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Sample records for growth hormone resistance

  1. Determinants of Growth Hormone Resistance in Malnutrition

    PubMed Central

    Fazeli, Pouneh K.; Klibanski, Anne

    2014-01-01

    States of under-nutrition are characterized by growth hormone resistance. Decreased total energy intake, as well as isolated protein-calorie malnutrition and isolated nutrient deficiencies result in elevated growth hormone levels and low levels of IGF-I. We review various states of malnutrition and a disease state characterized by chronic under-nutrition -- anorexia nervosa -- and discuss possible mechanisms contributing to the state of growth hormone resistance, including FGF-21 and SIRT1. We conclude by examining the hypothesis that growth hormone resistance is an adaptive response to states of under-nutrition, in order to maintain euglycemia and preserve energy. PMID:24363451

  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. Growth Hormone

    MedlinePlus

    ... the dose of glucose. Growth hormone stimulates the production of insulin-like growth factor-1 (IGF-1) . ... regular intervals for years afterward to monitor GH production and to detect tumor recurrence. Other blood tests ...

  5. 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.

  6. Impact of growth hormone resistance on female reproductive function: new insights from growth hormone receptor knockout mice.

    PubMed

    Zaczek, Denise; Hammond, James; Suen, Lii; Wandji, Serge; Service, Darlene; Bartke, Andrzej; Chandrashekar, Varadaraj; Coschigano, Karen; Kopchick, John

    2002-10-01

    We examined multiple aspects of reproductive function in growth hormone receptor gene knockout (GHR-KO) and normal mice to clarify the role of growth hormone in female reproduction. In adult animals, estrous cycle duration was comparable in all mice housed individually but was significantly longer in group-housed GHR-KO females. Histological evaluation of ovaries of adult females at estrus showed that the numbers of preovulatory follicles and corpora lutea were significantly reduced in GHR-KO mice, as was the plasma estradiol level. The number of atretic preovulatory follicles was reduced in GHR gene-ablated animals. Although reverse transcription polymerase chain reaction analysis revealed reduced ovarian insulin-like growth factor I (IGF-I) mRNA expression in GHR-KO females, the expression of several steroidogenic enzyme mRNAs did not differ between groups. The numbers of active corpora lutea and uterine implantation sites were reduced in GHR-KO females at Day 7 of gestation. When young females were mated to normal males, latency to first mating and age of the female at first mating were significantly delayed in GHR-KO females, but maternal age at first conception was similar between groups. Significantly fewer virgin GHR-KO females exhibited pseudopregnancies when initially placed with vasectomized normal males than did normal female counterparts. Growth hormone resistance and IGF-I insufficiency negatively impacted 1) follicular development/ovulation rate, 2) sexual maturation, 3) production of and responsiveness to pheromonal signals, and 4) the ability of virgin females to respond to coitus by activation of luteal function. Although GHR-KO female mice are fertile, they exhibit quantitative deficits in various parameters of reproductive function.

  7. The effect of adrenal steroids, corticotropin, and growth hormone on resistance to experimental infections.

    PubMed

    KASS, E H; LUNDGREN, M M; FINLAND, M

    1954-01-01

    Cortisone acetate, hydrocortisone, and hydrocortisone acetate depress the resistance of mice to pneumococcal and influenza viral infections, although hydrocortisone acetate is somewhat less effective than the free alcohol, when given subcutaneously. Pituitary adrenocorticotropin, even in highly purified form and in oil and beeswax, does not significantly alter the resistance of mice to these experimental infections, even when given in doses which may cause profound eosinopenia, lymphopenia, and weight loss, and which are at the limit of tolerance of the animals. Corticosterone depresses resistance to pneumococcal infections significantly, but fails to alter resistance to influenza viral infections. The findings suggest that murine adrenals may produce one of the known adrenal steroids such as corticosterone along with another steroid, or may produce a steroid other than cortisone, hydrocortisone, or corticosterone. When resistance is decreased by adrenal steroids, survival time is invariably shortened, and the effect of the steroid hormones is frequently demonstrable within the 1st day after infection with pneumococci, making it unlikely that the depression of resistance that is seen is primarily due to depression of antibody formation. A single dose of 5 mg. of cortisone may cause depression of resistance and may decrease the survival time for 3 to 6 days afterward. Growth hormone (somatotropic hormone) in highly purified form, and in the doses used, did not overcome the weight loss induced by cortisone, but the animals treated with growth hormone and cortisone regained their lost weight more rapidly than those receiving cortisone alone. Growth hormone alone caused a slight increase in the rate of gain in weight over controls. Growth hormone alone did not increase resistance to infection, and did not increase the survival time, in mice infected with either pneumococci or influenza virus. Growth hormone in various dosages failed to overcome the effect of cortisone

  8. THE EFFECT OF ADRENAL STEROIDS, CORTICOTROPIN, AND GROWTH HORMONE ON RESISTANCE TO EXPERIMENTAL INFECTIONS

    PubMed Central

    Kass, Edward H.; Lundgren, Marguerite M.; Finland, Maxwell

    1954-01-01

    Cortisone acetate, hydrocortisone, and hydrocortisone acetate depress the resistance of mice to pneumococcal and influenza viral infections, although hydrocortisone acetate is somewhat less effective than the free alcohol, when given subcutaneously. Pituitary adrenocorticotropin, even in highly purified form and in oil and beeswax, does not significantly alter the resistance of mice to these experimental infections, even when given in doses which may cause profound eosinopenia, lymphopenia, and weight loss, and which are at the limit of tolerance of the animals. Corticosterone depresses resistance to pneumococcal infections significantly, but fails to alter resistance to influenza viral infections. The findings suggest that murine adrenals may produce one of the known adrenal steroids such as corticosterone along with another steroid, or may produce a steroid other than cortisone, hydrocortisone, or corticosterone. When resistance is decreased by adrenal steroids, survival time is invariably shortened, and the effect of the steroid hormones is frequently demonstrable within the 1st day after infection with pneumococci, making it unlikely that the depression of resistance that is seen is primarily due to depression of antibody formation. A single dose of 5 mg. of cortisone may cause depression of resistance and may decrease the survival time for 3 to 6 days afterward. Growth hormone (somatotropic hormone) in highly purified form, and in the doses used, did not overcome the weight loss induced by cortisone, but the animals treated with growth hormone and cortisone regained their lost weight more rapidly than those receiving cortisone alone. Growth hormone alone caused a slight increase in the rate of gain in weight over controls. Growth hormone alone did not increase resistance to infection, and did not increase the survival time, in mice infected with either pneumococci or influenza virus. Growth hormone in various dosages failed to overcome the effect of cortisone

  9. 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. PMID:1550219

  10. Growth hormone.

    PubMed

    Bidlingmaier, Martin; Strasburger, Christian J

    2010-01-01

    Human growth hormone (hGH) is a proteohormone secreted by the pituitary gland. It acts through binding to the hGH receptor, inducing either direct effects or initiating the production of insulin-like growth-factor I (IGF-I), the most important mediator of hGH effects. Growth hormone is primarily known to promote longitudinal growth in children and adolescents, but has also various important metabolic functions throughout adult life. Effects of hGH on the adult organism are well established from studies with recombinant growth hormone (rhGH) therapy in growth hormone deficient subjects. In this particular group of patients, replacement of hGH leads to increased lipolysis and lean body mass, decreased fat mass, improvements in VO(2max), and maximal power output. Although extrapolation from these findings to the situation in well trained healthy subjects is impossible, and controlled studies in healthy subjects are scarce, abuse of hGH seems to be popular among athletes trying to enhance physical performance. Detection of the application of rhGH is difficult, especially because the amino acid sequence of rhGH is identical to the major 22,000 Da isoform of hGH normally secreted by the pituitary. Furthermore, some physiological properties of hGH secretion also hindered the development of a doping test: secreted in a pulsatile manner, it has a very short half-life in circulation, which leads to highly variable serum levels. Concentration alone therefore cannot prove the exogenous administration of hGH.Two approaches have independently been developed for the detection of hGH doping: The so-called "marker approach" investigates changes in hGH-dependent parameters like IGF-I or components of bone and collagen metabolism, which are increased after hGH injection. In contrast, the so-called "isoform approach" directly analyses the spectrum of molecular isoforms in circulation: the pituitary gland secretes a spectrum of homo- and heterodimers and - multimers of a variable

  11. 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

  12. Growth hormone test

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/003706.htm Growth hormone test To use the sharing features on this page, please enable JavaScript. The growth hormone test measures the amount of growth hormone in ...

  13. Effects of growth hormone overexpression and growth hormone resistance on neuroendocrine and reproductive functions in transgenic and knock-out mice.

    PubMed

    Bartke, A; Chandrashekar, V; Turyn, D; Steger, R W; Debeljuk, L; Winters, T A; Mattison, J A; Danilovich, N A; Croson, W; Wernsing, D R; Kopchick, J J

    1999-11-01

    Transgenic mice overexpressing growth hormone (GH) exhibit alterations in the function of the hypothalamic-pituitary-gonadal (HPG) axis and the H-P-adrenal axis. Alterations in the turnover of hypothalamic neurotransmitters, in plasma hormone levels, and in regulation of their release are associated with reproductive deficits, particularly in females. Results reported after publication of our minireview on this subject provided evidence that GH-transgenic mice have increased binding of GH to GH binding proteins in plasma, are hyperinsulinemic and insulin resistant, and have major alterations in energy budgets with increased allocation to growth. Reduced life span and fertility of these animals may be related to insufficient allocation of energy to reproduction and maintenance. Growth hormone resistance induced by transgenic expression of an antagonistic bGH analog or by targeted disruption (knock-out, KO) of the GH receptor (GH-R) gene leads to dramatic suppression of plasma levels of insulin-like growth factor-1 (IGF-1), and dwarf phenotype due to reduced growth and increased adiposity. In both models of GH resistance, there are marked reproductive deficits in females, decline of breeding performance of males, and alterations in the function of the HPG axis. In GH-R-KO females, puberty is delayed, and litter size is reduced. Fetal weights are reduced whereas placental weights are increased, and the weight of newborn pups is reduced despite an increase in the length of gestation. In GH-R-KO males, copulatory behavior and fertility are reduced, plasma PRL is elevated, and responses to luteinizing hormone releasing hormone (LHRH) in vivo and to LH in vitro are suppressed. However, reproductive deficits in GH-R-KO mice are very mild when compared to those described previously in IGF-KO animals. Apparently, the amounts of IGF-1 that may be produced locally in the absence of GH stimulation are sufficient for sexual maturation and fertility in both sexes, whereas

  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. Growth hormone deficiency - children

    MedlinePlus

    ... the same age. The child will have normal intelligence in most cases. In older children, puberty may ... hormones cause the body to make. Tests can measure these growth factors. Accurate growth hormone deficiency testing ...

  16. 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

  17. [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.

  18. Human growth hormone.

    PubMed

    Strobl, J S; Thomas, M J

    1994-03-01

    The study of human growth hormone is a little more than 100 years old. Growth hormone, first identified for its dramatic effect on longitudinal growth, is now known to exert generalized effects on protein, lipid, and carbohydrate metabolism. Additional roles for growth hormone in human physiology are likely to be discovered in the areas of sleep research and reproduction. Furthermore, there is some indication that growth hormone also may be involved in the regulation of immune function, mental well-being, and the aging process. Recombinant DNA technology has provided an abundant and safe, albeit expensive, supply of human growth hormone for human use, but the pharmacological properties of growth hormone are poor. Most growth hormone-deficient individuals exhibit a secretory defect rather than a primary defect in growth hormone production, however, and advances in our understanding of the neuroendocrine regulation of growth hormone secretion have established the basis for the use of drugs to stimulate release of endogenously synthesized growth hormone. This promises to be an important area for future drug development. PMID:8190748

  19. 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.

  20. 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. PMID:12970263

  1. 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.

  2. Effects of ginseng ingestion on growth hormone, testosterone, cortisol, and insulin-like growth factor 1 responses to acute resistance exercise.

    PubMed

    Youl Kang, Ho; Hwan Kim, Seung; Jun Lee, Woen; Byrne, Heidi K

    2002-05-01

    Ginseng, an herbal plant, has been ingested by many athletes in Oriental regions of the world in order to improve stamina and to facilitate rapid recovery from injuries. However, adequate investigation has not been conducted to examine the ergogenic effects of ginseng. To examine the effects of ginseng supplements on hormonal status following acute resistance exercise, eight male college students were randomly given water (control; CON) or 20 g of ginseng root extract (GIN) treatment immediately after a standardized exercise bout. Venous blood samples were drawn before and immediately after exercise and at 4 time points during a 2-hour recovery period. Human growth hormone, testosterone, cortisol, and insulin-like growth factor 1 (IGF-1) levels were determined by radioimmunoassay. The responses of plasma hormones following ginseng consumption were not significant between CON and GIN treatments during the 2-hour recovery period. These results do not support the use of ginseng to promote an anabolic hormonal status following resistance exercise.

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

    PubMed

    Cornford, Andrea S; Barkan, Ariel L; Hinko, Alexander; Horowitz, Jeffrey F

    2012-11-15

    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

  4. Growth Hormone Promotes Lymphangiogenesis

    PubMed Central

    Banziger-Tobler, Nadja Erika; Halin, Cornelia; Kajiya, Kentaro; Detmar, Michael

    2008-01-01

    The lymphatic system plays an important role in inflammation and cancer progression, although the molecular mechanisms involved are poorly understood. As determined using comparative transcriptional profiling studies of cultured lymphatic endothelial cells versus blood vascular endothelial cells, growth hormone receptor was expressed at much higher levels in lymphatic endothelial cells than in blood vascular endothelial cells. These findings were confirmed by quantitative real-time reverse transcriptase-polymerase chain reaction and Western blot analyses. Growth hormone induced in vitro proliferation, sprouting, tube formation, and migration of lymphatic endothelial cells, and the mitogenic effect was independent of vascular endothelial growth factor receptor-2 or -3 activation. Growth hormone also inhibited serum starvation-induced lymphatic endothelial cell apoptosis. No major alterations of lymphatic vessels were detected in the normal skin of bovine growth hormone-transgenic mice. However, transgenic delivery of growth hormone accelerated lymphatic vessel ingrowth into the granulation tissue of full-thickness skin wounds, and intradermal delivery of growth hormone resulted in enlargement and enhanced proliferation of cutaneous lymphatic vessels in wild-type mice. These results identify growth hormone as a novel lymphangiogenic factor. PMID:18583315

  5. 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

  6. 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

  7. 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

  8. Thyroid hormone resistance.

    PubMed

    Olateju, Tolulope O; Vanderpump, Mark P J

    2006-11-01

    Resistance to thyroid hormone (RTH) is a rare autosomal dominant inherited syndrome of reduced end-organ responsiveness to thyroid hormone. Patients with RTH have elevated serum free thyroxine (FT4) and free triiodothyronine (FT3) concentrations and normal or slightly elevated serum thyroid stimulating hormone (TSH) level. Despite a variable clinical presentation, the common characteristic clinical features are goitre but an absence of the usual symptoms and metabolic consequences of thyroid hormone excess. Patients with RTH can be classified on clinical grounds alone into either generalized resistance (GRTH), pituitary resistance (PRTH) or combined. Mutations in the thyroid hormone receptor (TR) beta gene are responsible for RTH and 122 different mutations have now been identified belonging to 300 families. With the exception of one family found to have complete deletion of the TRbeta gene, all others have been demonstrated to have minor alterations at the DNA level. The differential diagnosis includes a TSH-secreting pituitary adenoma and the presence of endogenous antibodies directed against thyroxine (T4) and triiodothyronine (T3). Failure to differentiate RTH from primary thyrotoxicosis has resulted in the inappropriate treatment of nearly one-third of patients. Although occasionally desirable, no specific treatment is available for RTH; however, the diagnosis allows appropriate genetic counselling. PMID:17132274

  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. 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.

  11. 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.

  12. Biosimilar growth hormone.

    PubMed

    Saenger, Paul

    2012-01-01

    As the first wave of biopharmaceuticals is expiring, biosimilars or follow-on -protein products (FOPP's) have emerged. Biosimilar drugs are cheaper than the originator/comparator drug. The regulatory foundation for these products is more advanced and better codified in Europe than in the US. Biosimilar soamtropin has been approved in both the US and Europe. The scientific viability of biosimilar drugs and especially growth hormone has been proven by several rigorously conducted clinical trials. Efficacy and safety data (growth rates, IGF-1 generation) for up to 7 y for pediatric indications measure up favorably to previously approved growth hormones which served as reference comparators. The Obama Administration appears to be committed to establish innovative pathways for the approval of biologics and biosimilars in the US. The cost savings in health care expenditures will be substantial as the global sales of biologics have reached $ 93 billion in 2009.

