a dual role, stimulating and inhibiting growth, depending on the species, tissue, and cell type, developmental stage, hormonal status, and environmental conditions. Moreover, ethylene signaling and response are part of an intricate network in cross talk with internal and external cues. Besides being a crucial factor in the growth control of roots and shoots, ethylene can promote flowering, fruit ripening and abscission, as well as leaf and petal senescence and abscission and, hence, plays a role in virtually every phase of plant life. Last but not least, together with jasmonates, salicylate, and abscisic acid, ethylene is important in steering stress responses.

  4. Plant growth hormones suppress the development of Harpophora maydis, the cause of late wilt in maize.

    PubMed

    Degani, Ofir; Drori, Ran; Goldblat, Yuval

    2015-01-01

    Late wilt, a severe vascular disease of maize caused by the fungus Harpophora maydis, is characterized by rapid wilting of maize plants before tasseling and until shortly before maturity. The pathogen is currently controlled by resistant maize cultivars, but the disease is constantly spreading to new areas. The plant's late phenological stage at which the disease appears suggests that plant hormones may be involved in the pathogenesis. This work revealed that plant growth hormones, auxin (Indole-3-acetic acid) and cytokinin (kinetin), suppress H. maydis in culture media and in a detached root assay. Kinetin, and even more auxin, caused significant suppression of fungus spore germination. Gibberellic acid did not alter colony growth rate but had a signal suppressive effect on the pathogens' spore germination. In comparison, ethylene and jasmonic acid, plant senescing and defense response regulators, had minor effects on colony growth and spore germination rate. Their associate hormone, salicylic acid, had a moderate suppressive effect on spore germination and colony growth rate, and a strong influence when combined with auxin. Despite the anti-fungal auxin success in vitro, field experiments with dimethylamine salt of  2,4-dichlorophenoxyacetic acid (that mimics the influence of auxin) failed to suppress the late wilt. The lines of evidence presented here reveal the suppressive influence of the three growth hormones studied on fungal development and are important to encourage further and more in-depth examinations of this intriguing hormonal complex regulatory and its role in the maize-H. maydis interactions.

  5. Plant growth-promoting hormones activate mammalian guanylate cyclase activity.

    PubMed

    Vesely, D L; Hudson, J L; Pipkin, J L; Pack, L D; Meiners, S E

    1985-05-01

    In vivo injections of plant growth-promoting hormones increase the growth of animals as well as plants. Plant growth-promoting hormones and positive plant growth regulators are known to increase RNA and protein synthesis. Since cyclic GMP also increases RNA and protein synthesis, the object of the present investigation was to determine whether physiological levels of plant growth-promoting hormones and positive plant growth regulators have part of their mechanism(s) of action through stimulation of the guanylate cyclase (EC 4.6.1.2)-cyclic GMP system. Representatives of the three classes of growth-promoting hormones were investigated. Thus, auxins (indole-3-acetic acid, indole-3-butyric acid, beta-naphthoxyacetic acid, and 2,4,5-trichlorophenoxy acetic acid), gibberellins (gibberellic acid), and cytokinins [N6-benzyl adenine, kinetin (6-furfuryl aminopurine), and beta-(2-furyl) acrylic acid] all increased rat lung, small intestine, liver, and renal cortex guanylate cyclase activity 2- to 4-fold at the 1 microM concentration. Dose response curves revealed that maximal stimulation of guanylate cyclase by these plant growth regulators was at 1 microM; there was no augmented cyclase activity at 1 nM. The guanylate cyclase cationic cofactor manganese was not essential for augmentation of guanylate cyclase by these plant growth-promoting regulators. The antioxidant butylated hydroxytoluene did not block the enhancement of guanylate cyclase by these plant growth-promoting factors. These data suggest that guanylate cyclase may play a role in the mechanism of action of plant growth-promoting hormones and even of positive plant regulators at the cellular level.

  6. Purification and cultivation of human pituitary growth hormone secreting cells

    NASA Technical Reports Server (NTRS)

    Hymer, W. C.

    1984-01-01

    A multiphase study was conducted to examine the properties of growth hormone cells. Topics investigated included: (1) to determine if growth hormone (GH) cells contained within the rat pituitary gland can be separated from the other hormone producing cell types by continuous flow electrophoresis (CFE); (2) to determine what role, if any, gravity plays in the electrophoretic separation of GH cells; (3) to compare in vitro GH release from rat pituitary cells previously exposed to microgravity conditions vs release from cells not exposed to microgravity; (4) to determine if the frequency of different hormone producing pituitary cell types contained in cell suspensions can be quantitated by flow cytometry; and (5) to determine if GH contained within the human post mortem pituitary gland can be purified by CFE. Specific experimental procedures and results are included.

  7. The role of growth hormone in diabetes mellitus.

    PubMed

    Holly, J M; Amiel, S A; Sandhu, R R; Rees, L H; Wass, J A

    1988-09-01

    The insulin and growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis are two endocrine systems that are interlinked at many levels. GH is one of the glucose counter-regulatory hormones, rising in response to hypoglycaemia, it has both intrinsic hyperglycaemic actions and causes insulin resistance. Both IGF-I and its receptor have high structural and functional homology to insulin and its receptor. Insulin can regulate IGF-I production, acting on the GH receptor or at a post-receptor site. Conversely IGF-I is thought to have a permissive effect on the pancreatic insulin response to glucose. Growth is compromised in poorly controlled diabetic children; however, a causal link with altered GH/IGF-I levels has not been proven. Insulin-dependent diabetes clearly causes derangements in the GH/IGF-I axis. In poorly controlled diabetics GH levels are invariably raised whilst normal or low levels of IGF-I are found, indicating a dissociation between the two factors. Altered IGF-binding protein levels are also found, with high levels of small binding protein and low levels of large binding protein. These derangements are probably the result of interactions at many levels although the exact mechanisms are not fully understood. Raised GH levels could result from altered hypothalamic/pituitary control or reduced feedback inhibition. The latter could, in turn, result from low IGF-I levels, reduced availability of IGF-I to relevant receptors or increased levels of inhibitors (possibly the small binding protein). Low IGF-I levels could be directly due to deficient insulin levels or simply to lack of available circulating binding protein. Alternative or altered molecular forms of circulating GH in diabetes seem unlikely on present evidence. That GH has an effect on glycaemic control is most evident from the abnormal glucose tolerance seen in acromegalics, but is also seen with physiological GH variations such as during the pubertal growth spurt. In diabetics the

  8. Effect of growth hormone therapy on Taiwanese children with growth hormone deficiency.

    PubMed

    Huang, Ying-Hua; Wai, Yau-Yau; Van, Yang-Hau; Lo, Fu-Sung

    2012-07-01

    Human growth hormone (GH) has been successfully used in children with GH deficiency (GHD). However, there are few published data on the effect of GH in Taiwanese children with GHD. We performed a retrospective cohort study to identify factors influencing the effect of GH therapy on ethnic Chinese children with GHD in Taiwan. Idiopathic GHD can be classified into isolated GHD (IGHD) and multiple pituitary hormone deficiency (MPHD). The study looked at the effect of GH on the auxological, biochemical, and imaging parameters of 51 patients (13 girls and 38 boys) in three different diagnostic groups: MPHD (n = 12), IGHD (n = 8), and transient GHD (TGHD; n = 31). TGHD is defined as a GH peak >10 μg/L in re-evaluation by two GH stimulation tests approximately 6 months after discontinuation of GH therapy. The height velocity for first-year GH therapy was 7.61 ± 1.46, 8.14 ± 1.92, and 9.99 ± 2.75 cm/y in the TGHD, IGHD, and MPHD groups, respectively. After post hoc comparison, the MPHD group had a significantly accelerated height velocity in the first year compared to the TGHD group. Correlation analysis showed that a change in height standard deviation score (SDS) in the first year had a significant negative correlation with the following variables: peak GH (r = -0.52, p < 0.001), pretreatment height SDS (r = -0.49, p < 0.001), and height-target height (Ht-TH) SDS (r = -0.49, p < 0.001). Change in height SDS in the first 2 years had a significantly negative correlation with peak GH (r = -0.51, p < 0.001), insulin-like growth factor-1 SDS (r = -0.35, p = 0.022), height SDS (r = -0.60, p < 0.001), difference between bone age and chronological age (r = -0.46, p = 0.001), and Ht-TH SDS (r = -0.50, p = 0.001). After using multiple linear regression, the pretreatment GH peak value was found to be significantly associated with height increments after 1 year of GH treatment (B = -0.07, p = 0.014). The administration of GH to children with GHD results in a pronounced

  9. Replacement treatment with biosynthetic human growth hormone in growth hormone-deficient hypopituitary adults.

    PubMed

    Beshyah, S A; Freemantle, C; Shahi, M; Anyaoku, V; Merson, S; Lynch, S; Skinner, E; Sharp, P; Foale, R; Johnston, D G

    1995-01-01

    The physiological role of growth hormone in adult life has recently attracted increased interest. We have studied the clinical effects and the effects on body composition of prolonged replacement with biosynthetic human GH in a large number of hypopituitary adults. A randomized double blind placebo controlled trial for 6 months followed by an open trial of GH treatment for 12 months. GH daily dose was 0.04 (0.02-0.05) IU/kg s.c. Forty GH deficient hypopituitary patients (19 M, 21 F; aged 19-67 years) on conventional replacement therapy were studied. Serum insulin like growth factor I (IGF-I), skinfold thickness, total body potassium, total body water (TBW), exercise tolerance and muscle strength, and well-being. During the 6-month double blind phase, two GH treated patients withdrew because of adverse events. Lean body mass (LBM) increased and percentage body fat (%BF) decreased on GH but not on placebo (P) (LBM: (GH: from 48.5 +/- 9.6 to 49.6 +/- 9.5 kg; P: from 50.9 +/- 9.2 to 50.1 +/- 9.0 kg, P < 0.05 GH vs P) and %BF (GH: from 34.7 +/- 11.4 to 34.2 +/- 10.7; P: from 37.4 +/- 7.6 to 38.7 +/- 8.1, P < 0.05 GH vs P)). TBW increased on GH (P < 0.01) but not on P. No change was observed in waist-to-hip ratio or in muscle strength. During longer-term follow-up combining the double blind and open phase components of the study, 34, 27 and 11 patients received GH for 6, 12 and 18 months respectively. Patients dropped out because of adverse events or lack of perceived benefit. Skinfold thicknesses decreased significantly at 6 and 12 months and the waist circumference at 6 months. Waist-to-hip ratio decreased significantly on GH at 12 months. LBM increased on GH treatment from 49.6 +/- 9.1 to 51.6 +/- 9.4 kg (P < 0.0006), 51.9 +/- 8.9 kg (P < 0.07) and 53.1 +/- 10.5 kg (P < 0.0001) at 6, 12 and 18 months respectively. Percentage body fat decreased on GH from 37.2 +/- 10.7 to 34.7 +/- 10.1 (P < 0.005), 35.1 +/- 12.8 (NS) and 34.5 +/- 8.6 (P < 0.04) at 6,12 and 18 months

  10. Efficacy and Safety of Sustained-Release Recombinant Human Growth Hormone in Korean Adults with Growth Hormone Deficiency

    PubMed Central

    Kim, Youngsook; Hong, Jae Won; Chung, Yoon-Sok; Kim, Sung-Woon; Cho, Yong-Wook; Kim, Jin Hwa; Kim, Byung-Joon

    2014-01-01

    Purpose The administration of recombinant human growth hormone in adults with growth hormone deficiency has been known to improve metabolic impairment and quality of life. Patients, however, have to tolerate daily injections of growth hormone. The efficacy, safety, and compliance of weekly administered sustained-release recombinant human growth hormone (SR-rhGH, Declage™) supplement in patients with growth hormone deficiency were evaluated. Materials and Methods This trial is 12-week prospective, single-arm, open-label trial. Men and women aged ≥20 years with diagnosed growth hormone deficiency (caused by pituitary tumor, trauma and other pituitary diseases) were eligible for this study. Each subject was given 2 mg (6 IU) of SR-rhGH once a week, subcutaneously for 12 weeks. Efficacy and safety at baseline and within 30 days after the 12th injection were assessed and compared. Score of Assessment of Growth Hormone Deficiency in Adults (AGHDA score) for quality of life and serum IGF-1 level. Results The IGF-1 level of 108.67±74.03 ng/mL was increased to 129.01±68.37 ng/mL (p=0.0111) and the AGHDA QoL score was decreased from 9.80±6.51 to 7.55±5.76 (p<0.0001) at week 12 compared with those at baseline. Adverse events included pain, swelling, erythema, and warmth sensation at the administration site, but many adverse events gradually disappeared during the investigation. Conclusion Weekly administered SR-rhGH for 12 weeks effectively increased IGF-1 level and improved the quality of life in patients with GH deficiency without serious adverse events. PMID:24954335

  11. Hormonal regulation of wheat growth during hydroponic culture

    NASA Technical Reports Server (NTRS)

    Wetherell, Donald

    1988-01-01

    Hormonal control of root growth has been explored as one means to alleviate the crowding of plant root systems experienced in prototype hydroponic biomass production chambers being developed by the CELSS Breadboard Project. Four plant hormones, or their chemical analogs, which have been reported to selectively inhibit root growth, were tested by adding them to the nutrient solutions on day 10 of a 25 day growth test using spring wheat in hydroponic cultures. Growth and morphological changes is both shoot and root systems were evaluated. In no case was it possible to inhibit root growth without a comparable inhibition of shoot growth. It was concluded that this approach is unlikely to prove useful for wheat.

  12. Growth Hormone Enhances Arachidonic Acid Metabolites in a Growth Hormone Transgenic Mouse

    PubMed Central

    Oberbauer, A. M.; German, J. B.; Murray, J. D.

    2016-01-01

    In a transgenic growth hormone (GH) mouse model, highly elevated GH increases overall growth and decreases adipose depots while low or moderate circulating GH enhances adipose deposition with differential effects on body growth. Using this model, the effects of low, moderate, and high chronic GH on fatty acid composition were determined for adipose and hepatic tissue and the metabolites of 20:4n-6 (arachidonic acid) were characterized to identify metabolic targets of action of elevated GH. The products of Δ-9 desaturase in hepatic, but not adipose, tissue were reduced in response to elevated GH. Proportional to the level of circulating GH, the products of Δ-5 and Δ-6 were increased in both adipose and hepatic tissue for the omega-6 lipids (e.g., 20:4n-6), while only the hepatic tissues showed an increase for omega-3 lipids (e.g., 22:6n-3). The eicosanoids, PGE2 and 12-HETE, were elevated with high GH but circulating thromboxane was not. Hepatic PTGS1 and 2 (COX1 and COX 2), SOD1, and FADS2 (Δ-6 desaturase) mRNAs were increased with elevated GH while FAS mRNA was reduced; SCD1 (ste-aroyl-coenzyme A desaturase) and SCD2 mRNA did not significantly differ. The present study showed that GH influences the net flux through various aspects of lipid metabolism and especially the desaturase metabolic processes. The combination of altered metabolism and tissue specificity suggest that the regulation of membrane composition and its effects on signaling pathways, including the production and actions of eicosanoids, can be mediated by the GH regulatory axis. PMID:21442273

  13. The cardiovascular system in growth hormone excess and growth hormone deficiency.

    PubMed

    Lombardi, G; Di Somma, C; Grasso, L F S; Savanelli, M C; Colao, A; Pivonello, R

    2012-12-01

    The clinical conditions associated with GH excess and GH deficiency (GHD) are known to be associated with an increased risk for the cardiovascular morbidity and mortality, suggesting that either an excess or a deficiency in GH and/or IGF-I is deleterious for cardiovascular system. In patients with acromegaly, chronic GH and IGF-I excess commonly causes a specific cardiomyopathy characterized by a concentric cardiac hypertrophy associated with diastolic dysfunction and, in later stages, with systolic dysfunction ending in heart failure if GH/IGF-I excess is not controlled. Abnormalities of cardiac rhythm and anomalies of cardiac valves can also occur. Moreover, the increased prevalence of cardiovascular risk factors, such as hypertension, diabetes mellitus, and insulin resistance, as well as dyslipidemia, confer an increased risk for vascular atherosclerosis. Successful control of the disease is accompanied by a decrease of the cardiac mass and improvement of cardiac function and an improvement in cardiovascular risk factors. In patients with hypopituitarism, GHD has been considered the under- lying factor of the increased mortality when appropriate standard replacement of the pituitary hormones deficiencies is given. Either childhood-onset or adulthood-onset GHD are characterized by a cluster of abnormalities associated with an increased cardiovascular risk, including altered body composition, unfavorable lipid profile, insulin resistance, endothelial dysfunction and vascular atherosclerosis, a decrease in cardiac mass together with an impairment of systolic function mainly after exercise. Treatment with recombinant GH in patients with GHD is followed by an improvement of the cardiovascular risk factors and an increase in cardiac mass together with an improvement in cardiac performance. In conclusion, acromegaly and GHD are associated with an increased risk for cardiovascular morbidity and mortality, but the control of GH/IGF-I secretion reverses cardiovascular

  14. Parathyroid hormone and growth in chronic kidney disease.

    PubMed

    Waller, Simon

    2011-02-01

    Growth failure is common in children with chronic kidney disease, and successful treatment is a major challenge in the management of these children. The aetiology is multi-factorial with "chronic kidney disease-metabolic bone disorder" being a key component that is particularly difficult to manage. Parathyroid hormone is at the centre of this mineral imbalance, consequent skeletal disease and, ultimately, growth failure. When other aetiologies are treated, good growth can be achieved throughout the course of the disease when parathyroid hormone (PTH) levels are in the normal range or slightly elevated. A direct correlation between PTH levels and growth has not been convincingly established, and the direct effect of PTH on growth has not been adequately described; furthermore, direct actions of PTH on the growth plate are unproven. The effects of PTH on growth stem from the pivotal role that PTH plays in the development of renal osteodystrophy. In severe secondary hyperparathyroidism, the growth plate is altered and growth is affected. At the other end of the spectrum, with an over-suppressed parathyroid gland, the rate of bone turnover and remodelling is markedly diminished, and some data suggest this is associated with poor growth. Most of the data available suggests that avoiding the development of significant bone disease through the strict control of PTH levels permits good growth. Absolute optimal ranges for PTH that maximise growth or minimise growth failure are not yet established.

  15. Hormones and Obesity: Changes in Insulin and Growth Hormone Secretion Following Surgically Induced Weight Loss

    PubMed Central

    Crockford, P. M.; Salmon, P. A.

    1970-01-01

    Ten obese patients were subjected to insulin tolerance tests (0.2 unit per kg. regular insulin intravenously) and/or treadmill exercise tolerance testing (2.6 m.p.h. at 11° angulation) before and after surgically induced weight reduction. Immunoreactive growth hormone (IRGH) responses returned to normal with weight reduction in all but one—a grossly obese woman studied relatively early in the postoperative period when still far from the ideal body weight. Five of these patients and two additional subjects had intravenous glucose tolerance tests (0.5 g. per kg.) before and after weight reduction. In all, there was a significant diminution in immunoreactive insulin (IRI) values, accompained by little or no change in the glucose disappearance rate (KG) and a significant improvement in insulin effectiveness as indicated by the calculated “insulinogenic index”. It was concluded that the abnormalities in IRGH and IRI secretion, as well as the insulin resistance in obesity, are probably secondary and not of primary importance in the etiology of this disorder. PMID:5430052

  16. Growth hormone and the kidney: the use of recombinant human growth hormone (rhGH) in growth-retarded children with chronic renal insufficiency.

    PubMed

    Fine, R N

    1991-04-01

    Hypothalamic production of growth hormone releasing hormone stimulates the anterior pituitary gland to release growth hormone (GH). The clinical manifestations of GH on tissues are either direct or are mediated by insulin-like growth factors (IGF). Both the somatic effects of GH and the renal manifestations of an increase in glomerular filtration rate and renal plasma flow are mediated by IGF. The increase in glomerular filtration rate/renal plasma flow that occurs with either exogenous or endogenous GH is not apparent in patients with chronic renal failure (CRF); therefore, it is unlikely that recombinant human growth hormone (rhGH) treatment of patients with CRF will result in glomerular hyperfiltration. Longitudinal studies are required to determine if the glomerulosclerosis and renal functional impairment occurring in GH and growth hormone releasing hormone transgenic mice occurs after rhGH treatment of growth-retarded uremic rats with GH resulted in an improvement in growth velocity. This led to preliminary studies in growth-retarded children with CRF by using rhGH. The acceleration of growth velocity was dramatic despite the fact that GH levels are elevated in uremia. The elevated IGF carrier proteins in uremic children may contribute to the growth retardation. Treatment with rhGH may be efficacious by stimulating a net increase in the free (unbound) IGF levels. Hyposecretion of GH may contribute to the failure to achieve optimal growth after successful renal transplantation. Treatment with rhGH may be efficacious in improving the growth velocity of renal allograft recipients.

  17. Purification and cultivation of human pituitary growth hormone secreting cells

    NASA Technical Reports Server (NTRS)

    Hymer, W. C.

    1978-01-01

    The maintainance of actively secreting human pituitary growth hormone cells (somatotrophs) in vitro was studied. The primary approach was the testing of agents which may be expected to increase the release of the human growth hormone (hGH). A procedure for tissue procurement is described along with the methodologies used to dissociate human pituitary tissue (obtained either at autopsy or surgery) into single cell suspensions. The validity of the Biogel cell column perfusion system for studying the dynamics of GH release was developed and documented using a rat pituitary cell system.

  18. Purification and cultivation of human pituitary growth hormone secreting cells

    NASA Technical Reports Server (NTRS)

    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.

  19. Relationship between initial treatment effect of recombinant human growth hormone and exon 3 polymorphism of growth hormone receptor in Chinese children with growth hormone deficiency

    PubMed Central

    Zheng, Zhangqian; Cao, Lingfeng; Pei, Zhou; Zhi, Dijing; Zhao, Zhuhui; Xi, Li; Cheng, Ruoqian; Luo, Feihong

    2015-01-01

    The aim of this study is to investigate the frequency distribution of exon 3 deleted (d3-GHR) genetic polymorphism of growth hormone receptor (GHR) in growth hormone deficient (GHD) Chinese children and to explore the correlation between the growth promoting effects of recombinant human growth hormone (rhGH) and exon 3 genetic polymorphism of GHR in GHD children. In this study, 111 GHD (excluded small for gestational age) children were treated with rhGH (0.20 mg/kg/week) for six months. The body height (Ht), body weight, bone age (BA) and growth velocity (GV) were measured before and after six months of treatment. The d3-GHR and full length GHR (fl-GHR) were analyzed to detect the frequency distribution of two isoforms and their influence on growth promoting effect of rhGH. The results indicated that the frequencies of fl/fl, fl/d3 and d3/d3 GHR genotypes were 67.6%, 18.9% and 13.5%. After six months of GH therapy, there were significant differences of ΔGV (ΔGV: 10.77±3.40 cm/year vs 12.18±3.08 cm/year) (P<0.05) and ΔHt (ΔHt: 5.38±1.70 cm vs 6.09±1.54 cm) (P<0.05) were found among GHD children with different genotypes (fl/fl vs fl/d3 and d3/d3). In conclusion, the frequency distribution of three GHR genotypes in 111 Chinese GHD children was different from that reported in Caucasian, indicating the existence of ethnic difference of exon 3 GHR polymorphism. There was a closely relationship between GHR genotypes and growth-promoting effect of rhGH in Chinese GHD children. PMID:26221355

  20. Neonatal detection of generalized resistance to thyroid hormone

    SciTech Connect

    Weiss, R.E.; Balzano, S.; Scherberg, N.H.; Refetoff, S. )

    1990-11-07

    Generalized resistance to thyroid hormone (GRTH) is an inherited disease that is usually suspected when elevated serum thyroid hormone levels are associated with nonsuppressed thyrotropin. Often these test results are obtained because of short stature, decreased intelligence, and/or hyperactivity with learning disability noted in childhood and adolescence, or because of goiter in adulthood. The authors detected GRTH at birth by analysis of blood obtained during routine neonatal screening. The proposita, born to a mother with GRTH, had a thyrotropin level of 26 mU/L and a corresponding thyroxine concentration of 656 nmol/L. Administration of thyroid hormone in doses eightfold to 10-fold above replacement levels were required to reduce serum thyrotropin to normal levels without induction of hypermetabolism. This case, and the retrospective finding of high thyroxine levels in five newborns subsequently diagnosed as having GRTH, suggest that measurement of thyroxine at birth, in conjunction with thyrotropin, could allow the early detection of GRTH.

  1. [Benefits and risks of growth hormone in adults with growth hormone deficiency].

    PubMed

    Díez, Juan J; Cordido, Fernando

    2014-10-21

    Adult growth hormone (GH) deficiency is a well-recognized clinical syndrome with adverse health consequences. Many of these may improve after replacement therapy with recombinant GH. This treatment induces an increase in lean body mass and a decrease in fat mass. In long-term studies, bone mineral density increases and muscle strength improves. Health-related quality of life tends to increase after treatment with GH. Lipid profile and markers of cardiovascular risk also improve with therapy. Nevertheless, GH replacement therapy is not without risk. According to some studies, GH increases blood glucose, body mass index and waist circumference and may promote long-term development of diabetes and metabolic syndrome. Risk of neoplasia does not appear to be increased in adults treated with GH, but there are some high-risk subgroups. Methodological shortcomings and difficulties inherent to long-term studies prevent definitive conclusions about the relationship between GH and survival. Therefore, research in this field should remain active. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  2. Growth hormone stimulation test - series (image)

    MedlinePlus

    ... skeletal growth in children. In adults, GH stimulates protein synthesis in muscle and the release of fatty acids ... acids. The amino acids are used in the synthesis of proteins, and the muscle shifts to using fatty acids ...

  3. Growth hormone and HIV infection: contribution to disease manifestations and clinical implications.

    PubMed

    Falutz, Julian

    2011-06-01

    In untreated HIV patients growth hormone deficiency contributes to loss of lean and fat mass. Pharmacologic doses of growth hormone successfully reverse this wasting process. In patients responding to antiretroviral therapies several non AIDS-related complications usually common among older, uninfected persons now occur more frequently in younger HIV patients. Among these conditions are cardiovascular disease and metabolic disorders. Although their etiology is multifactorial, changes in growth hormone biology reflecting relative growth hormone deficiency occur and may be involved. In these patients truncal obesity, and associated dyslipidemia and glucose homeostasis changes contribute to impaired quality of life and increased cardiovascular risk. Treatment with growth hormone and growth hormone releasing factor leads to short-term improvement of some of these abnormalities. This paper will review abnormalities of growth hormone biology and the use of growth hormone and growth hormone releasing factor as therapeutic agents in HIV patients. Copyright © 2010. Published by Elsevier Ltd.

  4. Hereditary gingival fibromatosis associated with growth hormone deficiency.

    PubMed

    Oikarinen, K; Salo, T; Käär, M L; Lahtela, P; Altonen, M

    1990-10-01

    A case report of gingival fibromatosis in association with growth hormone (GH) deficiency due to a lack of growth hormone releasing factor (GRF) is presented. The girl is the youngest member of a family of eight children, five of whom lack the same hormone and have or have had similar gingival enlargements. After the growth hormone deficiency had been diagnosed and hormone substitute administered the dental age of the girl presented came closer to that of her age and sex-matched controls but did not reach the corresponding values even though the teeth were exposed by excising the overgrown gingiva. Test fibroblasts cultured from the overgrown gingiva proliferated at a slower rate than those cultured from age-matched controls. Total RNA was extracted from the test and three control fibroblasts and examined by Northern hybridisation using cDNAs for pro alpha 1(I) and pro alpha 1(III) chains. The amount of type I and III procollagen mRNAs were lower in the test fibroblasts as compared to the controls.

  5. Association between thyroid hormones, insulin resistance, and metabolic syndrome.

    PubMed

    Kumar, Hari K; Yadav, Raj K; Prajapati, Jayaram; Reddy, Challa V K; Raghunath, Manchala; Modi, Kirtikumar D

    2009-07-01

    To determine the association between thyroid hormones, insulin resistance, and metabolic syndrome in euthyroid women. Forty-five women with no past medical history were studied in this cross-sectional study at the Department of Endocrinology, Medwin Hospitals, Hyderabad, India, from August 2008 to September 2008. The body fat was estimated using bio-impedance method, and fasting blood sample was analyzed for total triiodothyronine (T3), total thyroxine (T4), thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), lipid profile, insulin, and glucose. The mean age of the participants was 32.6 +/= 9.6 years with a body mass index (BMI) of 29.9 +/= 3.8 kg/m2. Evidence of homeostasis model assessment index for insulin resistance (HOMA-IR) more than 3 was seen in 34 (75%) and metabolic syndrome in 29 (64%) participants. Total T3 showed a positive correlation with triglycerides, low density lipoprotein- cholesterol (LDL-C), total cholesterol, insulin, HOMA-IR and negatively with body fat. Thyroid-stimulating hormone correlated positively with BMI, insulin, HOMA-IR, LDL-C and negatively with HDL-cholesterol (p<0.05). Free triiodothyronine correlated positively with waist circumference and T4 did not correlate with metabolic syndrome parameters. Our preliminary data show an association between thyroid hormones and some components specific of the metabolic syndrome in euthyroid women. Total triiodothyronine and TSH correlated more with variables of metabolic syndrome than FT3 and T4.

  6. Usability and Tolerability of the Norditropin NordiFlex® Injection Device in Children Never Previously Treated With Growth Hormone

    ClinicalTrials.gov

    2014-06-23

    Growth Hormone Disorder; Growth Hormone Deficiency in Children; Genetic Disorder; Turner Syndrome; Foetal Growth Problem; Small for Gestational Age; Chronic Kidney Disease; Chronic Renal Insufficiency; Delivery Systems

  7. The Physiology of Growth Hormone-Releasing Hormone (GHRH) in Breast Cancer

    DTIC Science & Technology

    2003-06-01

    production of growth hormone-releasing factor by carcinoid and pancreatic islet tumors associated with acromegaly . Prog Clin Biol Res 1981; 74:259-271. (16...promotion of apop- cause of acromegaly . More recently, expression has been tosis. These results indicate that disruption of enaog- demonstrated in tumors

  8. Effects of hypothalamic dopamine on growth hormone-releasing hormone-induced growth hormone secretion and thyrotropin-releasing hormone-induced prolactin secretion in goats.

    PubMed

    Jin, Jin; Hashizume, Tsutomu

    2015-06-01

    The aim of the present study was to clarify the effects of hypothalamic dopamine (DA) on the secretion of growth hormone (GH) in goats. The GH-releasing response to an intravenous (i.v.) injection of GH-releasing hormone (GHRH, 0.25 μg/kg body weight (BW)) was examined after treatments to augment central DA using carbidopa (carbi, 1 mg/kg BW) and L-dopa (1 mg/kg BW) in male and female goats under a 16-h photoperiod (16 h light, 8 h dark) condition. GHRH significantly and rapidly stimulated the release of GH after its i.v. administration to goats (P < 0.05). The carbi and L-dopa treatments completely suppressed GH-releasing responses to GHRH in both male and female goats (P < 0.05). The prolactin (PRL)-releasing response to an i.v. injection of thyrotropin-releasing hormone (TRH, 1 μg/kg BW) was additionally examined in male goats in this study to confirm modifications to central DA concentrations. The treatments with carbi and L-dopa significantly reduced TRH-induced PRL release in goats (P < 0.05). These results demonstrated that hypothalamic DA was involved in the regulatory mechanisms of GH, as well as PRL secretion in goats.

  9. Light-Mediated Hormonal Regulation of Plant Growth and Development.

    PubMed

    de Wit, Mieke; Galvão, Vinicius Costa; Fankhauser, Christian

    2016-04-29

    Light is crucial for plant life, and perception of the light environment dictates plant growth, morphology, and developmental changes. Such adjustments in growth and development in response to light conditions are often established through changes in hormone levels and signaling. This review discusses examples of light-regulated processes throughout a plant's life cycle for which it is known how light signals lead to hormonal regulation. Light acts as an important developmental switch in germination, photomorphogenesis, and transition to flowering, and light cues are essential to ensure light capture through architectural changes during phototropism and the shade avoidance response. In describing well-established links between light perception and hormonal changes, we aim to give insight into the mechanisms that enable plants to thrive in variable light environments.

  10. Effect of growth hormone treatment on craniofacial growth in children: Idiopathic short stature versus growth hormone deficiency.

    PubMed

    Choi, Sung-Hwan; Fan, Dong; Hwang, Mi-Soo; Lee, Hee-Kyung; Hwang, Chung-Ju

    2017-04-01

    Few studies have evaluated craniofacial growth in boys and girls with idiopathic short stature (ISS) during growth hormone (GH) treatment. The aim of this study was to evaluate the effect of GH treatment on craniofacial growth in children with ISS, compared with those with growth hormone deficiency (GHD). This study included 36 children (mean age, 11.3 ± 1.8 years) who were treated with GH consecutively. Lateral cephalograms were analyzed before and 2 years after start of GH treatment. There were no significant differences in age and sex between ISS and GHD groups and the reference group from semilongitudinal study (10 boys and 8 girls from each group). Before treatment, girls with ISS showed a skeletal Class II facial profile compared with the GHD and reference groups (p = 0.003). During GH treatment, the amount of maxillary length increased beyond norm in the ISS and GHD groups in boys (p = 0.035) > 3 standard deviation score (SDS). Meanwhile, mandibular ramus height (p = 0.001), corpus length, and total mandibular length (p = 0.007 for both) increased more in girls with ISS than in girls with GHD. Lower and total anterior facial heights increased more in girls with ISS than in girls with GHD (p = 0.021 and p = 0.007, respectively), > 7-11 SDS. GH should be administered carefully when treating girls with ISS, because GH treatment has great effects on vertical overgrowth of the mandible and can result in longer face. Copyright © 2016. Published by Elsevier B.V.

  11. Growth hormone benefits children with 18q deletions.

    PubMed

    Cody, Jannine D; Semrud-Clikeman, Margaret; Hardies, L Jean; Lancaster, Jack; Ghidoni, Patricia D; Schaub, Rebecca L; Thompson, Nora M; Wells, Lynda; Cornell, John E; Love, Tanzy M; Fox, Peter T; Leach, Robin J; Kaye, Celia I; Hale, Daniel E

    2005-08-15

    Most individuals with constitutional deletions of chromosome 18q have developmental delays, dysmyelination of the brain, and growth failure due to growth hormone deficiency. We monitored the effects of growth hormone treatment by evaluating 23 individuals for changes in growth, nonverbal intelligence quotient (nIQ), and quantitative brain MRI changes. Over an average of 37 months, the treated group of 13 children had an average nIQ increase of 17 points, an increase in height standard deviation score of 1.7, and significant change in T1 relaxation times in the caudate and frontal white matter. Cognitive changes of this magnitude are clinically significant and are anticipated to have an effect on the long-term outcomes for the treated individuals. Copyright 2005 Wiley-Liss, Inc.

  12. [Use of recombinant Human Growth Hormone (rHGH)].

    PubMed

    Calzada-León, Raúl

    2017-01-01

    Recombinant human growth hormone, synthesized in E.coli or mammalian cells cultures, is since 1985, a useful therapeutic resource to increase growth velocity and final height. In this paper are discussed the four phases (aims, security and efficacy, utility and efficiency) indispensables to define the start of treatment, as well as the absolute, relative and metabolic indications and the transitory and permanent conditions that contraindicate its use. It is commented the way to optimize the results (simple but indispensables indications for the physician, the patients and their family). Finally it is analyzed the results of treatment in patients with growth hormone deficiency, Turner syndrome, chronic renal failure, Prader-Willi syndrome, Noonan syndrome, SHOX deficiency, intrauterine growth retardation and idiopathic short stature.

  13. 21 CFR 862.1370 - Human growth hormone test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Human growth hormone test system. 862.1370 Section 862.1370 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test...

  14. Betaxolol and propranolol in glucagon stimulation of growth hormone.

    PubMed Central

    Colle, M; Battin, J; Coquelin, J P; Rochiccioli, P

    1984-01-01

    Both betaxolol and propranolol, beta blockers with different pharmacological properties, increase the reliability of somatotropic testing with glucagon. The combination of glucagon and betaxolol, however, is much better tolerated than that of glucagon and propranolol. The use of a beta 1 cardioselective adrenoceptor block for growth hormone testing is recommended. PMID:6147121

  15. 21 CFR 862.1370 - Human growth hormone test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Human growth hormone test system. 862.1370 Section 862.1370 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test...

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

    PubMed

    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.

  17. Secretory pattern and regulatory mechanism of growth hormone in cattle.

    PubMed

    Kasuya, Etsuko

    2016-02-01

    The ultradian rhythm of growth hormone (GH) secretion has been known in several animal species for years and has recently been observed in cattle. Although the physiological significance of the rhythm is not yet fully understood, it appears essential for normal growth. In this review, previous studies concerning the GH secretory pattern in cattle, including its ultradian rhythm, are introduced and the regulatory mechanism is discussed on the basis of recent findings.

  18. Growth and endocrine effects of recombinant bovine growth hormone treatment in non-transgenic and growth hormone transgenic coho salmon.

    PubMed

    Raven, P A; Sakhrani, D; Beckman, B; Neregård, L; Sundström, L F; Björnsson, B Th; Devlin, R H

    2012-05-15

    To examine the relative growth, endocrine, and gene expression effects of growth hormone (GH) transgenesis vs. GH protein treatment, wild-type non-transgenic and GH transgenic coho salmon were treated with a sustained-release formulation of recombinant bovine GH (bGH; Posilac). Fish size, specific growth rate (SGR), and condition factor (CF) were monitored for 14 weeks, after which endocrine parameters were measured. Transgenic fish had much higher growth, SGR and CF than non-transgenic fish, and bGH injection significantly increased weight and SGR in non-transgenic but not transgenic fish. Plasma salmon GH concentrations decreased with bGH treatment in non-transgenic but not in transgenic fish where levels were similar to controls. Higher GH mRNA levels were detected in transgenic muscle and liver but no differences were observed in GH receptor (GHR) mRNA levels. In non-transgenic pituitary, GH and GHR mRNA levels per mg pituitary decreased with bGH dose to levels seen in transgenic salmon. Plasma IGF-I was elevated with bGH dose only in non-transgenic fish, while transgenic fish maintained an elevated level of IGF-I with or without bGH treatment. A similar trend was seen for liver IGF-I mRNA levels. Thus, bGH treatment increased fish growth and influenced feedback on endocrine parameters in non-transgenic but not in transgenic fish. A lack of further growth stimulation of GH transgenic fish suggests that these fish are experiencing maximal growth stimulation via GH pathways.

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

    SciTech Connect

    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.

  20. Growth hormone treatment in growth hormone-deficient adults. II. Effects on exercise performance.

    PubMed

    Cuneo, R C; Salomon, F; Wiles, C M; Hesp, R; Sönksen, P H

    1991-02-01

    Growth hormone (GH) treatment in adults with GH deficiency increases lean body mass and thigh muscle cross-sectional area. The functional significance of this was examined by incremental cycle ergometry in 24 GH-deficient adults treated in a double-blind placebo-controlled trial with recombinant DNA human GH (rhGH) for 6 mo (0.07 U/kg body wt daily). Compared with placebo, the rhGH group increased mean maximal O2 uptake (VO2max) (+406 +/- 71 vs. +133 +/- 84 ml/min; P = 0.016) and maximal power output (+24.6 +/- 4.3 vs. +9.7 +/- 4.8 W; P = 0.047), without differences in maximal heart rate or ventilation. Forced expiratory volume in 1 s, vital capacity, and corrected CO gas transfer were within normal limits and did not change with treatment. Mean predicted VO2max, based on height and age, increased from 78.9 to 96.0% in the rhGH group (compared with 78.5 and 85.0% for placebo; P = 0.036). The anaerobic ventilatory threshold increased in the rhGH group (+159 +/- 39 vs. +1 +/- 51 ml/min; P = 0.02). The improvement in VO2max was noted when expressed per kilogram body weight but not lean body mass or thigh muscle area. We conclude that rhGH treatment in adults with GH deficiency improves and normalizes maximal exercise performance and improves submaximal exercise performance and that these changes are related to increases in lean body mass and muscle mass. Improved cardiac output may also contribute to the effect of rhGH on exercise performance.

  1. Enhanced basal and disorderly growth hormone secretion distinguish acromegalic from normal pulsatile growth hormone release.

    PubMed Central

    Hartman, M L; Pincus, S M; Johnson, M L; Matthews, D H; Faunt, L M; Vance, M L; Thorner, M O; Veldhuis, J D

    1994-01-01

    Pulses of growth hormone (GH) release in acromegaly may arise from hypothalamic regulation or from random events intrinsic to adenomatous tissue. To distinguish between these possibilities, serum GH concentrations were measured at 5-min intervals for 24 h in acromegalic men and women with active (n = 19) and inactive (n = 9) disease and in normal young adults in the fed (n = 20) and fasted (n = 16) states. Daily GH secretion rates, calculated by deconvolution analysis, were greater in patients with active acromegaly than in fed (P < 0.05) but not fasted normal subjects. Significant basal (nonpulsatile) GH secretion was present in virtually all active acromegalics but not those in remission or in fed and fasted normal subjects. A recently introduced scale- and model-independent statistic, approximate entropy (ApEn), was used to test for regularity (orderliness) in the GH data. All but one acromegalic had ApEn values greater than the absolute range in normal subjects, indicating reduced orderliness of GH release; ApEn distinguished acromegalic from normal GH secretion (fed, P < 10(-12); fasted, P < 10(-7)) with high sensitivity (95%) and specificity (100%). Acromegalics in remission had ApEn scores larger than those of normal subjects (P < 0.0001) but smaller than those of active acromegalics (P < 0.001). The coefficient of variation of successive incremental changes in GH concentrations was significantly lower in acromegalics than in normal subjects (P < 0.001). Fourier analysis in acromegalics revealed reduced fractional amplitudes compared to normal subjects (P < 0.05). We conclude that GH secretion in acromegaly is highly irregular with disorderly release accompanying significant basal secretion. Images PMID:8083369

  2. Diabetes, growth hormone-insulin-like growth factor pathways and association to benign prostatic hyperplasia.

    PubMed

    Wang, Zongwei; Olumi, Aria F

    2011-01-01

    Diabetes significantly increases the risk of benign prostatic hyperplasia (BPH) and low urinary tract symptoms (LUTS). The major endocrine aberration in connection with the metabolic syndrome is hyperinsulinemia. Insulin is an independent risk factor and a promoter of BPH. Insulin resistance may change the risk of BPH through several biological pathways. Hyperinsulinemia stimulates the liver to produce more insulin-like growth factor (IGF), another mitogen and an anti-apoptotic agent which binds insulin receptor/IGF receptor and stimulates prostate growth. The levels of IGFs and IGF binding proteins (IGFBPs) in prostate tissue and in blood are associated with BPH risk, with the regulation of circulating androgen and growth hormone. Stromal-epithelial interactions play a critical role in the development and growth of the prostate gland and BPH. Previously, we have shown that the expression of c-Jun in the fibroblastic stroma can promote secretion of IGF-I, which stimulates prostate epithelial cell proliferation through activating specific target genes. Here, we will review the epidemiologic, clinical, and molecular findings which have evaluated the relation between diabetes and development of BPH.

  3. [Use of growth hormone in children and adolescents].

    PubMed

    Bergadá, Ignacio

    2013-01-01

    Growth hormone treatment for children and adolescents with growth disorders has been used for more than five decades. Since 1985 recombinant human growth hormone (rhGH) is the only drug approved for treatment. In most of the countries rhGH is licensed for the treatment of children with growth hormone deficiency, Turner syndrome, Prader-Willi syndrome, chronic renal failure, and children born small for gestational age. The objective of the treatment is to improve the growth of these patients. The efficacy of rhGH treatment based on auxologic parameters has shown that growth response is variable and mostly dependent on each particular indication. Most of the reports on drug safety obtained from different databases that included thousands of patients, have shown that rhGH is a safe drug and that serious adverse events are rare. Regarding new indications to improve height in children, data on efficacy remains controversial, so we believe their ultimate indication must take into account potential risk versus benefits of this treatment.

  4. [Growth Hormone-Insulin Growth Factor I (GH-IGF-I) axis and growth].

    PubMed

    Castell, A-L; Sadoul, J-L; Bouvattier, C

    2013-10-01

    Normal human linear growth results from an evolutionary process expressing the sum effect of multiple genes. The growth hormone (GH) - insulin like growth factor (IGF)-I axis is one of the main actors in the growth process. Defects in this axis can be responsible for short or tall stature. Short stature is defined as smaller than - 2 standard deviations (SD). It is a very common reason for consultation in pediatrics; indeed, 2.5 % of children are concerned. Multiple causes make diagnosis difficult. In this article, we detail the most common constitutional causes of small size, including those related to a defect in the GH-IGF-I axis. Then, we report, the first results of the clinical and genetic study conducted on 213 patients with gigantism. Tall stature is defined by a height superior to 2 SD. Finally, recent work linking epigenetics and growth - via signaling pathways of GH-IGF-I axis - will be presented.

  5. Multiple genetic factors in the heterogeneity of thyroid hormone resistance

    SciTech Connect

    Weiss, R.E.; Refetoff, S. ); Marcocci, C.; Bruno-Bossio, G. )

    1993-01-01

    Generalized resistance to thyroid hormone (GRTH), a syndrome of inherited tissue hyposensitivity to thyroid hormone, is linked to thyroid hormone receptor (TR) mutations. A typical feature of GRTH is variable severity of organ involvement among families that, surprisingly, does not correlate with the degree of T[sub 3]-binding impairment of the corresponding in vitro synthesized mutant TRs. Furthermore, variations in the clinical severity among family members harboring identical TR[beta] mutations have been reported. The authors compared serum levels of thyroid hormones that maintained a normal TSH in members of a large family with GRTH divided in three groups: Group A, 8 affected subjects with a mutation replacing arginine-320 with a histidine in the T[sub 3]-binding domain of TR[beta]; Group B, 11 first degree relatives (sibs and children of affected subjects) with no TR[beta] mutation; Group C, 16 controls related by marriage. TSH values were not different among the three groups. As expected, total and free T[sub 4] and T[sub 3], and rT[sub 3] levels were significantly higher in Group A vs Groups B and C. However, with the exception of T[sub 3], the same tests were also significantly higher in Group B vs Group C. The latter differences are not due to thyroid hormone transport in serum since TBG concentrations were not different. It is postulated that genetic variability of factors that contribute to the action of thyroid hormone modulate the phenotype of GRTH associated with TR[beta] mutations. 23 refs., 2 figs., 1 tab.

  6. The role of growth hormone in fetal development.

    PubMed

    Waters, M J; Kaye, P L

    2002-06-01

    Studies across several species, particularly the mouse, show that growth hormone (GH, somatotrophin) is an important determinant of litter size, and to a lesser extent, of birth length. GH acts at all stages of development, from ovulation through preimplantation development to the late fetus, with actions on both embryo/fetus and mother contributing to successful fetal development. The fact that these are not more obvious in vivo is likely a result of redundancy of cytokine hormone action, particularly in relation to prolactin, which shares common actions and receptor locations with GH.

  7. [How safe is the recombinant human growth hormone?

    PubMed

    Calzada-León, Raúl

    2017-01-01

    In this paper, several aspects related to the safety of the use of biosynthetic human growth hormone are reviewed. For example, its classification as a biosynthetic drug, the phases that need to be performed in Mexico to verify its safety (obtaining, purification, preclinical studies, clinical trials, and finally observational clinical studies), as well as the evidence that exists in relation to the association of intracranial hypertension, muscular events, scoliosis, slipped capital femoral epiphysis, obstructive sleep apnea, pancreatitis, alterations in cortisol, thyroid hormones alterations, cardiovascular disease, metabolic risk, mortality and cancer, adverse events not related to its use, and finally dosing and safety.

  8. Human growth hormone (GH) immunoassay: standardization and clinical implications.

    PubMed

    Carrozza, Cinzia; Lapolla, Rosa; Canu, Giulia; Annunziata, Francesca; Torti, Eleonora; Baroni, Silvia; Zuppi, Cecilia

    2011-05-01

    The poor comparability of growth hormone (GH) results obtained using commercially available methods, is partly due to standard preparations used in calibration. The system relies on the use of the International Reference Preparation (IRP) international standard (IS) 80/505, of human pituitary origin, containing all GH isoforms. Recently, a 22K recombinant GH isoform IRP IS 98/574 was commercialized. Our aim was to evaluate the influence of both calibrators on GH results. GH concentration in 97 serum samples from children undergoing a growth hormone releasing hormone+arginine stimulation test was measured using Siemens IMMULITE electro-chemiluminescence method, calibrated with both IS 80/505 and IS 98/574 (GRH Growth hormone-Recombinant 98/574-kit). Comparison of our results obtained with the two sets of calibrators showed good correlation, although we found higher percentage variation (var%) than that stated by Siemens. The mean var% value was confirmed when all results were sub-divided into subgroups based on both high and low GH concentrations. Since the GH assay is influenced by a variety of binding proteins, isoforms and conversion factors, standardization of the assay is strongly required. In Italy, the Agenzia Italiana del Farmaco 39 note provides GH laboratory values which are useful for therapy. On the basis of our results, we therefore propose to adjourn these GH values in order to ensure better management of patients with GH-related disorders.

  9. Thyrotrophin-releasing hormone induces growth hormone secretion in adult hypothyroid fowl.

    PubMed

    Harvey, S; Scanes, C G; Klandorf, H

    1988-02-01

    While thyrotrophin-releasing hormone (TRH) stimulated growth hormone (GH) secretion in adult anesthetized cockerels, the GH response was blocked in anesthetized birds pretreated with thyroxine (T4) or triiodothyronine (T3). Moreover, whereas GH secretion in conscious adult birds was poorly responsive to TRH stimulation, conscious birds made hypothyroid by goitrogen pretreatment (with propylthiouracil, methimazole, or thiourea) were responsive to TRH challenge. Basal circulating GH concentrations in the goitrogen-pretreated birds were also higher than in the vehicle-injected controls. Surgical thyroidectomy similarly increased the basal GH concentration in adult birds and promoted TRH-induced GH secretion. These results demonstrate inhibitory effects of the thyroid hormones on basal and stimulated GH secretion in adult domestic fowl and suggest that GH release in adults is partly under tonic thyroidal inhibition.

  10. Growth hormone actions during development influence adult phenotype and longevity.

    PubMed

    Bartke, A; Sun, L; Fang, Y; Hill, C

    2016-12-15

    There is considerable evidence that exposure to undernutrition, overnutrition, stress or endocrine disruptors during fetal development can increase the probability of obesity, hypertension, cardiovascular disease and other problems in adult life. In contrast to these findings, reducing early postnatal growth by altering maternal diet or number of pups in a litter can increase longevity. In hypopituitary Ames dwarf mice, which are remarkably long lived, a brief period of growth hormone therapy starting at 1 or 2weeks of age reduces longevity and normalizes ("rescues") multiple aging-related traits. Collectively, these findings indicate that nutritional and hormonal signals during development can have profound impact on the trajectory of aging. We suspect that altered "programming" of aging during development may represent one of the mechanisms of the Developmental Origins of Health and Disease (DOHaD) and the detrimental effects of "catch-up" growth. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Diabetes mellitus in a girl with thyroid hormone resistance syndrome: a little recognized interaction between the two diseases.

    PubMed

    Stagi, Stefano; Manoni, Cristina; Cirello, Valentina; Covelli, Danila; Giglio, Sabrina; Chiarelli, Francesco; Seminara, Salvatore; de Martino, Maurizio

    2014-01-01

    The syndrome of resistance to thyroid hormone (RTH) is characterized by elevated serum free thyroid hormones (FT4 and FT3) in the presence of unsuppressed TSH levels, reflecting resistance to the normal negative feedback mechanisms in the hypothalamus and pituitary. The degree of resistance within peripheral tissues determines whether thyrotoxic clinical features are associated with this condition. Classic features include attention deficit hyperactivity disorder, growth delay, tachycardia, and goiter. However, other features, such as frequent ear, nose and throat infections, hearing deficit, and decreased bone mass have recently been recognized. The phenotype of RTH is variable, with most patients presenting with mild to moderate symptoms. In this report we describe a girl with familiar RTH and diabetes mellitus. This is, to our knowledge, the first report regarding this association. Nearly one year after long-term triiodothyroacetic acid (Triac) therapy, we observed a reduction of thyroid hormone levels with an amelioration of insulin resistance. The possible interactions between these disorders are discussed.

  12. Altered Metabolism of Growth Hormone Receptor Mutant Mice: A Combined NMR Metabonomics and Microarray Study

    PubMed Central

    Schirra, Horst Joachim; Anderson, Cameron G.; Wilson, William J.; Kerr, Linda; Craik, David J.; Waters, Michael J.; Lichanska, Agnieszka M.

    2008-01-01

    Background Growth hormone is an important regulator of post-natal growth and metabolism. We have investigated the metabolic consequences of altered growth hormone signalling in mutant mice that have truncations at position 569 and 391 of the intracellular domain of the growth hormone receptor, and thus exhibit either low (around 30% maximum) or no growth hormone-dependent STAT5 signalling respectively. These mutations result in altered liver metabolism, obesity and insulin resistance. Methodology/Principal Findings The analysis of metabolic changes was performed using microarray analysis of liver tissue and NMR metabonomics of urine and liver tissue. Data were analyzed using multivariate statistics and Gene Ontology tools. The metabolic profiles characteristic for each of the two mutant groups and wild-type mice were identified with NMR metabonomics. We found decreased urinary levels of taurine, citrate and 2-oxoglutarate, and increased levels of trimethylamine, creatine and creatinine when compared to wild-type mice. These results indicate significant changes in lipid and choline metabolism, and were coupled with increased fat deposition, leading to obesity. The microarray analysis identified changes in expression of metabolic enzymes correlating with alterations in metabolite concentration both in urine and liver. Similarity of mutant 569 to the wild-type was seen in young mice, but the pattern of metabolites shifted to that of the 391 mutant as the 569 mice became obese after six months age. Conclusions/Significance The metabonomic observations were consistent with the parallel analysis of gene expression and pathway mapping using microarray data, identifying metabolites and gene transcripts involved in hepatic metabolism, especially for taurine, choline and creatinine metabolism. The systems biology approach applied in this study provides a coherent picture of metabolic changes resulting from impaired STAT5 signalling by the growth hormone receptor, and

  13. Leptin alters the response of the growth hormone releasing factor- growth hormone--insulin-like growth factor-I axis to fasting.

    PubMed

    LaPaglia, N; Steiner, J; Kirsteins, L; Emanuele, M; Emanuele, N

    1998-10-01

    Proper nutritional status is critical for maintaining growth and metabolic function, playing an intimate role in neuroendocrine regulation. Leptin, the recently identified product of the obese gene, may very well be an integral signal which regulates neuroendocrine responses in times of food deprivation. The present study examines leptin's ability to regulate hormonal synthesis and secretion within the GRF-GH-IGF axis in the adult male rat during almost 3 days of fasting. Serum levels of GH and IGF-I were drastically suppressed by fasting. Daily leptin administration was able to fully prevent the fasting-induced fall in serum GH. Leptin failed to restore IGF-I to control levels, however, suggesting possible GH resistance. Fasting caused an insignificant increase in GH mRNA, while leptin injections significantly increased steady-state levels of this message. The GRF receptor (GRFr) message was not altered with fasting or leptin treatment. Leptin also exhibited effects at the hypothalamic level. Fasting induced a sharp fall in GRF mRNA expression and leptin injections partially prevented this fall. However, there were no observed changes in the hypothalamic GRF content. These results provide evidence that leptin may function as a neuromodulator of the GRF-GH-IGF axis communicating to this hormonal system the nutritional status of the animal.

  14. Effect of sericin on diabetic hippocampal growth hormone/insulin-like growth factor 1 axis

    PubMed Central

    Chen, Zhihong; Yang, Songhe; He, Yaqiang; Song, Chengjun; Liu, Yongping

    2013-01-01

    Previous studies have shown that sericin extracted from silk cocoon significantly reduces blood glucose levels and protects the nervous system against diabetes mellitus. In this study, a rat type 2 diabetes mellitus model was established by intraperitoneal injection of 25 mg/kg streptozotocin for 3 successive days, following which the rats were treated with sericin for 35 days. After treatment, the blood glucose levels of the diabetic rats decreased significantly, the growth hormone level in serum and its expression in the hippocampus decreased significantly, while the insulin-like growth factor-1 level in serum and insulin-like growth factor-1 and growth hormone receptor expression in the hippocampus increased significantly. The experimental findings indicate that sericin improves disorders of the growth hormone/insulin-like growth factor 1 axis to alleviate hippocampal damage in diabetic rats. PMID:25206472

  15. Regulatory mechanisms of growth hormone secretion are sexually dimorphic.

    PubMed Central

    Jaffe, C A; Ocampo-Lim, B; Guo, W; Krueger, K; Sugahara, I; DeMott-Friberg, R; Bermann, M; Barkan, A L

    1998-01-01

    Sexually dimorphic growth hormone (GH) secretory pattern is important in the determination of gender-specific patterns of growth and metabolism in rats. Whether GH secretion in humans is also sexually dimorphic and the neuroendocrine mechanisms governing this potential difference are not fully established. We have compared pulsatile GH secretion profiles in young men and women in the baseline state and during a continuous intravenous infusion of recombinant human insulin-like growth factor I (rhIGF-I). During the baseline study, men had large nocturnal GH pulses and relatively small pulses during the rest of the day. In contrast, women had more continuous GH secretion and more frequent GH pulses that were of more uniform size. The infusion of rhIGF-I (10 microg/kg/h) potently suppressed both spontaneous and growth hormone-releasing hormone (GHRH)-induced GH secretion in men. In women, however, rhIGF-I had less effect on pulsatile GH secretion and did not suppress the GH response to GHRH. These data demonstrate the existence of sexual dimorphism in the regulatory mechanisms involved in GH secretion in humans. The persistence of GH responses to GHRH in women suggests that negative feedback by IGF-I might be expressed, in part, through suppression of hypothalamic GHRH. PMID:9649569

  16. Hormonal growth promoting agents in food producing animals.

    PubMed

    Stephany, Rainer W

    2010-01-01

    In contrast to the use of hormonal doping agents in sports to enhance the performance of athletes, in the livestock industry hormonal growth promoters ("anabolics") are used to increase the production of muscle meat. This leads to international disputes about the safety of meat originating from animals treated with such anabolics.As a consequence of the total ban in the EU of all hormonal active growth promoters ("hormones") in livestock production, in contrast to their legal use [e.g. of five such hormones (17beta-estradiol, testosterone, progesterone, trenbolone and zeranol) as small solid ear implants and two hormones as feed additives for feedlot heifers (melengestrol acetate) and for swine (ractopamine) in the USA], the regulatory controls also differ sharply between the EU and the USA.In the EU the treatment of slaughter animals is the regulatory offence that has to be controlled in inspection programs. In the USA testing for compliance of a regulatory maximum residue level in the edible product (muscle, fat, liver or kidney) is the purpose of the inspection program (if any).The EU inspection programs focus on sample materials that are more suitable for testing for banned substances, especially if the animals are still on the farm, such as urine and feces or hair. In the case of slaughtered animals, the more favored sample materials are bile, blood, eyes and sometimes liver. Only in rare occasions is muscle meat sampled. This happens only in the case of import controls or in monitoring programs of meat sampled in butcher shops or supermarkets.As a result, data on hormone concentrations in muscle meat samples from the EU market are very rare and are obtained in most cases from small programs on an ad hoc basis. EU data for natural hormones in meat are even rarer because of the absence of "legal natural levels" for these hormones in compliance testing. With the exception of samples from the application sites - in the EU the site of injection of liquid hormone

  17. Growth Hormone Response to L-Dopa and Clonidine in Autistic Children.

    ERIC Educational Resources Information Center

    Realmuto, George M.; And Others

    1990-01-01

    Seven medication-free autistic subjects (ages 6-19) were administered clonidine and L-Dopa to investigate neuroendocrine responses through changes in growth hormone levels. Findings showed that, compared to normal controls, the L-Dopa-stimulated growth hormone peak was delayed and the clonidine growth hormone peak was premature. (Author/JDD)

  18. Growth Hormone Response to L-Dopa and Clonidine in Autistic Children.

    ERIC Educational Resources Information Center

    Realmuto, George M.; And Others

    1990-01-01

    Seven medication-free autistic subjects (ages 6-19) were administered clonidine and L-Dopa to investigate neuroendocrine responses through changes in growth hormone levels. Findings showed that, compared to normal controls, the L-Dopa-stimulated growth hormone peak was delayed and the clonidine growth hormone peak was premature. (Author/JDD)

  19. [New physiological and pharmacological aspects of the growth hormone (I). The effects in adults].

    PubMed

    Díez, J J; Gómez-Pan, A

    1993-04-01

    Growth hormone (GH), a well-known anabolizing agent, not only plays a physiological role in childhood by promoting longitudinal growth, but also it remains to be secreted during adult life. Many aspects on physiological and pharmacological actions of this hormone in adulthood have been clarified in the last years. GH induces the biosynthesis of insulin-like growth factor I (IGF-I), a peptidic compound that acts as a mediator of indirect actions of GH. In GH deficient adults, exogenous GH administration produces a decrease in adipose mass which is accompanied by an increase in lean body mass, mainly due to an enlargement of muscle cell mass. Sodium and water retention has been also described. An augmentation in muscle strength, basal metabolic rate and nitrogen retention by action of GH are expressions of the potential anabolizing effects of this hormone in adult life. Glucose tolerance is decreased by GH, and this effect is accompanied by a decrease in peripheral utilization of glucose and an increase in insulin secretion. GH behaves as a lipolytic hormone and gives rise to an increase in resistance to the lipogenetic action of insulin. GH treatment increases plasma levels of bone Gla protein and other marker of osteoblastic activity, what suggests a physiological role of GH in bone turnover regulation. Many other organic functions are also affected by GH administration.

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

    PubMed

    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.

  1. The Growth Hormone Secretagogue Receptor: Its Intracellular Signaling and Regulation

    PubMed Central

    Yin, Yue; Li, Yin; Zhang, Weizhen

    2014-01-01

    The growth hormone secretagogue receptor (GHSR), also known as the ghrelin receptor, is involved in mediating a wide variety of biological effects of ghrelin, including: stimulation of growth hormone release, increase of food intake and body weight, modulation of glucose and lipid metabolism, regulation of gastrointestinal motility and secretion, protection of neuronal and cardiovascular cells, and regulation of immune function. Dependent on the tissues and cells, activation of GHSR may trigger a diversity of signaling mechanisms and subsequent distinct physiological responses. Distinct regulation of GHSR occurs at levels of transcription, receptor interaction and internalization. Here we review the current understanding on the intracellular signaling pathways of GHSR and its modulation. An overview of the molecular structure of GHSR is presented first, followed by the discussion on its signaling mechanisms. Finally, potential mechanisms regulating GHSR are reviewed. PMID:24651458

  2. Recombinant DNA products: Insulin, interferon and growth hormone

    SciTech Connect

    Bollon, A.P.

    1984-01-01

    This book provides the discussion of products of biotechnology of recombinant DNA. The contents include: Recombinant DNA techniques; isolation, cloning, and expression of genes; from somatostatin to human insulin; yeast; an alternative organism for foreign protein production; background in human interferon; preclinical assessment of biological properties of recombinant DNA derived human interferons; human clinical trials of bacteria-derived human ..cap alpha.. interferon.f large scale production of human alpha interferon from bacteria; direct expression of human growth hormone in escherichia coli with the lipoprotein promoter; biological actions in humans of recombinant DNA synthesized human growth hormone; NIH guidelines for research involving recombinant DNA molecules; appendix; viral vectors and the NHY guidelines; FDA's role in approval and regulation of recombinant DNA drugs; and index.

  3. Metabolic clearance rate of radioiodinated human growth hormone in man

    PubMed Central

    Cameron, Donald P.; Burger, Henry G.; Catt, Kevin J.; Doig, Alison

    1969-01-01

    The nature of the disappearance of radioiodinated human growth hormone (HGH) from plasma has been reexamined. The metabolic clearance rate (MCR) was determined both from single injection and constant infusion studies. After single injection of highly purified radioiodinated HGH, the disappearance curve remained multiexponential during the period of study (4 hr). The shape of the curve was independent of the growth hormone preparation used. Similar disappearance curves were obtained with unlabeled HGH. MCR values calculated from constant infusion studies were 203 ±7.8 liters/day per m2 and values derived from single injection studies agreed closely with this. The multiexponential nature of the disappearance curve does not permit meaningful calculation of volume of distribution or half-time of disappearance. PMID:5822572

  4. Focus on growth hormone deficiency and bone in adults.

    PubMed

    Tritos, Nicholas A

    2017-02-01

    Growth hormone (GH) exerts several effects on the skeleton, mediated either directly or indirectly, leading to increased bone formation and resorption rates. Patients with growth hormone deficiency (GHD) of adult onset have decreased bone mineral density (BMD) and increased fracture risk. Some, but not all, studies have found that adults with childhood onset GHD also have lower BMD than healthy controls. Adults with GHD of childhood onset have smaller bone dimensions, leading to possible underestimation of areal BMD (measured by dual energy X-ray absorptiometry), thus potentially confounding the interpretation of densitometric data. Available data suggest that patients with childhood onset GHD are at increased fracture risk. Prospective studies and some clinical trials found that GH replacement for at least 18-24 months leads to increased BMD. Retrospective and prospective data suggest that GH replacement is associated with decreased fracture risk in adults. However, data from randomized clinical trials are lacking. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. AAS, growth hormone, and insulin abuse: psychological and neuroendocrine effects

    PubMed Central

    Graham, Michael R; Evans, Peter; Davies, Bruce; Baker, Julien S

    2008-01-01

    The nontherapeutic use of prescription medicines by individuals involved in sport is increasing. Anabolic-androgenic steroids (AAS) are the most widely abused drug. Much of our knowledge of the psychological and physiological effects of human growth hormone (hGH) and insulin has been learned from deficiency states. As a consequence of the Internet revolution, previously unobtainable and expensive designer drugs, particularly recombinant human growth hormone (rhGH) and insulin, have become freely available at ridiculously discounted prices from countries such as China and are being abused. These drugs have various physiological and psychological effects and medical personnel must become aware that such prescription medicine abuse appears to be used not only for performance and cosmetic reasons, but as a consequence of psychological pre-morbidity. PMID:18827854

  6. Plasma concentrations of luteinising hormone, follicle stimulating hormone, androgen, growth hormone, prolactin, thyroxine and triiodothyronine during growth and sexual development in the cockerel.

    PubMed

    Sterling, R J; Sharp, P J; Klandorf, H; Harvey, S; Lea, R W

    1984-07-01

    Changes in concentrations of plasma luteinising hormone (LH), follicle stimulating hormone (FSH), androgen, growth hormone (GH), prolactin (Prl), thyroxine (T4) and triiodothyronine (T3) were measured during growth and sexual maturation in broiler cockerels reared in continuous light to 7 weeks and 14 h light/d thereafter. Concentrations of LH and FSH began to increase between 13 and 15 weeks, while those of androgens increased between 16 and 17 weeks. FSH concentration increased faster than that of LH. Concentrations of GH and Prl were high at 3 weeks; that of GH decreasing progressively between 3 and 14 weeks of age and thereafter remaining low, while that of Prl was low between 5 and 9 weeks, relatively high between 10 and 13 weeks, and then temporarily decreasing before increasing progressively during sexual maturation. Concentrations of T3 and T4 were higher in juvenile than in adult birds.

  7. Thyroid Hormone Receptor Binds to a Site in the Rat Growth Hormone Promoter Required for Induction by Thyroid Hormone

    NASA Astrophysics Data System (ADS)

    Koenig, Ronald J.; Brent, Gregory A.; Warne, Robert L.; Reed Larsen, P.; Moore, David D.

    1987-08-01

    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. We have partially purified T3 receptor from rat liver and examined its interaction with these rGH sequences. We 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.

  8. Cancer vaccines for hormone/growth factor immune deprivation: a feasible approach for cancer treatment.

    PubMed

    González, G; Lage, A

    2007-05-01

    One of the older and most validated cancer treatments is endocrine therapy. Some tumors are dependent on hormone stimulation for growth, and therefore therapeutic interventions aiming to deprive the cells of the hormone are feasible and have been successful. Tumor growth also depends in some cases on growth factors, so that the concept of hormone-dependence can be extended to growth factors deprivation. Hormone deprivation has been therapeutically achieved up to now by surgical, radiation and chemical means. However, the immune system usually can be manipulated to recognize hormones and growth factors, and in fact some autoimmune diseases exists involving autoantibodies against hormones. The idea of inducing a deprivation of hormones and growth factors by active immunizations is appealing, and initial evidence about the feasibility of this approach is starting to appear in the literature. Clinical trials have been initiated using immunization with human chorionic gonadotrophin (hCG), gastrin, luteinizing hormone releasing hormone (LHRH) / gonadotropin releasing hormone (GnRH) and epidermal growth factor (EGF). Preliminary data already show that antibody titers can be elicited, which results in a decrease in the concentration of a given hormone or growth factor. Both the antibody titers and the decrease in the hormone level are related to survival. This immunological approach for hormone and growth factor deprivation creates the possibility of chronic management of advanced cancer patients.

  9. Regulation of growth hormone secretion by (pro)renin receptor.

    PubMed

    Tani, Yuji; Yamada, Shozo; Inoshita, Naoko; Hirata, Yukio; Shichiri, Masayoshi

    2015-06-03

    (Pro)renin receptor (PRR) has a single transmembrane domain that co-purifies with the vacuolar H(+)-ATPase (V-ATPase). In addition to its role in cellular acidification, V-ATPase has been implicated in membrane fusion and exocytosis via its Vo domain. Results from the present study show that PRR is expressed in pituitary adenoma cells and regulates growth hormone (GH) release via V-ATPase-induced cellular acidification. Positive PRR immunoreactivity was detected more often in surgically resected, growth hormone-producing adenomas (GHomas) than in nonfunctional pituitary adenomas. GHomas strongly expressing PRR showed excess GH secretion, as evidenced by distinctly high plasma GH and insulin-like growth factor-1 levels, as well as an elevated nadir GH in response to the oral glucose tolerance test. Suppression of PRR expression in rat GHoma-derived GH3 cells using PRR siRNA resulted in reduced GH secretion and significantly enhanced intracellular GH accumulation. GH3 treatment with bafilomycin A1, a V-ATPase inhibitor, also blocked GH release, indicating mediation via impaired cellular acidification of V-ATPase. PRR knockdown decreased Atp6l, a subunit of the Vo domain that destabilizes V-ATPase assembly, increased intracellular GH, and decreased GH release. To our knowledge, this is the first report demonstrating a pivotal role for PRR in a pituitary hormone release mechanism.

  10. Growth hormone, enhancement and the pharmaceuticalisation of short stature.

    PubMed

    Morrison, Michael

    2015-04-01

    This paper takes the biological drug human Growth Hormone (hGH) as a case study to investigate processes of pharmaceuticalisation and medicalisation in configuring childhood short stature as a site for pharmaceutical intervention. Human growth hormone is considered to have legitimate applications in treating childhood growth hormone deficiency and short stature associated with other recognised conditions. It is also regarded by bioethicists and others as a form of human biomedical enhancement when applied to children with idiopathic or 'normal' short stature. The purpose of this study is not to evaluate whether treatment of idiopathic short stature is enhancement or not, but to evaluate how some applications of hGH in treating short stature have come to be accepted and stabilised as legitimate 'therapies' while others remain contested as 'enhancements'. A comparative, historical approach is employed, drawing on approaches from medical sociology and Science and Technology Studies (STS) to set out a socio-technical history of hGH in the US and UK. Through this history the relative influence and interplay of drivers of pharmaceuticalisation, including industry marketing and networks of drug distribution, and processes of medicalisation will be employed to address this question and simultaneously query the value of enhancement as a sociological concept.

  11. Isolated growth hormone deficiency type 2: from gene to therapy.

    PubMed

    Miletta, Maria Consolata; Lochmatter, Didier; Pektovic, Vibor; Mullis, Primus-E

    2012-01-01

    Isolated growth hormone deficiency type-2 (IGHD-2), the autosomal-dominant form of GH deficiency, is mainly caused by specific splicing mutations in the human growth hormone (hGH) gene (GH-1). These mutations, occurring in and around exon 3, cause complete exon 3 skipping and produce a dominant-negative 17.5 kD GH isoform that reduces the accumulation and secretion of wild type-GH (wt-GH). At present, patients suffering from IGHD-2 are treated with daily injections of recombinant human GH (rhGH) in order to reach normal height. However, this type of replacement therapy, although effective in terms of growth, does not prevent toxic effects of the 17.5-kD mutant on the pituitary gland, which can eventually lead to other hormonal deficiencies. Considering a well-known correlation between the clinical severity observed in IGHD-2 patients and the increased expression of the 17.5-kD isoform, therapies that specifically target this isoform may be useful in patients with GH-1 splicing defects. This chapter focuses on molecular strategies that could represent future directions for IGHD-2 treatment.

  12. Insulin-like growth factor 1: common mediator of multiple enterotrophic hormones and growth factors

    PubMed Central

    Bortvedt, Sarah F.; Lund, P. Kay

    2013-01-01

    Purpose of review To summarize recent evidence that IGF1 mediates growth effects of multiple trophic factors and discuss clinical relevance. Recent findings Recent reviews and original reports indicate benefits of growth hormone (GH) and long-acting glucagon-like peptide 2 (GLP2) analogues in short bowel syndrome and Crohn’s disease. This review highlights evidence that biomarkers of sustained small intestinal growth or mucosal healing and evaluation of intestinal epithelial stem cell biomarkers may improve clinical measures of intestinal growth or response to trophic hormones. Compelling evidence that IGF1 mediates growth effects of GH and GLP2 on intestine or linear growth in preclinical models of resection or Crohn’s disease is presented, along with a concept that these hormones or IGF1 may enhance sustained growth if given early after bowel resection. Evidence that SOCS protein induction by GH or GLP2 in normal or inflamed intestine, may limit IGF1-induced growth, but protect against risk of dysplasia or fibrosis is reviewed. Whether IGF1 receptor mediates IGF1 action and potential roles of insulin receptors are addressed. Summary IGF1 has a central role in mediating trophic hormone action in small intestine. Better understanding of benefits and risks of IGF1, receptors that mediate IGF1 action, and factors that limit undesirable growth are needed. PMID:22241077

  13. [Growth hormone in adults. An elixir of youth?].