  13. 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.

  14. 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…

  15. 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.

  16. 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.

  17. Roles of the lactogens and somatogens in perinatal and postnatal metabolism and growth: studies of a novel mouse model combining lactogen resistance and growth hormone deficiency.

    PubMed

    Fleenor, Donald; Oden, Jon; Kelly, Paul A; Mohan, Subburaman; Alliouachene, Samira; Pende, Mario; Wentz, Sabrina; Kerr, Jennifer; Freemark, Michael

    2005-01-01

    To delineate the roles of the lactogens and GH in the control of perinatal and postnatal growth, fat deposition, insulin production, and insulin action, we generated a novel mouse model that combines resistance to all lactogenic hormones with a severe deficiency of pituitary GH. The model was created by breeding PRL receptor (PRLR)-deficient (knockout) males with GH-deficient (little) females. In contrast to mice with isolated GH or PRLR deficiencies, double-mutant (lactogen-resistant and GH-deficient) mice on d 7 of life had growth failure and hypoglycemia. These findings suggest that lactogens and GH act in concert to facilitate weight gain and glucose homeostasis during the perinatal period. Plasma insulin and IGF-I and IGF-II concentrations were decreased in both GH-deficient and double-mutant neonates but were normal in PRLR-deficient mice. Body weights of the double mutants were reduced markedly during the first 3-4 months of age, and adults had striking reductions in femur length, plasma IGF-I and IGF binding protein-3 concentrations, and femoral bone mineral density. By age 6-12 months, however, the double-mutant mice developed obesity, hyperleptinemia, fasting hyperglycemia, relative hypoinsulinemia, insulin resistance, and glucose intolerance; males were affected to a greater degree than females. The combination of perinatal growth failure and late-onset obesity and insulin resistance suggests that the lactogen-resistant/GH-deficient mouse may serve as a model for the development of the metabolic syndrome.

  18. Growth Hormone (GH) Hypersecretion and GH Receptor Resistance in Streptozotocin Diabetic Mice in Response to a GH Secretagogue

    PubMed Central

    Segev, Yael; Landau, Daniel; Phillip, Moshe; Flyvbjerg, Allan

    2003-01-01

    The growth hormone (GH) and insulin-like growth factor I (IGF-I) axis were studied in streptozotocin (STZ) diabetic and nondiabetic female mice following intravenous (IV) injection of the GH secretagogue (GHS) ipamorelin or saline. On day 14, blood samples were obtained before and 10 minutes after the injection. Livers were removed and frozen for determination of the mRNA expressions of the GH receptor, GH-binding protein, and IGF-I, and hepatic IGF-I peptide. Serum samples were analyzed for GH and IGF-I. Following ipamorelin injection, the GH levels were found to be 150 ± 35 μg/L and 62 ± 11 μg/L in the diabetic compared to the nondiabetic mice (P < .05). Serum IGF-I levels were lower in diabetic than in nondiabetic animals, and rose after stimulation only in the nondiabetic animals. Furthermore, hepatic GH resistance and IGF-I mRNA levels and IGF-I peptide were increased in nondiabetic animals in response to GH stimulation, whereas the low levels per se of all these parameters in diabetic mice were unaffected. The study shows that STZ diabetic mice demonstrate a substantial part of the clinical features of type 1 diabetes in humans, including GH hypersecretion and GH resistance. Accordingly, it is proposed that STZ diabetic mice may be a better model of the perturbations of the GH/IGF-I axis in diabetes than STZ diabetic rats. PMID:14630569

  19. Extrapituitary growth hormone.

    PubMed

    Harvey, S

    2010-12-01

    Pituitary somatotrophs secrete growth hormone (GH) into the bloodstream, to act as a hormone at receptor sites in most, if not all, tissues. These endocrine actions of circulating GH are abolished after pituitary ablation or hypophysectomy, indicating its pituitary source. GH gene expression is, however, not confined to the pituitary gland, as it occurs in neural, immune, reproductive, alimentary, and respiratory tissues and in the integumentary, muscular, skeletal, and cardiovascular systems, in which GH may act locally rather than as an endocrine. These actions are likely to be involved in the proliferation and differentiation of cells and tissues prior to the ontogeny of the pituitary gland. They are also likely to complement the endocrine actions of GH and are likely to maintain them after pituitary senescence and the somatopause. Autocrine or paracrine actions of GH are, however, sometimes mediated through different signaling mechanisms to those mediating its endocrine actions and these may promote oncogenesis. Extrapituitary GH may thus be of physiological and pathophysiological significance.

  20. Growth hormone neurosecretory dysfunction.

    PubMed

    Bercu, B B; Diamond, F B

    1986-08-01

    The basis for understanding clinical disorders in the neuroregulation of GH secretion is derived from the complexity of the CNS-hypothalamic-pituitary axis. Studies in animals and humans demonstrate an anatomic, physiological and pharmacological evidence for neurosecretory control over GH secretion including neurohormones (GRH, somatostatin), neurotransmitters (dopaminergic, adrenergic, cholinergic, serotonergic, histaminergic, GABAergic), and neuropeptides (gut hormones, opioids, CRH, TRH, etc). The observation of a defect in the neuroregulatory control of GH secretion in CNS-irradiated humans and animals led to the hypothesis of a disorder in neurosecretion, GHND, as a cause for short stature. We speculate that in this heterogeneous group of children a disruption in the neurotransmitter-neurohormonal functional pathway could modify secretion ultimately expressed as poor growth velocity and short stature.

  1. 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.

  2. Growth hormone stimulation test - series (image)

    MedlinePlus

    The growth hormone (GH) is a protein hormone released from the anterior pituitary gland under the control of the hypothalamus. ... performed on infants and children to identify human growth hormone (hGH) deficiency as a cause of growth retardation. ...

  3. Genetics Home Reference: isolated growth hormone deficiency

    MedlinePlus

    ... Health Conditions isolated growth hormone deficiency isolated growth hormone deficiency Enable Javascript to view the expand/collapse ... PDF Open All Close All Description Isolated growth hormone deficiency is a condition caused by a severe ...

  4. 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.

  5. Effects of 4 Weeks Recombinant Human Growth Hormone Administration on Insulin Resistance of Skeletal Muscle in Rats

    PubMed Central

    Park, Mi Jung; Jung, Su Ryun; Jung, Hyun Lyung; Craig, Bruce W.; Lee, Chong-Do

    2008-01-01

    Purpose Effect of recombinant human growth hormone (rhGH) administration on lipid storage, and its subsequent effect on insulin sensitivity have not yet been adequately examined. Thus, we investigated the effects of rhGH treatment on muscle triglyceride (TG) and ceramide content, and insulin sensitivity after 4 weeks of rhGH administration in rats. Materials and Methods Fourteen rats were randomly assigned to two groups: rhGH injection group (GH, n = 7) and saline injection group (CON, n = 7). GH received rhGH by subcutaneous injections (130 µg·kg-1·day-1, 6 days·week-1) for 4 weeks, while CON received saline injections that were equivalent in volume to GH group. Intramuscular TG and ceramide content and hepatic TG content were measured. To determine insulin sesitivity, oral glucose tolerance test (OGTT) and muscle incubation for glucose transport rate were performed in rats, and used as indicators of insulin sensitivity. We also examined plasm lipid profiles. Results After 4 weeks of rhGH treatment, the GH group had higher muscle and liver TG contents than the CON (p < 0.05). Ceramide content in GH was significantly greater than that in CON (p < 0.05). GH also had higher plasma levels of FFA (p < 0.05), glucose and insulin responses during OGTT (p < 0.05), and lower glucose transport rates in submaximal insulin concentration (p < 0.05) as compared with CON. Results indicate that rhGH treatment is associated with insulin resistance in rats. Conclusion rhGH treatment elevated muscle TG and ceramide content, and hepatic TG content. Thus, elevation of these compounde by rhGH treatment could contribute to the development of insulin resistance in rats. PMID:19108026

  6. 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

  7. 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

  8. 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

    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

  9. Sex hormone-related and growth hormone-related alopecias.

    PubMed

    Schmeitzel, L P

    1990-11-01

    Canine endocrine dermatoses are characterized by bilateral symmetrical alopecia. Although growth hormone-related and sex hormone-related dermatoses are less common than hypothyroidism and hyperadrenocorticism, they are important causes of hormonal skin disease. Several new syndromes associated with growth and sex hormones recently have been described.

  10. 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.

  11. Pathology of growth hormone excess.

    PubMed

    Kovacs, K

    1988-09-01

    This paper briefly reviews the pathology of growth hormone excess. Prolonged oversecretion of growth hormone is associated with elevated serum growth hormone as well as somatomedian C levels and the clinical signs and symptoms of acromegaly or gigantism. Morphologic studies, including immunohistochemistry and electron microscopy, revealed that several distinct morphologic lesions can be present in the pituitary gland of patients with acromegaly or gigantism. Although substantial progress has been achieved during the last two decades, more work is required to correlate the morphologic features of adenoma cells with their biologic behavior. We feel that the future can be viewed with optimism and further exciting results can be expected by the interaction of pathologists, clinical endocrinologists and basic scientists. PMID:3070506

  12. Growth Hormone and Cerebral Amyloidosis.

    PubMed

    Benvenga, S; Guarneri, F

    2016-08-01

    Great interest has recently been focused on a paper reporting characteristic deposits of amyloid-β protein associated with Alzheimer's disease in brains of adults who died of Creutzfeldt-Jakob disease. As they had contracted such disease after treatment with prion-contaminated human growth hormone extracted from cadaver-derived pituitaries, the authors have suggested that interhuman transmission of Alzheimer's disease had occurred. Our previous research led us to find that amyloid-forming peptides share amino acid sequence homology, summarized by a motif. Here, we probed the amino acid sequence of human growth hormone for such a motif, and found that 2 segments fit the motif and are potentially amyloid-forming. This finding was confirmed by Aggrescan, another well-known software for the prediction of amyloidogenic peptides. Our results, taken together with data from the literature that are missing in the aforementioned paper and associated commentaries, minimize the contagious nature of the iatrogenically-acquired coexistence of Creutzfeldt-Jakob disease and Alzheimer's disease. In particular, the above mentioned paper misses literature data on intratumoral amyloidosis in growth hormone- and prolactin-secreting adenomas, tumors relatively frequent in adults, which are often silent. It cannot be excluded that some pituitaries used to extract growth hormone contained clinically silent microadenomas, a fraction of which containing amyloid deposits, and patients might had received a fraction of growth hormone (with or without prolactin) that already was an amyloid seed. The intrinsic amyloidogenicity of growth hormone, in the presence of contaminating prion protein (and perhaps prolactin as well) and amyloid-β contained in some cadavers' pituitaries, may have led to the observed co-occurring of Creutzfeldt-Jakob disease and Alzheimer's disease. PMID:27214308

  13. Growth Hormone: Use and Abuse

    MedlinePlus

    ... than children of the same age), such as chronic kidney disease, Turner syndrome, and Prader-Willi syndrome In adults, GH is used to treat • Growth hormone deficiency • Muscle wasting (loss of muscle tissue) from HIV • Short bowel ...

  14. Aetiology of growth hormone deficiency.

    PubMed Central

    Herber, S M; Kay, R

    1987-01-01

    A retrospective analysis was performed in an attempt to identify perinatal risk factors for the development of growth hormone deficiency. More of the affected children were boys, and their birth weights were significantly lower than those of the national average; there were also considerably more preterm and post-term deliveries among boys. PMID:3632025

  15. 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.

  16. Growth hormone in musculoskeletal pain states.

    PubMed

    Bennett, Robert

    2004-08-01

    Growth hormone is essential for normal linear growth and the attainment of an adult mature height. It also plays an important role in cartilage growth and the attainment of normal bone mass. There is only one rheumatic disorder, namely acromegaly, in which abnormalities of growth hormone production play a major etiologic role. However, there is increasing appreciation that suboptimal growth hormone secretion, leading to a state of adult growth hormone deficiency, may occur in the setting of chronic inflammatory disease, chronic corticosteroid use, and fibromyalgia. Therefore, the evaluation and effective management of growth hormone oversecretion and undersecretion is relevant to practicing rheumatologists. PMID:15251074

  17. 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.

  18. Growth hormone and its disorders.

    PubMed

    Ayuk, J; Sheppard, M C

    2006-01-01

    Growth hormone (GH) is synthesised and secreted by the somatotroph cells of the anterior lobe of the pituitary gland. Its actions involve multiple organs and systems, affecting postnatal longitudinal growth as well as protein, lipid, and carbohydrate metabolism. GH hypersecretion results in gigantism or acromegaly, a condition associated with significant morbidity and mortality, while GH deficiency results in growth retardation in children and the GH deficiency syndrome in adults. This article, aimed at non-paediatric physicians, examines the clinical features, diagnosis, and current concepts in the management of these conditions. PMID:16397076

  19. 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.

  20. The growth hormone secretagogue receptor.

    PubMed

    Cruz, Conrad Russell Young; Smith, Roy G

    2008-01-01

    The neuroendocrine hormone ghrelin, a recently discovered acylated peptide with numerous activities in various organ systems, exerts most of its known effects on the body through a highly conserved G-protein-coupled receptor, the growth hormone secretagogue receptor (GHSR) type 1a. The GHSR's wide expression in different tissues reflects activity of its ligands in the hypothalamic-pituitary, cardiovascular, immune, gastrointestinal, and reproductive systems. Its extensive cellular distribution along with its important actions on the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis and other neuroendocrine and metabolic systems suggest a pivotal role in governing the mechanisms of aging. A more comprehensive characterization of the receptor, and a more thorough identification of its various agonists and antagonists, will undoubtedly introduce important clinical applications in age-related states like anorexia, cardiovascular pathology, cancer, impaired energy balance, and immune dysfunction. Although present knowledge points to a single functional receptor and a single endogenous ligand, recent investigations suggest the existence of additional GHSR subtypes, as well as other endogenous agonists. It has been more than a decade since the landmark cloning of this ubiquitous, highly conserved receptor, and the considerable extent of its effects on normal physiology and disease states have filled the literature with incredible insights on how organisms regulate various functions through subtle signaling processes. But science has barely scratched the surface, and we can be assured that the mysteries surrounding the precise nature of ghrelin and its receptor(s) are only beginning to unravel. PMID:17983853

  1. 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.

  2. 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

  3. [Laboratory diagnosis of growth hormone].

    PubMed

    Macchia, V; Mariano, A

    1993-09-01

    The role of Clinical Pathology Laboratory in normal and altered growth hormone secretion is discussed. In particular, it is reported that the normal GH secretion can be studied by serum and urine GH determinations whereas the diagnosis of GH deficiency rests upon the demonstration of an inadequate rise serum GH after provocative stimuli and serum measurement of somatomedins (IGF-I) by radioimmunoassay method. As it concerns increase GH secretion the diagnosis is clinically made (acromegaly and gigantism) and the laboratory has only the role to confirm it by the assessment of basal and stimulated GH secretion. PMID:7910655

  4. 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.

  5. Dietary Aflatoxin-Induced Stunting in a Novel Rat Model: Evidence for Toxin-Induced Liver Injury and Hepatic Growth Hormone Resistance

    PubMed Central

    Knipstein, Brittany; Huang, Jiansheng; Barr, Emily; Sossenheimer, Philip; Dietzen, Dennis; Egner, Patricia A.; Groopman, John D.; Rudnick, David A.

    2015-01-01

    Background Despite a strong statistical correlation between dietary aflatoxin B1 (AFB1)-exposure and childhood stunting, the causal mechanism remains speculative. This issue is important because of emerging interest in reduction of human aflatoxin exposure to diminish the prevalence and complications of stunting. Pediatric liver diseases cause growth impairment, and AFB1 is hepatotoxic. Thus, liver injury might mediate AFB1-associated growth impairment. We have developed a rat model of dietary AFB1-induced stunting to investigate these questions. Methods Newly-weaned rats were given AFB1-supplemented- or control-diets from age 3-9 weeks, and then euthanized for serum- and tissue-collection. Food intake and weight were serially assessed, with tibial-length determined at the experimental endpoint. Serum AFB1-adducts, hepatic gene and protein expression, and liver injury markers were quantified using established methodologies. Results AFB1-albumin adducts correlated with dietary toxin contamination, but such contamination did not affect food consumption. AFB1-exposed animals exhibited dose-dependent wasting and stunting, liver pathology, and suppression of hepatic targets of growth hormone (GH) signaling, but did not display increased mortality. Conclusion These data establish toxin-dependent liver injury and hepatic GH-resistance as candidate mechanisms by which AFB1-exposure causes growth impairment in this mammalian model. Interrogation of modifiers of stunting using this model could guide interventions in at-risk and affected children. PMID:25938735

  6. 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

  7. [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.

  8. [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. PMID:24954142

  9. 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

  10. 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. PMID:26936284

  11. 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

  12. Growth hormone insensitivity syndrome: unusual oral manifestations.

    PubMed

    Borges, Alvaro Henrique; Siqueira, Carlos Rodrigo Barros; Pedro, Fábio Luis Miranda; Palma, Vinícius Canavarros; Sakai, Vivien Thiemy; Volpato, Luiz Evaristo Ricci

    2013-01-01

    Children with significant growth retardation and normal levels of growth hormone are diagnosed with growth hormone insensitivity. The main oral findings observed in patients with growth hormone insensitivity syndrome (GHIS) are underdeveloped jaws, crowded teeth and delayed eruption of permanent teeth. This manuscript describes a 9-year-old child diagnosed with GHIS, who had delayed eruption of permanent teeth and 14 unerupted supernumerary teeth. All supernumerary teeth were extracted except for two maxillary and one mandibular teeth which were difficult to identify and access. Multiple supernumerary teeth have never been reported before in patients with GHIS.

  13. 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.

  14. 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.…

  15. Oral manifestations in growth hormone disorders.

    PubMed

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

    2012-05-01

    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

  16. Growth, growth hormone and cognitive functions.

    PubMed

    Sartorio, A; Conti, A; Molinari, E; Riva, G; Morabito, F; Faglia, G

    1996-01-01

    The interactions among short stature, growth hormone (GH) and cognitive functions have been extensively studied so far. However, although it seems well established that short stature is associated with cognitive problems, little effort has been made to point out the presence of specific psychological effects related to the different forms of short stature. In 'short normal' children, the presence of a scholastic underachievement seems to suggest that short stature 'itself' might predispose these patients to some of their psychosocial difficulties. The higher incidence of academic failure, in presence of a normal intellectual functioning, has been attributed to environmental and psychosocial factors, including over-protective parents and low self-esteem resulting from the impact of short stature. These problems appear to be common also to other forms of short stature (such as Turner's syndrome) where, however, they are frequently associated with other specific deficits. The in vivo model which might allow, at least in part, better understanding of GH (per se)-dependent effects is represented by GH deficiency (GHD), in which, however, the specific role of GH on psychological functioning is frequently masked by the presence of associated hormonal deficiencies. Children with isolated GHD are reported to have specific educational deficits, in particular learning disability and attention-deficit disorders, which have been tentatively attributed to a compromised intellectual potential. The psychological effects of long-term GH treatment in children with GHD still remain controversial, with some retrospective studies describing a generally beneficial outcome. Since early experiences in school are closely related to success in adult life, the possible implications that GHD during childhood holds during adulthood have been recently considered. Although regional differences have been observed in subgroups of adults with GHD, it seems that these patients have normal cognitive

  17. 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... Systems § 862.1370 Human growth hormone test system. (a) Identification. A human growth hormone test system is a device intended to measure the levels of human growth hormone in plasma. Human growth...

  18. 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... Systems § 862.1370 Human growth hormone test system. (a) Identification. A human growth hormone test system is a device intended to measure the levels of human growth hormone in plasma. Human growth...

  19. 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... Systems § 862.1370 Human growth hormone test system. (a) Identification. A human growth hormone test system is a device intended to measure the levels of human growth hormone in plasma. Human growth...

  20. 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... Systems § 862.1370 Human growth hormone test system. (a) Identification. A human growth hormone test system is a device intended to measure the levels of human growth hormone in plasma. Human growth...

  1. 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... Systems § 862.1370 Human growth hormone test system. (a) Identification. A human growth hormone test system is a device intended to measure the levels of human growth hormone in plasma. Human growth...

  2. 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.

  3. 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.

  4. 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…

  5. Interactions of growth hormone secretagogues and growth hormone-releasing hormone/somatostatin.

    PubMed

    Tannenbaum, G S; Bowers, C Y

    2001-02-01

    The class of novel synthetic compounds termed growth hormone secretagogues (GHSs) act in the hypothalamus through, as yet, unknown pathways. We performed physiologic and histochemical studies to further understand how the GHS system interacts with the well-established somatostatin (SRIF)/growth hormone-releasing hormone (GHRH) neuroendocrine system for regulating pulsatile GH secretion. Comparison of the GH-releasing activities of the hexapeptide growth hormone-releasing peptide-6 (GHRP-6) and GHRH administered intravenously to conscious adult male rats showed that the pattern of GH responsiveness to GHRP-6 was markedly time-dependent, similar to that observed with GHRH. Immunoneutralization of endogenous SRIF reversed the blunted GH response to GHRP-6 at trough times, suggesting that GHRP-6 neither disrupts nor inhibits the cyclical release of endogenous hypothalamic SRIF. By striking contrast, passive immunization with anti-GHRH serum virtually obliterated the GH responses to GHRP-6, irrespective of the time of administration. These findings suggest that the GHSs do not act by altering SRIF release but, rather, stimulate GH release via GHRH-dependent pathways. Our dual chromogenic and autoradiographic in situ hybridization experiments revealed that a subpopulation of GHRH mRNA-containing neurons in the arcuate (Arc) nucleus and ventromedial nucleus (VMN) of the hypothalamus expressed the GHS receptor (GHS-R) gene. These results provide strong anatomic evidence that GHSs may directly stimulate GHRH release into hypophyseal portal blood, and thereby influence GH secretion, through interaction with the GHS-R on GHRH- containing neurons. Altogether, these findings support the notion that an additional neuroendocrine pathway may exist to regulate pulsatile GH secretion, possibly through the influence of the newly discovered GHS natural peptide, ghrelin. PMID:11322498

  6. Growth Hormone Deficiency in Children

    MedlinePlus

    ... many reasons for slow growth and below-average height in children. At times, slow growth is normal ... same age Signs of GHD • Slowed growth in height in infants, children, or adolescents (teenagers) • A young- ...

  7. [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.

  8. Control of growth hormone synthesis.

    PubMed

    Tuggle, C K; Trenkle, A

    1996-01-01

    A large body of research, primarily in the rodent and human species, has elucidated many of the details regarding the control of GH synthesis and release. Cell type-specific transcriptional control has been identified as the main mechanism of the somatotroph-specific expression of GH. The recent detailed analysis in rodents and humans of a highly specific transcriptional activator protein, PIT-1, has opened several new areas of study. This is especially true for research in the farm animal species, where PIT-1 has been cloned and its binding elements on the GH gene are being investigated in a number of economically important species. Genetic and biochemical analyses of PIT-1 and other GH regulators have shown the central role of PIT-1 not only in the cell-autonomous stimulation of GH gene transcription, but also in the participation of PIT-1 in the response at the GH gene to exogenous hormones such as RA and TH. PIT-1 has been implicated in the proliferative development of the pituitary itself, in the maintenance of anterior pituitary cell types once cell types are defined, and in the mechanism by which the hypothalamic signal for GH release is transduced. However, PIT-1 by itself does not activate the GH gene, so that additional unknown factors exist that need to be identified to fully understand the cell type-specific activation of the GH gene. In addition, GH gene regulatory elements acting through well-characterized systems such as TH have seemingly different effects; the specific context of the regulatory elements relative to the promoter elements appear to be crucial. These contextual details of GH gene regulation are not well understood for any species and need to be further studied to be able to make predictions for particular elements and regulatory mechanisms across species. The regulation of the pulsatile secretion of GH by GHRH and SRIH is reasonably well understood after the cloning and analysis of the two releasing factors and their receptors

  9. Growth hormone and aging: A challenging controversy

    PubMed Central

    Bartke, Andrzej

    2008-01-01

    Although advanced age or symptoms of aging are not among approved indications for growth hormone (GH) therapy, recombinant human GH (rhGH) and various GH-related products are aggressively promoted as anti-aging therapies. Well-controlled studies of the effects of rhGH treatment in endocrinologically normal elderly subjects report some improvements in body composition and a number of undesirable side effects in sharp contrast to major benefits of GH therapy in patients with GH deficiency. Controversies surrounding the potential utility of GH in treatment of a geriatric patient are fueled by increasing evidence linking GH and cancer and by remarkably increased lifespan of GH-resistant and GH-deficient mice. Conservation of cellular signaling mechanisms that influence aging in organisms ranging from worms to mammals suggests that at least some of the results obtained in mutant mice are applicable to the human. We suggest that the normal, physiological functions of GH in promoting growth, sexual maturation and fecundity involve significant costs in terms of aging and life expectancy. Natural decline in GH levels during aging likely contributes to concomitant alterations in body composition and vigor but also may be offering important protection from cancer and other age-associated diseases. PMID:19281058

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  11. 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

  12. 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

  13. Partial end organ resistance to thyroid hormone in congenital hypothyroidism

    PubMed Central

    Connell, John M. C.; McLaren, E. H.

    1981-01-01

    End organ resistance to thyroid hormone has been described for a number of years: the defect may be partial or generalized. A case of partial end organ resistance to thyroid hormone in congenital hypothyroidism is described, with evidence of an alteration in TSH threshold to feedback inhibition by thyroid hormone. The implications of this factor in the management of hypothyroidism are discussed. PMID:7301701

  14. 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…

  15. 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)

  16. Growth hormone: health considerations beyond height gain

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  17. Development of growth hormone secretagogues.

    PubMed

    Smith, Roy G

    2005-05-01

    The GH secretagogues (GHS) were developed by reverse pharmacology. The objective was to develop small molecules with pharmacokinetics suitable for once-daily oral administration that would rejuvenate the GH/IGF-I axis. Neither the receptor nor the ligand that controlled pulse amplitude of hormone release was known; therefore, identification of lead structures was based on function. I reasoned that GH pulse amplitude could be increased by four possible mechanisms: 1) increasing GHRH release; 2) amplifying GHRH signaling in somatotrophs of the anterior pituitary gland; 3) reducing somatostatin release; and 4) antagonizing somatostatin receptor signaling. Remarkably, the GHS act through all four mechanisms to reproduce a young adult physiological GH profile in elderly subjects that was accompanied by increased bone mineral density and lean mass, modest improvements in strength, and improved recovery from hip fracture. Furthermore, restoration of thymic function was induced in old mice. The GHS receptor (GHS-R) was subsequently identified by expression cloning and found to be a previously unknown G protein-coupled receptor expressed predominantly in brain, pituitary gland, and pancreas. Reverse pharmacology was completed when the cloned GHS-R was exploited to identify an endogenous agonist (ghrelin) and a partial agonist (adenosine); ghsr-knockout mice studies confirmed that GHS are ghrelin mimetics. PMID:15814848

  18. [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.

  19. 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.

  20. Growth hormone: its physiology and control.

    PubMed

    Scanes, C G; Lauterio, T J

    1984-12-01

    Growth hormone (GH) is a protein hormone produced by the somatotrophs of the anterior pituitary gland of birds and other vertebrates. The secretion of GH in birds is under hypothalamic control; it involves three peptidergic releasing factors: growth hormone-releasing factor (GRF) (stimulatory); thyrotropin-releasing hormone (TRH) (stimulatory); and somatostatin (SRIF) (inhibitory). In addition, there is evidence for effects of biogenic amines (including serotonin and norepinephrine) and prostaglandins at the level of the hypothalamus and possibly also the pituitary gland. In all avian species examined, plasma concentrations of GH are high in young posthatching chicks but low in the adult and embryo. The difference in plasma concentrations of GH between young and adult birds is due to both greater GH secretion and reduced clearance. The lower secretion of GH in adult birds reflects fewer somatotrophs in the pituitary, changes in somatotroph structure, and reduced GH responses to TRH or GRF administration. There is only limited data on the role of GH in birds. GH appears to be required for normal growth; acting at least in part by increasing somatomedin production. However, plasma concentrations of GH do not necessarily correlate with growth rate. For instance, in chicks with reduced growth rate owing to either goitrogen or protein deficiency in the diet, plasma concentrations of GH are elevated. GH also can influence lipid metabolism by increasing lipolysis, decreasing lipogenesis, and stimulating the uptake of glucose by adipose tissue. The physiological significance of these actions is, however, not established. In addition, GH affects the secretion of other hormones, the immune system, and perhaps also the reproductive system. PMID:6151579

  1. 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.

  2. 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.

  3. 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. PMID:23392091

  4. 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.

  5. 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)

  6. 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.

  7. [Growth hormone in children and adolescents: facts and fiction].

    PubMed

    Burckhardt, Marie-Anne; Zumsteg, Urs

    2013-06-19

    Growth Hormone therapy has been used therapeutically for over 50 years. Until recently, growth hormone therapy has been restricted for children and adolescents with proven hypothalamic-pituitary short stature. Today some other causes - but not all - can be treated with growth hormone. To the well-established indications belong apart from proven growth hormone deficiency, children with Turner Syndrome and with Prader Willi Syndrome, children born small for gestational age without catch-up growth and children with chronic kidney disease and with some haematological and oncological diseases. Careful and accurate diagnosis is essential. Growth hormone therapy is rare in everyday practice and requires close cooperation with a pediatric endocrinologist.

  8. 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. PMID:25745347

  9. Ectopic acromegaly due to growth hormone releasing hormone.

    PubMed

    Ghazi, Ali A; Amirbaigloo, Alireza; Dezfooli, Azizollah Abbasi; Saadat, Navid; Ghazi, Siavash; Pourafkari, Marina; Tirgari, Farrokh; Dhall, Dheepti; Bannykh, Serguei; Melmed, Shlomo; Cooper, Odelia

    2013-04-01

    Acromegaly secondary to extra-pituitary tumors secreting growth hormone releasing hormone (GHRH) is rarely encountered. We review the literature on ectopic acromegaly and present the index report of ectopic acromegaly secondary to GHRH secretion from a mediastinal paraganglioma. Clinical and pathological manifestations and therapeutic management of 99 patients with ectopic acromegaly are reviewed. Acromegaly secondary to ectopic GHRH secretion is usually caused by a neuroendocrine tumor in the lung and pancreas. We report an additional cause of ectopic acromegaly from a mediastinal paraganglioma. Diagnostic criteria of ectopic GHRH syndrome include biochemical and pathologic tumoral confirmation of GHRH secretion and expression. Management of ectopic acromegaly consists of surgical resection of the primary tumor and biochemical normalization, with possible adjuvant use of somatostatin analogs. The review demonstrates that there are several tumor types, including paragangliomas which may secrete GHRH, leading to acromegaly. Clinical and laboratory manifestations of the syndrome and challenges in diagnosis and management of these rarely encountered patients require early diagnosis and appropriate treatment to prevent long-term morbidity and mortality with ectopic acromegaly. PMID:22983831

  10. Internet informs parents about growth hormone

    PubMed Central

    Cousounis, Pamela; Lipman, Terri H.; Ginsburg, Kenneth; Grimberg, Adda

    2013-01-01

    Background Parent knowledge influences decisions regarding medical care for their children. Methods Parents of pediatric primary care patients aged 9-14 years, irrespective of height, participated in open focus groups (OFG). Moderators asked, “How do people find out about growth hormone (GH)?” Because many parents cited the Internet, the top 10 results from the Google searches, growth hormone children and parents of children who take growth hormone, were examined as representative. Three investigators independently performed content analysis, then reached consensus. Results were tabulated via summary statistics. Results Eighteen websites were reviewed, most with the purpose of education (56%) and many funded by commercial sources (44%). GH treatment information varied, with 33% of sites containing content only about U.S Food and Drug Administration-approved indications. Fifty-six percent of sites included information about psychosocial benefits from treatment, 44% acknowledging them as controversial. Although important to OFG participants, risks and costs were each omitted from 39% of websites. Conclusion Parents often turn to the Internet for GH-related information for their children, though its content may be incomplete and/or biased. Clinicians may want to provide parents with tools for critically evaluating Internet-based information, a list of pre-reviewed websites, or their own educational materials. PMID:23942255

  11. 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

  12. Partial Target Organ Resistance to Thyroid Hormone

    PubMed Central

    Bode, Hans Henning; Danon, Marco; Weintraub, Bruce D.; Maloof, Farahe; Crawford, John D.