    PubMed

    Rainfray, M; Hamon-Vilcot, B; Cnockaert, X; Pellerin, J; Bouillanne, O; Durand, D; Piette, F

    1995-01-01

    Studies have revealed a partial deficiency of growth hormone (GH) secretion in the elderly. Aging has a central effect on the GH secretion and probably a peripheral effect on insulin-like growth factor 1 (IGF-1) or somatomedin C through changes in body composition. Simultaneously therapeutic efficiency of recombinant GH was confirmed in adults with GH deficiency. These notions have led to some controlled trials of GH treatment in elderly. Further studies of GH replacement are needed, examining issues such as dosage, tolerance (still inadequate) and efficacy before the widespread use of GH or IGH-F 1 in the elderly is advocated.

  14. The contribution of growth hormone to mammary neoplasia

    PubMed Central

    Perry, Jo K; Mohankumar, Kumarasamypet M; Emerald, B Starling; Mertani, Hichem C; Lobie, Peter E

    2008-01-01

    While the effects of growth hormone (GH) on longitudinal growth are well established, the observation that GH contributes to neoplastic progression is more recent. Accumulating literature implicates GH-mediated signal transduction in the development and progression of a wide range malignancies including breast cancer. Recently autocrine human GH been demonstrated to be an orthotopically expressed oncogene for the human mammary gland. This review will highlight recent evidence linking GH and mammary carcinoma and discuss GH-antagonism as a potential therapeutic approach for treatment of breast cancer. PMID:18253708

  15. Initiating growth hormone therapy for children and adolescents.

    PubMed

    Acerini, Carlo; Albanese, Assunta; Casey, Angela; Denvir, Louise; Jones, Julie; Mathew, Verghese; Musson, Pauline; Sparrow, Susan

    It is common for children and adolescents on growth hormone (GH) treatment to miss one or more injections per week, thereby compromising their linear growth outcome. Among factors likely to affect treatment concordance are patient education and support in the selection of the most appropriate GH injection device. The authors discovered inconsistencies in the process of starting patients on GH therapy throughout the UK, and found that there were no clinical recommendations to support health professionals starting patients on treatment. This article describes the issues involved and the development of practical recommendations for use when starting paediatric patients on long-term GH therapy.

  16. Diagnostic and therapeutic advances in growth hormone insensitivity.

    PubMed

    David, Alessia; Metherell, Louise A; Clark, Adrian J L; Camacho-Hübner, Cecilia; Savage, Martin O

    2005-09-01

    Diagnostic and therapeutic advances in growth hormone insensitivity (GHI) have occurred principally in two areas: the molecular characterization of patients with GHI and treatment with recombinant human insulin like growth factor-I (IGF-I). This article discusses the current status of molecular diagnosis across the spectrum of the disorder. Treatment with recombinant human IGF-I in classical cases is summarized, and potential new targets for treatment are discussed together with the potential for therapy using the newly developed compound recombinant human IGF-I/IGF binding protein-3.

  17. Hormonal modulation of brain tumour growth: a cell culture study.

    PubMed

    Gibelli, N; Zibera, C; Butti, G; Assietti, R; Sica, G; Scerrati, M; Iacopino, F; Roselli, R; Paoletti, P; Robustelli della Cuna, G

    1989-01-01

    Tissue samples derived from two neuroepithelial tumours and five meningiomas were obtained at surgery from seven patients and cultured in order to study the effect of dexamethasone (DEX) and testosterone acetate (TA) on cell proliferation. Glucocorticoid and androgen receptors (GR, AR) were determined both on tissue samples (7 cases) and on five out of the seven cell cultures obtained by tumours. GR and AR were present respectively in 5 and in 4 out of the tumour specimens assayed and in 4/5 and 2/3 of the tested cell cultures. DEX activity on cell growth was tested on six cell cultures. Four of them showed a significant growth inhibition at the highest drug concentration. On the contrary, a significant growth stimulation was observed in four out of the five cultures, where GR were present, using low hormone concentrations. Treatment with pharmacological doses of TA caused a significant cytotoxicity in all the tested cultures. Low TA concentrations inhibited cell growth in one out of the two cell cultures which contained AR, but were ineffective in cultures lacking AR. Our preliminary results suggest a possible role in growth regulation by DEX and TA in intracranial tumours, on the basis of the presence of specific hormone receptors.

  18. Ovariectomy attenuates dendritic growth in hormone-sensitive spinal motoneurons.

    PubMed

    Hebbeler, S L; Verhovshek, T; Sengelaub, D R

    2001-09-15

    The lumbar spinal cord of rats contains the sexually dimorphic, steroid-sensitive spinal nucleus of the bulbocavernosus (SNB). Dendritic development of SNB motoneurons in male rats is biphasic, initially showing exuberant growth through 4 weeks of age followed by a retraction to mature lengths by 7 weeks of age. The initial growth is steroid dependent, attenuated by castration or aromatase inhibition, and supported by hormone replacement. Dendritic retraction is also steroid sensitive and can be prevented by testosterone treatment, but is unaffected by aromatase inhibition. Together, these results suggest a role for estrogens during the initial growth phase of SNB development. In this study, we tested whether ovarian hormones could support SNB somal and dendritic development. Motoneuron morphology was assessed in normal males and in females perinatally masculinized with dihydrotestosterone and then either ovariectomized or left intact. SNB motoneurons were retrogradely labeled with cholera toxin-HRP at 4 or 7 weeks of age and reconstructed in three dimensions. Initial growth of SNB dendrites was reduced after ovariectomy in masculinized females. However, no differences in dendritic length were seen at 7 weeks of age between intact and ovariectomized masculinized females, and lengths in both groups were significantly lower than those of normal males. Together with previous findings, these results suggest that estrogens are involved in the early growth of SNB dendrites, but not in their subsequent retraction.

  19. Search for novel therapies for triple negative breast cancers (TNBC): analogs of luteinizing hormone-releasing hormone (LHRH) and growth hormone-releasing hormone (GHRH).

    PubMed

    Buchholz, Stefan; Seitz, Stephan; Engel, Jörg B; Montero, Alberto; Ortmann, Olaf; Perez, Roberto; Block, Norman L; Schally, Andrew V

    2012-04-01

    Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype that is clinically negative for the expression of estrogen and progesterone receptors (ER/PR) and human epidermal growth factor receptor-2 (HER2). Patients with TNBC have a worse clinical outcome, as measured by time to metastasis and median overall survival. Chemotherapy has been the mainstay of treatment of TNBC but responses are disappointing. A substantial proportion of TNBC expresses luteinizing hormone-releasing hormone (LHRH), receptors for LHRH, in addition to receptors for growth hormone-releasing hormone (GHRH). These receptors represent potential therapeutic targets. Potent antagonists of GHRH and LHRH receptors have been developed in recent years and these antagonists inhibit the growth, tumorigenicity and metastatic potential of various human experimental malignancies. These antagonists could be utilized for the treatment of TNBC. The targeted cytotoxic analog of LHRH, AN-152 (AEZS-108) containing doxorubicin, must also be strongly considered for therapy of TNBC. Experimental studies suggest the merit of clinical trials with LHRH antagonists and AEZS-108 in TNBC patients.

  20. Evaluation of growth hormone release and human growth hormone treatment in children with cranial irradiation-associated short stature

    SciTech Connect

    Romshe, C.A.; Zipf, W.B.; Miser, A.; Miser, J.; Sotos, J.F.; Newton, W.A.

    1984-02-01

    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.

  1. Clinical practice. Fibroblast growth factor (FGF)23: a new hormone.

    PubMed

    Alon, Uri S

    2011-05-01

    Until a decade ago, two main hormones were recognized as directly affecting phosphate homeostasis and, with that, bone metabolism: parathyroid hormone and 1,25(OH)(2) vitamin D (calcitriol). It was only a decade ago that the third major player hormone was found, linking gut, bone, and kidney. The physiologic role of fibrinogen growth factor (FGF)23 is to maintain serum phosphate concentration within a narrow range. Secreted from osteocytes, it modulates kidney handling of phosphate reabsorption and calcitriol production. Genetic and acquired abnormalities in FGF23 structure and metabolism cause conditions of either hyper-FGF23-manifested by hypophosphatemia, low serum calcitriol, and rickets/osteomalacia-or hypo-FGF23, expressed by hyperphosphatemia, high serum calcitriol, and extra-skeletal calcifications. In patients with chronic renal failure, FGF23 levels increase as kidney functions deteriorate and are under investigation to learn if the hormone actually participates in the pathophysiology of the deranged bone and mineral metabolism typical for these patients and, if so, whether it might serve as a therapeutic target. This review addresses the physiology and pathophysiology of FGF23 and its clinical applications.

  2. Growth Hormone Induces Recurrence of Infantile Hemangiomas After Apparent Involution: Evidence of Growth Hormone Receptors in Infantile Hemangioma.

    PubMed

    Munabi, Naikhoba C O; Tan, Qian Kun; Garzon, Maria C; Behr, Gerald G; Shawber, Carrie J; Wu, June K

    2015-01-01

    Infantile hemangiomas (IHs) are the most common benign tumor of infancy, characterized by a natural history of early proliferation in the first months of life to eventual involution during childhood, often with residual fibrofatty tissue. Once involution has been achieved, IHs do not typically recur. We present two cases of exogenous growth hormone therapy resulting in the recurrence of IHs in late childhood, supported by radiological, immunohistochemical, in vitro, and in vivo evidence.

  3. Gibberellins - a multifaceted hormone in plant growth regulatory network.

    PubMed

    Gantait, Saikat; Sinniah, Uma Rani; Ali, Md Nasim; Sahu, Narayan Chandra

    2015-01-01

    Plants tend to acclimatize to unfavourable environs by integrating growth and development to environmentally activated signals. Phytohormones strongly regulate convergent developmental and stress adaptive procedures and synchronize cellular reaction to the exogenous and endogenous conditions within the adaptive signaling networks. Gibberellins (GA), a group of tetracyclic diterpenoids, being vital regulators of plant growth, are accountable for regulating several aspects of growth and development of higher plants. If the element of reproduction is considered as an absolute requisite then for a majority of the higher plants GA signaling is simply indispensable. Latest reports have revealed unique conflicting roles of GA and other phytohormones in amalgamating growth and development in plants through environmental signaling. Numerous physiological researches have detailed substantial crosstalk between GA and other hormones like abscisic acid, auxin, cytokinin, and jasmonic acid. In this review, a number of explanations and clarifications for this discrepancy are explored based on the crosstalk among GA and other phytohormones.

  4. Growth hormone deficiency in children and young adults.

    PubMed

    Oświęcimska, Joanna; Roczniak, Wojciech; Mikołajczak, Agata; Szymlak, Agnieszka

    2016-09-13

    Growth hormone (GH) is a naturally occurring polypeptide hormone produced by somatotropic cells in the anterior pituitary. The main function of somatotropin is stimulation of linear growth, but it also affects carbohydrate metabolism, increases bone mass and has potent lipolytic, antinatriuretic and antidiuretic effects. Growth hormone deficiency (GHD) may occur both in children and in adults. At the moment there is no gold standard for the diagnosis of GHD, and the diagnosis should take into account clinical, auxological, biochemical and radiological changes and, if necessary, genetic testing. Recent studies have highlighted that the biochemical diagnosis of GH deficiency is still imperfect. Stimuli used in the tests are non-physiological, and various substances are characterized by a different mechanism of action and potency. A few years ago it was thought that GHD treatment in children must be completed at the end of linear growth. Studies performed in the last two decades have shown that GHD deficiency in adults may result in complex clinical problems, and if untreated shortens the life expectancy and worsens its comfort. Discontinuation of GH therapy after the final height has been reached in fact negatively impacts the physiological processes associated with the transition phase, which is the period of human life between achieving the final height and 25-30 years of age. Given the adverse metabolic effects of GH treatment interruption after linear growth has been completed, the latest recommendations propose reassessment of GH secretion in the period at least one month after cessation of treatment and continuation of the therapy in case of persistent deficit.

  5. Effect of acute endurance and resistance exercise on endocrine hormones directly related to lipolysis and skeletal muscle protein synthesis in adult individuals with obesity.

    PubMed

    Hansen, Dominique; Meeusen, Romain; Mullens, Annelies; Dendale, Paul

    2012-05-01

    In subjects with obesity, the implementation of long-term exercise intervention increases lean tissue mass and lowers adipose tissue mass. However, data indicate a blunted lipolytic response, and/or skeletal muscle protein synthesis, when subjects with obesity are exposed to acute endurance or resistance exercise, respectively. Therefore, subjects with obesity seem to display a suboptimal physiological response to acute exercise stimuli. It might be hypothesized that hormonal disturbances contribute, at least in part, to these abnormal physiological reactions in the obese. This review discusses the impact of acute endurance and resistance exercise on endocrine hormones directly related to lipolysis and/or skeletal muscle protein synthesis (insulin, [nor]epinephrine, cortisol, growth hormone, testosterone, triiodothyronine, atrial natriuretic peptide, insulin-like growth factor-1), as well as the impact of long-term endurance and resistance exercise intervention on these hormonal responses to acute endurance and resistance exercise. In the obese, some endocrinological disturbances during acute endurance and resistance exercise have been identified: a blunted blood growth hormone, atrial natriuretic peptide and epinephrine release, and greater cortisol and insulin release. These hormonal disturbances might contribute to a suppressed lipolytic response, and/or suppressed skeletal muscle protein synthesis, as a result of acute endurance or resistance exercise, respectively. In subjects with obesity, the impact of acute endurance and resistance exercise on other endocrine hormones (norepinephrine, testosterone, triiodothyronine, insulin-like growth factor-1) remains elusive. Furthermore, whether long-term endurance and resistance exercise intervention might reverse these hormonal disturbances during acute endurance and resistance exercise in these individuals remains unknown.

  6. Dramatic growth of mice that develop from eggs microinjected with metallothionein–growth hormone fusion genes

    PubMed Central

    Palmiter, Richard D.; Brinster, Ralph L.; Hammer, Robert E.; Trumbauer, Myrna E.; Rosenfeld, Michael G.; Birnberg, Neal C.; Evans, Ronald M.

    2016-01-01

    A DNA fragment containing the promoter of the mouse metallothionein-I gene fused to the structural gene of rat growth hormone was microinjected into the pronuclei of fertilized mouse eggs. Of 21 mice that developed from these eggs, seven carried the fusion gene and six of these grew significantly larger than their littermates. Several of these transgenic mice had extraordinarily high levels of the fusion mRNA in their liver and growth hormone in their serum. This approach has implications for studying the biological effects of growth hormone, as a way to accelerate animal growth, as a model for gigantism, as a means of correcting genetic disease, and as a method of farming valuable gene products. PMID:6958982

  7. Growth hormone therapy influences endothelial function in children with renal failure.

    PubMed

    Lilien, Marc R; Schröder, Cornelis H; Levtchenko, Elena N; Koomans, Hein A

    2004-07-01

    Endothelial dysfunction, an early step in atherogenesis, is prevalent in children with renal insufficiency. Endothelial dysfunction in growth hormone deficiency is reversed by growth hormone (rhGH) therapy. Renal failure induces growth hormone resistance at the receptor and post-receptor level, which can be overcome by rhGH therapy. This study investigates the influence of rhGH therapy in children with renal failure on flow-mediated dilation (FMD) of the brachial artery, a marker of endothelial function. We studied 8 patients, who were on rhGH for at least 6 months, and 8 healthy children for comparison. FMD of the brachial artery was measured non-invasively as the percentage increase in diameter during post-ischemic hyperemia. Patients were studied at baseline, after 4 weeks interruption of rhGH therapy, and 4 weeks after resumption of therapy. FMD was significantly lower in patients (4.7%) than healthy controls (13.8%) ( P=0.01). During the administration of rhGH, FMD was significantly higher (3.9%) than during interruption of the treatment (1.4%) ( P=0.04). Our data support the theory that a disturbance in the GH-IGF axis contributes to the endothelial dysfunction of renal failure. Treatment with rhGH not only improves growth but may also favorably influence the risk for atherogenesis.

  8. Sirolimus, Docetaxel, and Carboplatin in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer

    ClinicalTrials.gov

    2016-11-10

    Castration Levels of Testosterone; Hormone-Resistant Prostate Cancer; Metastatic Prostate Carcinoma; Prostate Carcinoma Metastatic in the Bone; PSA Progression; Recurrent Prostate Carcinoma; Stage IV Prostate Cancer

  9. Effects of growth hormone administration in pediatric renal allograft recipients.

    PubMed

    Bartosh, S; Kaiser, B; Rezvani, I; Polinsky, M; Schulman, S; Palmer, J; Baluarte, H J

    1992-01-01

    The efficacy of recombinant human growth hormone (rGH) was assessed in five pediatric allograft recipients with severe growth retardation despite successful renal transplants. rGH 0.05 mg/kg per dose was given six times weekly by subcutaneous injection to five prepubertal children (mean age 15.2 +/- 2.0 years) all of whom had bone ages less than or equal to 12 years (10.0 +/- 1.4 years), a height standard deviation score of less than -2.5 (-4.9 +/- 1.5), no evidence of catch-up growth, a calculated glomerular filtration rate (GFR) of more than 40 ml/min per 1.73 m2 (51 +/- 6.8 ml/min per 1.73 m2), and stable renal function on alternate-day prednisone (16.7 +/- 2.6 mg/m2 per dose). Growth hormone profiles were abnormal in all children before treatment. rGH administration led to a significant increase in both growth rate (3.5 +/- 1.6 cm/year pre therapy, 8.5 +/- 1.4 cm/year post therapy, P less than 0.001) and percentage of expected growth velocity for bone age (67 +/- 31% pre therapy, 163 +/- 27% post therapy, P less than 0.001) with evidence of true catch-up growth. During the study period, three children had the appearance of secondary sexual characteristics, and one had premature advancement of his bone age. GFR decreased in three children, and in one rGH was discontinued due to a steady rise in serum creatinine. No significant changes were seen in serum calcium, phosphorus, cholesterol, triglycerides, glucose, or thyroid function, although a significant increase in alkaline phosphatase was found. In summary, growth-retarded pediatric renal allograft recipients may have abnormal endogenous GH production and respond favorably to rGH.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Concentrations of triiodothyronine, growth hormone, and luteinizing hormone in the plasma of thyroidectomised fowl (Gallus domesticus).

    PubMed

    Harvey, S; Sterling, R J; Klandorf, H

    1983-05-01

    Surgical thyroidectomy increased (P less than 0.05) the basal concentrations of growth hormone (GH) and luteinizing hormone (LH) in the plasma of 10- to 12-week-old domestic fowl. The administration of thyrotrophin releasing hormone (TRH) (100 micrograms, sc) increased (P less than 0.01) the GH concentration in both intact and thyroidectomised birds. The magnitude of the TRH-induced increase in GH level was greater (P less than 0.01) in thyroidectomised birds than in intact controls. Although TRH had no effect on LH secretion in the controls, it induced a small (P less than 0.05) rise in the plasma LH level in thyroidectomised birds. In both the intact and thyroidectomised birds the LH concentration was enhanced (P less than 0.05) following the administration of LH-releasing hormone (LH-RH) (20 micrograms, sc). The increase in the LH level by LH-RH in the thyroidectomised birds was greater (P less than 0.001) than that in the intact controls. Plasma GH concentrations were unaffected by LH-RH treatment. These results suggest that thyroid hormones inhibit the secretion of LH and GH in birds. In thyroidectomised birds low levels of immunoreactive triiodothyronine (T3)-like material were measurable in the circulation, despite the absence of regenerated thyroid tissue. The administration of TRH (100 micrograms, sc) did not enhance the plasma level of this material in thyroidectomised birds, whereas plasma T3 concentrations were enhanced in intact birds following TRH treatment. These results suggest that the T3 immunoreactive substance in thyroidectomised birds is extrathyroidal in origin.

  11. Plant hormone cross-talk: the pivot of root growth.

    PubMed

    Pacifici, Elena; Polverari, Laura; Sabatini, Sabrina

    2015-02-01

    Root indeterminate growth and its outstanding ability to produce new tissues continuously make this organ a highly dynamic structure able to respond promptly to external environmental stimuli. Developmental processes therefore need to be finely tuned, and hormonal cross-talk plays a pivotal role in the regulation of root growth. In contrast to what happens in animals, plant development is a post-embryonic process. A pool of stem cells, placed in a niche at the apex of the meristem, is a source of self-renewing cells that provides cells for tissue formation. During the first days post-germination, the meristem reaches its final size as a result of a balance between cell division and cell differentiation. A complex network of interactions between hormonal pathways co-ordinates such developmental inputs. In recent years, by means of molecular and computational approaches, many efforts have been made aiming to define the molecular components of these networks. In this review, we focus our attention on the molecular mechanisms at the basis of hormone cross-talk during root meristem size determination.

  12. Nuclear hormone receptor coregulator: role in hormone action, metabolism, growth, and development.

    PubMed

    Mahajan, Muktar A; Samuels, Herbert H

    2005-06-01

    Nuclear hormone receptor coregulator (NRC) (also referred to as activating signal cointegrator-2, thyroid hormone receptor-binding protein, peroxisome proliferator activating receptor-interacting protein, and 250-kDa receptor associated protein) belongs to a growing class of nuclear cofactors widely known as coregulators or coactivators that are necessary for transcriptional activation of target genes. The NRC gene is also amplified and overexpressed in breast, colon, and lung cancers. NRC is a 2063-amino acid protein that harbors a potent N-terminal activation domain (AD1) and a second more centrally located activation domain (AD2) that is rich in Glu and Pro. Near AD2 is a receptor-interacting domain containing an LxxLL motif (LxxLL-1), which interacts with a wide variety of ligand-bound nuclear hormone receptors with high affinity. A second LxxLL motif (LxxLL-2) located in the C-terminal region of NRC is more restricted in its nuclear hormone receptor specificity. The intrinsic activation potential of NRC is regulated by a C-terminal serine, threonine, leucine-regulatory domain. The potential role of NRC as a cointegrator is suggested by its ability to enhance transcriptional activation of a wide variety of transcription factors and from its in vivo association with a number of known transcriptional regulators including CBP/p300. Recent studies in mice indicate that deletion of both NRC alleles leads to embryonic lethality resulting from general growth retardation coupled with developmental defects in the heart, liver, brain, and placenta. NRC(-/-) mouse embryo fibroblasts spontaneously undergo apoptosis, indicating the importance of NRC as a prosurvival and antiapoptotic gene. Studies with 129S6 NRC(+/-) mice indicate that NRC is a pleiotropic regulator that is involved in growth, development, reproduction, metabolism, and wound healing.

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

    PubMed

    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.

  14. Role of growth hormone-releasing hormone in sleep and growth impairments induced by upper airway obstruction in rats.

    PubMed

    Tarasiuk, A; Berdugo-Boura, N; Troib, A; Segev, Y

    2011-10-01

    Upper airway obstruction (UAO) can lead to abnormal growth hormone (GH) homeostasis and growth retardation but the mechanisms are unclear. We explored the effect of UAO on hypothalamic GH-releasing hormone (GHRH), which has a role in both sleep and GH regulation. The tracheae of 22-day-old rats were narrowed; UAO and sham-operated animals were sacrificed 16 days post-surgery. To stimulate slow-wave sleep (SWS) and GH secretion, rats were treated with ritanserin (5-HT(2) receptor antagonist). Sleep was measured with a telemetric system. Hypothalamic GHRH, hypothalamic GHRH receptor (GHRHR) and GH receptor, and orexin were analysed using ELISA, real-time PCR and Western blot. UAO decreased hypothalamic GHRH, GHRHR and GH receptor levels, while orexin mRNA increased (p<0.01). In UAO rats, the duration of wakefulness was elevated and the duration of SWS, paradoxical sleep and slow-wave activity was reduced (p<0.001). Ritanserin alleviated these effects, i.e. normalised hypothalamic GHRH content, decreased wake duration, increased duration and depth of SWS, and attenuated growth impairment (p<0.001). Here, we present evidence that growth retardation in UAO is associated with a reduction in hypothalamic GHRH content. Our findings show that abnormalities in the GHRH/GH axis underlie both growth retardation and SWS-disorder UAO.

  15. Experiment K-7-22: Growth Hormone Regulation Synthesis and Secretion in Microgravity. Part 3; Plasma Analysis Hormone Measurements

    NASA Technical Reports Server (NTRS)

    Grindeland, R. E.; Popova, I. A.; Grossman, E.; Rudolph, I.

    1994-01-01

    Plasma from space flight and tail suspended rats was analyzed for a number of constituents in order to evaluate their metabolic status and endocrine function. The data presented here cover plasma hormone measurements. Corticosterone, thyroxine, and testosterone were measured by radioimmunoassay. Prolactin and growth hormone were measured by double antibody immunoassays using hormones and antisera prepared in house. Data were evaluated by analysis of variance.

  16. Experiment K-7-22: Growth Hormone Regulation Synthesis and Secretion in Microgravity. Part 3; Plasma Analysis Hormone Measurements

    NASA Technical Reports Server (NTRS)

    Grindeland, R. E.; Popova, I. A.; Grossman, E.; Rudolph, I.

    1994-01-01

    Plasma from space flight and tail suspended rats was analyzed for a number of constituents in order to evaluate their metabolic status and endocrine function. The data presented here cover plasma hormone measurements. Corticosterone, thyroxine, and testosterone were measured by radioimmunoassay. Prolactin and growth hormone were measured by double antibody immunoassays using hormones and antisera prepared in house. Data were evaluated by analysis of variance.

  17. Glucocorticoids and the regulation of growth hormone secretion.

    PubMed

    Mazziotti, Gherardo; Giustina, Andrea

    2013-05-01

    Glucocorticoids modulate the secretion of growth hormone (GH) by various and competing effects on the hypothalamus and pituitary gland. The final effects of this modulation depend on hormone concentrations and the duration of exposure. The traditional hypothesis is that chronically raised levels of glucocorticoids suppress the secretion of GH. However, a functional impairment of the GH reserve might also be observed in patients with low levels of glucocorticoids, such as those with secondary hypoadrenalism, which is consistent with the model of biphasic dose-dependent effects of glucocorticoids on the somatotropic axis. This Review updates our current understanding of the mechanisms underlying the effects of glucocorticoids on the secretion of GH and the clinical implications of the dual action of glucocorticoids on the GH reserve in humans. This Review will also address the potential diagnostic and therapeutic implications of GH for patients with a deficiency or excess of glucocorticoids.

  18. Coexistence of resistance to thyroid hormone and papillary thyroid carcinoma

    PubMed Central

    Igata, Motoyuki; Tsuruzoe, Kaku; Kawashima, Junji; Kukidome, Daisuke; Kondo, Tatsuya; Motoshima, Hiroyuki; Shimoda, Seiya; Furukawa, Noboru; Nishikawa, Takeshi; Miyamura, Nobuhiro

    2016-01-01

    Summary Resistance to thyroid hormone (RTH) is a syndrome of reduced tissue responsiveness to thyroid hormones. RTH is majorly caused by mutations in the thyroid hormone receptor beta (THRB) gene. Recent studies indicated a close association of THRB mutations with human cancers, but the role of THRB mutation in carcinogenesis is still unclear. Here, we report a rare case of RTH with a papillary thyroid carcinoma (PTC). A 26-year-old woman was referred to our hospital due to a thyroid tumor and hormonal abnormality. She had elevated serum thyroid hormones and non-suppressed TSH levels. Genetic analysis of THRB identified a missense mutation, P452L, leading to a diagnosis of RTH. Ultrasound-guided fine-needle aspiration biopsy of the tumor and lymph nodes enabled the cytological diagnosis of PTC with lymph node metastases. Total thyroidectomy and neck lymph nodes dissection were performed. Following surgery, thyroxine replacement (≥500 μg) was necessary to avoid the symptoms of hypothyroidism and to maintain her TSH levels within the same range as before the operation. During the follow-up, basal thyroglobulin (Tg) levels were around 6 ng/ml and TSH-stimulated Tg levels were between 12 and 20 ng/ml. Up to present, the patient has had no recurrence of PTC. This indicates that these Tg values are consistent with a biochemical incomplete response or an indeterminate response. There is no consensus regarding the management of thyroid carcinoma in patients with RTH, but aggressive treatments such as total thyroidectomy followed by radioiodine (RAI) and TSH suppression therapy are recommended. Learning points There are only a few cases reporting the coexistence of RTH and thyroid carcinoma. Moreover, our case would be the first case presenting one with lymph node metastases. Recent studies indicated a close association of THRB mutations with human cancers, but the role of THRB mutation in carcinogenesis is still unclear. When total thyroidectomy is performed in

  19. Effect of growth hormone treatment on the adult height of children with chronic renal failure. German Study Group for Growth Hormone Treatment in Chronic Renal Failure.

    PubMed

    Haffner, D; Schaefer, F; Nissel, R; Wühl, E; Tönshoff, B; Mehls, O

    2000-09-28

    Growth hormone treatment stimulates growth in short children with chronic renal failure. However, the extent to which this therapy increases final adult height is not known. We followed 38 initially prepubertal children with chronic renal failure treated with growth hormone for a mean of 5.3 years until they reached their final adult height. The mean (+/-SD) age at the start of treatment was 10.4+/-2.2 years, the mean bone age was 7.1+/-2.3 years, and the mean height was 3.1+/-1.2 SD below normal. Fifty matched children with chronic renal failure who were not treated with growth hormone served as controls. The children treated with growth hormone had sustained catch-up growth, whereas the control children had progressive growth failure. The mean final height of the growth hormone-treated children was 165 cm for boys and 156 cm for girls. The mean final adult height of the growth hormone-treated children was 1.6+/-1.2 SD below normal, which was 1.4 SD above their standardized height at base line (P< 0.001). In contrast, the final height of the untreated children (2.1+/-1.2 SD below normal) was 0.6 SD below their standardized height at base line (P<0.001). Although prepubertal bone maturation was accelerated in growth hormone-treated children, treatment was not associated with a shortening of the pubertal growth spurt. The total height gain was positively associated with the initial target-height deficit and the duration of growth hormone therapy and was negatively associated with the percentage of the observation period spent receiving dialysis treatment. Long-term growth hormone treatment of children with chronic renal failure induces persistent catch-up growth, and the majority of patients achieve normal adult height.

  20. Position stand on androgen and human growth hormone use.

    PubMed

    Hoffman, Jay R; Kraemer, William J; Bhasin, Shalender; Storer, Thomas; Ratamess, Nicholas A; Haff, G Gregory; Willoughby, Darryn S; Rogol, Alan D

    2009-08-01

    Hoffman, JR, Kraemer, WJ, Bhasin, S, Storer, T, Ratamess, NA, Haff, GG, Willoughby, DS, and Rogol, AD. Position stand on Androgen and human growth hormone use. J Strength Cond Res 23(5): S1-S59, 2009-Perceived yet often misunderstood demands of a sport, overt benefits of anabolic drugs, and the inability to be offered any effective alternatives has fueled anabolic drug abuse despite any consequences. Motivational interactions with many situational demands including the desire for improved body image, sport performance, physical function, and body size influence and fuel such negative decisions. Positive countermeasures to deter the abuse of anabolic drugs are complex and yet unclear. Furthermore, anabolic drugs work and the optimized training and nutritional programs needed to cut into the magnitude of improvement mediated by drug abuse require more work, dedication, and preparation on the part of both athletes and coaches alike. Few shortcuts are available to the athlete who desires to train naturally. Historically, the NSCA has placed an emphasis on education to help athletes, coaches, and strength and conditioning professionals become more knowledgeable, highly skilled, and technically trained in their approach to exercise program design and implementation. Optimizing nutritional strategies are a vital interface to help cope with exercise and sport demands (). In addition, research-based supplements will also have to be acknowledged as a strategic set of tools (e.g., protein supplements before and after resistance exercise workout) that can be used in conjunction with optimized nutrition to allow more effective adaptation and recovery from exercise. Resistance exercise is the most effective anabolic form of exercise, and over the past 20 years, the research base for resistance exercise has just started to develop to a significant volume of work to help in the decision-making process in program design (). The interface with nutritional strategies has been less

  1. [Influence of growth hormone (GH) and nutrition on neonatal growth].

    PubMed

    Díaz-Gómez, N M; Doménech Martínez, E; Barroso Guerrero, F; Cortabarria Bayona, C; Rico Sevillano, J

    1997-01-01

    At present, growth regulating factors in the transition from fetal to postnatal life remain unknown. The purpose of this study was to analyze the influence of GH and nutrition on neonatal growth. Serum and 24-hour urine GH levels, various anthopometric variables and daily energy and nutrient intake were measured in appropriate (AGA), large (LGA) and small for gestational age (SGA) newborn infants. These variables were measured at 1 (n = 98), 3 (n = 41) and 5 weeks of postnatal age (n = 8). The highest GH levels at the 1st week of postnatal life were obtained in preterm SGA infants (GHs: 61.4 +/- 20.0 microUI/m; GHu: 18.6 +/- 10.3 ng/kg/24 h). GH levels decreased in preterm infants, so that differences between groups failed to be significant at the third and fifth weeks of postnatal life. Urinary GH excretion did not show significant variations in the control group during the study (1st wk 3.0 +/- 3.5; 3rd wk 2.3 +/- 2.7; 5th wk 3.2 +/- 4.7 ng/kg/24 h). Daily protein intake had a direct relationship with both triceps skinfold and weight and head perimeter increase. SGA preterm infants showed a higher fat increase compared to AGA preterm infants. Serum and urinary GH levels were not related to the anthopometric variables studied. There are differences in GH secretion and body composition between SGA and AGA preterm infants. GH probably does not contribute to neonatal growth.

  2. Growth Hormone-Releasing Hormone and Its Analogues: Significance for MSCs-Mediated Angiogenesis

    PubMed Central

    Tao, Quanwei; Ma, Qunchao; Chen, Huiqiang; Wang, Jian'an

    2016-01-01

    Mesenchymal stromal cells (MSCs) are promising candidates for regenerative medicine because of their multipotency, immune-privilege, and paracrine properties including the potential to promote angiogenesis. Accumulating evidence suggests that the inherent properties of cytoprotection and tissue repair by native MSCs can be enhanced by various preconditioning stimuli implemented prior to cell transplantation. Growth hormone-releasing hormone (GHRH), a stimulator in extrahypothalamus systems including tumors, has attracted great attentions in recent years because GHRH and its agonists could promote angiogenesis in various tissues. GHRH and its agonists are proangiogenic in responsive tissues including tumors, and GHRH antagonists have been tested as antitumor agents through their ability to suppress angiogenesis and cell growth. GHRH-R is expressed by MSCs and evolving work from our laboratory indicates that treatment of MSCs with GHRH agonists prior to cell transplantation markedly enhanced the angiogenic potential and tissue reparative properties of MSCs through a STAT3 signaling pathway. In this review we summarized the possible effects of GHRH analogues on cell growth and development, as well as on the proangiogenic properties of MSCs. We also discussed the relationship between GHRH analogues and MSC-mediated angiogenesis. The analyses provide new insights into molecular pathways of MSCs-based therapies and their augmentation by GHRH analogues. PMID:27774107

  3. Response of bovine serum prolactin and growth hormone to duodenal, abomasal, and oral administration of thyrotropin-releasing hormone.

    PubMed

    Smith, V G; Hacker, R R; Burton, J H; Veira, D M

    1977-10-01

    Thyrotropin-releasing hormone was injected into the duodenum of two 500-kg steers, placed into the abomasum of two prepubertal bulls, and fed to four bull calves (1 to 3 wk of age) to test the effect on concentrations of prolactin and growth hormone in blood serum. Before 20 and 200 mg of thyrotropin-releasing hormone were injected into the duodenum, prolactin in serum averaged 7.5 and 9.4 ng/ml and increased to 52.5 and 129.6 ng/ml at 45 and 35 min after treatment. Average growth hormone concentration of serum was increased also, but the response was more variable than prolactin. Peak concentrations of prolactin and growth hormone in blood serum were 5 to 10 times greater after treatment with thyrotropin-releasing hormone (40 mg/100 kg body weight into abomasum) than before treatment. Within 30 min after oral administration of thyrotropin-releasing hormone (0, .5, 1, and 2 mg/kg body weight) growth hormone concentration of serum was 30, 306, 356, and 317% greater than pretreatment. Prolactin concentration of serum, however, was increased in only one calf.

  4. Growth hormone treatment in short children with chronic kidney disease.

    PubMed

    Mehls, O; Wühl, E; Tönshoff, B; Schaefer, F; Nissel, R; Haffner, D

    2008-09-01

    Growth hormone (GH) has been used for treatment of impaired growth in children with chronic kidney disease (CKD) for nearly 17 years. Controlled and open-label studies have shown that GH is highly effective in improving growth velocity and adult height. The growth response is negatively correlated with age and height at start and time spent on dialysis treatment; it is positively correlated with dose and duration of treatment and the primary renal disease (renal hypodysplasia). In children with renal transplants, corticosteroid treatment is an additional factor negatively influencing spontaneous growth rates. However, GH treatment is able to compensate corticosteroid-induced growth failure. GH treatment improved final height by 0.5-1.7 standard deviation score (SDS) in various studies, whereas the control group lost about 0.5 SDS in comparable time intervals. These variable results are explained in part by the factors mentioned above. The adverse events are comparable to those in non-CKD children treated with GH. GH treatment is safe and highly effective in improving growth and final height of short children with all stages of CKD. The highest treatment success is obtained if treatment is started at an early age and with relatively well-preserved residual renal function and continued until final height.