    1973-01-01

    to TRH, but the BMR and insensible water loss remained normal. The data suggest that the patient's disorder is due to partial resistance to thyroid hormone. PMID:4632689

  13. 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

  14. Use of growth hormone in children.

    PubMed

    Hindmarsh, Peter C; Dattani, Mehul T

    2006-05-01

    The introduction of recombinant DNA-derived human growth hormone (rhGH) in the mid-1980s allowed studies to be undertaken in a number of growth disorders other than the classic indication--growth-hormone deficiency (GHD). In patients with GHD, optimizing the dose and frequency of rhGH administration, and early instigation of therapy, has led to near-normalization of final height. The use of rhGH in the treatment of Turner syndrome, Prader-Willi syndrome, intrauterine growth restriction, and chronic renal failure demonstrated the efficacy of therapy, although the increase in final height (5-7 cm) is less than that achieved in GHD. Cost-benefit implications need to be considered in the next phases of evaluating the role of rhGH therapy in these indications. To date, rhGH has only received approval for the management of idiopathic short stature in the US; as with the other wider growth indications, the lack of formal randomized, controlled trials hampers the full evaluation of efficacy, and a cautious approach should, therefore, be adopted for this particular indication. rhGH has a good safety record, although there are current concerns about the possible long-term increased risk of colonic and lymphatic malignancy, which will require monitoring through national cancer registries. PMID:16932297

  15. 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. PMID:27348437

  16. 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

  17. 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.

  18. Pathology of excessive production of growth hormone.

    PubMed

    Scheithauer, B W; Kovacs, K; Randall, R V; Horvath, E; Laws, E R

    1986-08-01

    Since its clinical description in the last century, much progress has been made in our understanding of acromegaly. From an initial description of pituitary enlargement as just another manifestation of generalized visceromegaly, the pituitary abnormality has come to be recognized, in most instances, as the underlying aetiological factor. Gigantism and acromegaly are manifestations of disordered pituitary physiology, but the lesion responsible may be hypothalamic, adenohypophyseal or ectopic in location. The best known pathological hypothalamic basis for acromegaly is represented by a neuronal malformation or 'gangliocytoma'. It usually takes the form of an intrasellar gangliocytoma or, more rarely, a hypothalamic hamartoma. The neuronal elaboration of GHRH may play a role in the development of a growth hormone adenoma; the pituitary process may pass through an intermediate stage of somatotropic hyperplasia. When acromegaly has its basis in a pituitary abnormality, the lesion is almost exclusively an adenoma; the non-tumorous adenohypophysis shows no evidence of coexistent hyperplasia. Surprisingly, such tumours are more often engaged in the formation of multiple hormones rather than GH alone. They frequently produce not only GH and prolactin, the products characteristics of cells of the acidophil line, but also glycoprotein hormones, usually TSH. The spectrum of adenomas also varies in its degree of differentiation from a histogenetically primitive lesion, the acidophil stem cell adenoma, to well-differentiated tumours of varying cellular composition and hormone content. Each adenoma type has its clinicopathological, histochemical, immunocytological and ultrastructural characteristics. The isolation and characterization of GHRH has permitted the identification of neuroendocrine tumours, most of foregut origin, elaborating this releasing hormone. Such functional tumours induce hyperplasia of pituitary somatotrophs and may, on occasion, result in the formation of

  19. Relationship between urinary and serum growth hormone and pubertal status.

    PubMed Central

    Crowne, E C; Wallace, W H; Shalet, S M; Addison, G M; Price, D A

    1992-01-01

    Urinary growth hormone (uGH) excretion and serum growth hormone concentrations have been compared in three groups of children. Group 1 consisted of 21 children who had had cranial irradiation as part of their treatment for acute lymphoblastic leukaemia; group 2, 18 normal children; and group 3, 12 boys with constitutional delay in growth and puberty who were in early puberty. Children in groups 1 and 2 each had a 24 hour serum growth hormone profile (sampling every 20 minutes) and concurrent urine collection. The 12 boys in group 3 had a total of 21 profiles (sampling every 15 minutes for 12 hours) and concurrent urine collections. In the prepubertal children (n = 17), in both groups 1 and 2, there was a significant correlation between mean serum growth hormone and total uGHng/g creatinine. There were also significant correlations between total uGHng/g creatinine and both peak serum growth hormone and mean amplitude of the pulses in the growth hormone profile. In the pubertal children (n = 22), in groups 1 and 2, whether combined or in separate groups, there was no significant correlation between total uGHng/g creatinine and mean serum growth hormone, peak serum growth hormone, or mean amplitude of the pulses in the growth hormone profile. In group 3 there were significant correlations between total uGHng/g creatinine and both the mean serum growth hormone and mean amplitude of the pulses in the profile. Therefore uGH estimations appear to correlate well with serum growth hormone profiles in children who are prepubertal or in early puberty, but not in those further advanced in pubertal development. These results may reflect a variation in the renal handling of growth hormone during pubertal development. uGH estimation may be an unreliable screening investigation for growth hormone sufficiency in mid to late puberty. PMID:1739346

  20. Sex steroids, growth hormone, leptin and the pubertal growth spurt.

    PubMed

    Rogol, Alan D

    2010-01-01

    A normal rate for the linear growth of a child or adolescent is a strong statement for the good general health of that child. Normal growth during childhood is primarily dependent on adequate nutrition, an adequate psychosocial environment, the absence of disease and adequate amounts thyroid hormone and growth hormone (and its downstream product, IGF-1). At adolescence there is the reawakening of the hypothalamic-pituitary-gonadal axis and its interaction with the GH/IGF-1 axis to subserve the pubertal growth spurt. The fat tissue-derived hormone, leptin and its receptor are likely involved in at least two aspects of pubertal development - sexual development itself and the alterations in body composition including the regional distribution of fat and bone mineralization. During the prepubertal years the male female differences in body composition are quite modest, but change remarkably during pubertal development with boys showing a relative decrement in fat percentage and girls a marked increase in concert with rising levels of circulating leptin. The boys show a much greater increase in lean body tissue and the relative proportions of water, muscle and bone. These may be observed as the differential growth of the shoulders and hips. The net effect of these pubertal changes is that the young adult woman has approximately 25% body fat in the 'gynoid' distribution while the male has much more muscle, especially in the shoulders and upper body but only approximately 13% body fat.

  1. Growth hormone secretagogues: prospects and potential pitfalls.

    PubMed

    Smith, Roy G; Sun, Yuxiang; Betancourt, Lorena; Asnicar, Mark

    2004-09-01

    The growth hormone secretagogues (GHSs) are the first well-characterised agents that rejuvenate the growth hormone (GH)/insulin-like growth factor (IGF-1) axis. This property was discovered during investigations of the underlying causative mechanisms of age-related endocrine changes. Chronic administration of the long acting GHS, MK-0677, reverses the age-related decline in pulse-amplitude of GH secretion and restores IGF-1 levels producing profiles typical of young adults. This restoration is accompanied by improvements in body composition in frail elderly subjects. When given acutely, the GHSs also increase appetite. Following cloning and characterisation of the GHS-receptor (GHS-R) an endogenous ligand, ghrelin, was isolated and identified. Ghrelin shares the GH releasing and orexigenic properties of the GHSs. Studies using Ghsr-null mice confirmed that the GHS-R was the ghrelin-receptor; hence, the GHSs should be considered to be 'ghrelin mimetics.' Ghrelin levels are reported to decline during ageing, therefore long-acting GHSs are ideal candidates for ghrelin replacement therapy. PMID:15261841

  2. 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.

  3. 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.

  4. 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.

  5. Potential role of human growth hormone in melanoma growth promotion.

    PubMed

    Handler, Marc Z; Ross, Andrew L; Shiman, Michael I; Elgart, George W; Grichnik, James M

    2012-10-01

    BACKGROUND Human growth hormone (HGH) and insulin-like growth factor-1 (IGF-1) have been shown to play a role in the malignant transformation and progression of a variety of cancers. HGH is also known to upregulate molecular signaling pathways implicated in the pathogenesis of melanoma. Although HGH has previously been implicated in promoting the clinical growth of both benign and malignant melanocytic neoplasms, to our knowledge there are no conclusive studies demonstrating an increased risk of melanoma following HGH therapy. Nevertheless, there are reports of melanoma developing subsequent to HGH coadministered with either other hormones or following irradiation. OBSERVATION A 49-year-old white man presented with a new pigmented papule that was diagnosed as melanoma. The patient reported using HGH for 3 months prior to the diagnosis. His 51-year-old wife, who also was white, had also been using exogenous HGH for 3 months and had been diagnosed as having a melanoma 2 weeks prior. CONCLUSIONS Given the unlikelihood of 2 unrelated people developing melanoma within a short time span, it is reasonable to assume that a common environmental component (HGH or other shared exposure) contributed to the development of both melanomas. Because of the increased use of exogenous HGH as an antiaging agent, it is important to be aware of the growth-promoting effects of this hormone. Until better data are available that determines the true risk of exogenous HGH, its use as an antiaging agent merits increased surveillance. PMID:23069955

  6. [Localized lipohypertrophy during growth hormone therapy].

    PubMed

    Mersebach, Henriette; Feldt-Rasmussen, Ulla F

    2002-04-01

    Accumulation of subcutaneous fat is described in a 51-year-old woman with panhypopituitarism treated on all insufficient pituitary axes, including growth hormone (GH). Malnutrition and alcoholic liver disease caused reduced synthesis of hepatic insulin-like growth factor I (IGF-I), and the function of IGF-I as biochemical marker of the GH effect was compromised. Peripheral levels of GH and IGF-I in tissues may have reached supra physiological levels and induced localised lipohypertrophy. Adjustment of GH treatment should not rest in all cases on IGF-I alone, but also depend on the clinical effect. Adjustment should follow suspected adverse events, such as lipohypertrophy, which is, however, an unusual complication of GH therapy.

  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. Detecting growth hormone misuse in athletes.

    PubMed

    Holt, Richard I G

    2013-10-01

    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.

  9. The growth hormone receptor: mechanism of activation and clinical implications.

    PubMed

    Brooks, Andrew J; Waters, Michael J

    2010-09-01

    Growth hormone is widely used clinically to promote growth and anabolism and for other purposes. Its actions are mediated via the growth hormone receptor, both directly by tyrosine kinase activation and indirectly by induction of insulin-like growth factor 1 (IGF-1). Insensitivity to growth hormone (Laron syndrome) can result from mutations in the growth hormone receptor and can be treated with IGF-1. This treatment is, however, not fully effective owing to the loss of the direct actions of growth hormone and altered availability of exogenous IGF-1. Excessive activation of the growth hormone receptor by circulating growth hormone results in gigantism and acromegaly, whereas cell transformation and cancer can occur in response to autocrine activation of the receptor. Advances in understanding the mechanism of receptor activation have led to a model in which the growth hormone receptor exists as a constitutive dimer. Binding of the hormone realigns the subunits by rotation and closer apposition, resulting in juxtaposition of the catalytic domains of the associated tyrosine-protein kinase JAK2 below the cell membrane. This change results in activation of JAK2 by transphosphorylation, then phosphorylation of receptor tyrosines in the cytoplasmic domain, which enables binding of adaptor proteins, as well as direct phosphorylation of target proteins. This model is discussed in the light of salient information from closely related class 1 cytokine receptors, such as the erythropoietin, prolactin and thrombopoietin receptors. PMID:20664532

  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. 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.

  12. Growth hormone modulation of arginine-induced glucagon release: studies of isolated growth hormone deficiency and acromegaly.

    PubMed

    Seino, Y; Taminato, T; Goto, Y; Inoue, Y; Kadowaki, S; Hattori, M; Mori, K; Kato, Y; Matsukura, S; Imura, H

    1978-12-01

    Plasma glucagon and insulin responses to L-arginine were compared in normal controls and patients with isolated growth hormone deficiency and acromegaly. Patients with isolated growth hormone deficiency were characterized by high plasma glucagon response and low plasma insulin response, whereas acromegalic patients showed exaggerated plasma glucagon response and almost normal insulin response. These results suggest that growth hormone is probably required for optimum function of the islets, and since hyperglucagonaemia was observed in both growth hormone deficiency and acromegaly, metabolic disturbances stemming from the respective primary diseases may affect glucagon secretion.

  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. Effects of aerobic exercise on ectopic lipids in patients with growth hormone deficiency before and after growth hormone replacement therapy

    PubMed Central

    Christ, Emanuel R.; Egger, Andrea; Allemann, Sabin; Buehler, Tania; Kreis, Roland; Boesch, Chris

    2016-01-01

    Growth hormone replacement therapy (GHRT) increases exercise capacity and insulin resistance while it decreases fat mass in growth hormone-deficient patients (GHD). Ectopic lipids (intramyocellular (IMCL) and intrahepatocellular lipids (IHCL) are related to insulin resistance. The effect of GHRT on ectopic lipids is unknown. It is hypothesized that exercise-induced utilization of ectopic lipids is significantly decreased in GHD patients and normalized by GHRT. GHD (4 females, 6 males) and age/gender/waist-matched control subjects (CS) were studied. VO2max was assessed on a treadmill and insulin sensitivity determined by a two-step hyperinsulinaemic-euglycaemic clamp. Visceral (VAT) and subcutaneous (SAT) fat were quantified by MR-imaging. IHCL and IMCL were measured before and after a 2 h exercise at 50–60% of VO2max using MR-spectroscopy (∆IMCL, ∆IHCL). Identical investigations were performed after 6 months of GHRT. VO2max was similar in GHD and CS and significantly increased after GHRT; GHRT significantly decreased SAT and VAT. 2 h-exercise resulted in a decrease in IMCL (significant in CS and GHRT) and a significant increase in IHCL in CS and GHD pre and post GHRT. GHRT didn’t significantly impact on ∆IMCL and ∆IHCL. We conclude that aerobic exercise affects ectopic lipids in patients and controls. GHRT increases exercise capacity without influencing ectopic lipids. PMID:26792091

  15. Effect of growth hormone on cardiac function.

    PubMed

    Lombardi, G; Colao, A; Ferone, D; Marzullo, P; Orio, F; Longobardi, S; Merola, B

    1997-01-01

    At present, there is a growing body of evidence implicating growth hormone (GH) and/or insulin-like growth factor-I (IGF-I) in the intricate cascade of events connected with the regulation of heart development and hypertrophy. In addition, advanced clinical manifestations of abnormal GH levels almost always include impaired cardiac function, which may reduce life expectancy. This finding is related both to a primary impairment of heart structure and function and to metabolic changes such as hyperlipidaemia, increased body fat and premature atherosclerosis. Acromegalic cardiomyopathy is better correlated with disease duration than with GH or IGF-I levels. Myocardial hypertrophy with interstitial fibrosis, lymphomononuclear infiltration and areas of monocyte necrosis often result in increased right and left ventricular mass concentric hypertrophy. Conversely, patients with childhood or adult-onset GH deficiency (GHD) have a reduced left ventricular mass (LVM) and ejection fraction (EF) and the indices of left ventricular systolic function remained markedly depressed during exercise. Cardiac function is reported to improve during octreotide and GH replacement treatment in acromegaly and GHD, respectively. The evidence that GH can increase cardiac mass suggests its use in the treatment of idiopathic dilated cardiomyopathy. In a recent study on such patients, the administration of recombinant GH (rGH) was demonstrated to increase myocardial mass and reduce the size of the left ventricular chamber, resulting in improved haemodynamics, myocardial energy metabolism and clinical status. PMID:9350445

  16. 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.