  5. Thyroid hormone mediates otolith growth and development during flatfish metamorphosis.

    PubMed

    Schreiber, A M; Wang, X; Tan, Y; Sievers, Q; Sievers, B; Lee, M; Burrall, K

    2010-11-01

    Flatfish begin life as bilaterally symmetrical larvae that swim up-right, then abruptly metamorphose into asymmetrically shaped juveniles with lateralized swimming postures. Flatfish metamorphosis is mediated entirely by thyroid hormone (TH). Changes in flatfish swim posture are thought to be regulated via vestibular remodeling, although the influence of TH on teleost inner ear development remains unclear. This study addresses the role of TH on the development of the three otolith end-organs (sacculus, utricle, and lagena) during southern flounder (Paralichthys lethostigma) metamorphosis. Compared with pre-metamorphosis, growth rates of the sacculus and utricle otoliths increase dramatically during metamorphosis in a manner that is uncoupled from general somatic growth. Treatment of P. lethostigma larvae with methimazol (a pharmacological inhibitor of endogenous TH production) inhibits growth of the sacculus and utricle, whereas treatment with TH dramatically accelerates their growth. In contrast with the sacculus and utricle otoliths that begin to form and mineralize during embryogenesis, a non-mineralized lagena otolith is first visible 10-12 days after hatching. The lagena grows during pre- and pro-metamorphosis, then abruptly mineralizes during metamorphic climax. Mineralization of the lagena, but not growth, can be induced with TH treatment, whereas treatment with methimazol completely inhibits lagena mineralization without inhibiting its growth. These findings suggest that during southern flounder metamorphosis TH exerts differential effects on growth and development among the three types of otolith.

  6. Role of melatonin in the control of growth and growth hormone secretion in poultry.

    PubMed

    Zeman, M; Buyse, J; Lamosová, D; Herichová, I; Decuypere, E

    1999-10-01

    The pineal hormone melatonin controls reproduction of photoperiodic mammals and is an integral part of the circadian organization in birds. Recent findings indicate an involvement of this hormone also in more basic physiological processes, including growth, development, and aging. Melatonin may modulate growth in poultry through interaction with transcriptional factors, through interaction with hormones involved in growth control, and by modulation of energy metabolism and decreasing physical activity. Our studies showed that a single melatonin injection increased plasma growth hormone (GH) concentrations in the Japanese quail. Specific serotonin receptor blocker ketanserin did not preclude a stimulatory action of melatonin on GH synthesis. Serotonin agonist quipazine increased GH levels but failed to enhance the stimulatory effect of melatonin. Pretreatment with melatonin in drinking water did not affect the magnitude of the GH response to subcutaneous (s.c.) administration of thyrotropin releasing hormone (TRH) that considerably stimulated GH secretion. Present data suggest that melatonin modulates rather central neural pathways involved in the control of GH synthesis at the hypothalamic level than the sensitivity of the pituitary gland.

  7. Mouse hypothalamic growth hormone-releasing hormone and somatostatin responses to probes of signal transduction systems.

    PubMed

    Sato, M; Downs, T R; Frohman, L A

    1993-01-01

    Signal transduction mechanisms involved in mouse growth hormone-releasing hormone (GRH) and somatostatin (SRIH) release were investigated using an in vitro perifusion system. Hypothalamic fragments were exposed to depolarizing agents, protein kinase A and C activators, and a calcium ionophore. The depolarizing agents, KCl (60 mM) and veratridine (50 microM), induced similar patterns of GRH and SRIH release. Somatostatin release in response to both agents was twofold greater than that of GRH. Forskolin (10 microM and 100 microM), an adenylate cyclase activator, stimulated both GRH and SRIH release, though with different secretory profiles. The SRIH response was prolonged and persisted beyond removal of the drug from the system, while the GRH response was brief, ending even prior to forskolin removal. Neither GRH nor SRIH were stimulated by 1,9-dideoxy-forskolin (100 microM), a forskolin analog with cAMP-independent actions. A23187 (5 microM), a calcium ionophore, stimulated the release of SRIH to a much greater extent than that of GRH. The GRH and SRIH secretory responses to PMA (1 microM), a protein kinase C activator, were similar, though delayed. The results suggest that 1) GRH and SRIH secretion are regulated by both protein kinase A and C pathways, and 2) depolarizing agents are important for the release of both hormones.

  8. Short stature: a psychosocial burden requiring growth hormone therapy?

    PubMed

    Sandberg, D E; Brook, A E; Campos, S P

    1994-12-01

    Changes in the diagnosis of endocrine-based growth disorders and the advent of biosynthetic growth hormone have altered the long-standing policy of treating only those individuals with "classic" growth hormone deficiency. One justification for treating short children is to improve their psychosocial adaptation. The present investigation assessed the positive and negative behavioral adaptation, self-perceptions of domain-specific competencies, and global self-worth of a large, diagnostically heterogeneous sample of children and adolescents referred to pediatric endocrinologists for a growth evaluation. All patients seen in a pediatric endocrine clinic (180 boys and 78 girls; 4 to 18 years) with a height at the fifth percentile or lower were included. Parents of all participating children completed the Child Behavior Checklist. Patients 8 years and older completed the Self-Perception Profile and those 11 years and older, in addition, completed the Youth Self Report. Short-stature (SS) subjects were compared with normative and psychiatric samples. The SS boys were described by parents as being significantly less socially competent and showing more behavioral and emotional problems than a normative sample selected for mental health. However, they were significantly more socially competent and showed fewer psychopathologic symptoms than a psychiatric referred sample of comparable age. The SS boys described themselves as less socially active but did not report more behavior disturbance than the normative sample. The SS boys' self-perceptions of domain-specific competencies and global self-worth were comparable to a normative comparison group with the exception that older subjects (13 years or older) described their athletic abilities more positively and their work competence more negatively. The SS girls were, with few exceptions, indistinguishable from the normal comparison groups on both parent- and self-report measures of social competency and behavior disturbance

  9. [Breast hormones--regulators of energy homeostasis: growth of infants].

    PubMed

    Kon', I Ia; Shilina, N M; Gmoshinskaia, M V; Ivanushkina, T A

    2011-01-01

    Studied the possible relationship between the growth rate of children who are breastfed, and the level of protein, fat, insulin-like growth factor- 1 (IGF-1), ghrelin, leptin, adiponectin in breast milk. Examined 71 pair--a mother and a healthy child, who is breastfed. All infants were divided into 3 groups: low, normal and high weight gain. Daily breast milk intake, the level of fat, protein and hormones proteins regulators of energy homeostasis (adiponectin, grelin, IGF-1 and leptin) in breast milk were measured at 1, 2 and 3 months of lactation. It was found that daily breast milk consumption was higher in the group of infants with high weight gain and the content of protein and fat in it did not differ in three groups. Total daily consumption of protein and fat with breast milk was higher in groups of infants with high weight gain. There was significantly higher IGF-1 level and the tendency to higher grelin level in breast milk of mothers of infants with higher weight gain. The possible link of breast milk hormones with growth velocity of breast-fed infants is discussed.

  10. Understanding the growth hormone therapy adherence paradigm: a systematic review.

    PubMed

    Fisher, Benjamin G; Acerini, Carlo L

    2013-01-01

    Growth hormone (GH) therapy is used to treat a variety of growth disorders in childhood/adolescence. Its efficacy is thought to be dependent on patients' adherence to their treatment regimen. PubMed was searched using the keywords 'growth hormone', 'child'[Mesh], 'adolescent'[Mesh], and 'patient compliance'[Mesh]. Most studies of adherence to paediatric GH therapy have used either issued/encashed GH prescriptions or questionnaires. Estimates of prevalence of non-adherence vary from 5-82%, depending on the methods and definitions used. Different studies have variously demonstrated an association (or lack thereof) between adherence and age, socioeconomic status, treatment duration, injection device used and injection-giver. A number of interventions have been proposed to improve adherence, including offering a choice of injection device, but none are supported by trials. Poor adherence is associated with reduced height velocity and likely increased economic costs; evidence for other effects is circumstantial. Adherence to paediatric GH therapy is suboptimal, which may partially explain why the mean final height attained is below that of the general population. Analysis of the causes of non-adherence is complicated by conflicting evidence from different studies. Multifactorial interventions are most likely to be successful in improving adherence. We make recommendations for further research. Copyright © 2013 S. Karger AG, Basel.

  11. Human Growth Hormone Promotes Corneal Epithelial Cell Migration in Vitro

    PubMed Central

    Ding, Juan; Wirostko, Barbara; Sullivan, David A

    2015-01-01

    Purpose Corneal wound healing is a highly regulated process that requires the proliferation and migration of epithelial cells and interactions between epithelial cells and stromal fibroblasts. Compounds that can be applied topically to the ocular surface and that have the capability of activating corneal epithelial cells to proliferate and/or migrate would be useful to promote corneal wound healing. We hypothesize that human growth hormone (HGH) will activate Signal Transducer and Activators of Transcription-5 (STAT5) signaling and promote corneal wound healing by enhancing corneal epithelial cell and fibroblast proliferation and/or migration in vitro. The purpose of this study is to test these hypotheses. Methods We studied cell signaling, proliferation and migration using an immortalized human corneal epithelial cell line and primary human corneal fibroblasts in vitro. We also examined whether insulin-like growth factor-1 (IGF-1), a hormone known to mediate many of HGH’s growth promoting actions, may play a role in this effect. Results We show that HGH activates STAT5 signaling and promotes corneal epithelial cell migration in vitro. The migratory effect requires an intact communication between corneal epithelia and fibroblasts, and is not mediated by IGF-1. Conclusion HGH may represent a topical therapeutic to promote corneal epithelial wound healing. This warrants further investigation. PMID:25782399

  12. Growth hormone reduces mortality and bacterial translocation in irradiated rats.

    PubMed

    Gómez-de-Segura, I A; Prieto, I; Grande, A G; García, P; Guerra, A; Mendez, J; De Miguel, E

    1998-01-01

    Growth hormone stimulates the growth of intestinal mucosa and may reduce the severity of injury caused by radiation. Male Wistar rats underwent abdominal irradiation (12 Gy) and were treated with either human growth hormone (hGH) or saline, and sacrificed at day 4 or 7 post-irradiation. Bacterial translocation, and the ileal mucosal thickness, proliferation, and disaccharidase activity were assessed. Mortality was 65% in irradiated animals, whereas hGH caused a decrement (29%, p < 0.05). Bacterial translocation was also reduced by hGH (p < 0.05). Treating irradiated rats with hGH prevented body weight loss (p < 0.05). Mucosal thickness increased faster in irradiated hGH-treated animals. The proliferative index showed an increment in hGH-treated animals (p < 0.05). Giving hGH to irradiated rats prevented decrease in sucrose activity, and increment in lactase activity. In conclusion, giving hGH to irradiated rats promotes the adaptative process of the intestine and acute radiation-related negative effects, including mortality, bacterial translocation, and weight loss.

  13. Role of abnormal anterior pituitary hormones-growth hormone and prolactin in active systemic lupus erythematosus

    PubMed Central

    Zhu, Xiaohua; Xu, Jinhua; Li, Shujuan; Huang, Wen; Li, Feng

    2015-01-01

    Background: The role of anterior pituitary hormones in systemic lupus erythematosus (SLE) remains controversial. Aims and Objectives: We determined the expression levels of human growth hormone (GH), prolactin (PRL), and their receptors in subjects presenting with SLE, and modulation of disease severity. Materials and methods: Forty-seven subjects and ten healthy controls were assessed for possible association between SLE disease activity and levels of serum PRL, GH and thyrotropin-releasing hormone (TRH). In peripheral blood mononuclear cells (PBMC), specific binding and mRNA expression of receptors for GH (GHR), and PRL (PRLR) were determined by receptor-ligand binding assay (RLBA) and RT-PCR. PBMC of recruited subjects were treated with hPRL and rhGH to assess IgG production and antibodies against dsDNA. Results: In active SLE subjects we found elevated PRL and GH levels. Study subject PBMCs displayed augmented GHR and PRLR protein and mRNA expression. Study subjects also showed a positive correlation in serum PRL levels and specific antibodies against dsDNA, SLE disease activity index (SLEDAI), and proteinuria. However, a negative correlation was found between serum PRL levels and complement component C3. We found a positive correlation between specific binding rates of PRLR and GHR and both SLE activity and dsDNA antibody titers. Enhanced IgG and anti-dsDNA secretion was observed in cultured PBMC stimulated by PRL or GH with/without PHA, PWM, IL-2 or IL-10. In active SLE, a close association was found between augmented PRL and GH levels, expression and specific binding activities of PRLR and GHR, and changes in the specific titer of anti-dsDNA. Conclusion: Anterior pituitary hormones play an important role in the pathogenesis of SLE. High levels of growth hormone (GH) and prolactin (PRL) play a role in pathogenesis of SLE, which is correlated with SLE disease activity and antibodies against dsDNA. The mechanism of GH and PRL in SLE was complicated and should

  14. Lead (Pb) attenuation of plasma growth hormone output

    SciTech Connect

    Berry, W.D.; Moriarty, C.M.; Lau, Y.S.; Edwards, G.L.

    1996-03-08

    Lead (Pb) induced growth retardation may occur through disruption of the hypothalamic-pituitary-growth hormone (GH) axis. Episodic GH secretion and GH response to exogenous growth hormone releasing hormone (GHRH) were measured in rats chronically exposed to Pb. Male rats received lead nitrate (1000 ppm) in their drinking water from 21 through 49 days of age gained less weight than non-Pb treated controls (242{plus_minus}3 g vs 309{plus_minus}8 g, P{le}0.01). Mean blood Pb was 40 {plus_minus} 5 ug/dl in Pb treated rats vs. nondetectable in controls. Total food intake was increased by Pb treatment (340 vs 260 g/rat). Mean plasma GH levels were significantly reduced by Pb treatment (40.21 {plus_minus} 7 vs 71.53 {plus_minus} 11 ng/mlP= 0.025). However, the temporal pattern of episodic GH release was maintained in the Pb-treated rats. This indicates that Pb does not disrupt the timing of GHRH and somatostatin (SS) release from the hypothalamus but may alter the relative levels of GHRH and SS released. Pb treated rats also retained the ability to secrete GH in response to exogenous GHRH. However, response to GHRH tended to be lower in the Pb treated rats. The greatest effect of Pb was seen at the highest dose of GHRH 5 {mu}g/kg GHRH dose (485.6 {plus_minus} 103 vs. 870.2 {plus_minus} 317 ng/ml; P =0.2). This suggests that Pb disrupts GH synthesis, signal transduction, or secretory mechanisms in the somatotrope.

  15. Long-term monitoring of insulin sensitivity in growth hormone-deficient adults on substitutive recombinant human growth hormone therapy.

    PubMed

    Giavoli, Claudia; Porretti, Silvia; Ronchi, Cristina L; Cappiello, Vincenzo; Ferrante, Emanuele; Orsi, Emanuela; Arosio, Maura; Beck-Peccoz, Paolo

    2004-06-01

    Since the effects of recombinant human growth hormone (rhGH) replacement therapy on glucose metabolism are still a matter of debate, the aim of the present study was to evaluate the impact of long-term rhGH treatment on insulin sensitivity. Simple indices of insulin resistance (IR) and insulin sensitivity (IS), based on fasting glucose and insulin, such as the homeostasis model assessment of insulin resistance (HOMA-IR) and the quantitative insulin check index (QUICKI), were used to estimate the degree of IR and IS in 20 normoglycemic patients (11 men and 9 women; mean age, 44 +/- 14 years) with severe adult-onset GH deficiency (GHD). Measurements were determined at baseline and after 1 and 5 years of continuous rhGH therapy. Basal values were compared to those obtained in 20 healthy sex- and age-matched controls. Starting rhGH dose ranged from 3 to 8 microg/kg/d in keeping with sex and age, then doses were titrated according to insulin-like growth factor-I (IGF-I) levels. At baseline all patients had low IGF-I levels (10 +/- 5.4 nmol/L), high body mas index (BMI; 27.5 +/- 4 kg/m(2)), and elevated body fat percentage (BF%; 31.8 +/- 9.6). Fasting glucose and insulin levels, as well as HOMA-IR and QUICKI, did not differ significantly from those recorded in the control group. After 1 year of rhGH replacement therapy, normalization in IGF-I levels and a significant reduction in BF% were observed (P <.001), and these effects were maintained after 5 years of treatment. Fasting glucose increased from 79 +/- 10 to 87 +/- 13, and 87 +/- 12 mg/dL (P <.05) after 1 and 5 years of therapy, respectively. Fasting insulin significantly increased after 1 year, without further modifications in the long-term follow-up. HOMA-IR significantly increased from 2.1 +/- 1.7 to 2.5 +/- 1.7 (P <.05) after 1 year, then decreased to 2.3 +/- 1.5 (P = not significant [NS] v basal) after 5 years. A specular decrease in QUICKI from 0.37 +/- 0.05 to 0.34 +/- 0.03 (P <.01) occurred after 1 year, with

  16. Human growth hormone: a case study in treatment priorities.

    PubMed

    Tauer, Carol A

    1995-01-01

    One of the most commonly cited examples of enhancement genetic engineering is insertion of the growth hormone (GH) gene into a medically normal child. At this time, insertion of the gene itself is not planned. However, the modification of height, which is possible through administration of biochemical GH, raises the same questions about therapeutic versus enhancement uses of genetics. While insertion of the gene is a more drastic measure and probably carries more risks, the question of appropriate limits on use of the GH drug raises similar ethical and policy questions.

  17. Insulin and growth hormone secretion in the nephrotic syndrome.

    PubMed

    Bridgman, J F; Summerskill, J; Buckler, J M; Hellman, B; Rosen, S M

    1975-01-01

    Carbohydrate metabolism was studied in a series of patients with the nephrotic syndrome and compared with a similar number of normal controls. The nephrotic syndrome was associated with a smaller secretion of insulin in response to intravenous glucose and tolbutamide than occurred in normals. In the syndrom fasting serum growth hormone (G.H.) concentrations were increased and did not show the characteristic suppression after glucose administration, and the disappearance rate of glucose (k value) was lower. well marked correlation existed between serum G.H. concentrations and the total urinary protein excreted. These abnormal findings returned to normal in a patient who underwent a repeat study when the nephrotic syndrome had resolved.

  18. Expression of growth hormone receptor in the human brain.

    PubMed

    Castro, J R; Costoya, J A; Gallego, R; Prieto, A; Arce, V M; Señarís, R

    2000-03-10

    This study was designed to investigate the presence of growth hormone receptor (GHR) expression in the human brain tissue, both normal and tumoral, as well as in the human glioblastoma cell line U87MG. Reverse transcription-polymerase chain reaction revealed the presence of GHR mRNA in all brain samples investigated and in U87MG cells. GHR immunoreactivity was also detected in this cell line using both immunocytochemistry and western blotting. All together, our data demonstrate the existence of GHR expression within the central nervous system (CNS), thus supporting a possible role for GH in the CNS physiology.

  19. Hormonal responses to resistance exercise after ingestion of carnosine and anserine.

    PubMed

    Goto, Kazushige; Maemura, Hirohiko; Takamatsu, Kaoru; Ishii, Naokata

    2011-02-01

    Intramuscular carnosine buffers protons (H+) in skeletal muscle. We examined the effects of supplementation with chicken breast meat extract (CBEX) containing carnosine and anserine on hormonal responses to resistance exercise. Twenty-two men were assigned to a CBEX drink group (CBEX containing total 2 g of carnosine and anserine) (n = 14) or a placebo drink group (n = 8). The subjects ingested the prescribed drink (100 mL) twice daily for 30 days without physical training. Before and after the supplementation period, the subjects completed 5 sets of bilateral knee extension exercises (with a 90-s rest between sets). The magnitude of the increase in exercise-induced free testosterone did not change significantly after supplementation in either group. The blood lactate response to exercise was attenuated after supplementation in both groups (p < 0.05). In the CBEX group, the plasma epinephrine and norepinephrine concentrations after exercise were significantly lower after supplementation (p < 0.05). The serum growth hormone response to exercise was also reduced in the CBEX group after supplementation (delta value: 5.4 ± 1.9 ng/mL [pre] vs. 1.6 ± 0.5 ng/mL [post], p = 0.05). No significant differences in exercise-induced strength reduction (fatigue index) were observed in the 2 groups after supplementation. These results suggest that short-term supplementation with CBEX attenuates the exercise-induced epinephrine, norepinephrine, and growth hormone responses.

  20. MANAGEMENT OF ENDOCRINE DISEASE: Growth and growth hormone therapy in short children born preterm.

    PubMed

    Boguszewski, Margaret Cristina da Silva; Cardoso-Demartini, Adriane de Andre

    2017-03-01

    Approximately 15 million babies are born preterm across the world every year, with less than 37 completed weeks of gestation. Survival rates increased during the last decades with the improvement of neonatal care. With premature birth, babies are deprived of the intense intrauterine growth phase, and postnatal growth failure might occur. Some children born prematurely will remain short at later ages and adult life. The risk of short stature increases if the child is also born small for gestational age. In this review, the effects of being born preterm on childhood growth and adult height and the hormonal abnormalities possibly associated with growth restriction are discussed, followed by a review of current information on growth hormone treatment for those who remain with short stature during infancy and childhood.

  1. Purification and Cultivation of Human Pituitary Growth Hormones Secreting Cells

    NASA Technical Reports Server (NTRS)

    Hymer, W. C.; Todd, P.; Grindeland, R.; Lanham, W.; Morrison, D.

    1985-01-01

    The rat and human pituitary gland contains a mixture of hormone producing cell types. The separation of cells which make growth hormone (GH) is attempted for the purpose of understanding how the hormone molecule is made within the pituitary cell; what form(s) it takes within the cell; and what form(s) GH assumes as it leaves the cell. Since GH has a number of biological targets (e.g., muscle, liver, bone), the assessment of the activities of the intracellular/extracellular GH by new and sensitive bioassays. GH cells contained in the mixture was separated by free flow electrophoresis. These experiments show that GH cells have different electrophoretic mobilities. This is relevant to NASA since a lack of GH could be a prime causative factor in muscle atrophy. Further, GH has recently been implicated in the etiology of motion sickness in space. Continous flow electrophoresis experiment on STS-8 showed that GH cells could be partially separated in microgravity. However, definitive cell culture studies could not be done due to insufficient cell recoveries.

  2. Algorithmic complexity of growth hormone release in humans

    SciTech Connect

    Prank, K.; Wagner, M.; Brabant, G.

    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.

  3. [New insights in growth hormone physiology and pathophysiology].

    PubMed

    Kamenicky, P; Lombès, M; Chanson, P

    2010-09-01

    This review focuses on new aspects in growth hormone (GH) biology and pathophysiology presented at the Endocrine Society's meeting, in San Diego, in June 2010. First, we will describe recent advances in the understanding of cytokine hormone signaling via STAT5 in mammary gland development, highlighting the primary role of miR193b for differentiation of mammary stem cells into alveolar progenitor cells. We will examine the potential implication of endocrine and autocrine GH for mammary gland carcinogenesis. Three novel murine models bearing tissue-specific inactivation of GH receptor or JAK2 bring new insights into the large spectrum of GH effects on energy homeostasis. We will also report new data supporting a paracrine regulation of GH secretion in women by estrogen's action in the brain. Thereafter we will question the reasons for GH abuse for doping by assessing the hormonal impact on body composition and physical performance in recreational athletes. Finally, we will discuss the controversial issue of GH replacement in acromegalic patients presenting GH deficiency after treatment of acromegaly. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  4. Purification and Cultivation of Human Pituitary Growth Hormones Secreting Cells

    NASA Technical Reports Server (NTRS)

    Hymer, W. C.; Todd, P.; Grindeland, R.; Lanham, W.; Morrison, D.

    1985-01-01

    The rat and human pituitary gland contains a mixture of hormone producing cell types. The separation of cells which make growth hormone (GH) is attempted for the purpose of understanding how the hormone molecule is made within the pituitary cell; what form(s) it takes within the cell; and what form(s) GH assumes as it leaves the cell. Since GH has a number of biological targets (e.g., muscle, liver, bone), the assessment of the activities of the intracellular/extracellular GH by new and sensitive bioassays. GH cells contained in the mixture was separated by free flow electrophoresis. These experiments show that GH cells have different electrophoretic mobilities. This is relevant to NASA since a lack of GH could be a prime causative factor in muscle atrophy. Further, GH has recently been implicated in the etiology of motion sickness in space. Continous flow electrophoresis experiment on STS-8 showed that GH cells could be partially separated in microgravity. However, definitive cell culture studies could not be done due to insufficient cell recoveries.

  5. Growth hormone secretion from chicken adenohypophyseal cells in primary culture: effects of human pancreatic growth hormone-releasing factor, thyrotropin-releasing hormone, and somatostatin on growth hormone release.

    PubMed

    Perez, F M; Malamed, S; Scanes, C G

    1987-03-01

    A primary culture of chicken adenohypophyseal cells has been developed to study the regulation of growth hormone (GH) secretion. Following collagenase dispersion, cells were exposed for 2 hr to vehicle (control) or test agents. Human pancreatic (tumor) growth hormone-releasing factor (hpGRF) and rat hypothalamic growth hormone-releasing factor stimulated GH release to similar levels. GH release was increased by the presence of dibutyryl cyclic AMP. Thyrotropin-releasing hormone (TRH) alone did not influence GH release; however, TRH plus hpGRF together exerted a synergistic (greater than additive) effect, increasing GH release by 100 to 300% over the sum of the values for each secretagogue acting alone. These relationships between TRH and hpGRF were further examined in cultured cells exposed to secretagogues for two consecutive 2-hr incubations. TRH pretreatment enhanced subsequent hpGRF-stimulated GH release by about 80% over that obtained if no secretagogue was present during the first incubation. In other experiments, somatostatin (SRIF) alone did not alter GH secretion. However, SRIF reduced hpGRF-stimulated GH release to levels found in controls. Furthermore, GH release stimulated by the presence of both TRH and hpGRF was lowered to control values by SRIF. The results of these studies demonstrate that a primary culture of chicken adenohypophyseal cells is a useful model for the study of GH secretion. Indeed, these results suggest that TRH and hpGRF regulate GH secretion by mechanisms which are not identical.

  6. Multicenter study on adult growth hormone level in postoperative pituitary tumor patients.

    PubMed

    Cheng, Jing-min; Gu, Jian-wen; Kuang, Yong-qin; Ma, Yuan; Xia, Xun; Yang, Tao; Lu, Min; He, Wei-qi; Sun, Zhi-yong; Zhang, Yan-chao

    2015-03-01

    The objective of this study is to observe the adult growth hormone level in postoperative pituitary tumor patients of multi-centers, and explore the change of hypophyseal hormones in postoperative pituitary tumor patients. Sixty patients with pituitary tumor admitted during March, 2011-March, 2012 were selected. Postoperative hypophyseal hormone deficiency and the change of preoperative, intraoperative, and postoperative growth hormone levels were recorded. Growth hormone hypofunction was the most common hormonal hypofunction, which took up to 85.0 %. Adrenocortical hormone hypofunction was next to it and accounted for 58.33 %. GH + ACTH + TSH + Gn deficiency was the most common in postoperative hormone deficiency, which took up to 40.00 %, and GH + ACTH + TSH + Gn + AVP and GH deficiencies were next to it and accounted for 23.33 and 16.67 %, respectively. The hormone levels in patients after total pituitary tumor resection were significantly lower than those after partial pituitary tumor resection, and the difference was statistically significant; growth hormone and serum prolactin levels after surgery in two groups were decreased, and the difference was statistically significant. The incidence rate of growth hormone deficiency in postoperative pituitary tumor patients is high, which is usually complicated with deficiency of various hypophyseal hormones. In clinical, we should pay attention to the levels of the hypopnyseal hormones, and take timely measures to avoid postoperative complications.

  7. Ontogeny of hepatic bovine growth hormone receptors in cattle.

    PubMed

    Badinga, L; Collier, R J; Thatcher, W W; Wilcox, C J; Head, H H; Bazer, F W

    1991-05-01

    A series of studies examined the binding characteristics and ontogeny of hepatic growth hormone binding sites in dairy bulls on d 2, 30, 180, and 365 of age. Binding of iodinated recombinant bovine growth hormone ([125I]rbGH) to liver membrane receptors was membrane protein-dependent. Receptors were considered growth hormone-specific, because physiological concentrations of bovine prolactin (bPRL) failed to displace [125I]rbGH from bovine hepatocyte membranes. Only 50% of [125I]rbGH was bound reversibly to hepatic microsomes. Addition of dithiothreitol (DTT) to the receptor-assay buffer increased the binding of [125I]rbGH to hepatic membranes in a time-dependent manner. Moderate concentrations of Ca++ and Mg++ in the receptor-assay buffer had no detectable effects on binding of [125I]rbGH to hepatic microsomes. In growing dairy bulls, specific binding of [125I]rbGH per milligram of membrane protein increased from 1.9 +/- 1.8% at d 2 to 14.1 +/- 1.8% at d 180 and then declined to 5.2 +/- 1.6% at d 365. Likewise, concentration of insulin-like growth factor (IGF)-I in serum was low during the 1st mo of age (d 2, 13.3 +/- 8.8 ng/ml; d 30, 9.7 +/- 8.8 ng/ml), but it became maximal at d 180 (151.0 +/- 8.8 ng/ml). Circulating concentrations of IGF-II increased linearly during the 1st yr of growth. Serum concentrations of GH, triiodothyronine, and thyroxine declined from 39.9 +/- 6.5, 2.7 +/- .2, and 75.4 +/- 4.6 ng/ml at d 2 to 16.5 +/- 6.5, 1.3 +/- .2, and 53.4 +/- 4.6 ng/ml at d 30, respectively, and remained low through 1 yr of age. Insulin concentration in serum did not change significantly with development. Results indicated that increasing concentrations of specific bGH receptors in the bovine liver may play a key role in regulating postnatal growth in cattle.

  8. Identification of Growth Hormone Receptor in Plexiform Neurofibromas of Patients with Neurofibromatosis Type 1

    PubMed Central

    Cunha, Karin Soares Gonçalves; Barboza, Eliane Porto; da Fonseca, Eliene Carvalho

    2008-01-01

    OBJECTIVE The aim of this study was to investigate the presence of growth hormone receptor in plexiform neurofibromas of neurofibromatosis type 1 patients. INTRODUCTION The development of multiple neurofibromas is one of the major features of neurofibromatosis type 1. Since neurofibromas commonly grow during periods of hormonal change, especially during puberty and pregnancy, it has been suggested that hormones may influence neurofibromatosis type 1 neurofibromas. A recent study showed that the majority of localized neurofibromas from neurofibromatosis type 1 patients have growth hormone receptor. METHODS Growth hormone receptor expression was investigated in 5 plexiform neurofibromas using immunohistochemistry. RESULTS Four of the 5 plexiform neurofibromas were immunopositive for growth hormone receptor. CONCLUSION This study suggests that growth hormone may influence the development of plexiform neurofibromas in patients with neurofibromatosis type 1. PMID:18297205

  9. Acceleration of wound healing by growth hormone-releasing hormone and its agonists.

    PubMed

    Dioufa, Nikolina; Schally, Andrew V; Chatzistamou, Ioulia; Moustou, Evi; Block, Norman L; Owens, Gary K; Papavassiliou, Athanasios G; Kiaris, Hippokratis

    2010-10-26

    Despite the well-documented action of growth hormone-releasing hormone (GHRH) on the stimulation of production and release of growth hormone (GH), the effects of GHRH in peripheral tissues are incompletely explored. In this study, we show that GHRH plays a role in wound healing and tissue repair by acting primarily on wound-associated fibroblasts. Mouse embryonic fibroblasts (MEFs) in culture and wound-associated fibroblasts in mice expressed a splice variant of the receptors for GHRH (SV1). Exposure of MEFs to 100 nM and 500 nM GHRH or the GHRH agonist JI-38 stimulated the expression of α-smooth muscle actin (αSMA) based on immunoblot analyses as well as the expression of an αSMA-β-galactosidase reporter transgene in primary cultures of fibroblasts isolated from transgenic mice. Consistent with this induction of αSMA expression, results of transwell-based migration assays and in vitro wound healing (scratch) assays showed that both GHRH and GHRH agonist JI-38 stimulated the migration of MEFs in vitro. In vivo, local application of GHRH or JI-38 accelerated healing in skin wounds of mice. Histological evaluation of skin biopsies showed that wounds treated with GHRH and JI-38 were both characterized by increased abundance of fibroblasts during the early stages of wound healing and accelerated reformation of the covering epithelium at later stages. These results identify another function of GHRH in promoting skin tissue wound healing and repair. Our findings suggest that GHRH may have clinical utility for augmenting healing of skin wounds resulting from trauma, surgery, or disease.

  10. Endogenous growth hormone (GH)-releasing hormone is required for GH responses to pharmacological stimuli.

    PubMed Central

    Jaffe, C A; DeMott-Friberg, R; Barkan, A L

    1996-01-01

    The roles of hypothalamic growth hormone-releasing hormone (GHRH) and of somatostatin (SRIF) in pharmacologically stimulated growth hormone (GH) secretion in humans are unclear. GH responses could result either from GHRH release or from acute decline in SRIF secretion. To assess directly the role of endogenous GHRH in human GH secretion, we have used a competitive GHRH antagonist, (N-Ac-Tyr1,D-Arg2)GHRH(1-29)NH2 (GHRH-Ant), which we have previously shown is able to block the GH response to GHRH. We first tested whether an acute decline in SRIF, independent of GHRH action, would release GH. Pretreatment with GHRH-Ant abolished the GH response to exogenous GHRH (0.33 microgram/kg i.v.) but did not modify the GH rise after termination of an SRIF infusion. We then investigated the role of endogenous GHRH in the GH responses to pharmacologic stimuli of GH release. The GH responses to arginine (30 g i.v. over 30 min), L-dopa (0.5 g orally), insulin hypoglycemia (0.1 U/Kg i.v.), clonidine (0.25 mg orally), or pyridostigmine (60 mg orally) were measured in healthy young men after pretreatment with either saline of GHRH-Ant 400 microgram/kg i.v. In every case, GH release was significantly suppressed by GHRH-Ant. We conclude that endogenous GHRH is required for the GH response to each of these pharmacologic stimuli. Acute release of hypothalamic GHRH may be a common mechanism by which these compounds mediate GH secretion. PMID:8613546

  11. Direct and in vitro observation of growth hormone receptor molecules in A549 human lung epithelial cells by nanodiamond labeling

    NASA Astrophysics Data System (ADS)

    Cheng, C.-Y.; Perevedentseva, E.; Tu, J.-S.; Chung, P.-H.; Cheng, C.-L.; Liu, K.-K.; Chao, J.-I.; Chen, P.-H.; Chang, C.-C.

    2007-04-01

    This letter presents direct observation of growth hormone receptor in one single cancer cell using nanodiamond-growth hormone complex as a specific probe. The interaction of surface growth hormone receptor of A549 human lung epithelial cells with growth hormone was observed using nanodiamond's unique spectroscopic signal via confocal Raman mapping. The growth hormone molecules were covalent conjugated to 100nm diameter carboxylated nanodiamonds, which can be recognized specifically by the growth hormone receptors of A549 cell. The Raman spectroscopic signal of diamond provides direct and in vitro observation of growth hormone receptors in physiology condition in a single cell level.

  12. Effect of 2 days of intensive resistance training on appetite-related hormone and anabolic hormone responses.

    PubMed

    Goto, Kazushige; Shioda, Kohei; Uchida, Sunao

    2013-03-01

    This study was designed to determine endocrine responses during 2 days of strenuous resistance training. Ten healthy men performed resistance training twice a day for two successive days to induce acute fatigue (excessive physical stress). The resistance training consisted of four exercises for the lower body in the morning and seven exercises for the upper body in the afternoon. Maximal isometric and isokinetic strengths were measured from day 1 (before the training period) to day 3 (after the training period). Fasting blood samples were taken on days 1-3. Maximal isometric and isokinetic strengths significantly decreased with two successive days of training (P<0·05), with significant increases in serum creatine phosphokinase and myoglobin concentrations (P<0·05). Significant reductions in the fasting concentrations of serum insulin-like growth factor-1, free testosterone, insulin and high-molecular-weight adiponectin were observed on day 3 (P<0·05), whereas there were no changes in the serum cortisol concentration or the free testosterone/cortisol ratio. Plasma active ghrelin and serum leptin concentrations decreased by -20·7 ± 2·8% and -29·6 ± 4·1%, respectively (P<0·05). Two days strenuous resistance training significantly affects the profiles of anabolic hormone and endocrine regulators of appetite and energy balance, such as ghrelin and leptin. The present findings suggest that decreased ghrelin and leptin concentrations might reflect excessive physical stress and may be early signs of accumulated fatigue. © 2012 The Authors Clinical Physiology and Functional Imaging © 2012 Scandinavian Society of Clinical Physiology and Nuclear Medicine.

  13. Effects of Plant Growth Hormones on Mucor indicus Growth and Chitosan and Ethanol Production.

    PubMed

    Safaei, Zahra; Karimi, Keikhosro; Golkar, Poorandokht; Zamani, Akram

    2015-07-22

    The objective of this study was to investigate the effects of indole-3-acetic acid (IAA) and kinetin (KIN) on Mucor indicus growth, cell wall composition, and ethanol production. A semi-synthetic medium, supplemented with 0-5 mg/L hormones, was used for the cultivations (at 32 °C for 48 h). By addition of 1 mg/L of each hormone, the biomass and ethanol yields were increased and decreased, respectively. At higher levels, however, an inverse trend was observed. The glucosamine fraction of the cell wall, as a representative for chitosan, followed similar but sharper changes, compared to the biomass. The highest level was 221% higher than that obtained without hormones. The sum of glucosamine and N-acetyl glucosamine (chitin and chitosan) was noticeably enhanced in the presence of the hormones. Increase of chitosan was accompanied by a decrease in the phosphate content, with the lowest phosphate (0.01 g/g cell wall) being obtained when the chitosan was at the maximum (0.45 g/g cell wall). In conclusion, IAA and KIN significantly enhanced the M. indicus growth and chitosan production, while at the same time decreasing the ethanol yield to some extent. This study shows that plant growth hormones have a high potential for the improvement of fungal chitosan production by M. indicus.