  17. Long-Acting Growth Hormone: An Update.

    PubMed

    Saenger, Paul H; Mejia-Corletto, Jorge

    2016-01-01

    After the introduction of recombinant human growth hormone (rhGH) in 1985, a myriad of children and adults have benefited from its growth-promoting and metabolic effects. Nowadays, current therapeutic regimens rely on daily subcutaneous GH injections that could be burdensome and inconvenient to pediatric patients. As expected with any long-term parenteral pharmacological treatment, these daily regimens may promote nonadherence, poor compliance, treatment abandonment and/or suboptimal clinical outcomes. In order to improve patient and caregiver acceptance of proposed regimens, simplified dosing schedules could potentially aid in reducing poor compliance and maximize the therapeutic end results. Long-acting GH formulations have been designed and perfected over the last two decades, and currently there are several formulations in advanced stages of research as a reasonable attempt to improve patient's adherence to GH treatment. A long-acting GH preparation allowing for reduced injection frequency is likely to improve treatment adherence and to decrease the distress and inconvenience associated with daily injections. This review presents an update about the status of current and recent efforts that have enabled the formulation of sustained-release, long-acting rhGH as it has been longed for many years in the pediatric endocrinology field.

  18. 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.

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

    PubMed Central

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

    1994-01-01

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

  20. Hormone activities and the cell cycle machinery in immunity-triggered growth inhibition.

    PubMed

    Reitz, M U; Gifford, M L; Schäfer, P

    2015-04-01

    Biotic stress and diseases caused by pathogen attack pose threats in crop production and significantly reduce crop yields. Enhancing immunity against pathogens is therefore of outstanding importance in crop breeding. However, this must be balanced, as immune activation inhibits plant growth. This immunity-coupled growth trade-off does not support resistance but is postulated to reflect the reallocation of resources to drive immunity. There is, however, increasing evidence that growth-immunity trade-offs are based on the reconfiguration of hormone pathways, shared by growth and immunity signalling. Studies in roots revealed the role of hormones in orchestrating growth across different cell types, with some hormones showing a defined cell type-specific activity. This is apparently highly relevant for the regulation of the cell cycle machinery and might be part of the growth-immunity cross-talk. Since plants are constantly exposed to Immuno-activating microbes under agricultural conditions, the transition from a growth to an immunity operating mode can significantly reduce crop yield and can conflict our efforts to generate next-generation crops with improved yield under climate change conditions. By focusing on roots, we outline the current knowledge of hormone signalling on the cell cycle machinery to explain growth trade-offs induced by immunity. By referring to abiotic stress studies, we further introduce how root cell type-specific hormone activities might contribute to growth under immunity and discuss the feasibility of uncoupling the growth-immunity cross-talk.

  1. Metabolism of growth hormone releasing peptides.

    PubMed

    Thomas, Andreas; Delahaut, Philippe; Krug, Oliver; Schänzer, Wilhelm; Thevis, Mario

    2012-12-01

    New, potentially performance enhancing compounds have frequently been introduced to licit and illicit markets and rapidly distributed via worldwide operating Internet platforms. Developing fast analytical strategies to follow these new trends is one the most challenging issues for modern doping control analysis. Even if reference compounds for the active drugs are readily obtained, their unknown metabolism complicates effective testing strategies. Recently, a new class of small C-terminally amidated peptides comprising four to seven amino acid residues received considerable attention of sports drug testing authorities due to their ability to stimulate growth hormone release from the pituitary. The most promising candidates are the growth hormone releasing peptide (GHRP)-1, -2, -4, -5, -6, hexarelin, alexamorelin, and ipamorelin. With the exemption of GHRP-2, the entity of these peptides represents nonapproved pharmaceuticals; however, via Internet providers, all compounds are readily available. To date, only limited information on the metabolism of these substances is available and merely one metabolite for GHRP-2 is established. Therefore, a comprehensive in vivo (po and iv administration in rats) and in vitro (with human serum and recombinant amidase) study was performed in order to generate information on urinary metabolites potentially useful for routine doping controls. The urine samples from the in vivo experiments were purified by mixed-mode cation-exchange solid-phase extraction and analyzed by ultrahigh-performance liquid chromatography (UHPLC) separation followed by high-resolution/high-accuracy mass spectrometry. Combining the high resolution power of a benchtop Orbitrap mass analyzer for the first metabolite screening and the speed of a quadrupole/time-of-flight (Q-TOF) instrument for identification, urinary metabolites were screened by means of a sensitive full scan analysis and subsequently confirmed by high-accuracy product ion scan experiments. Two

  2. PLGA microsphere-mediated growth hormone release hormone expression induces intergenerational growth.

    PubMed

    Ren, Xiao-Hui; Zhang, Yong-Liang; Luo, Hu-Ying; Li, Hong-Yi; Liu, Song-Cai; Zhang, Ming-Jun; Ouyang, Song-Ying; Xi, Qian-Yun; Jiang, Qing-Yan

    2009-01-01

    To improve animal growth, growth hormone-releasing hormone (GHRH) expression vectors that maintain constant GHRH expression can be directly injected into muscles. To deliver the GHRH expression vectors, biodegradable microspheres have been used as a sustained release system. Although administering GHRH through microspheres is a common practice, the intergenerational effects of this delivery system are unknown. To investigate the intergenerational effects of polylactic-co-glycolic acid (PLGA) encapsulated plasmid-mediated GHRH supplements, pCMV-Rep-GHRH microspheres were injected into pregnant mice. Growth and expression of GHRH were measured in the offspring. RT-PCR and immunohistochemistry reveal GHRH expression 3-21 days post-injection. The proportion of GH-positive cells in the GHRH treated offspring was 48.2% higher than in the control group (P < 0.01). The GHRH treated offspring were 6.15% (P < 0.05) larger than the control offspring. At day 49 post-injection, IGF-I serum levels were significantly higher in the treatment group than in the control group. This study confirms that intramuscular expression of GHRH mediated by PLGA microspheres significantly enhances intergenerational growth.

  3. Growth hormone-releasing factor (GRF) induced growth hormone advances puberty in female buffaloes.

    PubMed

    Haldar, A; Prakash, B S

    2006-05-01

    Exogenous bovine growth hormone-releasing factor (bGRF) at the dose rate of 10 microg/100 kg body weight was administered intravenously (i.v.) to six Murrah buffalo heifers as treatment group, while another six buffalo heifers served as control group which received the vehicle (0.9% NaCl solution) at an interval of 15 days for a period of 9 months to study the effect of bGRF on puberty onset associated with temporal hormonal changes in peri-pubertal buffalo heifers. Blood samples were collected at 3-day interval from all the animals during the experimental period and plasma harvested was assayed for growth hormonal (GH), luteinizing hormone (LH) and progesterone. The day that plasma progesterone was greater than 1.0 ng/ml for three consecutive sampling days was defined as the day of puberty. Exogenous bGRF administration increased (P = 0.02) plasma GH concentration in treatment group over control group during the treatment of bGRF as well as during the peri-pubertal period. Plasma progesterone concentrations increased transiently earlier (P = 0.05) by 58.5 days in bGRF-treated buffaloes than that in the control group. However, plasma LH concentrations were unaffected by the treatment of bGRF (P = 0.48). Both plasma GH and LH in the buffalo heifers increased (P < 0.01) over time preceding puberty and the higher hormonal concentrations were maintained during the onset of puberty, and thereafter, the concentrations of both the hormones declined (P < 0.05) after puberty. GH and LH were positively correlated both before puberty (r = +0.59 and +0.63; P < 0.05 for control and treatment group, respectively) and after puberty (r = +0.42 and +0.46; P < 0.05 for control and treatment group, respectively) indicating the interaction and/or close relationship of GH and LH in the mechanism of puberty in buffalo species. PMID:16011881

  4. Outcome of growth hormone therapy in children with growth hormone deficiency showing an inadequate response to growth hormone-releasing hormone.

    PubMed

    Saenger, P; Pescovitz, O H; Bercu, B B; Murray, F T; Landy, H; Brentzel, J; O'Dea, L; Hanson, B; Howard, C; Reiter, E O

    2001-06-01

    Saizen (recombinant growth hormone [GH]), 0.2 mg/(kg x wk), was given in an open-label fashion for an average of 51 mo to 27 children with presumed idiopathic GH deficiency who had withdrawn from a trial of Geref (recombinant GH-releasing hormone [GHRH] 1-29) because of inadequate height velocity (HV) (25 children), the onset of puberty (1 child), or injection site reactions (1 child). Measurements were made every 3-12 mo of a number of auxologic variables, including HV, height standard deviation score, and bone age. The children in the study showed excellent responses to Saizen. Moreover, first-year growth during Saizen therapy was inversely correlated with the GH response to provocative GHRH testing carried out 6 and 12 mo after the initiation of Geref treatment. These findings indicate that GH is effective in accelerating growth in GH-deficient children who do not show or maintain a satisfactory response to treatment with GHRH. In addition, they suggest that the initial response to GH therapy used in this way can be predicted by means of provoc-ative testing.

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

    PubMed

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

    2005-04-01

    Silent pituitary adenomas are a group of tumors showing heterogenous morphological features with no hormonal function observed clinically. To date no explanation has been provided as to why these tumors remain "silent". We report a case of a silent macroadenoma with both growth hormone (GH) and thyroid stimulating hormone (TSH) staining and secretion but with no clinical manifestations, in particular, the absence of features of acromegaly or hyperthyroidism. The relevant literature is reviewed. PMID:15851094

  6. Secretory pattern of canine growth hormone

    SciTech Connect

    French, M.B.; Vaitkus, P.; Cukerman, E.; Sirek, A.; Sirek, O.V.

    1987-02-01

    The aim of this paper was to define the secretory pattern of growth hormone (GH) under basal conditions in fasted, conscious, male dogs accustomed to handling. Blood samples were withdrawn from a cephalic vein at 15-min intervals. In this way, any ultradian rhythms, if present, could be detected within the frequency range of 0.042-2 cycles/h. In addition, samples were drawn at either 1- or 2.5-min intervals for 2.5 or 5 h to determine whether frequency components greater than 2 cycles/h were present. GH was measured by radioimmunoassay and the raw data were submitted to time series analysis employing power spectral estimation by means of fast Fourier transformation techniques. Peak plasma levels were up to 12 times higher than the baseline concentration of approx. 1 ng/ml. Spectral analysis revealed an endogenous frequency of 0.22 cycles/h, i.e., a periodicity of 4.5 h/cycle. The results indicate that under basal conditions the secretory bursts of canine GH are limited to one peak every 4.5 h.

  7. Signal transduction by the growth hormone receptor

    SciTech Connect

    Waters, M.J.; Rowlinson, S.W.; Clarkson, R.W.

    1994-12-31

    It has been proposed that dimerization of identical receptor subunits by growth hormone (GH) is the mechanism of signal transduction across the cell membrane. We present here data with analogs of porcine GH (pGH), with GH receptors (GHR) mutated in the dimerization domain and with monoclonal antibodies to the GHR which indicate that dimerization is necessary but not sufficient for transduction. We also report nuclear uptake of GH both in vivo and in vitro, along with nuclear localization of the receptor and GH-binding protein (GHBP). This suggests that GH acts directly at the nucleus, and one possible target for this action is a rapid increase in transcription of C/EBP delta seen in 3T3-F442A cells in response to GH. This tyrosine kinase-dependent event may be an archetype for induction of other immediate early gene transcription factors which then interact to determine the programming of the subsequent transcriptional response to GH. 29 refs., 1 fig., 1 tab.

  8. 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

  9. Effects of growth hormone in osteoporosis.

    PubMed

    Aloia, J F; Zanzi, I; Ellis, K; Jowsey, J; Roginsky, M; Wallach, S; Cohn, S H

    1976-11-01

    The effect of chronic administration of growth hormone (GH) to osteoporotic patients was studied using the techniques of total body neutron activation analysis, whole body counting, calcium tracer kinetics, photon absorptiometry, quantitative microradiography, and urinary hydroxyproline. Two dosage schedules were utilized for six months each: 2 units daily and 0.2 w3/4 units of GH daily (where W represents body weight expressed in kg). The lower dosage (2 units) did not produce any appreciable change in the indices studied. Following the higher dose, no evidence of any anabolic effect was apparent in most patients (i.e., no increase in total body levels of Ca, Na, K, P, or Cl). Increases were noted in the urinary calcium excretion rate and in the urinary hydroxyproline excretion. Bone mineral content decreased. The bone biopsies displayed an increase in bone formation and resorption surfaces in response to treatment, but these changes were not statistically significant. It may be concluded that under the conditions of this study, GH administration did not result in an increment in skeletal mass. Several side effects that are characteristic of acromegaly were observed, including hyperglycemia, hypertension, arthralgia, and the carpal tunnel syndrome. Because of the lack of demonstrated benefit and the associated complications of therapy, GH administration does not appear to be of value in the treatment of osteoporosis.

  10. The physiology of growth hormone and sport.

    PubMed

    Widdowson, W Matthew; Healy, Marie-Louise; Sönksen, Peter H; Gibney, James

    2009-08-01

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

  11. Detecting growth hormone abuse in athletes.

    PubMed

    Holt, Richard I G

    2011-08-01

    It is believed that athletes have been abusing growth hormone (GH) for its anabolic and lipolytic effects since the early 1980s, at least a decade before endocrinologists began to treat adults with GH deficiency. There is an on-going debate about whether GH is performance enhancing. Although many of the early studies were negative, more recent studies suggest that GH improves strength and sprint capacity, particularly when it is combined with anabolic steroids. Although use of GH is banned by the World Anti-Doping Agency (WADA), its detection remains challenging. Two approaches have been developed to detect GH abuse. The first is based on measurement of pituitary GH isoforms; after injection of recombinant human GH, which comprises solely the 22-kDa isoform, endogenous production is down-regulated leading to an increase in the 22-kDa isoform relative to other isoforms. The second is based on measurement of markers of GH action. Insulin-like growth factor-I (IGF-I) and N-terminal pro-peptide of type III collagen (P-III-NP) increase in response to GH administration in a dose-dependent manner. When combined with discriminant function analysis, use of these markers differentiates between individuals taking GH and placebo. Subsequent studies have shown that the test is applicable across different ethnicities and is unaffected by injury. WADA regulations state that when analytes are measured by immunoassay, two assays are needed. Final validation of the marker test is currently being undertaken with modern commercially available immunoassays to finalise the threshold values to be used to determine whether a doping offence has been committed.

  12. Growth hormone, insulin-like growth factor system and carcinogenesis.

    PubMed

    Boguszewski, Cesar Luiz; Boguszewski, Margaret Cristina da Silva; Kopchick, John J

    2016-01-01

    The growth hormone (GH) and insulin-like growth factor (IGF) system plays an important role in the regulation of cell proliferation, differentiation, apoptosis, and angiogenesis. In terms of cell cycle regulation, the GH-IGF system induces signalling pathways for cell growth that compete with other signalling systems that result in cell death; thus the final effect of these opposed forces is critical for normal and abnormal cell growth. The association of the GH-IGF system with carcinogenesis has long been hypothesised, mainly based on in vitro studies and the use of a variety of animal models of human cancer, and also on epidemiological and clinical evidence in humans. While ample experimental evidence supports a role of the GH-IGF system in tumour promotion and progression, with several of its components being currently tested as central targets for cancer therapy, the strength of evidence from patients with acromegaly, GH deficiency, or treated with GH is much weaker. In this review, we will attempt to consolidate this data. (Endokrynol Pol 2016; 67 (4): 414-426). PMID:27387246

  13. 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

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

    PubMed

    Loche, Sandro; Carta, Luisanna; Ibba, Anastasia; Guzzetti, Chiara

    2014-03-01

    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

  15. Growth hormone producing prolactinoma in juvenile cystinosis: a simple coincidence?

    PubMed Central

    Besouw, Martine T. P.; Willemsen, Michèl A. A. P.; Noordam, Kees

    2007-01-01

    Juvenile cystinosis was diagnosed in a patient who presented with severe headache attacks and photophobia. Treatment with oral cysteamine and topical cysteamine eye drops was started. One-and-a-half years later, he developed unilateral gynecomastia and elevated prolactin and growth hormone levels. A pituitary macroprolactinoma was discovered and successfully treated with the dopamine agonist cabergoline. Increased serum growth hormone levels were attributed to enhanced growth hormone production by the prolactinoma and somatostatin inhibition by cysteamine. Although the occurrence of prolactinoma in this patient could be a simple coincidence, it might also be a rare yet unrecognised complication of cystinosis. PMID:17638022

  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. A growth hormone receptor mutation impairs growth hormone autofeedback signaling in pituitary tumors.