  14. Effects of Plant Growth Hormones on Mucor indicus Growth and Chitosan and Ethanol Production

    PubMed Central

    Safaei, Zahra; Karimi, Keikhosro; Golkar, Poorandokht; Zamani, Akram

    2015-01-01

    The objective of this study was to investigate the effects of indole-3-acetic acid (IAA) and kinetin (KIN) on Mucor indicus growth, cell wall composition, and ethanol production. A semi-synthetic medium, supplemented with 0–5 mg/L hormones, was used for the cultivations (at 32 °C for 48 h). By addition of 1 mg/L of each hormone, the biomass and ethanol yields were increased and decreased, respectively. At higher levels, however, an inverse trend was observed. The glucosamine fraction of the cell wall, as a representative for chitosan, followed similar but sharper changes, compared to the biomass. The highest level was 221% higher than that obtained without hormones. The sum of glucosamine and N-acetyl glucosamine (chitin and chitosan) was noticeably enhanced in the presence of the hormones. Increase of chitosan was accompanied by a decrease in the phosphate content, with the lowest phosphate (0.01 g/g cell wall) being obtained when the chitosan was at the maximum (0.45 g/g cell wall). In conclusion, IAA and KIN significantly enhanced the M. indicus growth and chitosan production, while at the same time decreasing the ethanol yield to some extent. This study shows that plant growth hormones have a high potential for the improvement of fungal chitosan production by M. indicus. PMID:26204839

  15. Orthopedic complications related to growth hormone therapy in a pediatric population.

    PubMed

    Haidar, Rachid K; Nasrallah, Mona P; Der-Boghossian, Asdghig H; Ghanem, Ismat B

    2011-01-01

    Since the introduction of recombinant growth hormone, its use has diversified and multiplied. Growth hormone is now the recommended therapy for a growing indication to all forms of short stature because of its direct and indirect role on bone growth. Hereby, we discuss the orthopedic complications associated with growth hormone treatment in pediatric patients. These complications include carpal tunnel syndrome, Legg-Calve-Perthes' disease, scoliosis, and slipped capital femoral epiphysis. Their incidence rates recorded in several growth hormone therapy-related pharmacovigilance studies will be summarized in this study with focused discussion on their occurrence in the pediatric and adolescent age groups. The pathogenesis of these complications is also reviewed.

  16. Effect of prolactin and bromocriptine on growth of transplanted hormone-dependent mouse mammary tumours.

    PubMed Central

    Briand, P.; Thorpe, S. M.; Daehnfeldt, J. L.

    1977-01-01

    Administration of ovine prolactin alone supported growth of hormone-dependent GR mouse mammary tumours. Growth of hormone-independent tumours was not stimulated. Furthermore, administration of bromocriptine, a compound that inhibits release of prolactin from the pituitary gland, was shown to inhibit the growth of hormone-dependent tumours in animals receiving treatment with progesterone + oestrone. Administration of prolactin or bromocriptine to mice bearing tumours that grew independently of progesterone + oestrone treatment had no influence on tumour growth. We conclude that direct as well as indirect evidence has been found for the involvement of prolactin in the growth of transplanted, hormone-dependent GR mouse mammary tumours. PMID:577471

  17. Studies on the bioassayable growth hormone-like activity of plasma

    NASA Technical Reports Server (NTRS)

    Ellis, S.; Vodian, M. A.; Grindeland, R. E.

    1978-01-01

    Evidence supporting the existence of bioassayable growth hormone-like activity in blood plasma distinct from the growth hormone measurable by radioimmunoassay and from somatomedin is presented. Tibial assays of the growth-hormone-like activity of injected, concentrated normal human and rat plasma in hypophysectomized rats reveal 200- and 50-fold activity excesses, respectively, with respect to the amount of growth hormone detected by radioimmunoassay. The origin of this bioassayable plasma hormone has been localized to the region of the pituitary, the origin of growth hormone, a distribution not followed by somatomedin C. Purification of the bioassayable agent indicates that is has a molecular weight of between 60,000 and 80,000, in contrast to that of growth hormone (20,000), and that the bioassayable activity is distinct from that of somatomedin C. Growth hormone-like activity detected in Cohn fraction IV as well as plasma activity, are found to be collectable on Dowex 50 resin, in contrast to somatomedin C and nonsuppressible insulin-like activity. The formation of bioassayable growth hormone-activity agents from radioimmunoassayable growth hormone and directly in the pituitary is suggested.

  18. Central effects of growth hormone-releasing hexapeptide (GHRP-6) on growth hormone release are inhibited by central somatostatin action.

    PubMed

    Fairhall, K M; Mynett, A; Robinson, I C

    1995-03-01

    Growth hormone (GH) release is stimulated by a variety of synthetic secretagogues, of which growth hormone-releasing hexapeptide (GHRP-6) has been most thoroughly studied; it is thought to have actions at both pituitary and hypothalamic sites. To evaluate the central actions of this peptide, we have studied GH release in response to direct i.c.v. injections in anaesthetized guinea pigs. GHRP-6 (0.04-1 microgram) stimulated GH release > 10-fold 30-40 min after i.c.v. injection. The same GH response required > 20-fold more GHRP-6 when given by i.v. injection. GH release could also be elicited by a non-peptide GHRP analogue (L-692,585, 1 microgram i.c.v.), whereas a growth hormone-releasing factor (GRF) analogue (human GRF27Nle(1-29)NH2, 2 micrograms, i.c.v.) was ineffective. A long acting somatostatin analogue (Sandostatin, SMS 201-995, 10 micrograms i.c.v.) (SMS) given 20 min before 200 ng GHRP-6 blocked GH release. This was unlikely to be due to a direct effect of SMS leaking out to the pituitary, since central SMS injections did not affect basal GH release, nor did they block GH release in response to i.v. GRF injections. We conclude that the hypothalamus is a major target for GHRP-6 in vivo. Since the GH release induced by central GHRP-6 injections can be inhibited by a central action of somatostatin, and other data indicate that GHRP-6 activates GRF neurones, we suggest that somatostatin may block this activation via receptors known to be located on or near the GRF cells themselves. Somatostatin may therefore be a functional antagonist of GHRP-6 acting centrally, as well as at the pituitary gland.

  19. The Role of Growth Hormone and Insulin-Like Growth Factor 1 in Human Breast Cancer Growth in a Mouse Xenograft Model

    DTIC Science & Technology

    1998-10-01

    The purpose of this research is to determine the role of human growth hormone (hGH) and insulin-like growth factor 1(IGF-1) in the development of an...progression of tumor growth in the animal model. In addition, growth hormone may be semi-inhibitory to growth for tumors dependent upon estrogen

  20. The Role of Growth Hormone and Insulin-Like Growth Factor-1 in Human Breast Cancer Growth in a Mouse Xenograft Model

    DTIC Science & Technology

    1999-10-01

    The purpose of this research is to determine the role of human growth hormone (hGH) and insulin-like growth factor 1 (IGF- 1) in the development of...the progression of tumor growth in the animal model. In addition growth hormone may be semi-inhibitory to growth for tumors dependent upon estrogen

  1. Sexual hormones modulate compensatory renal growth and function.

    PubMed

    Azurmendi, Pablo J; Oddo, Elisabet M; Toledo, Jorge E; Martin, Rodolfo S; Ibarra, Fernando R; Arrizurieta, Elvira E

    2013-01-01

    The role played by sexual hormones and vasoactive substances in the compensatory renal growth (CRG) that follows uninephrectomy (uNx) is still controversial. Intact and gonadectomized adult Wistar rats of both sexes, with and without uNx, performed at 90 days age, were studied at age 150 days. Daily urine volume, electrolyte excretion and kallikrein activity (UKa) were determined. Afterwards, glomerular filtration rate and blood pressure were measured, the kidneys weighed and DNA, protein and RNA studied to determine nuclei content and cell size. When the remnant kidney weight at age 150 days was compared with the weight of the kidney removed at the time of uNx, male uNx rats showed the greatest CRG (50%) while growth in the other uNx groups was 25%, 15% and 19% in orchidectomized, female and ovariectomized rats, respectively. The small CRG observed in the uNx female rats was accompanied by the lowest glomerular filtration value, 0.56 ± 0.02 ml/ min/g kwt compared, with the other uNx groups, p < 0.05. Cell size (protein or RNA/DNA) was similar for all the groups except for uNx orchidectomized rats. In this group the cytoplasmatic protein or RNA content was lower than in the other groups while DNA (nuclei content) was similar. Some degree of hyperplasia was determined by DNA content in the uNx groups. Male sexual hormones positively influenced CRG and its absence modulated cell size. Female sexual hormones, instead, did not appear to stimulate CRG. The kallikrein kinin system may not be involved in CRG.

  2. Growth hormone and exercise tolerance in patients with cystic fibrosis.

    PubMed

    Hütler, Matthias; Beneke, Ralph

    2004-01-01

    Cystic fibrosis (CF) is a life-limiting inherited disorder characterised by pulmonary disease, pancreatic dysfunction and symptoms of malnutrition that are all interrelated with low exercise capacity and poor survival rate. Therapy with growth hormone (GH) may improve the reduced dimensional and functional capacity associated with poor nutritional status and catabolism and therefore improve exercise tolerance, quality of life and survival rate in patients with CF. The literature about GH treatment and its effect on exercise tolerance are rather limited, not always consistent and methodological concerns restrict further analysis. GH treatment may have beneficial effects on both growth and exercise tolerance without serious complications in prepubertal children with CF. The observed dimensional changes of the muscular, cardiovascular and pulmonary system seem to improve aerobic exercise capacity and respiratory and peripheral muscle strength. The physiological background of the observed changes is not yet fully understood, therefore, larger-scale studies with an optimised design are required.

  3. Effects of growth hormone on female reproductive organs.

    PubMed

    Kaiser, G G; Sinowatz, F; Palma, G A

    2001-10-01

    During the last decade many experiments have been performed to study the effects of growth hormone (GH, somatotropin) on reproductive functions. Most of the studies found only slight or no effects of GH treatment, both on the oestrous cycle and on gonadotropin, progesterone. or oestrogen serum levels. In GH-treated animals, elevated levels of insulin-like growth factor I and GH in the serum could be correlated with an increased number of small (< 5 mm in diameter) ovarian follicles, possibly as a consequence of a reduction of apoptosis and follicular atresia. There is still controversy over the effects of GH on in vivo and in vitro embryo production and on the gestation period. Recent studies produced some evidence that GH-receptor is expressed in ovarian tissue, implying a direct role for GH in the ovary.

  4. Extrapituitary growth hormone in the chicken reproductive system.

    PubMed

    Luna, Maricela; Martínez-Moreno, Carlos G; Ahumada-Solórzano, Marisela S; Harvey, Steve; Carranza, Martha; Arámburo, Carlos

    2014-07-01

    Increasing evidence shows that growth hormone (GH) expression is not limited to the pituitary, as it can be produced in many other tissues. It is known that growth hormone (GH) plays a role in the control of reproductive tract development. Acting as an endocrine, paracrine and/or autocrine regulator, GH influences proliferation, differentiation and function of reproductive tissues. In this review we substantiate the local expression of GH mRNA and GH protein, as well as the GH receptor (GHR) in both male and female reproductive tract, mainly in the chicken. Locally expressed GH was found to be heterogeneous, with a 17 kDa variant being predominant. GH secretagogues, such as GHRH and TRH co-localize with GH expression in the chicken testis and induce GH release. In the ovarian follicular granulosa cells, GH and GHR are co-expressed and stimulate progesterone production, which was neutralized by a specific GH antibody. Both testicular and follicular cells in primary cultures were able to synthesize and release GH to the culture medium. We also characterized GH and GH mRNA expression in the hen's oviduct and showed that it had 99.6% sequence identity with pituitary GH. Data suggest local reproductive GH may have important autocrine/paracrine effects.

  5. Prader-Willi syndrome and growth hormone deficiency.

    PubMed

    Aycan, Zehra; Baş, Veysel Nijat

    2014-01-01

    Prader-Willi syndrome (PWS) is a rare multisystem genetic disorder demonstrating great variability with changing clinical features during patient's life. It is characterized by severe hypotonia with poor sucking and feeding difficulties in early infancy, followed by excessive eating and gradual development of morbid obesity in later infancy or early childhood. The phenotype is most probably due to hypothalamic dysfunction which is also responsible for growth hormone (GH) and thyroid-stimulating hormone (TSH) deficiencies, central adrenal insufficiency and hypogonadism. The multidimensional problems of patients with PWS can be managed with multidisciplinary approach. Reduced GH secretion, low peak GH response to stimulation, decreased spontaneous GH secretion and low serum IGF-1 levels in PWS patients have been documented in many studies. GH therapy has multiple beneficial effects on growth and body composition, motor and mental development in PWS patients. The recommended dosage for GH is 0.5-1 mg/m2/day. GH therapy should not be started in the presence of obstructive sleep apnea syndrome, adenotonsillar hypertrophy, severe obesity and diabetes mellitus. GH treatment should be considered for patients with genetically confirmed PWS in conjunction with dietary, environmental and life-style measures.

  6. Production of recombinant mink growth hormone in E. coli.

    PubMed

    Sereikaite, Jolanta; Statkute, Alina; Morkunas, Mindaugas; Radzevicius, Kostas; Borromeo, Vitaliano; Secchi, Camillo; Bumelis, Vladas-Algirdas

    2007-02-01

    Escherichia coli cells expressing mink (Mustela vison) growth hormone were grown in a batch fermentation process. The expression level was estimated to be 27% of the total cellular protein after 3 h of induction with 1 mM isopropyl beta-D-thiogalactoside (IPTG). If the expression of mink growth hormone (mGH) was induced with 0.2 mM IPTG, the concentration of target protein was slightly lower and was found to be 23% at the same time after induction. mGH expressed as inclusion bodies was solubilized in 8 M urea and renatured by dilution protocol at a protein concentration of 1.4-2.1 mg/ml in the presence of glutathione pair in a final concentration of 11.3 mM. [GSH]/[GSSG] ratio equal to 2/1 was used. Two-step purification process comprising of ion-exchange chromatography on Q-Sepharose and hydrophobic chromatography on Phenyl-Sepharose was developed. Some 25-30 mg of highly purified and biologically active mGH was obtained from 4 g of biomass. The method presented in this study allows producing large quantities of mGH and considering initiation of scientific investigation on mGH effect on mink in vivo and availability in fur industry.

  7. Harmonization of growth hormone measurement results: the empirical approach.

    PubMed

    Ross, H A; Lentjes, E W G M; Menheere, P M M; Sweep, C G J

    2014-05-15

    Growth hormone (hGH) is a measurand belonging to ISO category 4, indicating intrinsic unavailability of a reference measurement procedure and primary standard material. Large between-method differences have been raising confusion, especially in the interpretation of results of stimulation tests for exclusion of juvenile growth hormone deficiency. Within the framework of the external quality assessment scheme (EQAS) of the SKML (Dutch Foundation for Quality Assessment in Clinical Laboratories), attempts to reduce between-method variation of hGH measurements have been made, starting in 1994 with an inter-laboratory comparison of 9 different immunoassays by using a panel of sera and standard materials available at that time. Methods appeared to differ from each other largely in a systematic, sample-independent manner. These systematic differences are reflected in the hGH measurement results obtained in commutable sera. A commutable serum pool was introduced as a consensus reference material, permitting correction of each method's results to a common scale. Pair wise comparisons ("twin studies") were carried out to investigate and corroborate the effectiveness of this material for harmonization. A significant reduction of the between-laboratory coefficient (CV) of variation from 22 to 9.0% was attained.

  8. Baraitser and Winter syndrome with growth hormone deficiency

    PubMed Central

    Chentli, Farida; Zellagui, Hadjer

    2014-01-01

    Baraitser–Winter syndrome (BWS), first reported in 1988, is apparently due to genetic abnormalities that are still not well-defined, although many gene abnormalities are already discovered and de novo missense changes in the cytoplasmic actin-encoding genes (called ACTB and ACTG1) have been recently discovered. The syndrome combines facial and cerebral malformations. Facial malformations totally or partially present in the same patient are: Iris coloboma, bilateral ptosis, hypertelorism, broad nasal bridge, and prominent epicanthic folds. The various brain malformations are probably responsible for growth and mental retardation. To the best of our knowledge, the syndrome is very rare as few cases have been reported so far. Our aim was to describe a child with a phenotype that looks like BWS with proved partial growth hormone (GH) deficiency which was not reported before. A girl aged 7-year-old of consanguineous parents was referred for short stature and mental retardation. Clinical examination showed dwarfism and a delay in her mental development. Other clinical features included: Strabismus, epicanthic folds, broad nasal bridge, and brain anomalies such as lissencephaly, bilateral hygroma, and cerebral atrophy. Hormonal assessment showed partial GH deficiency without other endocrine disorders. Our case looks exactly like BWS. However, apart from facial and cerebral abnormalities, there is a partial GH deficiency which can explain the harmonious short stature. This case seems worth to be reported as it adds GH deficiency to the very rare syndrome. PMID:25624931

  9. Growth hormone treatment of infants with chronic kidney disease: requirement, efficacy, and safety.

    PubMed

    Haffner, Dieter; Fischer, Dagmar-Christiane

    2009-06-01

    Growth failure is still a challenge in infants suffering from chronic kidney disease (CKD). Persistent growth failure is associated with the excessive mortality rate seen in these patients and markedly hampers later psychosocial integration. Infancy is an extremely sensitive period of growth, since physiological growth rates are several times higher than in later life. Growth failure in infants with CKD has multiple reasons, originating preferentially from malnutrition and, to a lesser extent, from water and electrolyte losses, metabolic acidosis, anemia, and renal osteodystrophy. Although, recombinant human growth hormone (rhGH) has been proven to be safe and effective for treatment of uremic growth failure in later childhood, its usage has not been adequately investigated in infants. Mencarelli et al. (Pediatric Nephrology 24:1039-1046, 2009) reported on their retrospective analysis of the longitudinal growth of 27 infants with early onset CKD that were receiving either standard therapy or additional rhGH treatment. Although their results were encouraging with respect to a sustained catch-up growth in rhGH-treated children, this issue has to be further addressed in prospective randomized controlled trials. In these trials special emphasis has to be given to the safety of this treatment modality, since rhGH might induce insulin resistance and glucose intolerance, especially in infants on high caloric intake and peritoneal dialysis.

  10. Generalized resistance to thyroid hormone associated with a mutation in the ligand-binding domain of the human thyroid hormone receptor. beta

    SciTech Connect

    Sakurai, A.; Takeda, K.; Ain, K.; Ceccarelli, P.; Nakai, A.; Seino, S.; Bell, G.I.; Refetoff, S.; DeGroot, L.J. )

    1989-11-01

    The syndrome of generalized resistance to thyroid hormone is characterized by elevated circulating levels of thyroid hormone in the presence of an overall eumetabolic state and failure to respond normally to triiodothyronine. The authors have evaluated a family with inherited generalized resistance to thyroid hormone for abnormalities in the thyroid hormone nuclear receptors. A single guanine {yields} cytosine replacement in the codon for amino acid 340 resulted in a glycine {yields} arginine substitution in the hormone-binding domain of one of two alleles of the patient's thyroid hormone nuclear receptor {beta} gene. In vitro translation products of this mutant human thyroid hormone nuclear receptor {beta} gene did not bind triiodothyronine. Thus, generalized resistance to thyroid hormone can result from expression of an abnormal thyroid hormone nuclear receptor molecule.

  11. Anti-idiotypic antibody: A new strategy for the development of a growth hormone receptor antagonist.

    PubMed

    Lan, Hainan; Zheng, Xin; Khan, Muhammad Akram; Li, Steven

    2015-11-01

    In general, traditional growth hormone receptor antagonist can be divided into two major classes: growth hormone (GH) analogues and anti-growth hormone receptor (GHR) antibodies. Herein, we tried to explore a new class of growth hormone receptor (GHR) antagonist that may have potential advantages over the traditional antagonists. For this, we developed a monoclonal anti-idiotypic antibody growth hormone, termed CG-86. A series of experiments were conducted to characterize and evaluate this antibody, and the results from a competitive receptor-binding assay, Enzyme Linked Immunosorbent Assays (ELISA) and epitope mapping demonstrate that CG-86 behaved as a typical Ab2β. Next, we examined its antagonistic activity using in vitro cell models, and the results showed that CG-86 could effectively inhibit growth hormone receptor-mediated signalling and effectively inhibit growth hormone-induced Ba/F3-GHR638 proliferation. In summary, these studies show that an anti-idiotypic antibody (CG-86) has promise as a novel growth hormone receptor antagonist. Furthermore, the current findings also suggest that anti-idiotypic antibody may represent a novel strategy to produce a new class of growth hormone receptor antagonist, and this strategy may be applied with other cytokines or growth factors. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Effect of growth hormone deficiency on brain structure, motor function and cognition.

    PubMed

    Webb, Emma A; O'Reilly, Michelle A; Clayden, Jonathan D; Seunarine, Kiran K; Chong, Wui K; Dale, Naomi; Salt, Alison; Clark, Chris A; Dattani, Mehul T

    2012-01-01

    The growth hormone-insulin-like growth factor-1 axis plays a role in normal brain growth but little is known of the effect of growth hormone deficiency on brain structure. Children with isolated growth hormone deficiency (peak growth hormone <6.7 µg/l) and idiopathic short stature (peak growth hormone >10 µg/l) underwent cognitive assessment, diffusion tensor imaging and volumetric magnetic resonance imaging prior to commencing growth hormone treatment. Total brain, corpus callosal, hippocampal, thalamic and basal ganglia volumes were determined using Freesurfer. Fractional anisotropy (a marker of white matter structural integrity) images were aligned and tract-based spatial statistics performed. Fifteen children (mean 8.8 years of age) with isolated growth hormone deficiency [peak growth hormone <6.7 µg/l (mean 3.5 µg/l)] and 14 controls (mean 8.4 years of age) with idiopathic short stature [peak growth hormone >10 µg/l (mean 15 µg/l) and normal growth rate] were recruited. Compared with controls, children with isolated growth hormone deficiency had lower Full-Scale IQ (P < 0.01), Verbal Comprehension Index (P < 0.01), Processing Speed Index (P < 0.05) and Movement-Assessment Battery for Children (P < 0.008) scores. Verbal Comprehension Index scores correlated significantly with insulin-like growth factor-1 (P < 0.03) and insulin-like growth factor binding protein-3 (P < 0.02) standard deviation scores in isolated growth hormone deficiency. The splenium of the corpus callosum, left globus pallidum, thalamus and hippocampus (P < 0.01) were significantly smaller; and corticospinal tract (bilaterally; P < 0.045, P < 0.05) and corpus callosum (P < 0.05) fractional anisotropy were significantly lower in the isolated growth hormone deficiency group. Basal ganglia volumes and bilateral corticospinal tract fractional anisotropy correlated significantly with Movement-Assessment Battery for Children scores, and

  13. Impact of hormonal crosstalk on plant resistance and fitness under multi-attacker conditions

    PubMed Central

    Vos, Irene A.; Moritz, Liselotte; Pieterse, Corné M. J.; Van Wees, Saskia C. M.

    2015-01-01

    The hormone salicylic acid (SA) generally induces plant defenses against biotrophic pathogens. Jasmonic acid (JA) and its oxylipin derivatives together with ethylene (ET) are generally important hormonal regulators of induced plant defenses against necrotrophic pathogens, whereas JAs together with abscisic acid (ABA) are implicated in induced plant defenses against herbivorous insects. Hormonal crosstalk between the different plant defense pathways has often been hypothesized to be a cost-saving strategy that has evolved as a means of the plant to reduce allocation costs by repression of unnecessary defenses, thereby minimizing trade-offs between plant defense and growth. However, proof for this hypothesis has not been demonstrated yet. In this study the impact of hormonal crosstalk on disease resistance and fitness of Arabidopsis thaliana when under multi-species attack was investigated. Induction of SA- or JA/ABA-dependent defense responses by the biotrophic pathogen Hyaloperonospora arabidopsidis or the herbivorous insect Pieris rapae, respectively, was shown to reduce the level of induced JA/ET-dependent defense against subsequent infection with the necrotrophic pathogen Botrytis cinerea. However, despite the enhanced susceptibility to this second attacker, no additional long-term negative effects were observed on plant fitness when plants had been challenged by multiple attackers. Similarly, when plants were grown in dense competition stands to enlarge fitness effects of induced defenses, treatment with a combination of SA and MeJA did not cause additional negative effects on plant fitness in comparison to the single MeJA treatment. Together, these data support the notion that hormonal crosstalk in plants during multi-attacker interactions allows plants to prioritize their defenses, while limiting the fitness costs associated with induction of defenses. PMID:26347758

  14. Potentiation of cytotoxic chemotherapy by growth hormone-releasing hormone agonists

    PubMed Central

    Jaszberenyi, Miklos; Rick, Ferenc G.; Popovics, Petra; Block, Norman L.; Zarandi, Marta; Cai, Ren-Zhi; Vidaurre, Irving; Szalontay, Luca; Jayakumar, Arumugam R.; Schally, Andrew V.

    2014-01-01

    The dismal prognosis of malignant brain tumors drives the development of new treatment modalities. In view of the multiple activities of growth hormone-releasing hormone (GHRH), we hypothesized that pretreatment with a GHRH agonist, JI-34, might increase the susceptibility of U-87 MG glioblastoma multiforme (GBM) cells to subsequent treatment with the cytotoxic drug, doxorubicin (DOX). This concept was corroborated by our findings, in vivo, showing that the combination of the GHRH agonist, JI-34, and DOX inhibited the growth of GBM tumors, transplanted into nude mice, more than DOX alone. In vitro, the pretreatment of GBM cells with JI-34 potentiated inhibitory effects of DOX on cell proliferation, diminished cell size and viability, and promoted apoptotic processes, as shown by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide proliferation assay, ApoLive-Glo multiplex assay, and cell volumetric assay. Proteomic studies further revealed that the pretreatment with GHRH agonist evoked differentiation decreasing the expression of the neuroectodermal stem cell antigen, nestin, and up-regulating the glial maturation marker, GFAP. The GHRH agonist also reduced the release of humoral regulators of glial growth, such as FGF basic and TGFβ. Proteomic and gene-expression (RT-PCR) studies confirmed the strong proapoptotic activity (increase in p53, decrease in v-myc and Bcl-2) and anti-invasive potential (decrease in integrin α3) of the combination of GHRH agonist and DOX. These findings indicate that the GHRH agonists can potentiate the anticancer activity of the traditional chemotherapeutic drug, DOX, by multiple mechanisms including the induction of differentiation of cancer cells. PMID:24379381

  15. Cognitive and Adaptive Advantages of Growth Hormone Treatment in Children with Prader-Willi Syndrome

    ERIC Educational Resources Information Center

    Dykens, Elisabeth M.; Roof, Elizabeth; Hunt-Hawkins, Hailee

    2017-01-01

    Background: People with Prader-Willi syndrome (PWS) typically have mild to moderate intellectual deficits, compulsivity, hyperphagia, obesity, and growth hormone deficiencies. Growth hormone treatment (GHT) in PWS has well-established salutatory effects on linear growth and body composition, yet cognitive benefits of GHT, seen in other patient…

  16. Cognitive and Adaptive Advantages of Growth Hormone Treatment in Children with Prader-Willi Syndrome

    ERIC Educational Resources Information Center

    Dykens, Elisabeth M.; Roof, Elizabeth; Hunt-Hawkins, Hailee

    2017-01-01

    Background: People with Prader-Willi syndrome (PWS) typically have mild to moderate intellectual deficits, compulsivity, hyperphagia, obesity, and growth hormone deficiencies. Growth hormone treatment (GHT) in PWS has well-established salutatory effects on linear growth and body composition, yet cognitive benefits of GHT, seen in other patient…

  17. Diminished growth hormone secretion in blind males after L-dopa stimulation.

    PubMed

    Fatranská, M; Jurcovicová, J; Németh, S; Vigas, M

    1988-12-01

    Growth hormone secretion after L-dopa administration (1000 mg p.o.) was investigated in young adult normal and blind volunteers. The average increment of plasma growth hormone after L-dopa stimulation in the blind was below the criterion for a positive response (less than 5 ng ml-1). The control volunteers showed normal response. After L-dopa stimulation there was a significantly diminished growth hormone response in the young adult blind compared to control volunteers.

  18. Growth hormone excess and the effect of octreotide in cats with diabetes mellitus.

    PubMed

    Slingerland, L I; Voorhout, G; Rijnberk, A; Kooistra, H S

    2008-11-01

    In this prospective study 16 cats with diabetes mellitus were examined for concurrent acromegaly by measuring plasma growth hormone (GH) and insulin-like growth factor-I concentrations, and magnetic resonance imaging (MRI) of the pituitary fossa. Additionally, the effects of octreotide administration on the plasma concentrations of glucose, GH, alpha-melanocyte-stimulating hormone (alpha-MSH), adrenocorticotrophic hormone (ACTH), and cortisol were measured. Five cats were diagnosed with hypersomatotropism. The pituitary was enlarged in these 5 cats and in 2 other cats. Six cats that required a maximum lente insulin dosage >or=1.5 IU/kg body weight per injection had pituitary enlargement and 5 of these cats had acromegaly. Plasma concentrations of GH, ACTH, and cortisol decreased significantly after single intravenous administration of the somatostatin analogue octreotide in the acromegalic cats. The effect on GH concentrations was more pronounced in some of the acromegalic cats than in others. In the non-acromegalic cats only ACTH concentrations decreased significantly. In both groups plasma glucose concentrations increased slightly but significantly, whereas alpha-MSH concentrations were not significantly affected. In conclusion, the incidence of hypersomatotropism with concomitant pituitary enlargement appears to be high among diabetic cats with severe insulin resistance. Some of these cats responded to octreotide administration with a pronounced decrease in the plasma GH concentration, which suggests that octreotide administration could be used as a pre-entry test for treatment with somatostatin analogues.

  19. A Critical Appraisal of Growth Hormone Therapy in Growth Hormone Deficiency and Turner Syndrome Patients in Turkey

    PubMed Central

    Yavaş Abalı, Zehra; Darendeliler, Feyza; Neyzi, Olcay

    2016-01-01

    Early detection of abnormal growth, identification of the underlying cause, and appropriate treatment of the medical condition is an important issue for children with short stature. Growth hormone (GH) therapy is widely used in GH-deficient children and also in non-GH-deficient short stature cases who have findings conforming to certain indications. Efficacy of GH therapy has been shown in a multitude of short- and long-term studies. Age at onset of GH therapy is the most important factor for a successful treatment outcome. Optimal dosing is also essential. The aim of this review was to focus on challenges in the early diagnosis and appropriate management of short stature due to GH deficiency (GHD) and Turner syndrome. These are the most frequent two indications for GH therapy in Turkey approved by the Ministry of Health for coverage by the national insurance system. PMID:27354120

  20. Neither bovine somatotropin nor growth hormone-releasing factor alters expression of thyroid hormone receptors in liver and mammary tissues.

    PubMed

    Capuco, A V; Binelli, M; Tucker, H A

    2011-10-01

    Physiological effects of thyroid hormones are mediated primarily by binding of triiodothyronine to specific nuclear receptors. Organ-specific changes in production of triiodothyronine from its prohormone, thyroxine, have been hypothesized to target the action of thyroid hormones on the mammary gland and play a role in mediating or augmenting a galactopoietic response to bovine somatotropin (bST). Additionally, tissue responsiveness to thyroid hormones may be altered by changes in the number or affinity of nuclear receptors for thyroid hormones. In the present study, effects of bST and bovine growth hormone-releasing factor (bGRF) on thyroid hormone receptors in liver and mammary gland were studied. Lactating Holstein cows received continuous infusions of bST or bGRF for 63 d or served as uninfused controls. Nuclei were isolated from harvested mammary and liver tissues and incubated with [(125)I]-triiodothyronine. Treatments did not alter the capacity or affinity of specific binding sites for triiodothyronine in liver or mammary nuclei. Evaluation of transcript abundance for thyroid hormone receptors showed that isoforms of thyroid hormone receptor or retinoid receptor (which may influence thyroid receptor action) expressed in the mammary gland were not altered by bST or bGRF treatment. Data do not support the hypothesis that administration of bST or bGRF alters sensitivity of mammary tissue by changing expression of thyroid hormone receptors.

  1. MODULATION OF GROWTH HORMONE RECEPTOR ABUNDANCE AND FUNCTION: ROLES FOR THE UBIQUITIN-PROTEASOME SYSTEM

    PubMed Central

    Frank, Stuart J.; Fuchs, Serge Y.

    2008-01-01

    Summary Growth hormone plays an important role in regulating numerous functions in vertebrates. Several pathways that negatively regulate the magnitude and duration of its signaling (including expression of tyrosine phosphatases, SOCS and PIAS proteins) are shared between signaling induced by growth hormone itself and by other cytokines. Here we overview downregulation of the growth hormone receptor as the most specific and potent mechanism of restricting cellular responses to growth hormone and analyze the role of several proteolytic systems and, specifically, ubiquitin-dependent pathways in this regulation. PMID:18586085

  2. Third party data gene data set of eutherian growth hormone genes.

    PubMed

    Premzl, Marko

    2015-12-01

    Among 146 potential coding sequences, the most comprehensive eutherian growth hormone gene data set annotated 100 complete coding sequences. The eutherian comparative genomic analysis protocol first described 5 major gene clusters of eutherian growth hormone genes. The present updated gene classification and nomenclature of eutherian growth hormone genes integrated gene annotations, phylogenetic analysis and protein molecular evolution analysis into new framework of future experiments. The curated third party data gene data set of eutherian growth hormone genes was deposited in European Nucleotide Archive under accession numbers LM644135-LM644234.

  3. Functional Changes after Recombinant Human Growth Hormone Replacement in Patients with Chronic Traumatic Brain Injury and Abnormal Growth Hormone Secretion.

    PubMed

    Mossberg, Kurt A; Durham, William J; Zgaljardic, Dennis J; Gilkison, Charles R; Danesi, Christopher P; Sheffield-Moore, Melinda; Masel, Brent E; Urban, Randall J

    2017-02-15

    We explored the effects of recombinant human growth hormone (rhGH) replacement on physical and cognitive functioning in subjects with a moderate-to-severe traumatic brain injury (TBI) with abnormal growth hormone (GH) secretion. Fifteen individuals who sustained a TBI at least 12 months prior to study enrollment were identified as having abnormal GH secretion by glucagon stimulation testing (maximum GH response less than 8 ng/mL). Peak cardiorespiratory capacity, body composition, and muscle force testing were assessed at baseline and one year after rhGH replacement. Additionally, standardized neuropsychological tests that assess memory, processing speed, and cognitive flexibility, as well as self-report inventories related to depression and fatigue, were administered at baseline and 1 year after rhGH replacement. Comparison tests were performed with proper post hoc analyses. All analyses were carried out at α < 0.05. Peak O2 consumption, peak oxygen pulse (estimate of cardiac stroke volume), and peak ventilation all significantly increased (p < 0.05). Maximal isometric and isokinetic force production were not altered. Skeletal muscle fatigue did not change but the perceptual rating of fatigue was reduced by ∼25% (p = 0.06). Cognitive performance did not change significantly over time, whereas self-reported symptoms related to depression and fatigue significantly improved. The observed changes suggest that rhGH replacement has a positive impact on cardiorespiratory fitness and a positive impact on perceptual fatigue in survivors of TBI with altered GH secretion.

  4. Efficacy and safety of growth hormone treatment in adults with growth hormone deficiency: a systematic review of studies on morbidity.

    PubMed

    van Bunderen, Christa C; van Varsseveld, Nadège C; Erfurth, Eva Marie; Ket, Johannes C F; Drent, Madeleine L

    2014-07-01

    Due to the positive effects demonstrated in randomized clinical trials on cardiovascular surrogate markers and bone metabolism, a positive effect of growth hormone (GH) treatment on clinically relevant end-points seems feasible. In this review, we discuss the long-term efficacy and safety of GH treatment in adult patients with growth hormone deficiency (GHD) with emphasis on morbidity: fatal and nonfatal cardiovascular disease (CVD) and stroke, fractures, fatal and nonfatal malignancies and recurrences, and diabetes mellitus. A positive effect of GH treatment on CVD and fracture risk could be concluded, but study design limitations have to be considered. Stroke and secondary brain tumours remained more prevalent. However, other contributing factors have to be taken into account. Regrowth and recurrences of (peri)pituitary tumours were not increased in patients with GH treatment compared to similar patients without GH treatment. All fatal and nonfatal malignancies were not more prevalent in GH-treated adults compared to the general population. However, follow-up time is still relatively short. The studies on diabetes are difficult to interpret, and more evidence is awaited. In clinical practice, a more individualized assessment seems appropriate, taking into consideration the underlying diagnosis of GHD, other treatment regimens, metabolic profile and the additional beneficial effects of GH set against the possible risks. Large and thoroughly conducted observational studies are needed and seem the only feasible way to inform the ongoing debate on health care costs, drug safety and clinical outcomes.

  5. Growth hormone-specific induction of the nuclear localization of porcine growth hormone receptor in porcine hepatocytes.

    PubMed

    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.