    PubMed

    Asa, Sylvia L; Digiovanni, Rebecca; Jiang, Jing; Ward, Megan L; Loesch, Kimberly; Yamada, Shozo; Sano, Toshiaki; Yoshimoto, Katsuhiko; Frank, Stuart J; Ezzat, Shereen

    2007-08-01

    Pituitary tumors are a diverse group of neoplasms that are classified based on clinical manifestations, hormone excess, and histomorphologic features. Those that cause growth hormone (GH) excess and acromegaly are subdivided into morphologic variants that have not yet been shown to have pathogenetic significance or predictive value for therapy and outcome. Here, we identify a selective somatic histidine-to-leucine substitution in codon 49 of the extracellular domain of the GH receptor (GHR) in a morphologic subtype of human GH-producing pituitary tumors that is characterized by the presence of cytoskeletal aggresomes. This GHR mutation significantly impairs glycosylation-mediated receptor processing, maturation, ligand binding, and signaling. Pharmacologic GH antagonism recapitulates the morphologic phenotype of pituitary tumors from which this mutation was identified, inducing the formation of cytoskeletal keratin aggresomes. This novel GHR mutation provides evidence for impaired hormone autofeedback in the pathogenesis of these pituitary tumors. It explains the lack of responsiveness to somatostatin analogue therapy of this tumor type, in contrast to the exquisite sensitivity of tumors that lack aggresomes, and has therapeutic implications for the safety of GH antagonism as a therapeutic modality in acromegaly. PMID:17671221

  18. 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.

  19. [Growth hormone receptor antagonist in the treatment of acromegaly].

    PubMed

    Hubina, Erika; Tóth, Agnes; Kovács, Gábor László; Dénes, Judit; Kovács, László; Góth, Miklós

    2011-05-01

    Exploration of construction, function and interaction of human growth hormone and growth hormone receptor in details resulted in the innovation of the new growth hormone receptor antagonist, pegvisomant. Pegvisomant with different mechanism of action extended the tools of medical management of acromegaly. Importance of the novel treatment modality is high. In one hand the necessity of the strict control of growth hormone/insulin-like growth factor-I axis has been proven regarding the mortality of the disease. On the other hand, despite the use of all current modes of treatment (surgery, radiotherapy, dopamine agonists, somatostatin analogs), a significant cohort of patients with acromegaly remains inadequately controlled. Pegvisomant has been registered in 2004. Since 2006, it has been used in Hungary for the treatment of acromegaly in patients who have had an inadequate response to surgery and/or radiation therapy and/or other medical therapies, or for whom these therapies are not appropriate. Clinical use of pegvisomant in the treatment of acromegaly is effective, well tolerated, and safe, based on international Acrostudy database. In order to improve the efficacy of therapy clinical trials started with pegvisomant and somatostatin analog combination treatment. Evidence of several further effects of the growth hormone/insulin-like growth factor-I axis suggests other potential uses of growth hormone receptor antagonists. PMID:21498159

  20. Growth hormone replacement in patients with Langerhan's cell histiocytosis

    PubMed Central

    Howell, S; Wilton, P; Shalet, S

    1998-01-01

    OBJECTIVES—To assess the impact of growth hormone on growth and the underlying disease in children with growth hormone deficiency as a result of Langerhan's cell histiocytosis.
STUDY DESIGN—Retrospective analysis of data from the Kabi (Pharmacia & Upjohn) international growth database (KIGS) for 82 children with Langerhan's cell histiocytosis treated with recombinant growth hormone.
RESULTS—At the start of treatment the median (10-90th centile) age was 9.0 (5.2 to 14.7) years, with a median height standard deviation score (SDS) of −2.0 (−3.5 to −0.9). The median pretreatment height velocity (measured in cm/year) was 3.6 (0.9 to 6.4); this increased to 8.8 (3.8 to 12.0) in the first year of treatment with growth hormone, and then remained significantly greater than the pretreatment height velocity at 7.3 (4.4 to 9.7) and 7.1 (4.1 to 9.3) cm/year in the second and third years, respectively. The median height SDS increased from −2.0 to −0.8 (−2.3 to 0.6) by the end of three years of treatment. There was no increase in the recurrence rate of the underlying disease and no adverse event could be directly attributed to growth hormone treatment, apart from one case of benign intracranial hypertension that resolved on stopping treatment with growth hormone.
CONCLUSIONS—Growth hormone replacement treatment for patients with Langerhan's cell histiocytosis with growth hormone deficiency is beneficial and safe.

 PMID:9659097

  1. Growth Hormone and Insulin-Like Growth Factor-1.

    PubMed

    Nicholls, Adam R; Holt, Richard I G

    2016-01-01

    Human growth hormone (GH) was first isolated from the human pituitary gland in 1945 and found to promote the growth of children with hypopituitarism. Since the formation of the World Anti-Doping Association, human GH has appeared on the list of forbidden substances. There is a significant amount of anecdotal evidence that human GH is misused by athletes to enhance performance, and there have been a number of high-profile cases of GH use in professional sport. GH secretagogues (GH-Ss), which increase GH secretion, and insulin-like growth factor (IGF-1), which mediates many of the effects of GH, are also misused, although there is less evidence for this. The effectiveness of GH, IGF-1, and GH-Ss as performance-enhancing drugs remains unclear. Evidence from studies of GH use in people with hypopituitarism show several desirable outcomes, including increased lean body mass, increased strength, and increased exercise capacity. These anabolic and metabolic properties, coupled with the difficulty in detecting them, make them attractive as agents of misuse. Studies in healthy young adults have also demonstrated a performance benefit with GH and IGF-1. PMID:27347885

  2. New detection methods of growth hormone and growth factors.

    PubMed

    Bidlingmaier, Martin

    2012-01-01

    Human growth hormone (GH), but also GH related growth factors like the insulin-like growth factor-1 (IGF-1) are known to be abused in sports. Although the scientific evidence supporting a distinct effect of GH on performance in healthy trained subjects is limited, it has been repeatedly found with athletes or trainers, and the recent introduction of a first test to detect GH doping has led to a number of positive cases. Currently, there is no test for the detection of IGF-1 introduced worldwide, but confiscation of the drug from sports teams can be taken as indirect evidence for its abuse. The major biochemical difficulty for the detection of GH is that the recombinant form is identical in physicochemical properties to the endogenous GH secreted by the pituitary gland. Furthermore, the very short half-life of GH in circulation inherently shortens the window of opportunity where the drug can be detected. Two strategies have been followed for more than a decade to develop a test to detect the application of recombinant GH: the marker approach, which is based on the elevation of GH-dependent markers above the level seen under physiological conditions evoked by administration of recombinant GH, and the isoform approach, which is based on a change in the pattern of GH isoforms in circulation following the injection of recombinant GH.

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

    PubMed

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

    2015-09-01

    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

  4. Vascular remodeling in the growth hormone transgenic mouse.

    PubMed

    Dilley, R J; Schwartz, S M

    1989-11-01

    Using mice transgenic for the growth hormone gene (TGHM), we have studied the effects of a systemic elevation of growth hormone on vascular growth with the aim of investigating the role of vascular mass changes in producing hypertension. In contrast to human acromegaly or gigantism, there was no elevation of blood pressure in TGHM, but there were significant increases in vascular wall mass. In accordance with a presumably increased perfusion of larger organs, the medial cross-sectional areas of thoracic aorta and mesenteric resistance vessels were greater in the TGHM. These differences could be normalized in the aorta by body weight and in the mesenteric vessel by small intestine weight. Furthermore, the brain was not significantly heavier in the TGHM, and their carotid and cerebral vessels also were not larger. Wall-to-lumen ratios were similar in the aorta, carotid, and middle cerebral arteries suggesting that wall stress was the controlling factor in wall thickness. Surprisingly, the mesenteric vessels had increased wall-to-lumen ratio, which was similar to that seen in hypertensive vascular remodeling but in a normotensive animal. In an attempt to explain this finding it was noted that the pattern of mesenteric vascular networks and even organized structure within the vessel wall itself appeared to be fixed, perhaps by genetic mechanisms. Thus, vascular network structure may be a potentially limiting factor in the ability of the vessel wall to remodel and may have been responsible for the greater wall-to-lumen ratio in TGHM mesenteric vessels. A similar situation in human acromegaly or gigantism could result in a circulation marginally able to correct for other demands on blood flow resulting in about one third of cases being hypertensive. PMID:2805241

  5. 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

  6. Hormone activities and the cell cycle machinery in immunity-triggered growth inhibition

    PubMed Central

    Reitz, M. U.; Gifford, M. L.; Schäfer, P.

    2015-01-01

    Biotic stress and diseases caused by pathogen attack pose threats in crop production and significantly reduce crop yields. Enhancing immunity against pathogens is therefore of outstanding importance in crop breeding. However, this must be balanced, as immune activation inhibits plant growth. This immunity-coupled growth trade-off does not support resistance but is postulated to reflect the reallocation of resources to drive immunity. There is, however, increasing evidence that growth–immunity trade-offs are based on the reconfiguration of hormone pathways, shared by growth and immunity signalling. Studies in roots revealed the role of hormones in orchestrating growth across different cell types, with some hormones showing a defined cell type-specific activity. This is apparently highly relevant for the regulation of the cell cycle machinery and might be part of the growth–immunity cross-talk. Since plants are constantly exposed to Immuno-activating microbes under agricultural conditions, the transition from a growth to an immunity operating mode can significantly reduce crop yield and can conflict our efforts to generate next-generation crops with improved yield under climate change conditions. By focusing on roots, we outline the current knowledge of hormone signalling on the cell cycle machinery to explain growth trade-offs induced by immunity. By referring to abiotic stress studies, we further introduce how root cell type-specific hormone activities might contribute to growth under immunity and discuss the feasibility of uncoupling the growth–immunity cross-talk. PMID:25821072

  7. 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

  8. 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

    2016-06-01

    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 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. PMID:27226307

  9. Growth hormone receptor polymorphism and growth hormone therapy response in children: a Bayesian meta-analysis.

    PubMed

    Renehan, Andrew G; Solomon, Mattea; Zwahlen, Marcel; Morjaria, Reena; Whatmore, Andrew; Audí, Laura; Binder, Gerhard; Blum, Werner; Bougnères, Pierre; Santos, Christine Dos; Carrascosa, Antonio; Hokken-Koelega, Anita; Jorge, Alexander; Mullis, Primus E; Tauber, Maïthé; Patel, Leena; Clayton, Peter E

    2012-05-01

    Recombinant human growth hormone (rhGH) therapy is used in the long-term treatment of children with growth disorders, but there is considerable treatment response variability. The exon 3-deleted growth hormone receptor polymorphism (GHR(d3)) may account for some of this variability. The authors performed a systematic review (to April 2011), including investigator-only data, to quantify the effects of the GHR(fl-d3) and GHR(d3-d3) genotypes on rhGH therapy response and used a recently established Bayesian inheritance model-free approach to meta-analyze the data. The primary outcome was the 1-year change-in-height standard-deviation score for the 2 genotypes. Eighteen data sets from 12 studies (1,527 children) were included. After several prior assumptions were tested, the most appropriate inheritance model was codominant (posterior probability = 0.93). Compared with noncarriers, carriers had median differences in 1-year change-in-height standard-deviation score of 0.09 (95% credible interval (CrI): 0.01, 0.17) for GHR(fl-d3) and of 0.14 (95% CrI: 0.02, 0.26) for GHR(d3-d3). However, the between-study standard deviation of 0.18 (95% CrI: 0.10, 0.33) was considerable. The authors tested by meta-regression for potential modifiers and found no substantial influence. They conclude that 1) the GHR(d3) polymorphism inheritance is codominant, contrasting with previous reports; 2) GHR(d3) genotypes account for modest increases in rhGH effects in children; and 3) considerable unexplained variability in responsiveness remains.

  10. Data-driven synthesis of proteolysis-resistant peptide hormones.

    PubMed

    Prothiwa, Michaela; Syed, Ismail; Huising, Mark O; van der Meulen, Talitha; Donaldson, Cynthia J; Trauger, Sunia A; Kahn, Barbara B; Saghatelian, Alan

    2014-12-24

    Peptide hormones are key physiological regulators, and many would make terrific drugs; however, the therapeutic use of peptides is limited by poor metabolism including rapid proteolysis. To develop novel proteolysis-resistant peptide hormone analogs, we utilize a strategy that relies on data from simple mass spectrometry experiments to guide the chemical synthesis of proteolysis-resistant analogs (i.e., data-driven synthesis). Application of this strategy to oxyntomodulin (OXM), a peptide hormone that stimulates insulin secretion from islets and lowers blood glucose in vivo, defined the OXM cleavage site in serum, and this information was used to synthesize a proteolysis-resistant OXM analog (prOXM). prOXM and OXM have similar activity in binding and glucose stimulated-insulin secretion assays. Furthermore, prOXM is also active in vivo. prOXM reduces basal glucose levels and improves glucose tolerance in mice. The discovery of prOXM suggests that proteolysis-resistant variants of other important peptide hormones can also be found using this strategy to increase the number of candidate therapeutic peptides. PMID:25496053

  11. Growth Charts for Prader-Willi Syndrome During Growth Hormone Treatment.

    PubMed

    Butler, Merlin G; Lee, Jaehoon; Cox, Devin M; Manzardo, Ann M; Gold, June-Anne; Miller, Jennifer L; Roof, Elizabeth; Dykens, Elisabeth; Kimonis, Virginia; Driscoll, Daniel J

    2016-09-01

    The purpose of the current study was to develop syndrome-specific standardized growth curves for growth hormone-treated Prader-Willi syndrome (PWS) individuals aged 0 to 18 years. Anthropometric growth-related measures were obtained on 171 subjects with PWS who were treated with growth hormone for at least 40% of their lifespan. They had no history of scoliosis. PWS standardized growth curves were developed for 7 percentile ranges using the LMS method for weight, height, head circumference, weight/length, and BMI along with normative 3rd, 50th, and 97th percentiles plotted using control data from the literature and growth databases. Percentiles were plotted on growth charts for comparison purposes. Growth hormone treatment appears to normalize stature and markedly improves weight in PWS compared with standardized curves for non-growth hormone-treated PWS individuals. Growth chart implications and recommended usage are discussed. PMID:26842920

  12. 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.

  13. [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.

  14. 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

  15. Nitric oxide may mediate the hemodynamic effects of recombinant growth hormone in patients with acquired growth hormone deficiency. A double-blind, placebo-controlled study.

    PubMed Central

    Böger, R H; Skamira, C; Bode-Böger, S M; Brabant, G; von zur Muhlen, A; Frolich, J C

    1996-01-01

    We studied the effects of recombinant growth hormone on systemic nitric oxide (NO) formation and hemodynamics in a double-blind, placebo-controlled trial in adult patients with acquired growth hormone deficiency. 30 patients were randomly allocated to either recombinant human growth hormone (r-hGH; 2.0 IU/d) or placebo for 12 mo. In the subsequent 12 mo, the study was continued with both groups of patients receiving r-hGH. In months 1, 3, 6, 9, and 12 of each year, urine and plasma samples were collected for the determination of urinary nitrate and cyclic GMP as indices of systemic NO production, and of plasma IGF-1 levels. Cardiac output was measured in months 1, 12, and 24 by echocardiography. r-hGH induced a fourfold increase in plasma IGF-1 concentrations within the first month of treatment. Urinary nitrate and cyclic GMP excretion rates were low at baseline in growth hormone-deficient patients (nitrate, 96.8+/-7.4 micromol/mmol creatinine; cyclic GMP, 63.6+/-7.1 nmol/mmol creatinine) as compared with healthy controls (nitrate, 167.3+/-7.5 micromol/mmol creatinine; cyclic GMP, 155.2+/-6.9 nmol/mmol creatinine). These indices of NO production were significantly increased by r-hGH, within the first 12 mo in the GH group, and within the second 12 mo in the placebo group. While systolic and diastolic blood pressure were not significantly altered by r-hGH, cardiac output significantly increased by 30-40%, and total peripheral resistance decreased by approximately 30% in both groups when they were assigned to r-hGH treatment. In the second study year, when both groups were given r-hGH, there were no significant differences in plasma IGF-1, urinary nitrate, or cyclic GMP excretion, or hemodynamic parameters between both groups. In conclusion, systemic NO formation is decreased in untreated growth hormone-deficient patients. Treatment with recombinant human growth hormone normalizes urinary nitrate and cyclic GMP excretion, possibly via IGF-1 stimulation of endothelial

  16. Pathology of growth hormone-producing tumors of the human pituitary.

    PubMed

    Kovacs, K; Horvath, E

    1986-02-01

    This paper reviews the morphologic features of growth hormone-producing tumors of the human pituitary. These tumors are associated with elevated blood growth hormone levels and acromegaly or gigantism and can be classified into the following morphologically distinct entities by the combined application of histology, immunocytology, and electron microscopy: densely granulated growth hormone cell adenoma; sparsely granulated growth hormone cell adenoma; mixed growth hormone cell- prolactin cell-adenoma; acidophil stem cell adenoma; mammosomatotroph cell adenoma; growth hormone cell carcinoma; plurihormonal adenoma with growth hormone production. PMID:3303228

  17. A major thyroid hormone response element in the third intron of the rat growth hormone gene.

    PubMed Central

    Sap, J; de Magistris, L; Stunnenberg, H; Vennström, B

    1990-01-01

    The rat growth hormone (RGH) gene constitutes a well-documented model system for the direct regulation of transcription by thyroid hormones. In order to analyse its interaction with sequences in the RGH gene, we have overproduced the thyroid hormone receptor-alpha (c-erbA) protein using a vaccinia virus expression system. The expressed protein bound T3 and DNA-cellulose with expected affinities, and the major binding site for the receptor protein was found to be located in the third intron of the RGH gene. This site displayed significantly higher affinity for the receptor protein than a previously described thyroid hormone response element (TRE) in the promoter of this gene, and also conferred stronger hormone responsiveness in vivo to a heterologous promoter. The data suggest that this novel TRE plays a major role in the regulation of rat growth hormone gene expression by thyroid hormones. Images Fig. 1. Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. Fig. 8. PMID:2155782

  18. 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. PMID:25649030

  19. 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.