  6. Nutritional state modulates growth hormone-stimulated lipolysis.

    PubMed

    Bergan, Heather E; Kittilson, Jeffrey D; Sheridan, Mark A

    2015-01-01

    Growth hormone (GH) regulates several processes in vertebrates, including two metabolically disparate processes: promotion of growth, an anabolic action, and mobilization of stored lipid, a catabolic action. In this study, we used hepatocytes isolated from continuously fed and long-term (4weeks) fasted rainbow trout (Oncorhynchus mykiss) as a model to investigate the mechanistic basis of the anabolic and catabolic actions of GH. Our hypothesis was that nutritional state modulates the lipolytic responsiveness of cells by adjusting the signal transduction pathways to which GH links. GH stimulated lipolysis as measured by increased glycerol release in both a time- and concentration-related manner from cells of fasted fish but not from cells of fed fish. Expression of mRNAs that encode the lipolytic enzyme hormone-sensitive lipase (HSL), HSL1 and HSL2, also was stimulated by GH in cells from fasted fish and not in cells from fed fish. Activation of the signaling pathways that mediate GH action also was studied. In cells from fed fish, GH activated the JAK-STAT, PI3K-Akt, and ERK pathways, whereas in cells from fasted fish, GH activated the PLC/PKC and ERK pathways. In hepatocytes from fasted fish, blockade of PLC/PKC and of the ERK pathway inhibited GH-stimulated lipolysis and GH-stimulated HSL mRNA expression, whereas blockade of JAK-STAT or of the PI3K-Akt pathway had no effect on lipolysis or HSL expression stimulated by GH. These results indicate that during fasting GH activates the PLC/PKC and ERK pathways resulting in lipolysis but during periods of feeding GH activates a different complement of signal elements that do not promote lipolysis. These findings suggest that the responsiveness of cells to GH depends on the signal pathways to which GH links and helps resolve the growth-promoting and lipid catabolic actions of GH.

  7. Growth of long bones in renal failure: roles of hyperparathyroidism, growth hormone and calcitriol.

    PubMed

    Sanchez, C P; Salusky, I B; Kuizon, B D; Abdella, P; Jüppner, H; Goodman, W G

    1998-12-01

    The treatment of secondary hyperparathyroidism (2 degrees HPT) associated with chronic renal failure adversely affects skeletal growth. We assessed epiphyseal growth plate morphology by quantitative histology and measured mRNA levels for selected markers of chondrocyte proliferation and differentiation by in situ hybridization in the growth plate cartilage of subtotally nephrectomized rats with either mild or advanced 2 degrees HPT. The width of the growth plate cartilage in the proximal tibia and mRNA levels for PTH/PTHrP receptor were unchanged in rats with mild 2 degrees HPT, however, they were markedly less in nephrectomized rats with advanced 2 degrees HPT than in intact controls. Treatment with growth hormone 10 IU/kg/day increased growth plate thickness both in mild and in advanced 2 degrees HPT and raised mRNA levels for type II and type X collagen in rats with advanced 2 degrees HPT. The administration of calcitriol 50 ng/kg/day attenuated these responses in animals with advanced 2 degrees HPT. Overall, PTH/PTHrP receptor mRNA levels did not correspond to the serum levels of PTH indicating that PTH/PTHrP receptor expression is down-regulated in renal failure by a PTH-independent mechanism. Calcitriol counteracts the trophic actions of growth hormone on epiphyseal growth plate cartilage and modifies chondrocyte differentiation in vivo, and these mechanisms may contribute to disturbances in longitudinal bone growth in renal failure.

  8. Thyroid hormone and estrogen regulate exercise-induced growth hormone release.

    PubMed

    Ignacio, Daniele Leão; da S Silvestre, Diego H; Cavalcanti-de-Albuquerque, João Paulo Albuquerque; Louzada, Ruy Andrade; Carvalho, Denise P; Werneck-de-Castro, João Pedro

    2015-01-01

    Growth hormone (GH) regulates whole body metabolism, and physical exercise is the most potent stimulus to induce its secretion in humans. The mechanisms underlying GH secretion after exercise remain to be defined. The aim of this study was to elucidate the role of estrogen and pituitary type 1 deiodinase (D1) activation on exercise-induced GH secretion. Ten days after bilateral ovariectomy, animals were submitted to 20 min of treadmill exercise at 75% of maximum aerobic capacity and tissues were harvested immediately or 30 min after exercise. Non-exercised animals were used as controls. A significant increase in D1 activity occurred immediately after exercise (~60%) in sham-operated animals and GH was higher (~6-fold) 30 min after exercise. Estrogen deficient rats exhibited basal levels of GH and D1 activity comparable to those found in control rats. However, after exercise both D1 activity and serum GH levels were blunted compared to sedentary rats. To understand the potential cause-effect of D1 activation in exercise-induced GH release, we pharmacologically blocked D1 activity by propylthiouracil (PTU) injection into intact rats and submitted them to the acute exercise session. D1 inhibition blocked exercise-induced GH secretion, although basal levels were unaltered. In conclusion, estrogen deficiency impairs the induction of thyroid hormone activating enzyme D1 in the pituitary, and GH release by acute exercise. Also, acute D1 activation is essential for exercise-induced GH response.

  9. Thyroid Hormone and Estrogen Regulate Exercise-Induced Growth Hormone Release

    PubMed Central

    Ignacio, Daniele Leão; da S. Silvestre, Diego H.; Cavalcanti-de-Albuquerque, João Paulo Albuquerque; Louzada, Ruy Andrade

    2015-01-01

    Growth hormone (GH) regulates whole body metabolism, and physical exercise is the most potent stimulus to induce its secretion in humans. The mechanisms underlying GH secretion after exercise remain to be defined. The aim of this study was to elucidate the role of estrogen and pituitary type 1 deiodinase (D1) activation on exercise-induced GH secretion. Ten days after bilateral ovariectomy, animals were submitted to 20 min of treadmill exercise at 75% of maximum aerobic capacity and tissues were harvested immediately or 30 min after exercise. Non-exercised animals were used as controls. A significant increase in D1 activity occurred immediately after exercise (~60%) in sham-operated animals and GH was higher (~6-fold) 30 min after exercise. Estrogen deficient rats exhibited basal levels of GH and D1 activity comparable to those found in control rats. However, after exercise both D1 activity and serum GH levels were blunted compared to sedentary rats. To understand the potential cause-effect of D1 activation in exercise-induced GH release, we pharmacologically blocked D1 activity by propylthiouracil (PTU) injection into intact rats and submitted them to the acute exercise session. D1 inhibition blocked exercise-induced GH secretion, although basal levels were unaltered. In conclusion, estrogen deficiency impairs the induction of thyroid hormone activating enzyme D1 in the pituitary, and GH release by acute exercise. Also, acute D1 activation is essential for exercise-induced GH response. PMID:25874614

  10. Caloric Restriction Effect on Proinflammatory Cytokines, Growth Hormone, and Steroid Hormone Concentrations during Exercise in Judokas

    PubMed Central

    Abedelmalek, Salma; Chtourou, Hamdi; Souissi, Nizar; Tabka, Zouhair

    2015-01-01

    The aim of this study was to evaluate the effect of caloric restriction on the immune and hormonal responses during exercise in judo athletes. In a randomised order, 11 male judokas (age: 20.45 ± 0.51; height: 1.71 ± 0.3 m; and body weight: 75.9 ± 3.1 kg) participate in this study during a period of weight maintenance (baseline) and after 7 days of caloric restriction (CR). All subjects performed the Special Judo Fitness Test (SJFT) during the two conditions. Values for nutrient intakes were obtained from a 7 d food record kept during a period of weight maintenance and after a 7-day food restriction (−5~6 MJ/day). Our results showed that CR resulted in significant decreases in body weight (P < 0.05) and performance (P < 0.05). However, heart rate and SJFT index (P < 0.05) increase significantly during CR in comparison to baseline. Moreover, exercise leads to a significant increase in testosterone, cortisol, growth hormone (GH), leukocytes, neutrophils, TNF-α, and IL-6, in both CR and baseline conditions. Compared to baseline, TNF-α and IL-6 were significantly higher during CR condition (P < 0.05). Additionally, CR leads to an increase in cortisol and GH (P < 0.05) and a decrease in testosterone concentrations (P < 0.05). PMID:26075039

  11. The Influence of a 12-Week Conditioning Program on Growth Hormone and Somatomedin C Concentrations in Moderately Overweight Males.

    ERIC Educational Resources Information Center

    Kinard, James D.; Bazzarre, Terry L.

    The growth hormone is a lipolytic hormone and somatomedin C mediates the metabolic effects of the growth hormone in many tissues. Growth hormone plasma levels are often depressed in obese individuals, and this low plasma level has been postulated as a reason for perpetuation of excess weight. Substantial weight loss in obese subjects improves…

  12. The Influence of a 12-Week Conditioning Program on Growth Hormone and Somatomedin C Concentrations in Moderately Overweight Males.

    ERIC Educational Resources Information Center

    Kinard, James D.; Bazzarre, Terry L.

    The growth hormone is a lipolytic hormone and somatomedin C mediates the metabolic effects of the growth hormone in many tissues. Growth hormone plasma levels are often depressed in obese individuals, and this low plasma level has been postulated as a reason for perpetuation of excess weight. Substantial weight loss in obese subjects improves…

  13. Elevations in ostensibly anabolic hormones with resistance exercise enhance neither training-induced muscle hypertrophy nor strength of the elbow flexors

    PubMed Central

    West, Daniel W. D.; Burd, Nicholas A.; Tang, Jason E.; Moore, Daniel R.; Staples, Aaron W.; Holwerda, Andrew M.; Baker, Steven K.

    2010-01-01

    The aim of our study was to determine whether resistance exercise-induced elevations in endogenous hormones enhance muscle strength and hypertrophy with training. Twelve healthy young men (21.8 ± 1.2 yr, body mass index = 23.1 ± 0.6 kg/m2) trained their elbow flexors independently for 15 wk on separate days and under different hormonal milieu. In one training condition, participants performed isolated arm curl exercise designed to maintain basal hormone concentrations (low hormone, LH); in the other training condition, participants performed identical arm exercise to the LH condition followed immediately by a high volume of leg resistance exercise to elicit a large increase in endogenous hormones (high hormone, HH). There was no elevation in serum growth hormone (GH), insulin-like growth factor (IGF-1), or testosterone after the LH protocol but significant (P < 0.001) elevations in these hormones immediately and 15 and 30 min after the HH protocol. The hormone responses elicited by each respective exercise protocol late in the training period were similar to the response elicited early in the training period, indicating that a divergent postexercise hormone response was maintained over the training period. Muscle cross-sectional area (CSA) increased by 12% in LH and 10% in HH (P < 0.001) with no difference between conditions (condition × training interaction, P = 0.25). Similarly, type I (P < 0.01) and type II (P < 0.001) muscle fiber CSA increased with training with no effect of hormone elevation in the HH condition. Strength increased in both arms, but the increase was not different between the LH and HH conditions. We conclude that exposure of loaded muscle to acute exercise-induced elevations in endogenous anabolic hormones enhances neither muscle hypertrophy nor strength with resistance training in young men. PMID:19910330

  14. Elevations in ostensibly anabolic hormones with resistance exercise enhance neither training-induced muscle hypertrophy nor strength of the elbow flexors.

    PubMed

    West, Daniel W D; Burd, Nicholas A; Tang, Jason E; Moore, Daniel R; Staples, Aaron W; Holwerda, Andrew M; Baker, Steven K; Phillips, Stuart M

    2010-01-01

    The aim of our study was to determine whether resistance exercise-induced elevations in endogenous hormones enhance muscle strength and hypertrophy with training. Twelve healthy young men (21.8 +/- 1.2 yr, body mass index = 23.1 +/- 0.6 kg/m(2)) trained their elbow flexors independently for 15 wk on separate days and under different hormonal milieu. In one training condition, participants performed isolated arm curl exercise designed to maintain basal hormone concentrations (low hormone, LH); in the other training condition, participants performed identical arm exercise to the LH condition followed immediately by a high volume of leg resistance exercise to elicit a large increase in endogenous hormones (high hormone, HH). There was no elevation in serum growth hormone (GH), insulin-like growth factor (IGF-1), or testosterone after the LH protocol but significant (P < 0.001) elevations in these hormones immediately and 15 and 30 min after the HH protocol. The hormone responses elicited by each respective exercise protocol late in the training period were similar to the response elicited early in the training period, indicating that a divergent postexercise hormone response was maintained over the training period. Muscle cross-sectional area (CSA) increased by 12% in LH and 10% in HH (P < 0.001) with no difference between conditions (condition x training interaction, P = 0.25). Similarly, type I (P < 0.01) and type II (P < 0.001) muscle fiber CSA increased with training with no effect of hormone elevation in the HH condition. Strength increased in both arms, but the increase was not different between the LH and HH conditions. We conclude that exposure of loaded muscle to acute exercise-induced elevations in endogenous anabolic hormones enhances neither muscle hypertrophy nor strength with resistance training in young men.

  15. Interrelationships of Prenatal and Postnatal Growth, Hormones, Diet, and Breast Cancer

    DTIC Science & Technology

    2006-03-01

    higher albumin and sex hormone binding globulin among Chinese women could decrease the bioavailability of oestrogens . This may partially explain the...Kohen F, and Nagamani M: De- creased ovarian hormones during a soya diet: implications for breast cancer prevention. Cancer Res 60, 4112–4121, 2000. 22...1-0340 TITLE: Interrelationships of Prenatal and Postnatal Growth, Hormones , Diet, and Breast Cancer PRINCIPAL

  16. Effect of growth hormone treatment on pubertal growth in a boy with cystinosis and growth failure after renal transplantation.

    PubMed

    Haffner, D; Wühl, E; Nissel, R; Schaefer, F; Mehls, O

    1996-08-01

    Recombinant human growth hormone (rhGH) has proven effective in improving growth in short prepubertal children with chronic renal failure (CRF) before and after renal transplantation. However, its effect in pubertal patients is still doubtful. We report the case of a boy with nephropathic cystinosis and persistent growth failure despite successful renal transplantation who was treated with rhGH (30 i.u./m2 body surface area/week sc) from early puberty up to final height.

  17. Growth Hormone Utilization Review in a Pediatric Primary Care Setting

    PubMed Central

    Sayarifard, Fatemeh; Imcheh, Fereshteh Bakhshi; Badri, Shirinsadat; Faghihi, Toktam; Qorbani, Mostafa; Radfar, Mania

    2017-01-01

    Objective: One of the main problems facing public health providers and administrators in many countries is ensuring the rational use of high-cost drugs. In this regard, on-going process of medication use evaluation can be considered as a useful tool. In this study, we evaluated certain usage aspects of a highly-cost medication, that is, recombinant growth hormone (GH). Methods: This cross-sectional study conducted from August 2012 to August 2014. Children receiving GH ± gonadotropin releasing hormone (GnRH) analogs were included in the study. A researcher-designed checklist was developed to evaluate the GH utilization in these patients. Baseline demographic characteristics and background clinical and growth data, as well as any aspects of drug therapy including indications, dosing, monitoring, and discontinuation were collected from the patients' medical records. Findings: Seventy children receiving GH entered the study, of which 23 patients (32.85%) received GH and GnRH analogs simultaneously. At the baseline, 67 children (95.7%) had GH stimulation test, whereas serum insulin-like growth factor-1 (IGF-1) levels were measured in 63 (90%) patients. Sixty-seven patients (95.71%) had thyroid function test, whereas bone age was determined in 68 children (97.14%). The mean ± standard deviation of GH dose for idiopathic short stature, GH deficiency, Turner's syndrome and born small for gestational age in our study was 0.22 ± 0.025 mg/kg/week, 0.23 ± 0.04 mg/kg/week, 0.22 ± 0.015 mg/kg/week, and 0.23 ± 0.02 mg/kg/week, respectively. Height and weight of all patients were followed every 3–6 months, regularly. Thirty patients were treated with GH for at least 1 year, of which thyroid hormones and IGF-1 levels were measured annually in 25 (83.33%) and 26 (86.66%) patients, respectively; while bone age was evaluated in 13 (43.33%) children, annually. GH treatment was discontinued in 15 patients (21.42%), while financial problem was the major reason. Conclusion

  18. USE OF MOLECULAR BIOLOGICAL TECHNIQUES TO EVALUATE EFFECT OF ENDOGENOUS HORMONES AND A XENOBIOTIC PESTICIDE ON GROWTH OF SHEEPSHEAD MINNOW

    EPA Science Inventory

    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...

  19. USE OF MOLECULAR BIOLOGICAL TECHNIQUES TO EVALUATE EFFECT OF ENDOGENOUS HORMONES AND A XENOBIOTIC PESTICIDE ON GROWTH OF SHEEPSHEAD MINNOW

    EPA Science Inventory

    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...

  20. Hormones, vitamins, and growth factors in cancer treatment and prevention. A critical appraisal.

    PubMed

    Lupulescu, A P

    1996-12-01

    Hormones, hormone agonists, hormone antagonists, vitamins and their synthetic analogues, and growth factors are currently the most widely used anticancer drugs. Although in many cases they provide dramatic results, in other cases their effects are conflicting. A critical appraisal of the effects of these drugs is needed. To evaluate the potential therapeutic and preventive roles of these drugs as well as their areas of controversy, data published in the literature in the last two decades are reviewed in this article, and the author's personal findings are also reviewed. Hormones, hormone agonists, hormone antagonists, vitamins and their synthetic analogues, growth factors, and cytokines are replacing conventional cancer therapies (chemotherapy, surgical therapy, and radiation therapy) for many purposes, and recently became the "fourth arm" of cancer treatment. However, their mechanisms of action have not yet been elucidated. This article critically reviews the mechanisms of their action on cancer cells (specifically, DNA, RNA, oncogenes, and antioncogenes); their role in cancer cell division, cell cycle, apoptosis, and angiogenesis; and their relation to human cancers. Since hormones, vitamins, growth factors (GFs), and GF receptors play a cardinal role in multistage carcinogenesis, using monoclonal antibodies to develop novel hormone antagonists, vitamin synthetic analogues, and GF inhibitors will be of paramount significance for neoadjuvant systemic therapy and cancer prevention. It is hoped that the data presented in this review regarding the role of hormones, hormone agonists, hormone antagonists, vitamins, growth factors, and growth factor inhibitors will provide a rationale for designing effective new cancer chemoprevention strategies and clinical trials.

  1. Estrogens Regulate the Hepatic Effects of Growth Hormone, a Hormonal Interplay with Multiple Fates

    PubMed Central

    Fernández-Pérez, Leandro; Guerra, Borja; Díaz-Chico, Juan C.; Flores-Morales, A.

    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 with endocrine, metabolic, and sex-differentiated functions of GH. Most previous studies have been focused on the influence of estrogens on pituitary GH secretion, which has a great impact on hepatic transcriptional regulation. However, there is strong evidence that estrogens can influence the GH-regulated endocrine and metabolic functions in the human liver by acting at the level of GHR-STAT5 signaling pathway. This crosstalk is relevant because the widespread exposition of estrogen or estrogen-related compounds in human. Therefore, GH or estrogen signaling deficiency as well as the influence of estrogens on GH biology can cause a dramatic impact in liver physiology during mammalian development and in adulthood. In this review, we will summarize the current status of the influence of estrogen on GH actions in liver. A better understanding of estrogen-GH interplay in liver will lead to improved therapy of children with growth disorders and of adults with GH deficiency. PMID:23761784

  2. Skeletal Effects of Growth Hormone and Insulin-like Growth Factor-I Therapy

    PubMed Central

    Lindsey, Richard C.; Mohan, Subburaman

    2015-01-01

    The growth hormone/insulin-like growth factor (GH/IGF) axis is critically important for the regulation of bone formation, and deficiencies in this system have been shown to contribute to the development of osteoporosis and other diseases of low bone mass. The GH/IGF axis is regulated by a complex set of hormonal and local factors which can act to regulate this system at the level of the ligands, receptors, IGF binding proteins (IGFBPs), or IGFBP proteases. A combination of in vitro studies, transgenic animal models, and clinical human investigations has provided ample evidence of the importance of the endocrine and local actions of both GH and IGF-I, the two major components of the GH/IGF axis, in skeletal growth and maintenance. GH- and IGF-based therapies provide a useful avenue of approach for the prevention and treatment of diseases such as osteoporosis. PMID:26408965

  3. Effects of Hypergravity Rearing on Growth Hormone and Insulin-Like Growth Factor in Rat Pups

    NASA Technical Reports Server (NTRS)

    Baer, L. A.; Chowdhury, J. H.; Grindeland, R. E.; Wade, C. E.; Ronca, A. E.

    2003-01-01

    Body weights of rat pups reared during exposure to hypergravity (hg) are significantly reduced relative to 1 g controls. In the present study, we examined in hg-reared rat pups two major contributors to growth and development, namely growth hormone (GH) and insulin-like growth factor-1 (IGF-1). Beginning on Gestational day (G)11 of the rats 22 day pregnancy, rat dams and their litters were continuously exposed to either 1.5-g or 2.0-g. On Postnatal day (P)l0, plasma GH and IGF-1 were analyzed using radioimmunoassay (RIA). Both hormones were significantly elevated in hg pups relative to 1-g control pups. Together, these findings suggest that GH and IGF-1 are not primary determinants of reduced body weights observed in hg-reared pups. The significant elevations in pup GH and IGF-1 may be related to increased physical stimulation in hypergravity.

  4. Effects of Hypergravity Rearing on Growth Hormone and Insulin-Like Growth Factor in Rat Pups

    NASA Technical Reports Server (NTRS)

    Baer, L. A.; Chowdhury, J. H.; Grindeland, R. E.; Wade, C. E.; Ronca, A. E.

    2003-01-01

    Body weights of rat pups reared during exposure to hypergravity (hg) are significantly reduced relative to 1 g controls. In the present study, we examined in hg-reared rat pups two major contributors to growth and development, namely growth hormone (GH) and insulin-like growth factor-1 (IGF-1). Beginning on Gestational day (G)11 of the rats 22 day pregnancy, rat dams and their litters were continuously exposed to either 1.5-g or 2.0-g. On Postnatal day (P)l0, plasma GH and IGF-1 were analyzed using radioimmunoassay (RIA). Both hormones were significantly elevated in hg pups relative to 1-g control pups. Together, these findings suggest that GH and IGF-1 are not primary determinants of reduced body weights observed in hg-reared pups. The significant elevations in pup GH and IGF-1 may be related to increased physical stimulation in hypergravity.

  5. Parathyroid hormone levels in pubertal uremic adolescents treated with growth hormone.

    PubMed

    Picca, Stefano; Cappa, Marco; Martinez, Chiara; Moges, Seyoum Ido; Osborn, John; Perfumo, Francesco; Ardissino, Gianluigi; Bonaudo, Roberto; Montini, Giovanni; Rizzoni, Gianfranco

    2004-01-01

    We have previously described severe hyperparathyroidism during the pubertal growth spurt in three uremic adolescents treated with recombinant human growth hormone (rhGH). Here we investigate the possible role of puberty in the genesis of hyperparathyroidism during rhGH treatment of a large cohort of patients. Data from 67 uremic patients treated with rhGH from five Italian pediatric nephrology centers were retrospectively recorded every 3 months starting 1 year before rhGH administration. The mean (+/-SD) rhGH treatment observation period was 19.9+/-5.9 months. The mean age at the start of rhGH treatment was 8.3+/-3.6 years. Of the 67 patients, 15 reached pubertal stage 2 during the 1st year of rhGH treatment and 12 of these 15 progressed to pubertal stage 3. The relative increase in parathyroid hormone (PTH) levels after rhGH initiation was greater in pubertal [1.95, 95% confidence interval (CI) 1.43-2.66] than in prepubertal patients (1.19, 95% CI 1.01-1.40). Increases in PTH levels were significantly different between the two groups (Delta=1.64, 95% CI 1.16-3.19, P=0.007). Multiple regression analysis showed an inverse correlation between PTH and calcium levels and a positive correlation between PTH and pubertal stage 3. There was no correlation with phosphate levels and calcitriol dosage. In conclusion, these results suggest that in uremic adolescents treated with rhGH puberty may influence PTH levels.

  6. Pituitary Function and Growth Hormone Dynamics in Acromegaloidism

    PubMed Central

    Mims, Robert B.

    1978-01-01

    Acromegaloidism is a condition which resembles acromegaly by its clinical manifestations but is not due to pituitary or hypothalamic dysfunction. Twenty patients were diagnosed as having this disorder and the results from studying growth hormone (GH) responses in 15 patients (11 women and four men) were included in this report. Clinical manifestations closely resembled those of acromegalics, including history of progressive changes, acral enlargement, visual disturbances, abnormal visual fields in four patients, and sella turcica enlargement in two patients. The glucose tolerance test (GTT) was abnormal in 12/15 patients, 13/15 were > 10 percent obese, 8/15 had hypertension, 7/15 had large-statured relatives, but lactorrhea was absent in all patients. The mean serum GH concentration was 2.2 ng/ml, which suppressed to 0.6 ng/ml during the GTT; increased to 24 ng/ml during hypoglycemia; and increased to 10.3 ng/ml after L-dopa ingestion. Other pituitary hormones (LH, FSH, TSH, prolactin), the metyrapone test, 24-hour random and nocturnal sleeping GH concentrations were normal. These GH values and responses helped to differentiate acromegaloidism from treated and untreated acromegaly. The pathogenesis of acromegaloidism was not determined, but somatomedin studies may prove helpful in further defining this disorder. PMID:731719

  7. Association of chicken growth hormone polymorphisms with egg production.

    PubMed

    Su, Y J; Shu, J T; Zhang, M; Zhang, X Y; Shan, Y J; Li, G H; Yin, J M; Song, W T; Li, H F; Zhao, G P

    2014-07-04

    Growth hormone (GH) has diverse functions in animals, together with other hormones from the somatotropic axis. Here, chicken GH (cGH) was investigated in recessive white chickens and Qingyuan partridge chickens as a candidate gene affecting egg production traits. Chicken egg production traits were studied in association with 4 selected single nucleotide polymorphisms (T185G, G662A, T3094C, and C3199T). Genotyping was performed by the polymerase chain reaction-ligase detection reaction method. T185G was significantly associated with the egg production traits of body weight at first egg (BW), egg weight at first egg (EW), and the total egg production of 300-day old birds (EN 300). T3094C was also significantly associated with certain egg production traits; however, it affected the 2 breeds differently. Haplotypes of the 4 single nucleotide polymorphisms were also significantly associated with egg production traits of chicken age at first egg laying, BW, EW, and EN 300. H1H6 was the most advantageous diplotype for egg production. We putatively concluded that polymorphisms in the cGH gene and its haplotypes could be used as potential molecular markers for egg production traits to enhance the breeding programs of indigenous chickens.

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

    PubMed

    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.

  9. Long-term effects of growth hormone replacement therapy on thyroid function in adults with growth hormone deficiency.

    PubMed

    Losa, Marco; Scavini, Marina; Gatti, Elisa; Rossini, Alessandro; Madaschi, Sara; Formenti, Ilaria; Caumo, Andrea; Stidley, Christine A; Lanzi, Roberto

    2008-12-01

    Clinical studies on the effect of growth hormone (GH) on thyroid function in patients with GH deficiency are contradictory. Further, the majority of published observations are limited to the first 6-12 months of GH replacement therapy. The aim of our study was to estimate the incidence of clinically relevant hypothyroidism in a cohort of patients with adult GH deficiency (AGHD) during long-term therapy with recombinant human GH (rhGH). The study was designed as a retrospective collection of data on thyroid function in 49 AGHD patients of whom 44 (90%) had multiple hormone deficiency. Thirty-seven patients (76%) were on stable levothyroxine (LT4) replacement therapy (HYPO), and 12 (24%) were euthyroid (EUT). Therapy with rhGH was started at a dose of 3.5 microg/kg body weight and adjusted according to insulin-like growth factor-I (IGF-I) levels. At baseline, 6 months, 12 months, and yearly thereafter we measured free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone, and IGF-I. Study outcome was fT4 level below the normal range (9 pmol/L), irrespectively of fT3 or thyroid-stimulating hormone levels. During a follow-up of 115 patient-years, mean fT4 level decreased significantly, although remaining within the normal range (p = 0.0242; month 48 vs. baseline). The largest decrease was between baseline and month 6, when fT4 decreased of 1.43 pmol/L (95% confidence interval, 0.33-2.53) per 1 unit (microg/kg body weight) increase in rhGH dose. The incidence of hypothyroidism was 1.2 (HYPO group) and 6.7 (EUT group) events per 100 patient-years. We confirm that in patients with AGHD, rhGH therapy is associated with a small, although significant, decrement of fT4 in the first 6 months of replacement therapy. However, the incidence of hypothyroidism is low. Monitoring of thyroid function during rhGH therapy is advisable, particularly in the first year of therapy when the largest decrease in fT4 occurs.

  10. Adult height after long term treatment with recombinant growth hormone for idiopathic isolated growth hormone deficiency: observational follow up study of the French population based registry

    PubMed Central

    Carel, Jean-Claude; Ecosse, Emmanuel; Nicolino, Marc; Tauber, Maïté; Leger, Juliane; Cabrol, Sylvie; Bastié-Sigeac, Irène; Chaussain, Jean-Louis; Coste, Joël

    2002-01-01

    Objective To evaluate the efficacy of recombinant growth hormone for increasing adult height in children treated for idiopathic isolated growth hormone deficiency. Design Observational follow up study. Setting Population based registry. Participants All 2852 French children diagnosed as having isolated idiopathic growth hormone deficiency whose treatment started between 1987 and 1992 and ended before 1996. Main outcome measures Change in height between the start of treatment and adulthood; classification of patients according to whether treatment was completed as scheduled or stopped early. Results Adult height was obtained for 2165 (76%) patients. The mean dose of growth hormone at start of treatment was 0.42 IU/kg/week. Height gain was 1.1 (SD 0.9) standard deviation (SD) scores, resulting in an adult height of –1.6 (0.9) SD score (girls, 154 (5) cm; boys, 167 (6) cm). Patients who completed the treatment gained 1.0 (0.7) SD score of height in 3.6 (1.4) years. Patients with treatments stopped early gained 0.6 (0.6) SD score in 2.7 (1.4) years while receiving treatment and a further 0.4 (0.9) SD score after the end of treatment. Most of the variation in height gain was explained by regression towards the mean, patients' characteristics, and delay in starting puberty. Severe growth hormone deficiency was associated with better outcome. Each year of treatment was associated with a gain of 0.2 SD score(1.3 cm). Conclusion The effect of growth hormone is unclear in many patients treated for so called idiopathic isolated growth hormone deficiency. Most of the patients have pubertal delay and a spontaneous growth potential, which must be taken into account when measuring the effect and cost effectiveness of treatments. Growth hormone deficiency should be clearly distinguished from pubertal delay, and criteria should restrict the definition to patients with severely and permanently altered growth hormone secretion as our results support the use of growth hormone in

  11. Development of additional pituitary hormone deficiencies in pediatric patients originally diagnosed with isolated growth hormone deficiency due to organic causes.

    PubMed

    Child, Christopher J; Blum, Werner F; Deal, Cheri; Zimmermann, Alan G; Quigley, Charmian A; Drop, Stenvert L S; Cutler, Gordon B; Rosenfeld, Ron G

    2016-05-01

    To determine characteristics of children initially diagnosed with isolated growth hormone deficiency (IGHD) of organic aetiology, who later developed multiple pituitary hormone deficiencies (MPHD). Data were analysed for 716 growth hormone-treated children with organic IGHD, who were growth hormone-naïve at baseline in the multinational, observational Genetics and Neuroendocrinology of Short Stature International Study. Development of MPHD was ascertained from investigator-provided diagnoses, adverse events and concomitant medications. Analyses were performed for all patients and separately for those who developed MPHD within 4.5 years or had >3.5 years follow-up and continued to have IGHD (4-year cohort). MPHD developed in 71/716 (9.9%) children overall, and in 60/290 (20.7%) in the 4-year cohort. The most frequent additional deficiencies were thyroid-stimulating hormone (47 patients) and gonadotropins (23 patients). Compared with those who remained with IGHD, children who developed MPHD had more severe GHD at study entry, significantly lower baseline insulin-like growth factor1, peak stimulated growth hormone, and more frequent diagnosis of intracranial tumour or mutation of gene(s) controlling hypothalamic-pituitary development and/or function. Multivariate logistic regression analyses identified female gender, longer follow-up, higher baseline age and lower peak stimulated growth hormone as predictors of MPHD development. MPHD is more likely to develop in patients with severe organic IGHD, especially those with history of intracranial tumour or mutation of gene(s) controlling hypothalamic-pituitary development and/or function. Older baseline age, female gender and longer follow-up duration were also associated with higher incidence of MPHD. Long-term monitoring of pituitary function is recommended, irrespective of the aetiology of GHD. © 2016 European Society of Endocrinology.

  12. Human growth hormone - great promise at a price.

    PubMed

    Lein, B

    1995-05-01

    Serono Laboratories has announced an expanded access program for recombinant human growth hormone (rHGH, called Serostim) to treat wasting syndrome among people with unwanted weight loss of greater than ten percent who have failed approved therapies. The program is rife with problems. The company has decided to implement a cost recovery program and charge for the drug. Underground sources say they can supply rHGH from European suppliers for a third of the price if necessary, raising the question of possible price gouging on the part of Serono. However, foreign manufacturers have borne none of the research costs necessary to obtain Food and Drug Administration (FDA) approval. Access to the drug is critical to determine its benefit for improving the quality of life. Government and company officials need to discuss pricing fairness and find ways to make this treatment feasible as well as available. For more information, call the PI hotline at 1-800-822-7422.

  13. Status of long-acting-growth hormone preparations--2015.

    PubMed

    Høybye, Charlotte; Cohen, Pinchas; Hoffman, Andrew R; Ross, Richard; Biller, Beverly M K; Christiansen, Jens Sandahl

    2015-10-01

    Growth hormone (GH) treatment has been an established therapy for GH deficiency (GHD) in children and adults for more than three decades. Numerous studies have shown that GH treatment improves height, body composition, bone density, cardiovascular risk factors, physical fitness and quality of life and that the treatment has few side effects. Initially GH was given as intramuscular injections three times per week, but daily subcutaneous injections were shown to be more effective and less inconvenient and the daily administration has been used since its introduction in the 1980s. However, despite ongoing improvements in injection device design, daily subcutaneous injections remain inconvenient, painful and distressing for many patients, leading to noncompliance, reduced efficacy and increased health care costs. To address these issues a variety of long-acting formulations of GH have been developed. In this review we present the current status of long-acting GH preparations and discuss the specific issues related to their development.

  14. Reevaluation of lipolytic activity of growth hormone in rabbit adipocytes.

    PubMed

    Barenton, B; Batifol, V; Combarnous, Y; Dulor, J P; Durand, P; Vezinhet, A

    1984-07-18

    The lipolytic activities of porcine pituitary fractions and purified growth hormone (GH) from human (h), porcine (p), ovine (o) and rabbit (Rb) origin as well as ovine placental lactogen (oPL), were compared to that of ACTH on rabbit adipocytes. All the GH preparations and oPL were equivalent in inhibiting the binding of labelled oGH to liver plasma membranes from pregnant rabbits. ACTH, and to a lesser extent porcine pituitary fractions and hGH, stimulated free fatty acid production by isolated adipocytes. The sensitivity of the adipocytes to these factors was increased when adenosine deaminase was added to the incubation medium. But, RbGH, pGH, oGH and oPL had no effect. We conclude that GH is not directly involved in the control of lipolysis in rabbit adipocytes and that the effect of hGH is rather due to a contamination of this preparation by other pituitary factors.

  15. Growth hormone prevents neuronal loss in the aged rat hippocampus.

    PubMed

    Azcoitia, Iñigo; Perez-Martin, Margarita; Salazar, Veronica; Castillo, Carmen; Ariznavarreta, Carmen; Garcia-Segura, Luis M; Tresguerres, Jesus A F

    2005-05-01

    Decline of growth hormone (GH) with aging is associated to memory and cognitive alterations. In this study, the number of neurons in the hilus of the dentate gyrus has been assessed in male and female Wistar rats at 3, 6, 12, 14, 18, 22 and 24 months of age, using the optical fractionator method. Male rats had more neurons than females at all the ages studied. Significant neuronal loss was observed in both sexes between 22 and 24 months of age. In a second experiment, 22 month-old male and female rats were treated for 10 weeks with 2 mg/kg/day of GH or saline. At 24 months of age, animals treated with GH had more neurons in the hilus than animals treated with saline. These findings indicate that GH is neuroprotective in old animals and that its administration may ameliorate neuronal alterations associated to aging.

  16. [Growth hormone treatment inTurner syndrome: data and reflections].

    PubMed

    Guedes, Alexis D; Bianco, Bianca; Callou, Emmanuela Q; Gomes, Ana Luíza; Lipay, Mônica V N; Verreschi, Ieda T N

    2008-07-01

    Short stature is the major characteristic of Turner syndrome. The statural appeal is premature and become evident in the puberty. Haploinsufficiency of SHOX gene has been related as main factor on final height of these patients. Despite the majority of the patients are not growth hormone deficient, the GHr therapy improves the final height. Recently, a great number of publications have described the association between GH and cancer. The cancer risk, in these patients, is mainly associated with the presence of Y chromosome sequences that can lead to the gonadoblastoma development. In conclusion, the GHr therapy in ST patients deserves caution. The investigation of Y chromosome sequences should be performed as well as the prophylactic gonadectomy in the positive cases conferring confidence to the treatment.

  17. Oral hydration during growth hormone stimulation with clonidine.

    PubMed

    May, Melissa; Rose, Susan R

    2007-10-01

    The arginine-clonidine growth hormone (GH) stimulation test causes hypotension, requiring intravenous fluids to stabilize blood pressure (BP) and delaying departure from clinic. We hypothesized that oral hydration during the stimulation test would decrease need for intravenous fluids and shorten clinic stay. Children drank a diet electrolyte drink (10 ml/kg) on arrival to the test, which was repeated after clonidine. Fifteen children (7 girls) were tested without oral hydration, and 23 (6 girls) were tested with oral hydration (age range, 2-15 years). Compared with no oral hydration, intake of >13 ml/kg rarely required intravenous fluids, improved diastolic BP, and permitted discharge at the end of the GH test, with a higher BP.

  18. Growth hormone and adipose tissue: beyond the adipocyte

    PubMed Central

    Berryman, Darlene E.; List, Edward O.; Sackmann-Sala, Lucila; Lubbers, Ellen; Munn, Rachel; Kopchick, John J.

    2011-01-01

    The last two decades have seen resurgence in the interest in, and research on, adipose tissue. In part, the increased 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 adipose tissue, a better appreciation of the newer complexities 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 how GH may influence and contribute to these newer complexities with special focus on the available data from mice with altered GH action. PMID:21470887

  19. A comparison of the growth responses following intramuscular GHRH plasmid administration versus daily growth hormone injections in young pigs

    USDA-ARS?s Scientific Manuscript database

    The efficacy of daily porcine growth hormone (GH) injections versus plasmid-driven porcine GH-releasing hormone (pGHRH) production to promote growth was assessed. Ten-day-old piglets were injected intramuscularly with 0.1, 1, or 3 mg pGHRH, or a control plasmid followed by electroporation. Plasmid c...

  20. Successful Growth Hormone Therapy in Cornelia de Lange Syndrome.

    PubMed

    de Graaf, Michael; Kant, Sarina G; Wit, Jan Maarten; Willem Redeker, Egbert Johan; Eduard Santen, Gijs Willem; Henriëtta Verkerk, Annemieke Johanna Maria; Uitterlinden, André Gerardus; Losekoot, Monique; Oostdijk, Wilma

    2017-06-07

    Cornelia de Lange Syndrome (CdLS) is a heterogeneous syndrome, both clinically and genetically, in its classical form characterised by distinctive facial features, intra-uterine growth retardation, short stature, developmental delay and anomalies in multiple organ systems. NIPBL, SMC1A, SMC3, RAD21 and HDAC8, all involved in the Cohesin pathway, have been identified to cause CdLS. Growth hormone (GH) secretion has been reported as normal, and to our knowledge there are no reports on the effect of recombinant human GH (r-hGH) treatment in CdLS patients. We present a patient born small for gestational age (SGA) with persistent severe growth retardation (height -3.4 SDS) and mild dysmorphic features, who was treated with GH from 4.3 years of age onward, and diagnosed 6 years later with CdLS using whole exome sequencing. Treatment led to a height gain of 1.6 standard deviation score (SDS) over 8 years. Treatment was interrupted shortly due to high serum IGF-1 serum values. We conclude that GH therapy appears effective and safe for short children with CdLS.

  1. Growth hormone use in the treatment of idiopathic short stature.

    PubMed

    Zucchini, Stefano

    2008-04-01

    Human growth hormone (hGH) therapy has been used for the possible improvement of adult height in individuals with idiopathic short stature (ISS) for more than 20 years. However, given its heterogeneity, and the distinction between 'partial' or 'transient' GH deficiency, the exact definition of ISS is difficult. Since recombinant hGH became available, individuals with all types of GH deficiency have been extensively treated, often without the need for diagnostic justifications. On the other hand, for ISS individuals GH treatment has so far only been possible in a few countries, or in the context of clinical trials. If hGH is certainly effective in individuals with severe GH deficiency, its efficacy is lower and with a high individual-to-individual variability of response in those with non-severe GH deficiency and with ISS. The most important variables associated with a favorable growth response to hGH therapy in GH- and non-GH-deficient individuals are first-year growth response, younger age at start of treatment, difference at start from target height standard deviation score, GH dose, and other variables not necessarily associated with GH peak levels after provocative stimuli. A better choice of individuals to be treated successfully will improve the cost-effectiveness of the treatment, making it more acceptable to the scientific community and other stakeholders.

  2. Genetic polymorphisms and protein structures in growth hormone, growth hormone receptor, ghrelin, insulin-like growth factor 1 and leptin in Mehraban sheep.

    PubMed

    Bahrami, A; Behzadi, Sh; Miraei-Ashtiani, S R; Roh, S-G; Katoh, K

    2013-09-15

    The somatotropic axis, the control system for growth hormone (GH) secretion and its endogenous factors involved in the regulation of metabolism and energy partitioning, has promising potentials for producing economically valuable traits in farm animals. Here we investigated single nucleotide polymorphisms (SNPs) of the genes of factors involved in the somatotropic axis for growth hormone (GH1), growth hormone receptor (GHR), ghrelin (GHRL), insulin-like growth factor 1 (IGF-I) and leptin (LEP), using polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and DNA sequencing methods in 452 individual Mehraban sheep. A nonradioactive method to allow SSCP detection was used for genomic DNA and PCR amplification of six fragments: exons 4 and 5 of GH1; exon 10 of GH receptor (GHR); exon 1 of ghrelin (GHRL); exon 1 of insulin-like growth factor-I (IGF-I), and exon 3 of leptin (LEP). Polymorphisms were detected in five of the six PCR products. Two electrophoretic patterns were detected for GH1 exon 4. Five conformational patterns were detected for GH1 exon 5 and LEP exon 3, and three for IGF-I exon 1. Only GHR and GHRL were monomorphic. Changes in protein structures due to variable SNPs were also analyzed. The results suggest that Mehraban sheep, a major breed that is important for the animal industry in Middle East countries, has high genetic variability, opening interesting prospects for future selection programs and preservation strategies.

  3. Growth hormones therapy in immune response against Trypanosoma cruzi.

    PubMed

    Frare, Eduardo Osório; Santello, Fabricia Helena; Caetano, Leony Cristina; Caldeira, Jerri C; Toldo, Míriam Paula Alonso; Prado, José Clóvis do

    2010-04-01

    Growth hormone (GH) is an important hypophyseal hormone that is primarily involved in body growth and metabolism. In mammals, control of Trypanosoma cruzi parasitism during the acute phase of infection is considered to be critically dependent on direct macrophage activation by cytokines. To explore the possibility that GH might be effective in the treatment of Chagas' disease, we investigated its effects on the course of T. cruzi infection in rats, focusing our analyses on its influences on parasitemia, NO, TNF-alpha and IFN-gamma concentration and on histopathological alterations and parasite burden in heart tissue. T. cruzi-infected male Wistar rats were intraperitoneally treated with 5 ng/10 g body weight/day of GH. Animals treated with GH showed a significant reduction in the number of blood trypomastigotes during the acute phase of infection compared with untreated animals (P<0.05). For all experimental days (7, 14 and 21 post infection) of the acute phase, infected and GH treated animals reached higher concentrations of TNF-alpha, IFN-gamma and nitric oxide as compared to untreated and infected counterparts (P<0.05) Histopathological observations of heart tissue revealed that GH administration also resulted in fewer and smaller amastigote burdens, and less inflammatory infiltrate and tissue disorganization, indicating a reduced parasitism of this tissue. These results show that GH can be considered as an immunomodulator substance for controlling parasite replication and combined with the current drug used may represent in the future a new therapeutic tool to reduce the harmful effects of Chagas' disease.

  4. Growth hormone isoforms in a girl with gigantism.

    PubMed

    Ng, L L; Chasalow, F I; Escobar, O; Blethen, S L

    1999-01-01

    Several previous investigations have suggested that there may be different growth hormone isoforms in patients with acromegaly. We used three different site-specific monoclonal antibodies (MAbs) to investigate growth hormone (GH) isoforms in serum from an 8 year-old girl with a GH and prolactin secreting adenoma. The pattern of GH-immunoreactivity was dependent on the circumstances of collection. Serum obtained after oral glucose had very little cross reactivity with MAb 352 although concentrations of up to 15 micrograms/l were found with two other MAbs, 033 and 665. MAb 352 does not recognize the 20,000 dalton isoform of GH (20K) while both MAb 033 and 665 do. The same pattern of GH immunoreactivity (low MAb 352, equal and higher MAb 033 and 665) was seen in other baseline samples. In contrast, samples obtained after TRH/GnRH showed immunoreactivity patterns expected for a mixture of 22,000 dalton isoform of GH (22K) with only a small amount of 20K. GH samples obtained during sleep showed both patterns with episodic peaks with equal immunoreactivity superimposed on the basal pattern (decreased activity with MAb 352). Affinity chromatography of basal samples showed that a portion of the GH immunoreactivity was neither 22K nor 20K, although in stimulated samples, over 70% of GH was 22K or 20K GH. In conclusion, the nature of GH isoforms present in serum varies with GH concentration. These differences may contribute to the known difficulty in correlating disease activity and random GH measurements in patients with GH secreting adenomas.

  5. Growth patterns and the use of growth hormone in the mucopolysaccharidoses

    PubMed Central

    Polgreen, L.E.; Miller, B.S.

    2010-01-01

    Short stature is characteristic of patients with mucopolysaccharidosis (MPS) diseases. For children with skeletal dysplasias, such as MPS, it is important to know the natural history of growth. An understanding of the natural growth pattern in each MPS disease provides a measurement to which treatments can be compared, as well as data which can help families and providers make individualized decisions about growth promoting treatments. Multiple advancements have been made in the treatment of MPS with both hematopoietic cell transplantation (HCT) and enzyme replacement therapy (ERT). The long term benefit of these treatments on growth is unknown. This article will review the published data on growth in children with MPS, and describe preliminary data on the use of human growth hormone (hGH) in children with MPS. PMID:20563263

  6. Polymorphism of growth hormone receptor (GHR) gene in Nilagiri sheep.

    PubMed

    Sahu, Amiya Ranjan; Jeichitra, V; Rajendran, R; Raja, A

    2017-02-01

    The allelic variation in the regulatory sequence of growth hormone receptor (GHR) gene influences the growth traits of sheep. A study was carried out to find out the polymorphisms associated with exon 10 of GHR gene and its association with growth traits of Nilagiri sheep. The blood samples were collected from Nilagiri sheep (n = 103) reared at Sheep Breeding Research Station, Sandynallah, Tamil Nadu, India. DNA was isolated using the phenol-chloroform extraction procedure and eight samples having amplified product of part of exon 10 (895 bp) sequenced. The results indicated transitions of nucleotide G>A at loci G177624A and G177878A. The genotyping frequencies estimated using the tetra-primer amplification refractory mutation system-PCR for GG, GA and AA were 0.262, 0.544 and 0.194, and 0.349, 0.505 and 0.146, respectively. The estimated allele frequencies of G and A nucleotides were 0.5340 and 0.4660, and 0.6015 and 0.3985, respectively, at loci G177624A and G177878A. The effects of both the mutations on growth-related traits viz., birth, weaning (3 months) 6, 9 and 12 months weight in Nilagiri sheep were found to be non-significant. This can be a novel approach to assess growth of sheep using the mutation in GHR gene. Thus, this approach can be useful for further investigation as a molecular marker associated with genetic improvement.

  7. Parents' views on growth hormone treatment for their children: psychosocial issues.

    PubMed

    van Dongen, Nadine; Kaptein, Ad A

    2012-01-01

    We evaluated the opinions of parents in The Netherlands concerning treatment of their children with growth hormone, and examined beliefs and perceptions about treatment and quality of health care communication and support. An Internet survey was completed by 69 parents who had children prescribed growth hormone and were part of the Patient Intelligence Panel. Acceptance of the diagnosis and treatment was investigated with reference to four topics, ie, search and quality of information, involvement in decision-making process, operational aspects, and emotional problems and support. Among the parents surveyed, 48% reported a lack of freedom to choose the type of growth hormone device that best suited their needs, 92% believed that their children (and they themselves) would benefit if the children self-administered growth hormone, and 65% believed training to support self-administration would be helpful. According to 79%, the availability of support from another parent with experience of treating their own child with growth hormone, alongside their doctor, would be valuable. Thirty-seven percent of the parents indicated that their children felt anxious about administration of growth hormone, and 83% of parents would appreciate psychological support to overcome their anxiety. An increase in reluctance to receive treatment with growth hormone was observed by 40% of parents after the children reached puberty, and 57% of these parents would appreciate psychological support to overcome this reluctance. Understanding how growth hormone treatments and their implications are perceived by parents is a first step towards addressing quality of growth hormone treatment, which may be instrumental in improving adherence. The data show a need for support and involvement of parents in the process of choosing a growth hormone device. This decision-making process may be instrumental in improving acceptance and diminishing emotional problems for children using growth hormone.

  8. Pharmacokinetics and acute lipolytic actions of growth hormone. Impact of age, body composition, binding proteins, and other hormones.

    PubMed

    Hansen, Troels Krarup

    2002-10-01

    The biologic actions of endogeneous growth hormone (GH) depend on its secretion and clearance rates as well as sensitivity at the receptor level. Aberrations in GH pharmacokinetics and pharmacodynamics may occur with increasing age, and have been implicated in diseases such as obesity, diabetes mellitus, and critical illness. In this review, recent insights into the association between GH metabolism and age, body composition, binding proteins and other hormones are discussed.

  9. [Serum insulin, leptin and growth hormone levels are associated with body mass index and obesity index in adolescents].

    PubMed

    Molero-Conejo, Emperatriz; Morales, Luz Marina; Fernández, Virginia; Raleigh, Xiomara; Casanova, Angel; Connell, Lissette; Gómnez, Maria Esther; Ryder, Elena; Campos, Gilberto

    2006-03-01

    Leptin, insulin and growth hormone levels seem to regulate body composition, fat distribution and fat mass. The purpose of this study was to determine the relationship among insulin, leptin and growth hormone levels in a group of adolescents. Ninety five adolescents (31 boys and 64 girls) between 13 and 18 y. of age were studied. A medical and nutritional history was made which included body mass index (BMI) and subcutaneous skinfolds measurements. Basal levels of glucose, triglycerides, total cholesterol, HDL-C, LDL-C, VLDL-C, leptin, insulin and growth hormone were determined. The leptin and insulin levels were positively associated with body mass index (BMI) and obesity index (OBI). Insulin, leptin and obesity markers were negatively associated with growth hormone level. Fifty two percent of the adolescents with BMI = 21.09 kg/m2 were considered metabolically obese because they had elevated levels of insulin (18.68 +/- 1.52 vs. 10.08 +/- 0.38 microU/ml), HOMA IR (3.34 +/- 0.24 vs. 1.76 +/- 0.07), leptin (16.30 +/- 1.24 vs. 8.11 +/- 1.32 ng./dl) and triglycerides (78.56 +/- 4.38 vs. 64.39 +/- 5.48 mg/dl) and lower levels of HDL-C (39.09 +/- 1.27 vs. 43.30 +/- 2.38 mg/dl), compared with normal group. The same alterations were observed in the obese group, in which significative decrease in growth hormone level was added. We conclude that hyperinsulinemia, hyperleptinemia and low growth hormone levels, may be established as risk factors related to obesity markers, lipid alterations and insulin resistance that can lead to an early development of Type II diabetes and cardiovascular disease.

  10. Craniopharyngioma cell growth is promoted by growth hormone (GH) and is inhibited by tamoxifen: involvement of growth hormone receptor (GHR) and IGF-1 receptor (IGF-1R).

    PubMed

    Li, Qiang; You, Chao; Liu, Liang; Rao, Zhengxi; Sima, Xiutian; Zhou, Liangxue; Xu, Jianguo

    2013-01-01

    Hormone receptors are related to the biological behavior and recurrence of craniopharyngioma (CP). The effect of therapeutic growth hormone (GH) replacement on CP growth remains largely unclear. We intended to study expression patterns of GH-related receptors in CP, and to study the effect of GH and its mediator, insulin-like growth factor-1 (IGF-1), as well as tamoxifen, on primary CP cell cultures. Primary cell cultures were established from fresh tumor specimens. The expression of GH receptor (GHR) and IGF-1 receptor (IGF-1R) in tumor specimens was studied using immunohistochemistry. Cell cultures were treated with various concentrations of recombinant GH, IGF-1 and tamoxifen. Cell growth promotion or inhibition was assayed using the Trypan blue dye exclusion test of cell viability. Expression of GHR, IGF-1R, phosphorylated-Akt and Akt after treatment was studied using Western blot assay. Twenty-nine primary cultures from 36 patients were established. GHR and IGF-1R were expressed in tumor tissue. The promotion of cell growth by GH compared to control was most prominent at 100 ng/mL, while inhibition by tamoxifen was concentration dependent. IGF-1 was more effective in promoting growth in CP cell cultures with high IGF-1R expression, and it increased phosphorylation of Akt protein. Primary cell cultures can be established in more than 80% of fresh CP specimens. GH and its endogenous mediator, IGF-1, promotes CP cell growth in vitro, while tamoxifen inhibits growth. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Induction of growth hormone release by Pueraria thunbergiana BENTH.

    PubMed

    Jung, D Y; Ha, H; Kim, C

    2004-02-01

    Puerariae Radix (PR), Puerariae Flos (PF), and Puerariae Surculus (PS) as well as their constituents were tested for induction of rat growth hormone (rGH) release by both rat pituitary cell culture and in vivo experimentation in order to develop them to novel drugs. Through a calibration curve of the rGH released by addition of rat growth hormone-releasing hormone (rGHRH) to rat pituitary cells, the 70 % ethanol extracts of PR and PS increased rGH release by about 1.6 and 1.7 times as high, respectively, as the control group (264.6 +/- 13.6 pM). However, each puerarin type as a representative constituent of PR in Korea Pharmacopeia (KP) and tectorigenin and an important ingredient of PF were twice as effective as in the control group. The acid hydrolysate of Puerariae Surculus (HPS) increased rGH release concentration-dependently, and its EC (50) was approximately 10.4 microg/ml. The T (max) value for rGH after injection of 20 microg/kg of rGHRH was 10 - 30 min, while the C (max) value was increased by approximately 12-fold compared to the control group (198.2 +/- 25.0 pM) and the AUC (0 - 45) was increased to 10 times the level of the control group (10,840.9 +/- 845.5 min. pM). On the other hand, T (max) for the HPS was 60 min, while C (max) was increased approximately to 5.8 fold compared to control (244.1 +/- 36.4 pM). C (max) for puerarin was 1,028.6 +/- 502.7 pM, that is, approximately 5.2 times as high as the control level. However, tectorigenin (20 microg/kg) was of no statistical significance. Therefore, we suggest that the HPS and puerarin act either on GH secretagogue receptors or on GHRH receptor of somatotrophin as possible agonists or an inhibitor on somatostatin receptor to release rGH, respectively.

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

    SciTech Connect

    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){sup +} 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){sup +}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 ({sup 3}H)uridine, and quantitating ({sup 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.

  13. Changing Concepts on the Control of Growth Hormone Secretion in Man

    PubMed Central

    VanderLaan, W. P.

    1971-01-01

    New facts have emerged about growth hormone (hgh) secretion in man giving rise to new conceptions and to new questions. • In well-nourished, lean human beings growth hormone is released in early deep sleep and the pattern of release observed from night to night is fairly constant. • The release of growth hormone in sleep occurs when plasma glucose is not fluctuating and after insulin has fallen to a very low level. Plasma-free fatty acids may rise about two hours later but insulin does not rise in response to nocturnal hgh release. • The releases of growth hormone in sleep appear to meet the needs for a physiological test for the study of problems of growth. Correlations of this test with the many pharmacologic maneuvers in current use for diagnosis remain to be made. • Growth hormone secretion as judged by plasma concentrations relates to protein intake, such that protein depletion initiates compensatory elevation of plasma concentrations of growth hormone. Further elevations may occur with glucose loading—so-called “paradoxical” responses. In contrast, there is compensatory suppression of growth hormone secretion in obesity. Repletion of protein in the malnourished and reduction of weight in obesity cause return toward normal secretion of hgh. • Levodopa as a possible specific stimulus to growth hormone release has just been reported and the implications of this finding for the child of short stature cannot yet be assessed. PMID:4935302

  14. Insulin resistance and delayed clearance of peptide hormones in cirrhotic rat liver

    SciTech Connect

    Shankar, T.P.; Drake, S.; Solomon, S.S.

    1987-06-01

    Clearance of porcine insulin, glucagon, and human growth hormone was measured in intact perfused cirrhotic and normal rat livers. Binding and degradation of /sup 125/I-insulin by hepatocytes isolated from cirrhotic and normal livers were also studied. The half-lives (t/sub 1/2/) of immunoreactive insulin and glucagon were 14.0 +/- 3.1 and 9.6 +/- 2.1 min in normal livers and 26.0 +/- 6.1 and 25.0 +/- 7.1 min in cirrhotic livers. Insulin binding and degradation by hepatocytes from control and cirrhotic livers showed no significant differences. Intraportal insulin infusion in perfusion studies suppressed glucagon-stimulated increases in glucose output from control livers but failed to suppress glucose production by cirrhotic livers, suggesting the presence of hepatic insulin resistance in cirrhosis. Impaired clearance of insulin and glucagon by the intact cirrhotic liver and normal binding and degradation of insulin by isolated hepatocytes suggest that factors such as intrahepatic fibrosis and shunting and postbinding defects may be responsible for the impaired hormone clearance and hepatic insulin resistance.

  15. Zip1, Zip2, and Zip8 mRNA expressions were associated with growth hormone level during the growth hormone provocation test in children with short stature.

    PubMed

    Sun, Ping; Wang, Shifu; Jiang, Yali; Tao, Yanting; Tian, Yuanyuan; Zhu, Kai; Wan, Haiyan; Zhang, Lehai; Zhang, Lianying

    2013-10-01

    Short stature of children is affected by multiple factors. One of them is growth hormone (GH) deficiency. Growth hormone therapy can increase the final height of children with growth hormone deficiency. Zinc is found to induce dimerization and to enhance the bioactivity of human GH. Two gene families have been identified involved in zinc homeostasis. Previous studies in our laboratory have shown that Zip1, Zip2, Zip6, and ZnT1 mRNA were associated with zinc level in established human breast cancer in nude mice model; Zip8 was significantly lower in zinc-deficient Wistar rats in kidney. In this study, five zinc transporters: Zip1, Zip2, Zip6, Zip8, and ZnT1 were chosen. We aimed to investigate the mRNA expression of zinc transporters and to explore the relationship between zinc transporters and growth hormone in short stature children. Growth hormone provocation test is used to confirm the diagnosis of growth hormone deficiency. Six short children for the test were enrolled. At the same time, 15 sex- and age-matched normal children were enrolled as control. The expression levels of zinc transporters in peripheral blood mononuclear cells were determined by quantitative real-time PCR. Zip1 and Zip2 mRNA expression positively correlated with growth hormone level (r = 0.5133, P = 0.0371; r = 0.6719, P = 0.0032); Zip8 mRNA expression negatively correlated with growth hormone level (r = -0.5264, P = 0.0285) during the test in short stature children. The average expression level of Zip2 was significantly higher and Zip6, Zip8 mRNA levels were significantly lower in short stature children than in health controls at 0 min (P < 0.05, P < 0.05).

  16. Growth hormone treatment of renal growth failure during infancy and early childhood.

    PubMed

    Franke, Doris; Zivicnjak, Miroslav; Ehrich, Jochen H H

    2009-06-01

    Despite major progress in dialysis, nutrition and drug treatment in the past 20 years, growth of infants and toddlers with chronic kidney disease (CKD) remains a major challenge in paediatric nephrology. Our hypothesis is that early growth deficit is one of the most important factors for impaired final height in children with CKD, and we conclude that early implementation of recombinant human growth hormone (rhGH) therapy should be offered to infants with growth failure. Infants with delayed growth, adequate caloric intake and stable parameters of bone metabolism are candidates for rhGH therapy. One predictive factor for the selection of infants for rhGH treatment may be growth retardation at birth. Our conclusion from the limited published data is that the use of rhGH in young children with CKD is effective and safe. Compared with its use in older children, the early use of growth hormone requires lower absolute dosages of rhGH, which therefore reduce the annual treatment costs and allow earlier renal transplantation. Furthermore, an early start on rhGH improves the psychosocial situation later in childhood and may lead to a further improvement in adult height. A multi-centre randomised controlled study should be initiated to analyse the short-term and long-term effects of early rhGH therapy on infants with CKD.

  17. Osteocalcin induces growth hormone/insulin-like growth factor-1 system by promoting testosterone synthesis in male mice.

    PubMed

    Li, Y; Li, K

    2014-10-01

    Osteocalcin has been shown to enhance testosterone production in men. In the present study, we investigated the effects of osteocalcin on testosterone and on induction of the growth hormone/insulin-like growth factor-1 axis. Osteocalcin injection stimulated growth, which could be inhibited by castration. In addition, osteocalcin induced testosterone secretion in testes both in vivo and in vitro. Using real-time polymerase chain reaction and Western blotting, we showed that growth hormone expression was significantly increased in the pituitary after osteocalcin injection (p<0.05). Growth hormone expression in CLU401 mouse pituitary cells was also significantly stimulated (p<0.05) by osteocalcin-induced MA-10 cells. Osteocalcin injection also promoted hepatic expression of growth hormone receptor and insulin-like growth factor-1 (p<0.05), as demonstrated by real-time polymerase chain reaction and Western blotting. Similarly, osteocalcin-induced MA-10 cells promoted growth hormone receptor and insulin-like growth factor-1 expression in NCTC1469 cells. These results suggest that the growth-stimulating activities of osteocalcin are mediated by testicular testosterone secretion, and thus provide valuable information regarding the regulatory effects of osteocalcin expression on the growth hormone/insulin-like growth factor-1 axis via reproductive activities.

  18. Consequences of not treating children with laron syndrome (primary growth hormone insensitivity).

    PubMed

    Laron, Z

    2001-01-01

    The follow-up of a large cohort of patients with Laron syndrome (LS) from infancy to adult age has enabled us to determine the effects of long-term insulin-like growth factor-I (IGF-I) deficiency on auxological, biochemical, physiological and psychological parameters. We found that early and continuous IGF-I deficiency (the anabolic effector of growth hormone) causes dwarfism, acromicria, organomicria, marked obesity, insulin resistance, retardation of skeletal maturation and osteoporosis, as well as muscular and central nervous tissue underdevelopment, and a series of biochemical changes including hypercholesterolemia. These multiple pathologies impair the quality of life of these patients. It is concluded that patients with LS need IGF-I replacement treatment throughout life.

  19. Effects of recombinant human growth hormone in patients with severe sepsis.

    PubMed Central

    Voerman, H J; van Schijndel, R J; Groeneveld, A B; de Boer, H; Nauta, J P; van der Veen, E A; Thijs, L G

    1992-01-01

    The objective of this study was to evaluate the safety and the effect of recombinant exogenous growth hormone (GH) on nitrogen production in patients with severe sepsis. It was designed as a prospective, randomized, placebo-controlled trial, and performed in the medical intensive care unit of a university hospital. Twenty patients admitted with septic shock and receiving standard parenteral nutrition served as subjects. Treatment consisted of GH 0.1 mg/kg/day or placebo administered as continuous intravenous infusion on the second, third, and fourth days after admission. The study period was eight days. During GH administration, nitrogen production decreased significantly in the GH group and increased in controls (p < 0.01). Nitrogen balance became slightly positive in the GH group during treatment: 1.2 +/- 6.4 versus controls -3.7 +/- 3.8 g/day (day 3) (p < 0.05). Within 24 hours after cessation of treatment, differences between GH and controls disappeared. 3-Methylhistidine excretion as a measure of absolute muscle breakdown declined during the study period, but did not differ between groups. The levels of insulin, insulinlike growth factor 1, glycerol, free fatty acids, and beta-hydroxybutyrate increased during treatment. Despite continuous intravenous administration, GH levels gradually declined during the 3 treatment days, indicating increased metabolic clearance. Side effects other than insulin resistance were not observed. Growth hormone administration reduces nitrogen production and improves nitrogen balance in patients with severe sepsis. These effects are not sustained after cessation of treatment. PMID:1466618

  20. Triiodothyronine stimulates specifically growth hormone mRNA in rat pituitary tumor cells.

    PubMed

    Seo, H; Vassart, G; Brocas, H; Refetoff, S

    1977-05-01

    In a cell-free protein-synthesizing system from a rabbit reticulocyte lysate, total RNA extracted from cultured rat pituitary tumor (GH3) cells directed, in a dose-related manner, the synthesis of proteins that were precipitated by antisera specific to rat growth hormone (somatotropin) and rat prolactin. A marked decrease in growth hormone secretion and growth hormone mRNA activity was observed when cells were grown in a medium deficient in thyroid hormone. Addition of triiodothyronine in physiologic amounts both prevented and completely reversed this effect within 48 hr. Thyroid hormone had no effect on prolactin secretion or prolactin mRNA activity. These data suggest that thyroid hormone may stimulate synthesis of growth hormone through induction of transcriptional activity. The possibility of an additional effect at the posttranscriptional level has not been excluded. Although thyroid hormone is believed to have a general effect on a variety of metabolic processes, some effects, at the molecular level, may be quite selective, as indicated by the observed changes in growth hormone but not prolactin mRNA activity. The GH3 cell model is useful in the study of triiodothyronine action because of independence from secondary hormonal effects caused by hypothyroidism and because simultaneous measurement of prolactin mRNA activity serves as a unique internal control.

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

    MedlinePlus

    ... hGH in other countries also got CJD: In France, 120 people got CJD out of 1,700 ... not identical to hormone distributed by the NHPP. France, Britain, and Holland produced their own hormone. The ...

  2. Combination growth hormone and gonadotropin releasing hormone analog therapy in 11beta-hydroxylase deficiency.

    PubMed

    Bajpai, Anurag; Kabra, Madhulika; Menon, P S N

    2006-06-01

    Diagnosis of 11beta-hydroxylase deficiency was made in a boy at the age of 2 1/2 years on the basis of peripheral precocious puberty, growth acceleration (height standard deviation score +4.4) with advanced skeletal maturation (bone age 8.4 years) and elevated deoxycortisol levels. Glucocorticoid supplementation led to normalization of blood pressure but was associated with progression to central precocious puberty and increase in bone age resulting in decrease in predicted adult height to 133.7 cm (target height 163 cm). The child was started on GnRH analog (triptorelin 3.75 mg every 28 days), which led to improvement in predicted adult height by 3.1 cm over 15 months. Addition of growth hormone (0.1 IU/kg/day) resulted in improvement in predicted adult height (151 cm) and height deficit (12 cm) over the next 3.6 years. Final height (151 cm) exceeded predicted height at the initiation of GnRH analog treatment by 17.3 cm. This report suggests that combination GH and GnRH analog treatment may be useful in improving height outcome in children with 11beta-hydroxylase deficiency and compromised final height.

  3. Gigantism caused by growth hormone secreting pituitary adenoma.

    PubMed

    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.

  4. Gigantism caused by growth hormone secreting pituitary adenoma

    PubMed Central

    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

  5. Juvenile hormone regulates extreme mandible growth in male stag beetles.

    PubMed

    Gotoh, Hiroki; Cornette, Richard; Koshikawa, Shigeyuki; Okada, Yasukazu; Lavine, Laura Corley; Emlen, Douglas J; Miura, Toru

    2011-01-01

    The morphological diversity of insects is one of the most striking phenomena in biology. Evolutionary modifications to the relative sizes of body parts, including the evolution of traits with exaggerated proportions, are responsible for a vast range of body forms. Remarkable examples of an insect trait with exaggerated proportions are the mandibular weapons of stag beetles. Male stag beetles possess extremely enlarged mandibles which they use in combat with rival males over females. As with other sexually selected traits, stag beetle mandibles vary widely in size among males, and this variable growth results from differential larval nutrition. However, the mechanisms responsible for coupling nutrition with growth of stag beetle mandibles (or indeed any insect structure) remain largely unknown. Here, we demonstrate that during the development of male stag beetles (Cyclommatus metallifer), juvenile hormone (JH) titers are correlated with the extreme growth of an exaggerated weapon of sexual selection. We then investigate the putative role of JH in the development of the nutritionally-dependent, phenotypically plastic mandibles, by increasing hemolymph titers of JH with application of the JH analog fenoxycarb during larval and prepupal developmental periods. Increased JH signaling during the early prepupal period increased the proportional size of body parts, and this was especially pronounced in male mandibles, enhancing the exaggerated size of this trait. The direction of this response is consistent with the measured JH titers during this same period. Combined, our results support a role for JH in the nutrition-dependent regulation of extreme mandible growth in this species. In addition, they illuminate mechanisms underlying the evolution of trait proportion, the most salient feature of the evolutionary diversification of the insects.

  6. Rasch Measurement in the Assessment of Growth Hormone Deficiency in Adult Patients.

    ERIC Educational Resources Information Center

    Prieto, Luis; Roset, Montse; Badia, Xavier

    2001-01-01

    Tested the metric properties of a Spanish version of the Assessment of Growth Hormone Deficiency in Adults (AGHDA) questionnaire through Rasch analysis with a sample of 356 adult patients in Spain. Results suggest that the Spanish AGHDA could be a useful complement of the clinical evaluation of growth hormone deficiency patients at group and…

  7. Participation of JAK and STAT proteins in growth hormone-induced signaling.

    PubMed

    Han, Y; Leaman, D W; Watling, D; Rogers, N C; Groner, B; Kerr, I M; Wood, W I; Stark, G R

    1996-03-08

    The binding of growth hormone leads to dimerization of its receptor, accompanied by phosphorylation and activation of intracellular tyrosine kinases (JAKs) and the latent cytoplasmic transcriptions factors STAT1, STAT3, and STAT5. Both JAK1 and JAK2 are phosphorylated in response to growth hormone in mouse 3T3 F442A and human HT1080 cells. The roles of JAKs in growth hormone signal transduction were examined by using mutant HT1080 cells missing either JAK1 or JAK2. JAK2 is absolutely required for growth hormone-dependent phosphorylation of the receptor, STAT1 and STAT3, JAK1, and the SH2-containing adaptor molecule Shc. In contrast, JAK1 is not required for any of the above functions. These data indicate that JAK2 is both necessary and sufficient for the growth hormone-dependent phosphorylation events required to couple the receptor both to STAT-dependent signaling pathways and to pathways involving Shc. Furthermore, STAT5 is activated by growth hormone in 3T3 F442A cells, but not in HT1080 cells, revealing that the set of STATs activated by growth hormone can vary, possibly contributing to the specificity of the growth hormone response in different cell types.

  8. Messenger RNA patterns in rat liver nuclei before and after treat-ment with growth hormone.

    PubMed

    Drews, J; Brawerman, G

    1967-06-09

    Like cortisol, growth hormone enhances RNA synthesis in rat liver nuclei. However, DNA-RNA hybridization experiments show that the application of growth hormone does not stimulate the formation of new species of messenger RNA. The latter phenomenon was observed after treatment with cortisol.

  9. Recurrent hormone-binding domain truncated ESR1 amplifications in primary endometrial cancers suggest their implication in hormone independent growth

    PubMed Central

    Holst, Frederik; Hoivik, Erling A.; Gibson, William J.; Taylor-Weiner, Amaro; Schumacher, Steven E.; Asmann, Yan W.; Grossmann, Patrick; Trovik, Jone; Necela, Brian M.; Thompson, E. Aubrey; Meyerson, Matthew; Beroukhim, Rameen; Salvesen, Helga B.; Cherniack, Andrew D.

    2016-01-01

    The estrogen receptor alpha (ERα) is highly expressed in both endometrial and breast cancers, and represents the most prevalent therapeutic target in breast cancer. However, anti-estrogen therapy has not been shown to be effective in endometrial cancer. Recently it has been shown that hormone-binding domain alterations of ERα in breast cancer contribute to acquired resistance to anti-estrogen therapy. In analyses of genomic data from The Cancer Genome Atlas (TCGA), we observe that endometrial carcinomas manifest recurrent ESR1 gene amplifications that truncate the hormone-binding domain encoding region of ESR1 and are associated with reduced mRNA expression of exons encoding the hormone-binding domain. These findings support a role for hormone-binding alterations of ERα in primary endometrial cancer, with potentially important therapeutic implications. PMID:27160768

  10. Surface display of human growth hormone on Bacillus subtilis spores for oral administration.

    PubMed

    Lian, Chaoqun; Zhou, Yang; Feng, Fan; Chen, Liang; Tang, Qi; Yao, Qin; Chen, Keping

    2014-04-01

    Human growth hormone (hGH) is the major and important hormone component of human being. At present, hGH for clinical uses is mostly produced in Escherichia coli, which requires costly denaturation and refolding to recover functionality. To obtain long-term bioactive hormone, we used hGH as a foreign gene and constructed a recombinant plasmid pJS700-hGH which carries a recombinant gene cotC-hgh with an enterokinase site under the control of cotC promoter. Plasmid pJS700-hGH was transformed into Bacillus subtilis by double crossover and an amylase-inactivated mutant was produced. After spore formation, Western blot and fluorescence immunoassay were used to monitor hGH surface expression on spores. Oral administration to silkworm with spores displaying hGH further showed that the recombinant spores may have potential ability to be digested and absorbed into the silkworm's hemolymph due to both the resistant characters of spores and the addition of enterokinase site.

  11. Is the growth outcome of children with idiopathic short stature and isolated growth hormone deficiency following treatment with growth hormone and a luteinizing hormone-releasing hormone agonist superior to that obtained by GH alone?