  20. 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.

  1. 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.

  2. Human growth hormone and the development of osteochondritis dissecans lesions.

    PubMed

    Hussain, Waqas M; Hussain, Haroon M; Hussain, Mohammed S; Ho, Sherwin S W

    2011-12-01

    No single etiology regarding the cause of osteochondritis dissecans (OCD) lesions is unanimously accepted. This report documents a novel case of multiple OCD lesions affecting the left knee and a solitary defect of the right elbow in a patient with acquired human growth hormone (hGH) deficiency and supplementation. hGH deficiency and hormone replacement may be related to the development of OCD lesions.

  3. 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

  4. Postexercise hypertrophic adaptations: a reexamination of the hormone hypothesis and its applicability to resistance training program design.

    PubMed

    Schoenfeld, Brad J

    2013-06-01

    It has been well documented in the literature that resistance training can promote marked increases in skeletal muscle mass. Postexercise hypertrophic adaptations are mediated by a complex enzymatic cascade whereby mechanical tension is molecularly transduced into anabolic and catabolic signals that ultimately lead to a compensatory response, shifting muscle protein balance to favor synthesis over degradation. Myocellular signaling is influenced, in part, by the endocrine system. Various hormones have been shown to alter the dynamic balance between anabolic and catabolic stimuli in muscle, helping to mediate an increase or decrease in muscle protein accretion. Resistance training can have an acute impact on the postexercise secretion of several of these hormones including insulin-like growth factor, testosterone, and growth hormone (GH). Studies show that hormonal spikes are magnified after hypertrophy-type exercise that involves training at moderate intensities with shortened rest intervals as compared with high-intensity strength-oriented training. The observed positive relationship between anabolic hormones and hypertrophy-type training has led to the hormone hypothesis, which postulates that acute postexercise hormonal secretions mediate increases in muscle size. Several researchers have suggested that these transient hormonal elevations may be more critical to hypertrophic adaptations than chronic changes in resting hormonal concentrations. Theoretically, high levels of circulating hormones increase the likelihood of interaction with receptors, which may have particular hypertrophic importance in the postworkout period when muscles are primed for anabolism. Moreover, hormonal spikes may enhance intracellular signaling so that postexercise protein breakdown is rapidly attenuated and anabolic processes are heightened, thereby leading to a greater supercompensatory response. Although the hormone hypothesis has received considerable support in the literature

  5. 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.

  6. 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.

  7. 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

  8. Regulation of human growth hormone secretion and its disorders.

    PubMed

    Kato, Yuzuru; Murakami, Yoshio; Sohmiya, Motoi; Nishiki, Masateru

    2002-01-01

    Growth hormone (GH) secretion from anterior pituitary is regulated by the hypothalamus and the mediators of GH actions. Major regulatory factors include GH releasing hormone (GHRH), somatostatin (SRIF), GH releasing peptide (ghrerin) and insulin-like growth factor (IGF-I). The principal physiological regulation mechanisms of GH secretion are neural endogenous rhythm, sleep, stress, exercise, and nutritional and metabolic signals. GH deficiency results from various hereditary or acquired causes, which may be isolated or combined with other pituitary hormone deficiencies. GH deficiency can be treated with recombinant human GH, which results in accelerating growth in children and normalization of intermediary metabolism in adults. GH hypersecretion mostly results from a pituitary tumor and causes acromegaly or gigantism. Hypersecretion of GH can be treated by transshenoidal surgery. Medical treatment with octreotide and analogs is also effective to reduce GH secretion in combination with or without the surgery. PMID:11838603

  9. Neuroendocrine hormones such as growth hormone and prolactin are integral members of the immunological cytokine network.

    PubMed

    Redelman, Doug; Welniak, Lisbeth A; Taub, Dennis; Murphy, William J

    2008-01-01

    Neuroendocrine hormones such as growth hormone (GH) and prolactin (PRL) have been demonstrated to accelerate the recovery of the immune response after chemotherapy and bone marrow transplantation and to enhance the restoration of immunity in individuals infected with HIV and in normal individuals with compromised immune systems associated with aging. As the mechanism of action of these hormones has been elucidated, it has become clear that they are integral members of the immunological cytokine/chemokine network and share regulatory mechanisms with a wide variety of cytokines and chemokines. The members of this cytokine network induce and can be regulated by members of the suppressor of cytokine signaling (SOCS) family of intracellular proteins. In order to take advantage of the potential beneficial effects of hormones such as GH or PRL, it is essential to take into consideration the overall cytokine network and the regulatory effects of SOCS proteins.

  10. 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.

  11. GH responses to growth hormone releasing factor in depression.

    PubMed

    Thomas, R; Beer, R; Harris, B; John, R; Scanlon, M

    1989-01-01

    The growth hormone (GH), thyrotrophin (TSH) and prolactin response to growth hormone releasing factor (GRF) was investigated in 18 patients suffering from major depression with melancholia and in 18 age- and sex-matched normal controls. There was no significant difference in the GH response to GRF stimulation between the patients and controls and in neither subject group was there a demonstrable TSH or prolactin response to GRF. These findings indicate that the pathophysiology underlying the blunted GH response to pharmacological challenge, demonstrated in other studies, must lie at a suprapituitary level.

  12. 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.

  13. 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.

  14. Recurrent PRKAR1A mutation in acrodysostosis with hormone resistance.

    PubMed

    Linglart, Agnès; Menguy, Christine; Couvineau, Alain; Auzan, Colette; Gunes, Yasemin; Cancel, Mathilde; Motte, Emmanuelle; Pinto, Graziella; Chanson, Philippe; Bougnères, Pierre; Clauser, Eric; Silve, Caroline

    2011-06-01

    The skeletal dysplasia characteristic of acrodysostosis resembles the Albright's hereditary osteodystrophy seen in patients with pseudohypoparathyroidism type 1a, but defects in the α-stimulatory subunit of the G-protein (GNAS), the cause of pseudohypoparathyroidism type 1a, are not present in patients with acrodysostosis. We report a germ-line mutation in the gene encoding PRKAR1A, the cyclic AMP (cAMP)-dependent regulatory subunit of protein kinase A, in three unrelated patients with acrodysostosis and resistance to multiple hormones. The mutated subunit impairs the protein kinase A response to stimulation by cAMP; this explains our patients' hormone resistance and the similarities of their skeletal abnormalities with those observed in patients with pseudohypoparathyroidism type 1a. PMID:21651393

  15. Comparative pharmacokinetics and pharmacodynamics of a PEGylated recombinant human growth hormone and daily recombinant human growth hormone in growth hormone-deficient children

    PubMed Central

    Hou, Ling; Chen, Zhi-hang; Liu, Dong; Cheng, Yuan-guo; Luo, Xiao-ping

    2016-01-01

    Objective Recombinant human growth hormone (rhGH) replacement therapy in children generally requires daily subcutaneous (sc) injections, which may be inconvenient for patients. Jintrolong® is a PEGylated rhGH with the purpose of weekly sc injections. The aim of the current study was to examine the pharmacokinetics, pharmacodynamics, safety, and tolerability of multiple sc doses of Jintrolong® vs daily doses of rhGH. Design and methods Twelve children with growth hormone deficiency participated in this single-center, open-label, crossover Phase I trial. All subjects received daily sc injections of rhGH at 0.0286 mg/kg/d for 7 days, followed by a 4-week washout period and six weekly doses of Jintrolong® at 0.2 mg/kg/w. Results In comparison with rhGH, sc injection of Jintrolong® produced a noticeably higher Cmax, significantly longer half-life (t1/2), and slower plasma clearance, signifying a profile suitable for long-term treatment. The ratio of the area under the concentration vs time curve (AUC) after the seventh and first injections (AUC(0–∞)7th/AUC(0–∞)1st) of rhGH was 1.02, while the AUC(0–∞)6th/AUC(0–∞)1st of Jintrolong ® was 1.03, indicating no accumulation of circulating growth hormone. There was no significant difference in the change in insulin-like growth factor-1 expression produced by 7 days of sc rhGH and weekly Jintrolong® injections. There were no severe adverse events during the trial. Conclusion The elimination rate of Jintrolong® was slower than that of sc rhGH. No progressive serum accumulation of Jintrolong® was found. The changes in insulin-like growth factor-1 expression produced by rhGH and Jintrolong® were comparable, indicating similar pharmacodynamics. Our results demonstrate that Jintrolong® is suitable for long-term growth hormone treatment in children with growth hormone deficiency. PMID:26719670

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. Growth and hormonal status of children treated for brain tumours.

    PubMed

    Shalet, S M

    1982-01-01

    The adult survivors of the treatment of brain tumours in childhood are often short. Several adverse factors contribute to the impaired growth of these children including growth hormone (GH) deficiency, impaired spinal growth following spinal irradiation, chemotherapy, poor nutritional intake and recurrent tumour. The GH deficiency is due to radiation-induced damage to the hypothalamic-pituitary axis. GH is always the first pituitary hormone to be affected by such radiation damage but panhypopituitarism may occur if the radiation dose is sufficiently great. Preliminary results suggest that GH therapy will improve the growth rate of children with radiation-induced GH deficiency. Additional endocrine complications, which may occur following spinal irradiation, include thyroid dysfunction and ovarian failure due to direct radiation damage to the thyroid and the ovary.

  1. 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.

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

    PubMed Central

    2016-01-01

    Abstract 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. PMID:26260675

  3. [TREATMENT OF SHORT STATURE PATIENTS WITH NOPMAL GROWTH HORMONE SECRETION OF HYPOPHIS].

    PubMed

    Sprinchuk, N A; Samson, O J; Bol'shova, E V

    2014-12-01

    The article presents the treatment outcome in 86 children with short stature associated with different endocrine pathology and saved growth hormone secretion (congenital adrenal hyperplasia chondrodystrophy, Turner syndrome, idiopathic short stature, syndrome biologically inactive growth hormone and other genetically determined pathology). This study extends prior knowledge about the outcomes of the treatment with recombinant growth hormone and luteinizing hormone--releasing hormone analogue (alone or in combination) in short patients with poor prognosis of final height. PMID:26638471

  4. 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.

  5. Expression of the human growth hormone variant gene in cultured fibroblasts and transgenic mice

    SciTech Connect

    Selden, R.F.; Wagner, T.E.; Blethen, S.; Yun, J.S.; Rowe, M.E.; Goodman, H.M. )

    1988-11-01

    The nucleotide sequence of the human growth hormone variant gene, one of the five members of the growth hormone gene family, predicts that it encodes a growth hormone-like protein. As a first step in determining whether this gene is functional in humans, the authors have expressed a mouse methallothionein I/human growth hormone variant fusion gene in mouse L cells and in transgenic mice. The growth hormone variant protein expressed in transiently transfected L cells is distinct from growth hormone itself with respect to reactivity with anti-growth hormone monoclonal antibodies, behavior during column chromatography, and isoelectric point. Transgenic mice expressing the growth hormone variant protein are 1.4- to 1.9-fold larger than nontransgenic controls, suggesting that the protein has growth-promoting properties.

  6. Modified Clonidine Testing for Growth Hormone Stimulation Reveals α2-Adrenoreceptor Sub Sensitivity in Children with Idiopathic Growth Hormone Deficiency

    PubMed Central

    Willaschek, Christian; Meint, Sebastian; Rager, Klaus; Buchhorn, Reiner

    2015-01-01

    Introduction The association between short stature and increased risk of ischemic heart disease has been subject to studies for decades. The recent discussion of cardiovascular risk during growth hormone therapy has given new importance to this question. We have hypothesized that the autonomic system is a crucial element relating to this subject. Methods Heart rate variability calculated from 24-hour electrocardiogram data is providing insight into the regulatory state of the autonomous nervous system and is an approved surrogate parameter for estimating cardiovascular risk. We have calculated heart rate variability during clonidine testing for growth hormone stimulation of 56 children. As clonidine is a well-known effector of the autonomous system, stimulating vagal tone and decreasing sympathetic activity, we compared the autonomous reactions of children with constitutional growth delay (CGD), growth hormone deficiency (GHD) and former small for gestational age (SGA). Results During clonidine testing children with CGD showed the expected α2-adrenoreceptor mediated autonomous response of vagal stimulation for several hours. This vagal reaction was significantly reduced in the SGA group and nearly non- existent in the GHD group. Discussion Children with GHD show a reduced autonomous response to clonidine indicating α2-adrenoreceptor sub sensitivity. This can be found prior to the start of growth hormone treatment. Since reduction of HRV is an approved surrogate parameter, increased cardiovascular risk has to be assumed for patients with GHD. In the SGA group a similar but less severe reduction of the autonomous response to clonidine was found. These findings may enrich the interpretation of the data on growth hormone therapy, which are being collected by the SAGhE study group. PMID:26361394

  7. [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. PMID:24356290

  8. [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.

  9. Growth hormone, insulin-like growth factor-1 and the aging cardiovascular system.

    PubMed

    Khan, Amir S; Sane, David C; Wannenburg, Thomas; Sonntag, William E

    2002-04-01

    There is a large body of evidence that biological aging is related to a series of long-term catabolic processes resulting in decreased function and structural integrity of several physiological systems, among which is the cardiovascular system. These changes in the aging phenotype are correlated with a decline in the amplitude of pulsatile growth hormone secretion and the resulting decrease in plasma levels of its anabolic mediator, insulin like growth factor-1 (IGF-1). The relationship between growth hormone and biological aging is supported by studies demonstrating that growth hormone administration to old animals and humans raises plasma IGF-1 and results in increases in skeletal muscle and lean body mass, a decrease in adiposity, increased immune function, improvements in learning and memory, and increases in cardiovascular function. Since growth hormone and IGF-1 exert potent effects on the heart and vasculature, the relationship between age-related changes in cardiovascular function and the decline in growth hormone levels with age have become of interest. Among the age-related changes in the cardiovascular system are decreases in myocyte number, accumulation of fibrosis and collagen, decreases in stress-induced cardiac function through deterioration of the myocardial conduction system and beta-adrenergic receptor function, decreases in exercise capacity, vessel rarefaction, decreased arterial compliance and endothelial dysfunction leading to alterations in blood flow. Growth hormone has been found to exert potent effects on cardiovascular function in young animals and reverses many of the deficits in cardiovascular function in aged animals and humans. Nevertheless, it has been difficult to separate the effects of growth hormone deficiency from age-related diseases and associated pathologies. The development of novel animal models and additional research are required in order to elucidate the specific effects of growth hormone deficiency and assess its

  10. Physiologic growth hormone replacement improves fasting lipid kinetics in patients with HIV lipodystrophy syndrome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    HIV lipodystrophy syndrome (HLS) is characterized by accelerated lipolysis, inadequate fat oxidation, increased hepatic reesterification, and a high frequency of growth hormone deficiency (GHD). The effect of growth hormone (GH) replacement on these lipid kinetic abnormalities is unknown. We aimed ...