    PubMed

    Colmenares, Ana; González, Laura; Gunczler, Peter; Lanes, Roberto

    2012-01-01

    The aim of this study was to evaluate the effect of combined therapy with growth hormone (GH) and luteinizing hormone-releasing hormone agonist (LHRHa) on the near-final height (NFH) of children with idiopathic short stature (ISS) and growth hormone deficiency (GHD) in early puberty. A retrospective analysis of 20 patients with ISS and 9 patients with GHD treated with combined therapy was undertaken. Twelve children with ISS and ten with GHD, treated with GH alone, served as controls. Patients were matched at baseline for chronological age, bone age, height standard deviation score (SDS), and pubertal development. Patients with ISS or GHD treated with combined therapy improved both their predicted adult height (PAH) at 2 years of therapy (ISS, p < 0.001; GHD, p = 0.03) and their NFH (ISS, p < 0.05; GHD, p = 0.05). Treatment with combined therapy did not generate additional benefits on the PAH after 2 years of therapy (ISS children, an increase of 7.9 +/- 4.9 cm with combined therapy vs. 7.3 +/- 6.0 cm with GH; GHD children, an increase of 6.8 +/- 7.8 cm with combined therapy vs. 5 +/- 5.9 cm with GH). The total height gain SDS was higher in patients treated with GH alone compared with those with combined therapy, but the difference was not significant (ISS children, a gain of 2.4 SDS with GH vs. 0.8 SDS with combined therapy; GHD children, a gain of 1.8 SDS with GH vs. 0.6 SDS with combined therapy). Although 2 years of combined treatment with GH and LHRHa improved the PAH and the NFH of ISS and GHD patients in early puberty, this improvement was not significant compared with that observed in similar subjects treated with GH alone.

  12. Placental growth hormone and growth hormone binding protein are first trimester maternal serum markers of Down syndrome.

    PubMed

    Christiansen, Michael

    2009-12-01

    Placental growth hormone (PGH) is synthesised by the placenta, and its function is modulated by growth hormone binding protein (GHBP). The potential of PGH and GHBP as maternal serum screening markers for Down syndrome (DS) was examined. Maternal serum concentrations of PGH and GHBP were determined by ELISA in 74 DS and 261 control pregnancies in gestational week 8(+0) to 13(+4). Log(10) MoM distributions of the markers were established. The performance of DS screening was estimated by Monte Carlo simulation. PGH log(10) MoM (SD) was decreased (p < 0.001) to -0.201 (0.373) and GHBP log(10) MoM to -0.116 (0.265) (p = 0.04), in DS pregnancies (n = 34) in week 8(+0) to 10(+0). In week 10(+1) to 13(+4), neither PGH (p = 0.16) nor GHBP (p = 0.13) was reduced in DS pregnancies. The detection rate (DR) for PGH in screening for DS in week 8(+0) to 10(+0) was 39% for a false positive rate (FPR) of 5%; increasing to 72% in combination with PAPP-A + hCGbeta. PGH + GHBP in combination with PAPP-A + hCGbeta + nuchal translucency (NT) (CUB test) had a DR of 91% compared with 80% for the CUB test. PGH and GHBP are early first trimester maternal serum markers for DS [Correction made here after initial online publication]. Copyright (c) 2009 John Wiley & Sons, Ltd.

  13. Hormone responses to an acute bout of low intensity blood flow restricted resistance exercise in college-aged females.

    PubMed

    Kim, Eonho; Gregg, Lee D; Kim, Ldaeyeol; Sherk, Vanessa D; Bemben, Michael G; Bemben, Debra A

    2014-01-01

    The purpose of this study was to determine whether the acute hormone response to exercise differed between low intensity blood flow restricted resistance exercise and traditional high-intensity resistance exercise in college-aged women. A total of 13 healthy women (aged 18-25 yrs), who were taking oral contraceptives, volunteered for this randomized crossover study. Subjects performed a session of low intensity blood flow restricted resistance exercise (BFR) (20% of 1-RM, 1 set 30 reps, 2 sets 15 reps) and a session of traditional high intensity resistance exercise without blood flow restriction (HI) (3 sets of 10 repetitions at 80% of 1-RM) on separate days. Fasting serum cortisol and growth hormone (GH) and blood lactate responses were measured in the morning pre and post exercise sessions. GH (Change: HI: 6.34 ± 1.72; BFR: 4.22 ± 1.40 ng·mL(-1)) and cortisol (Change: HI: 4.46 ± 1.53; BFR: 8.10 ± 2.30 ug·dL(-1)) significantly (p < 0.05) increased immediately post exercise for both protocols compared to baseline and there were no significant differences between the protocols for these responses. In contrast, blood lactate levels (HI: 7.35 ± 0.45; BFR: 4.02 ± 0.33 mmol·L(-1)) and ratings of perceived exertion were significantly (p < 0.01) higher for the HI protocol. In conclusion, acute BFR restricted resistance exercise stimulated similar increases in anabolic and catabolic hormone responses in young women. Key PointsGrowth hormone and cortisol levels significantly increased after a single bout of low intensity blood flow restricted resistance exercise in young women.There were no significant differences in hormone responses between the low intensity blood flow restricted protocol and the traditional high intensity higher total workload protocol.Low intensity blood flow restricted resistance exercise provides a sufficient stimulus to elicit anabolic and catabolic hormone responses in young women.

  14. Acute hormonal responses to heavy resistance exercise in strength athletes versus nonathletes.

    PubMed

    Ahtiainen, Juha P; Pakarinen, Arto; Kraemer, William J; Häkkinen, Keijo

    2004-10-01

    The aim of the present study was to investigate acute hormonal and neuromuscular responses and recovery in strength athletes versus nonathletes during heavy resistance exercise performed with the forced and maximum repetitions training protocol. Eight male strength athletes (SA) with several years of continuous resistance training experience and 8 physically active but non-strength athletes (NA) volunteered as subjects. The experimental design comprised two loading sessions: maximum repetitions (MR) and forced repetitions (FR). MR included 12-RM squats for 4 sets with a 2-min recovery between sets. In FR the initial load was higher than in MR so that the subject could lift approximately 8 repetitions by himself and 4 additional repetitions with assistance. Before and after the loading protocols, blood samples were drawn to determine serum testosterone, free testosterone, cortisol and growth hormone concentrations, and blood lactate. Maximal voluntary isometric force and EMG activity of the leg extensors was measured before and after the loading as well as 24 and 48 hrs after the loading. The concentrations of the hormones measured increased significantly (p < .01-.001) after both loadings in both groups. The responses tended to be higher in FR than the MR loading and the increases of testosterone concentrations were significantly (p < .01) greater in both loadings in SA than in NA. Both loading protocols in both groups also led to neuromuscular fatigue observable with significant acute decreases in isometric strength by 32-52% (p < .001) and in maximal iEMG (p < .05-01) associated with large increases in blood lactate. These data suggest that, at least in experienced strength athletes, the forced-repetition protocol is a viable alternative to the more traditional maximum-repetition protocol and may even be a superior approach.

  15. Hyperphagia in male melanocortin 4 receptor deficient mice promotes growth independently of growth hormone.

    PubMed

    Tan, H Y; Steyn, F J; Huang, L; Cowley, M; Veldhuis, J D; Chen, C

    2016-12-15

    Loss of function of the melanocortin 4 receptor (MC4R) results in hyperphagia, obesity and increased growth. Despite knowing that MC4Rs control food intake, we are yet to understand why defects in the function of the MC4R receptor contribute to rapid linear growth. We show that hyperphagia following germline loss of MC4R in male mice promotes growth while suppressing the growth hormone-insulin-like growth factor-1 (GH-IGF-1) axis. We propose that hyperinsulinaemia promotes growth while suppressing the GH-IGF-1 axis. It is argued that physiological responses essential to maintain energy flux override conventional mechanisms of pubertal growth to promote the storage of excess energy while ensuring growth. Defects in melanocortin-4-receptor (MC4R) signalling result in hyperphagia, obesity and increased growth. Clinical observations suggest that loss of MC4R function may enhance growth hormone (GH)-mediated growth, although this remains untested. Using male mice with germline loss of the MC4R, we assessed pulsatile GH release and insulin-like growth factor-1 (IGF-1) production and/or release relative to pubertal growth. We demonstrate early-onset suppression of GH release in rapidly growing MC4R deficient (MC4RKO) mice, confirming that increased linear growth in MC4RKO mice does not occur in response to enhanced activation of the GH-IGF-1 axis. The progressive suppression of GH release in MC4RKO mice occurred alongside increased adiposity and the progressive worsening of hyperphagia-associated hyperinsulinaemia. We next prevented hyperphagia in MC4RKO mice through restricting calorie intake in these mice to match that of wild-type (WT) littermates. Pair feeding of MC4RKO mice did not prevent increased adiposity, but attenuated hyperinsulinaemia, recovered GH release, and normalized linear growth rate to that seen in pair-fed WT littermate controls. We conclude that the suppression of GH release in MC4RKO mice occurs independently of increased adipose mass, and is a

  16. Growth hormone polymorphisms and growth traits in Chinese Tibetan sheep Ovis aries.

    PubMed

    Han, Y C; Sun, Y G; Li, Q

    2016-08-26

    Growth hormone (GH) plays an important role in promoting growth, protein and muscle accretion, and fat catabolism, suggesting that GH is a potential candidate gene affecting growth traits in vertebrates. In this paper, polymorphisms in GH were investigated in 632 Chinese Tibetan sheep, by using DNA sequencing. Three single nucleotide polymorphisms were identified, including two mutations (g.616G>A and g.624G>A) in intron 2 and one synonymous mutation (g.498G>C) in exon 2. Association analyses showed that both g.498G>C and g.616G>A were significantly associated with several growth traits (at P < 0.01 or P < 0.05) in three investigated breeds. Our results demonstrate that GH variation may be used as a molecular marker for growth traits in Chinese Tibetan sheep.

  17. Contribution of human growth hormone-releasing hormone receptor (GHRHR) gene sequence variation to isolated severe growth hormone deficiency (ISGHD) and normal adult height.

    PubMed

    Camats, Núria; Fernández-Cancio, Mónica; Carrascosa, Antonio; Andaluz, Pilar; Albisu, M Ángeles; Clemente, María; Gussinyé, Miquel; Yeste, Diego; Audí, Laura

    2012-10-01

    Molecular causes of isolated severe growth hormone deficiency (ISGHD) in several genes have been established. The aim of this study was to analyse the contribution of growth hormone-releasing hormone receptor (GHRHR) gene sequence variation to GH deficiency in a series of prepubertal ISGHD patients and to normal adult height. A systematic GHRHR gene sequence analysis was performed in 69 ISGHD patients and 60 normal adult height controls (NAHC). Four GHRHR single-nucleotide polymorphisms (SNPs) were genotyped in 248 additional NAHC. An analysis was performed on individual SNPs and combined genotype associations with diagnosis in ISGHD patients and with height-SDS in NAHC. Twenty-one SNPs were found. P3, P13, P15 and P20 had not been previously described. Patients and controls shared 12 SNPs (P1, P2, P4-P11, P16 and P21). Significantly different frequencies of the heterozygous genotype and alternate allele were detected in P9 (exon 4, rs4988498) and P12 (intron 6, rs35609199); P9 heterozygous genotype frequencies were similar in patients and the shortest control group (heights between -2 and -1 SDS) and significantly different in controls (heights between -1 and +2 SDS). GHRHR P9 together with 4 GH1 SNP genotypes contributed to 6·2% of height-SDS variation in the entire 308 NAHC. This study established the GHRHR gene sequence variation map in ISGHD patients and NAHC. No evidence of GHRHR mutation contribution to ISGHD was found in this population, although P9 and P12 SNP frequencies were significantly different between ISGHD and NAHC. Thus, the gene sequence may contribute to normal adult height, as demonstrated in NAHC. © 2012 Blackwell Publishing Ltd.

  18. Aberrant alternative splicing of thyroid hormone receptor in a TSH-secreting pituitary tumor is a mechanism for hormone resistance.

    PubMed

    Ando, S; Sarlis, N J; Krishnan, J; Feng, X; Refetoff, S; Zhang, M Q; Oldfield, E H; Yen, P M

    2001-09-01

    Patients with TSH-secreting pituitary tumors (TSHomas) have high serum TSH levels despite elevated thyroid hormone levels. The mechanism for this defect in the negative regulation of TSH secretion is not known. We performed RT-PCR to detect mutations in TRbeta from a surgically resected TSHoma. Analyses of the RT-PCR products revealed a 135-bp deletion within the sixth exon that encodes the ligand-binding domain of TRbeta2. This deletion was caused by alternative splicing of TRbeta2 mRNA, as near-consensus splice sequences were found at the junction site and no deletion or mutations were detected in the tumoral genomic DNA. This TRbeta variant (TRbeta2spl) lacked thyroid hormone binding and had impaired T3-dependent negative regulation of both TSHbeta and glycoprotein hormone alpha-subunit genes in cotransfection studies. Furthermore, TRbeta2spl showed dominant negative activity against the wild-type TRbeta2. These findings strongly suggest that aberrant alternative splicing of TRbeta2 mRNA generated an abnormal TR protein that accounted for the defective negative regulation of TSH in the TSHoma. This is the first example of aberrant alternative splicing of a nuclear hormone receptor causing hormonal dysregulation. This novel posttranscriptional mechanism for generating abnormal receptors may occur in other hormone-resistant states or tumors in which no receptor mutation is detected in genomic DNA.

  19. Exogenous recombinant bovine growth hormone stimulates growth and hepatic IGF expression in shovelnose sturgeon Scaphirhynchus platorhynchus.

    PubMed

    Fenn, Carlin M; Small, Brian C

    2015-02-01

    Sturgeon are a unique fish for physiological research as they are long-lived, slow-growing, and late-maturing. Furthermore, sturgeon growth hormones appear to share greater structural and molecular similarity with mammalian somatotropins than teleostean somatotropins. In this study, changes in insulin-like growth factor (IGF)-I and IGF-II mRNA expression and corresponding whole-body growth and composition following 6 weeks of bi-weekly recombinant bovine growth hormone (rbGH) administration in shovelnose sturgeon Scaphirhynchus platorhynchus were evaluated. Fish were injected intraperitoneally with 240 μg rbGH/g body weight or a sesame oil sham. Hepatic IGF-I and IGF-II mRNA abundance was significantly higher (P≤0.02) in rbGH-treated fish, as were length (P<0.001) and weight gain (P<0.001). In addition, proximate whole-body analysis demonstrated a significant (P<0.05) increase in protein composition of rbGH-treated fish versus sham-treated fish. There were no significant differences in whole-body moisture, lipid, or ash between the two treatments. These results demonstrate functional roles for GH and IGFs in the promotion of lean growth within this ancient fish species and support the view that the functional effects of GH on hepatic IGF-I expression and somatic growth are conserved from chondostrean to teleostean fishes. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Hormonal interactions during root tropic growth: hydrotropism versus gravitropism.

    PubMed

    Takahashi, Hideyuki; Miyazawa, Yutaka; Fujii, Nobuharu

    2009-03-01

    Terrestrial plants have evolved remarkable morphological plasticity that enables them to adapt to their surroundings. One of the most important traits that plants have acquired is the ability to sense environmental cues and use them as a basis for governing their growth orientation. The directional growth of plant organs relative to the direction of environmental stimuli is a tropism. The Cholodny-Went theory proposes that auxin plays a key role in several tropisms. Recent molecular genetic studies have strongly supported this hypothesis for gravitropism. However, the molecular mechanisms of other tropisms are far less clear. Hydrotropism is the response of roots to a moisture gradient. Since its re-discovery in 1985, root hydrotropism has been shown to be common among higher plant species. Additionally, in some species, gravitropism interferes with hydrotropism, suggesting that both shared and divergent mechanisms mediating the two tropisms exist. This hypothesis has been supported by recent studies, which provide an understanding of how roots sense multiple environmental cues and exhibit different tropic responses. In this review, we focus on the overlapping and unique mechanisms of the hormonal regulation underlying gravitropism and hydrotropism in roots.

  1. Do deficiencies in growth hormone and insulin-like growth factor-1 (IGF-1) shorten or prolong longevity?

    PubMed

    Laron, Zvi

    2005-02-01

    Present knowledge on the effects of growth hormone (GH) and insulin-like growth factor-I (IGF-I) deficiency on aging and lifespan are controversial. Studying untreated patients with either isolated GH deficiency due to GH gene deletion, patients with multiple pituitary hormone deficiency due to PROP-1 gene mutation and patients with isolated IGF-I deficiency due to deletions or mutations of the GH receptor gene (Laron syndrome); it was found, that these patients despite signs of early aging (wrinkled skin, obesity, insulin resistance and osteopenia) have a long life span reaching ages of 80-90 years. Animal models of genetic GH deficiencies such as Snell mice (Pit-1 gene mutations) the Ames mice (PROP-1 gene mutation) and the Laron mice (GH receptor gene knock-out) have a statistically significant higher longevity compared to normal controls. On the contrary, mice transgenic for GH and acromegalic patients secreting high amounts of GH have premature death. Those data raise the question whether pharmacological GH administration to adults is deleterious, in contrast to policies advocating such therapies.

  2. A study of cell electrophoresis as a means of purifying growth hormone secreting cells

    NASA Technical Reports Server (NTRS)

    Plank, Lindsay D.; Hymer, W. C.; Kunze, M. Elaine; Marks, Gary M.; Lanham, J. Wayne

    1983-01-01

    Growth hormone secreting cells of the rat anterior pituitary are heavily laden with granules of growth hormone and can be partialy purified on the basis of their resulting high density. Two methods of preparative cell electrophoresis were investigated as methods of enhancing the purification of growth hormone producing cells: density gradient electrophoresis and continuous flow electrophoresis. Both methods provided a two- to four-fold enrichment in growth hormone production per cell relative to that achieved by previous methods. Measurements of electrophoretic mobilities by two analytical methods, microscopic electrophoresis and laser-tracking electrophoresis, revealed very little distinction between unpurified anterior pituitary cell suspensions and somatotroph-enriched cell suspensions. Predictions calculated on the basis of analytical electrophoretic data are consistent with the hypothesis that sedimentation plays a significant role in both types of preparative electrophoresis and the electrophoretic mobility of the growth hormone secreting subpopulation of cells remains unknown.

  3. A study of cell electrophoresis as a means of purifying growth hormone secreting cells

    NASA Technical Reports Server (NTRS)

    Plank, Lindsay D.; Hymer, W. C.; Kunze, M. Elaine; Marks, Gary M.; Lanham, J. Wayne

    1983-01-01

    Growth hormone secreting cells of the rat anterior pituitary are heavily laden with granules of growth hormone and can be partialy purified on the basis of their resulting high density. Two methods of preparative cell electrophoresis were investigated as methods of enhancing the purification of growth hormone producing cells: density gradient electrophoresis and continuous flow electrophoresis. Both methods provided a two- to four-fold enrichment in growth hormone production per cell relative to that achieved by previous methods. Measurements of electrophoretic mobilities by two analytical methods, microscopic electrophoresis and laser-tracking electrophoresis, revealed very little distinction between unpurified anterior pituitary cell suspensions and somatotroph-enriched cell suspensions. Predictions calculated on the basis of analytical electrophoretic data are consistent with the hypothesis that sedimentation plays a significant role in both types of preparative electrophoresis and the electrophoretic mobility of the growth hormone secreting subpopulation of cells remains unknown.

  4. Hormone-Mediated Pattern Formation in Seedling of Plants: a Competitive Growth Dynamics Model

    NASA Astrophysics Data System (ADS)

    Kawaguchi, Satoshi; Mimura, Masayasu; Ohya, Tomoyuki; Oikawa, Noriko; Okabe, Hirotaka; Kai, Shoichi

    2001-10-01

    An ecologically relevant pattern formation process mediated by hormonal interactions among growing seedlings is modeled based on the experimental observations on the effects of indole acetic acid, which can act as an inhibitor and activator of root growth depending on its concentration. In the absence of any lateral root with constant hormone-sensitivity, the edge effect phenomenon is obtained depending on the secretion rate of hormone from the main root. Introduction of growth-stage-dependent hormone-sensitivity drastically amplifies the initial randomness, resulting in spatially irregular macroscopic patterns. When the lateral root growth is introduced, periodic patterns are obtained whose periodicity depends on the length of lateral roots. The growth-stage-dependent hormone-sensitivity and the lateral root growth are crucial for macroscopic periodic-pattern formation.

  5. Effect of obesity and starvation on thyroid hormone, growth hormone, and cortisol secretion.

    PubMed

    Douyon, Liselle; Schteingart, David E

    2002-03-01

    Obesity and starvation have opposing affects on normal physiology and are associated with adaptive changes in hormone secretion. The effects of obesity and starvation on thyroid hormone, GH, and cortisol secretion are summarized in Table 1. Although hypothyroidism is associated with some weight gain, surveys of obese individuals show that less than 10% are hypothyroid. Discrepancies have been reported in some studies, but in untreated obesity, total and free T4, total and free T3, TSH levels, and the TSH response to TRH are normal. Some reports suggest an increase in total T3 and decrease in rT3 induced by overfeeding. Treatment of obesity with hypocaloric diets causes changes in thyroid function that resemble sick euthyroid syndrome. Changes consist of a decrease in total T4 and total and free T3 with a corresponding increase in rT3. untreated obesity is also associated with low GH levels; however, levels of IGF-1 are normal. GH-binding protein levels are increased and the GH response to GHRH is decreased. These changes are reversed by drastic weight reduction. Cortisol levels are abnormal in people with abdominal obesity who exhibit an increase in urinary free cortisol but exhibit normal or decreased serum cortisol and normal ACTH levels. These changes are explained by an increase in cortisol clearance. There is also an increased response to CRH. Treatment of obesity with very low calorie diets causes a decrease in serum cortisol explained by a decrease in cortisol-binding proteins. The increase in cortisol secretion seen in patients with abdominal obesity may contribute to the metabolic syndrome (insulin resistance, glucose intolerance, dyslipidemia, and hypertension). States of chronic starvation such as seen in anorexia nervosa are also associated with changes in thyroid hormone, GH, and cortisol secretion. There is a decrease in total and free T4 and T3, and an increase in rT3 similar to findings in sick euthyroid syndrome. The TSH response to TRH is

  6. Diverse roles of growth hormone and insulin-like growth factor-1 in mammalian aging: progress and controversies.

    PubMed

    Sonntag, William E; Csiszar, Anna; deCabo, Raphael; Ferrucci, Luigi; Ungvari, Zoltan

    2012-06-01

    Because the initial reports demonstrating that circulating growth hormone and insulin-like growth factor-1 decrease with age in laboratory animals and humans, there have been numerous studies related to the importance of these hormones for healthy aging. Nevertheless, the role of these potent anabolic hormones in the genesis of the aging phenotype remains controversial. In this chapter, we review the studies demonstrating the beneficial and deleterious effects of growth hormone and insulin-like growth factor-1 deficiency and explore their effects on specific tissues and pathology as well as their potentially unique effects early during development. Based on this review, we conclude that the perceived contradictory roles of growth hormone and insulin-like growth factor-1 in the genesis of the aging phenotype should not be interpreted as a controversy on whether growth hormone or insulin-like growth factor-1 increases or decreases life span but rather as an opportunity to explore the complex roles of these hormones during specific stages of the life span.

  7. Diverse Roles of Growth Hormone and Insulin-Like Growth Factor-1 in Mammalian Aging: Progress and Controversies

    PubMed Central

    Csiszar, Anna; de Cabo, Raphael; Ferrucci, Luigi; Ungvari, Zoltan

    2012-01-01

    Because the initial reports demonstrating that circulating growth hormone and insulin-like growth factor-1 decrease with age in laboratory animals and humans, there have been numerous studies related to the importance of these hormones for healthy aging. Nevertheless, the role of these potent anabolic hormones in the genesis of the aging phenotype remains controversial. In this chapter, we review the studies demonstrating the beneficial and deleterious effects of growth hormone and insulin-like growth factor-1 deficiency and explore their effects on specific tissues and pathology as well as their potentially unique effects early during development. Based on this review, we conclude that the perceived contradictory roles of growth hormone and insulin-like growth factor-1 in the genesis of the aging phenotype should not be interpreted as a controversy on whether growth hormone or insulin-like growth factor-1 increases or decreases life span but rather as an opportunity to explore the complex roles of these hormones during specific stages of the life span. PMID:22522510

  8. Traditional and novel aspects of the metabolic actions of growth hormone.

    PubMed

    Sperling, Mark A

    2016-06-01

    Growth hormone has been known to be diabetogenic for almost a century and it's diabetogenic properties fostered consideration of excessive and abnormal GH secretion as a cause of diabetes, as well as a role in the microvascular complications, especially retinopathy. However, besides inducing insulin resistance, GH also is lipolytic and a major anabolic hormone for nitrogen retention and protein synthesis. These actions are best illustrated at the extremes of GH secretion: Gigantism/acromegaly is characterized by excessive growth, CHO intolerance, hyperplasia of bone, little body fat and prominent muscle development, whereas total deficiency of GH secretion or action is associated with adiposity, poor growth, and poor muscle development. These actions also become apparent during puberty and pregnancy, times when GH secretion is increased and account for the characteristic changes in body composition and tendency to diabetes. More recently, tissue specific deletions of the GH receptor (GHR), have uncovered newer metabolic effects including it's essential role in triglyceride export from the liver when GHR is deleted in the liver, leading to hepatic steatosis and ultimately to hepatic adenoma formation, effects which may explain these findings in obesity, a state of diminished GH secretion and action. In addition deletion of GH action in muscle and fat is associated with specific patterns of disturbed phenotype and metabolic effects in CHO, fat, and protein metabolism affecting the specific tissue and whole body function. This chapter provides an overview of these classic and newer metabolic functions of GH, placing this hormone and its actions in a central role of body fuel economy in health and disease.

  9. Hormone resistance caused by mutations in G proteins and G protein-coupled receptors.

    PubMed

    Spiegel, A M

    1999-04-01

    G proteins couple receptors for many hormones to effectors that regulate second messenger metabolism. Several endocrine disorders have been shown to be caused by either loss or gain of function mutations in G proteins or G protein-coupled receptors. Pseudohypoparathyroidism (PHP), the first described example of a hormone resistance disorder, is characterized by renal resistance to parathyroid hormone (PTH) proximal to generation of the second messenger, cAMP. In PHP Ia there is more generalized hormone resistance (PTH, TSH, gonadotropins) and associated abnormal physical features, Albright hereditary osteodystrophy (AHO). Subjects with PHP Ib are normal in appearance and resistant exclusively to PTH. Germline loss of function mutations have been identified in the Gs-alpha gene in PHP Ia, and recent evidence suggests that the Gs-alpha gene is paternally imprinted in a tissue-specific manner. In PHP Ib, several studies have excluded PTH receptor gene mutations, and the molecular basis has not yet been defined.

  10. Vaccine Therapy and Pembrolizumab in Treating Patients With Hormone-Resistant, Metastatic Prostate Cancer

    ClinicalTrials.gov

    2016-11-23

    Hormone-Resistant Prostate Cancer; Metastatic Malignant Neoplasm in the Bone; Metastatic Malignant Neoplasm in the Soft Tissues; Metastatic Prostate Carcinoma; Prostate Adenocarcinoma; Recurrent Prostate Carcinoma; Stage IV Prostate Cancer

  11. Effect of zinc sulphate and zinc methionine on growth, plasma growth hormone concentration, growth hormone receptor and insulin-like growth factor-I gene expression in mice.

    PubMed

    Yu, Ze-Peng; Le, Guo-Wei; Shi, Yong-Hui

    2005-04-01

    1. The current experiment was conducted to investigate the effect of zinc sulphate (ZnSO4) and zinc methionine (Zn-Met) on growth and their effect on plasma growth hormone (GH) concentration, growth hormone receptor (GHR) and insulin-like growth factor I (IGF-I) mRNA expression in mice. 2. Ninety male KunMing (KM) mice were randomly divided into three treatments. The control group was fed on a basal diet containing 11.67 mg/kg of zinc. The ZnSO4 group and Zn-Met group were fed on the diets supplemented with ZnSO4 or Zn-Met at 30 mg/kg (containing zinc of 40.05 and 40.75 mg/kg, respectively). The mice were offered the test diets for 10 days. Weight gains and food intake were measured at the end of the experiment, zinc contents in liver and serum were determined using atomic absorption spectrophotometry; GH was determined by radioimmunoassay, the levels of GHR and IGF-I mRNA were determined with reverse transcript polymerase chain reaction. 3. Both ZnSO4 and Zn-Met enhanced weight gain and food intake in the mice, Zn-Met improved the growth and food intake more effectively than ZnSO4 did (P < 0.05). The both forms of zinc had no effect on GH and the level of GHR mRNA expression (P > 0.05) and they up-regulated the expression of IGF-I mRNA (P < 0.05). As compared to ZnSO4, Zn-Met enhanced the level of IGF-I mRNA significantly (P < 0.05). 4. Both ZnSO4 and Zn-Met had no effect on plasma GH and the expression of GHR mRNA, but they enhanced the expression of IGF-I mRNA. Zinc methionine enhanced the weight gain and up-regulated IGF-I mRNA expression more effectively than ZnSO4.

  12. Hepatic receptors for homologous growth hormone in the eel

    SciTech Connect

    Hirano, T. )

    1991-03-01

    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.

  13. A statistical model of diurnal variation in human growth hormone

    NASA Technical Reports Server (NTRS)

    Klerman, Elizabeth B.; Adler, Gail K.; Jin, Moonsoo; Maliszewski, Anne M.; Brown, Emery N.

    2003-01-01

    The diurnal pattern of growth hormone (GH) serum levels depends on the frequency and amplitude of GH secretory events, the kinetics of GH infusion into and clearance from the circulation, and the feedback of GH on its secretion. We present a two-dimensional linear differential equation model based on these physiological principles to describe GH diurnal patterns. The model characterizes the onset times of the secretory events, the secretory event amplitudes, as well as the infusion, clearance, and feedback half-lives of GH. We illustrate the model by using maximum likelihood methods to fit it to GH measurements collected in 12 normal, healthy women during 8 h of scheduled sleep and a 16-h circadian constant-routine protocol. We assess the importance of the model components by using parameter standard error estimates and Akaike's Information Criterion. During sleep, both the median infusion and clearance half-life estimates were 13.8 min, and the median number of secretory events was 2. During the constant routine, the median infusion half-life estimate was 12.6 min, the median clearance half-life estimate was 11.7 min, and the median number of secretory events was 5. The infusion and clearance half-life estimates and the number of secretory events are consistent with current published reports. Our model gave an excellent fit to each GH data series. Our analysis paradigm suggests an approach to decomposing GH diurnal patterns that can be used to characterize the physiological properties of this hormone under normal and pathological conditions.

  14. A statistical model of diurnal variation in human growth hormone

    NASA Technical Reports Server (NTRS)

    Klerman, Elizabeth B.; Adler, Gail K.; Jin, Moonsoo; Maliszewski, Anne M.; Brown, Emery N.

    2003-01-01

    The diurnal pattern of growth hormone (GH) serum levels depends on the frequency and amplitude of GH secretory events, the kinetics of GH infusion into and clearance from the circulation, and the feedback of GH on its secretion. We present a two-dimensional linear differential equation model based on these physiological principles to describe GH diurnal patterns. The model characterizes the onset times of the secretory events, the secretory event amplitudes, as well as the infusion, clearance, and feedback half-lives of GH. We illustrate the model by using maximum likelihood methods to fit it to GH measurements collected in 12 normal, healthy women during 8 h of scheduled sleep and a 16-h circadian constant-routine protocol. We assess the importance of the model components by using parameter standard error estimates and Akaike's Information Criterion. During sleep, both the median infusion and clearance half-life estimates were 13.8 min, and the median number of secretory events was 2. During the constant routine, the median infusion half-life estimate was 12.6 min, the median clearance half-life estimate was 11.7 min, and the median number of secretory events was 5. The infusion and clearance half-life estimates and the number of secretory events are consistent with current published reports. Our model gave an excellent fit to each GH data series. Our analysis paradigm suggests an approach to decomposing GH diurnal patterns that can be used to characterize the physiological properties of this hormone under normal and pathological conditions.

  15. Hormones and the Resistance of Women to Paracoccidioidomycosis

    PubMed Central

    Shankar, Jata; Restrepo, Angela; Clemons, Karl V.; Stevens, David A.

    2011-01-01

    Summary: Paracoccidioidomycosis, one of the most important endemic and systemic mycoses in Latin America, presents several clinical pictures. Epidemiological studies indicate a striking rarity of disease (but not infection) in females, but only during the reproductive years. This suggested a hormonal interaction between female hormones and the etiologic dimorphic fungus Paracoccidioides brasiliensis. Many fungi have been shown to use hormonal (pheromonal) fungal molecules for intercellular communication, and there are increasing numbers of examples of interactions between mammalian hormones and fungi, including the specific binding of mammalian hormones by fungal proteins, and suggestions of mammalian hormonal modulation of fungal behavior. This suggests an evolutionary conservation of hormonal receptor systems. We recount studies showing the specific hormonal binding of mammalian estrogen to proteins in P. brasiliensis and an action of estrogen to specifically block the transition from the saprophytic form to the invasive form of the fungus in vitro. This block has been demonstrated to occur in vivo in animal studies. These unique observations are consistent with an estrogen-fungus receptor-mediated effect on pathogenesis. The fungal genes responsive to estrogen action are under study. PMID:21482727

  16. Growth hormone deficiency: new approaches to the diagnosis.

    PubMed

    Binder, Gerhard

    2011-09-01

    . Because of the well known intrinsic diagnostic inaccuracy of any GH test, the correct selection of the child to be tested remains of utmost importance. The diagnosis of growth hormone deficiency (GHD) in childhood is guided by recommendations of national and international consensus statements which are based on the experience of experts. Most of these recommendations reach only a low level of evidence. Research on two central topics of these guidelines has recently been published by us and will be reviewed here.

  17. Hormones

    MedlinePlus

    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, ...

  18. Growth hormone stimulates protein synthesis during hypocaloric parenteral nutrition. Role of hormonal-substrate environment.

    PubMed Central

    Manson, J M; Smith, R J; Wilmore, D W

    1988-01-01

    The influence of growth hormone (GH) on protein metabolism and fuel utilization was investigated in eight paired studies of normal volunteers. GH (10 mg) was given daily during one period, and saline was injected during control studies. For 6 days, subjects received parenteral nutrition that provided adequate dietary nitrogen, vitamin, and minerals, but energy intake varied to provide 30-100% of requirements. On Day 7, the feedings were discontinued and an oral glucose load (100 g) was administered. The level of energy intake did not markedly influence the actions of GH. During nutrient infusions, GH caused positive nitrogen balance (1.0 +/- 0.3 g/m2/day vs. -1.2 +/- 0.3 in controls, p less than 0.001) and increased protein synthesis (16.8 +/- 0.7 g N/m2/day vs. 13.9 +/- 0.8, p less than 0.01). No change in the rate of protein breakdown or excretion of 3-methylhistidine occurred. GH was associated with an increase in insulin and insulin-like growth factor-I concentrations (IGF-I, 9.1 +/- 0.6 IU/ml vs. 3.3 +/- 0.5, p less than 0.001). After discontinuation of the parenteral nutrition and administration of the oral glucose load, glucose concentrations tended to be higher after GH; however, despite a two- to threefold increase in insulin response, muscle glucose uptake was attenuated (1.10 +/- 0.19 g/kg forearm vs. 1.64 +/- 0.30 in controls, p less than 0.05). Compared with control conditions, GH appeared to attenuate the increase in amino acid nitrogen efflux from muscle after the administration of oral glucose. These data demonstrate that the protein anabolic effect of GH, which occurs even during hypocaloric feedings, is related to multiple mechanisms that favor protein synthesis. These include the increase in plasma concentrations of GH, insulin IGF-I and fat utilization. GH administration results in a hormonal-substrate environment that favors nitrogen retention and protein synthesis. GH may be beneficial in promoting protein synthesis in surgical patients

  19. Comparative effects of recombinant ovine placental lactogen and bovine growth hormone on galactopoiesis in ewes.

    PubMed

    Min, S H; Mackenzie, D D; McCutcheon, S N; Breier, B H; Gluckman, P D

    1997-04-01

    The effects of recombinant ovine placental lactogen and bovine growth hormone on milk yield, milk composition, and concentrations of blood hormones and metabolites were compared in ewes during an established lactation. Beginning on d 17 of lactation, ewes were treated for 5 d with twice daily subcutaneous injections of ovine placental lactogen (n = 9), bovine growth hormone (n = 10) at a dose of 0.10 mg/d per kg of body weight, or saline (n = 10). Circulating concentrations of ovine placental lactogen were 24.6 +/- 1.6 ng/ml on d 5 for ewes treated with ovine placental lactogen, but concentrations of ovine placental lactogen were undetectable in ewes treated with either saline or bovine growth hormone. Treatment with bovine growth hormone increased circulating concentrations of growth hormone, insulin-like growth factor-I, and nonesterified fatty acids and decreased urea concentrations relative to those in ewes treated with ovine placental lactogen or saline. Compared with saline treatment, no parameters were affected by treatment with ovine placental lactogen. Treatment with bovine growth hormone or ovine placental lactogen treatment had no significant effects on plasma concentrations of insulin, glucose, or creatinine. Treatment with bovine growth hormone, but not ovine placental lactogen, increased yields of milk, fat, and lactose. Weight of the mammary gland was increased by bovine growth hormone, but not by ovine placental lactogen. Despite the fact that ovine placental lactogen is a potent somatogen, it does not appear to exhibit the same galactopoietic activity as bovine growth hormone in lactating ewes.

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

    SciTech Connect

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

    2012-11-15

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