  11. Influence of prostaglandins and thyrotropin releasing hormone (TRH) on hormone secretion and growth in wether lambs.

    PubMed

    Davis, S L; Anfinson, M S; Klindt, J; Ohlson, D L

    1977-06-01

    A series of experiments were conducted in ewes and whether (castrate male) lambs to evaluate the influence of prostaglandins on secretion of anabolic hormones and to determine if repeated injections of prostaglandin (PG) F2alpha would chronically influence the secretion of these hormones and perhaps growth rate as well. A single intravenous injection of PGA1 and PGB1 (100 microgram/kg) exerted no significant (P greater than .10) influence on plasma concentrations of prolactin (PRL), growth hormone (GH) or thyrotropin (TSH) in ewes. PGA1, but not PGB1, stimulated an increase in the plasma concentration of insulin. Infusion of PGF2alpha for 5.5 hr into ewes resulted in increased (P less than .05) plasma concentrations of both GH and ARL while TSH and insulin were not significantly influenced. Prostaglandin F2alpha, when injected subcutaneously into wether lambs (10 mg twice weekly) stimulated (P less than .05) plasma GH concentrations after the first injection, but not after 3 weeks of treatment. Changes in plasma PRL or TSH were not observed consistently in the lambs treated chronically with PGF2alpha or TRH. Prostaglandin F2alpha, in the present studies, and PGE1 in previously reported studies (1-3), has been demonstrated to be stimulatory to the secretion of PRL and GH. In contrast, PGA1 and PGB1, which lack an 11-hydroxyl group, failed to influence the secretion of either PRL or GH. It would, therefore, appear that the 11-hydroxyl group is a structural requirement for prostaglandins to influence the secretion of these two hormones in sheep. Treatment with thyrotropin releasing hormone (TRH), alone or in combination with PGF 2alpha, significantly (P less than .05) increased growth rate (average daily gains) while PGF2alpha did not, despite the fact that both compounds exerted similar effects on plasma GH.

  12. Central administration of chicken growth hormone-releasing hormone decreases food intake in chicks.

    PubMed

    Tachibana, Tetsuya; Sugimoto, Ikue; Ogino, Madoka; Khan, Md Sakirul Islam; Masuda, Keiko; Ukena, Kazuyoshi; Wang, Yajun

    2015-02-01

    Growth hormone-releasing hormone (GHRH) is well known as a stimulator of growth hormone (GH) secretion. GHRH not only stimulates GH release but also modifies feeding behavior and energy homeostasis in rodents. In chickens (Gallus gallus domesticus), on the other hand, two types of GHRH, namely, chicken GHRH (cGHRH) and cGHRH-like peptide (cGHRH-LP), have been identified. The purpose of the present study was to investigate the effect of central injection of cGHRH and cGHRH-LP on feeding behavior in chicks. Intracerebroventricular (ICV) injection of both cGHRH and cGHRH-LP (0.04 to 1 nmol) significantly decreased food intake without any abnormal behavior in chicks. Furthermore, the feeding-inhibitory effect was not abolished by co-injection of the antagonist for pituitary adenylate cyclase-activating polypeptide (PACAP) or corticotropin-releasing hormone (CRH) receptors, suggesting that the anorexigenic effect of cGHRH and cGHRH-LP might not be related to the PACAP and CRH systems in the brain of chicks. Finally, 24-h food deprivation increased mRNA expression of cGHRH but not cGHRH-LP in the diencephalon. These results suggest that central cGHRH is related to inhibiting feeding behavior and energy homeostasis in chicks.

  13. 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

  14. 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)

  15. Vitamin D interferes with transactivation of the growth hormone gene by thyroid hormone and retinoic acid.

    PubMed Central

    Garcia-Villalba, P; Jimenez-Lara, A M; Aranda, A

    1996-01-01

    The thyroid hormone, retinoic acid (RA), and vitamin D regulate gene expression by binding to similar receptors which act as ligand-inducible transcription factors. Incubation of pituitary GH4C1 cells with nanomolar concentrations of vitamin D markedly reduces the response of the rat growth hormone mRNA to thyroid hormone triiodothyronine (T3) and RA. The stimulation of growth hormone gene expression by both ligands is mediated by a common hormone response element (TREGH) present in the 5'-flanking region of the gene, and the inhibition caused by vitamin D is due to transcriptional interference of the vitamin D receptor on this DNA element. No inhibition of the basal promoter activity by the vitamin was observed. The response to T3 and RA of a heterologous promoter containing this element, the palindromic T3- and RA-responsive sequence TREPAL, or a direct repeat of the same motif is also inhibited by vitamin D. In contrast, vitamin D strongly induces the activity of constructs containing a vitamin D response element, and neither T3 nor RA reduces vitamin D-mediated transactivation. Transfection with an expression vector for the retinoid X receptor alpha (RXR alpha) increases transactivation by T3 and RA but does not abolish the inhibition caused by the vitamin. Gel retardation experiments show that the vitamin D receptor (VDR) as a heterodimer with RXR weakly binds to the T3- and RA-responsive elements. Additionally, VDR displaces binding of T3 and RA receptors in a dose-dependent manner. Our data suggest the formation of TR-VDR and RAR-VDR heterodimers with RXR. The fact that the same response element mediates opposite effects of at least four different nuclear receptors provides a greater complexity and flexibility of the transcriptional responses to their ligands. PMID:8524311

  16. Recombinant-derived chicken growth hormone used for radioimmunoassay

    SciTech Connect

    Proudman, J.A.

    1984-04-01

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

  17. 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.

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

    PubMed Central

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

    1987-01-01

    Transcription of the rat growth hormone (rGH) gene in pituitary cells is increased by addition of thyroid hormone (T3). This induction is dependent on the presence of specific sequences just upstream of the rGH promoter. 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. Images PMID:3475698

  19. Olaparib With or Without Cediranib in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer

    ClinicalTrials.gov

    2016-09-08

    Hormone-Resistant Prostate Cancer; Metastatic Prostate Carcinoma; Prostate Adenocarcinoma With Focal Neuroendocrine Differentiation; Prostate Carcinoma Metastatic in the Bone; Prostate Small Cell Carcinoma; Stage IV Prostate Adenocarcinoma

  20. 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.

  1. Serum Growth Hormone Levels and the Response of Diabetic Retinopathy to Pituitary Ablation*

    PubMed Central

    Wright, A. D.; Kohner, E. M.; Oakley, N. W.; Hartog, M.; Joplin, G. F.; Fraser, T. Russell

    1969-01-01

    Serum growth hormone levels were measured during insulin tolerance tests in 36 patients after yttrium-90 pituitary implantation for diabetic retinopathy. The response of the new blood vessels was more clearly related to loss of growth hormone function than was the improvement of retinal haemorrhages and microaneurysms. The overall response of the retinopathy was greatest when growth hormone function was lost. Since the loss of growth hormone function was related to the loss of other aspects of anterior pituitary function, a unique role of growth hormone in the response of diabetic retinopathy to pituitary ablation could not be established. PMID:5768460

  2. Hormones and the growth of plants in response to gravity.

    PubMed

    Osborne, D J

    1976-01-01

    Plants are remarkable amongst living things in that all their parts (leaves, stems, roots and flowers) can orientate their position in response to gravity. Roots normally grow downwards towards the stimulus, shoots upwards away from the stimulus, while leaves and special kinds of stems like underground rhizomes or aerial runners have adaptations to grow horizontally, approximately at right angles to the gravitational field. This directional positioning of the organ in relation to gravity is achieved by a regulation of the growth of enlarging cells below the meristems or within the organ. Mature tissues in which further cell growth is precluded are therefore unable to reorientate if their position in the field is changed. Under conditions of zero gravity, roots and shoots continue to grow in opposite directions and the orientation of laterals with respect to the apex is essentially normal. This demonstrates the inherent polarity of plant cells and the internal correlative growth regulation that each organ exerts upon its neighbours. The perception of gravity, involving statoliths, membranes and "wound" ethylene, is discussed, together with the mechanisms by which the subsequent growth responses can be mediated by changes in endogenous hormones. Evidence for how such hormonal changes can lead to modifications of the rate, extent and reorientation of cell growth is reviewed for several geotropically responding systems.

  3. Infantile Growth Hormone Deficiency and X- Linked Adrenal Hypoplasia Congenita

    PubMed Central

    Chung, Stephanie T.; Chi, Carolyn H.; Haymond, Morey W.; Jeha, George S.

    2015-01-01

    Context X-linked adrenal hypoplasia congenita (AHC) is a rare but important cause of primary adrenal insufficiency and can be associated with significant morbidity and mortality. AHC is caused by mutations within the NROB1 gene that codes for the DAX-1 protein, an orphan nuclear receptor essential for the development of the hypothalamic-pituitary-adrenal axis. Affected individuals typically present in early infancy with adrenal insufficiency and growth is usually normal once medical therapy is instituted. Here we report the first case of growth hormone deficiency in an infant with AHC and a novel NROB1 missense mutation. Case A two-week old infant presented with salt-losing adrenal crises and a normal newborn screen. Tests of adrenal function confirmed adrenal hypoplasia congenita and molecular evaluation revealed a novel missense NROB1 mutation. Replacement steroid therapy was promptly initiated, but he subsequently developed growth failure despite optimal nutritional and medical steroid therapy. Further biochemical analyses confirmed isolated idiopathic growth hormone deficiency. Conclusions Growth failure in adequately treated infants with adrenal hypoplasia congenita is rare and the role of DAX-1 in the development of pituitary somatotropes is not known. There is variable genotype-phenotype correlation in X-linked adrenal hypoplasia congenita but novel NROB1 missense mutations could offer insight into the function of the various DAX-1 ligand-binding domains. PMID:27110597

  4. 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.

  5. 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

  6. Early growth and postprandial appetite regulatory hormone responses.

    PubMed

    Perälä, Mia-Maria; Kajantie, Eero; Valsta, Liisa M; Holst, Jens J; Leiviskä, Jaana; Eriksson, Johan G

    2013-11-14

    Strong epidemiological evidence suggests that slow prenatal or postnatal growth is associated with an increased risk of CVD and other metabolic diseases. However, little is known whether early growth affects postprandial metabolism and, especially, the appetite regulatory hormone system. Therefore, we investigated the impact of early growth on postprandial appetite regulatory hormone responses to two high-protein and two high-fat content meals. Healthy, 65-75-year-old volunteers from the Helsinki Birth Cohort Study were recruited; twelve with a slow increase in BMI during the first year of life (SGI group) and twelve controls. Subjects ate a test meal (whey meal, casein meal, SFA meal and PUFA meal) once in a random order. Plasma glucose, insulin, TAG, NEFA, ghrelin, peptide tyrosine-tyrosine (PYY), glucose-dependent insulinotropic peptide, glucagon-like peptide-1 and a satiety profile were measured in the fasting state and for 4 h after each test meal. Compared with the controls, the SGI group had about 1·5-fold higher insulin responses after the whey meal (P= 0·037), casein meal (P= 0·023) and PUFA meal (P= 0·002). TAG responses were 34-69 % higher for the SGI group, but only the PUFA-meal responses differed significantly between the groups. The PYY response of the SGI group was 44 % higher after the whey meal (P= 0·046) and 115 % higher after the casein meal (P= 0·025) compared with the controls. No other statistically significant differences were seen between the groups. In conclusion, early growth may have a role in programming appetite regulatory hormone secretion in later life. Slow early growth is also associated with higher postprandial insulin and TAG responses but not with incretin levels.

  7. Resistance to thyroid hormone α, revelation of basic study to clinical consequences.

    PubMed

    Tang, Yaling; Yu, Miao; Lian, Xiaolan

    2016-05-01

    In the past 3 years, 15 patients with resistance to thyroid hormone α (RTHα), nine THRA gene mutations have been reported, reforming classification of RTH. RTHα exhibits distinguished clinical manifestations from RTHβ, including growth retardation, skeletal dysplasia, impaired neurodevelopment, cardiovascular dysfunction, constipation and specific thyroid axis type. This review focuses on possible pathogenesis by revelatory basic science of RTHα animal models in vivo, and patients' mutant thyroid hormone receptor α (TRα) in vitro. Clinical manifestations and L-T4 effects are summarized, showing strong correlation to the severity of mutation mostly within the domain which dominated TR interaction with T3 and its corepressors/coactivators. In particular, we propose the diagnosis clues and promising treatment for clinicians. PMID:26812777

  8. Growth hormone, prolactin and thyrotrophin responses to thyrotrophin-releasing hormone in diabetic patients.

    PubMed Central

    Harrower, A. D.

    1980-01-01

    Growth hormone (GH), prolactin (PRL) and thyrotrophin (TSH) responses to thyrotrophin-releasing hormone (TRH) were studied in 15 insulin-dependent diabetic patients. Basal plasma GH levels were raised above 5 mu./l in 6 patients and following the injection of TRH there was a significant rise in plasma GH levels in 9. The mean rise in plasma GH from basal to peak values was significant in the group as a whole (P < 0.01). Basal PRL and TSH levels were normal and rose normally in response to TRH. GH release may be qualitatively abnormal in some diabetics and any such loss of specificity of GH-releasing mechanisms would further contribute to the raised GH levels found in many diabetics which would be of importance if GH is a factor in the aetiology of diabetic microangiopathy. PMID:6777767

  9. Regulation of hypothalamic somatostatin and growth hormone releasing hormone mRNA levels by inhibin.

    PubMed

    Carro, E; Señarís, R M; Mallo, F; Diéguez, C

    1999-03-20

    Although it is well established that inhibin plays a major role in the regulation of the hypothalamic-pituitary-gonadal axis, its influence in the regulation of other neuroendocrine functions is still poorly understood. Recent results indicate that inhibin suppresses plasma GH levels, but its site of action is yet unknown. Therefore, in the present work we investigated the effects of inhibin on somatostatin and growth hormone releasing hormone (GHRH) mRNA levels in the hypothalamus by 'in situ' hybridization. We found that inhibin administration (4, 12 and 24 h, i.c.v.) led to an increase in somatostatin mRNA levels in the periventricular nucleus, and to a decrease in GHRH mRNA content in the arcuate nucleus of the hypothalamus. These findings indicate that inhibin regulates the hypothalamic levels of somatostatin and GHRH mRNA.

  10. 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.

  11. Growth hormone and insulin-like growth factor I plasma levels in patients with hypophosphatemic rickets.

    PubMed

    Jasper, H; Cassinelli, H

    1993-01-01

    The cause of the growth retardation present in patients with hypophosphatemic rickets has not been totally elucidated. There has been a previous report of a growth hormone deficit in a group of these patients. To verify this abnormality we studied two groups of patients with hypophosphatemic rickets, one with (n = 6) and the other without (n = 7) treatment with calcitriol and oral phosphates. All patients in both groups showed a normal growth hormone response (> 10 micrograms/l) to standard stimulatory tests and normal IGF-I plasma levels. Mean IGF-I plasma levels were not significantly different (untreated 1.46 +/- 0.80 U/ml, treated 1.25 +/- 0.69 U/ml) and the mean logarithmic deviation of IGF-I plasma levels from both groups did not differ from normal. In summary, we found no abnormalities of the growth hormone-IGF-I axis in our patients with hypophosphatemic rickets.

  12. Growth hormone response to a growth hormone-releasing hormone stimulation test in a population-based study following cranial irradiation of childhood brain tumors.

    PubMed

    Schmiegelow, M; Lassen, S; Poulsen, H S; Feldt-Rasmussen, U; Schmiegelow, K; Hertz, H; Müller, J

    2000-01-01

    Children with brain tumors are at high risk of developing growth hormone deficiency (GHD) after cranial irradiation (CI) if the hypothalamus/pituitary (HP) axis falls within the fields of irradiation. The biological effective dose (BED) of irradiation to the HP region was determined, since BED gives a means of expressing the biological effect of various irradiation treatment schedules in a uniform way. Hypothalamic versus pituitary damage as cause of GHD was distinguished in 62 patients by comparing the growth hormone (GH) peak response to an insulin tolerance test (ITT)/arginine stimulation test and the GH response to a growth hormone-releasing hormone (GHRH) stimulation test. Peak GH response to a GHRH test was significantly higher (median 7.3 mU/l; range: 0.5--79.0 mU/l) than that of an ITT/arginine test (median 4.7 mU/l; range: 0.01--75.0 mU/l) (p = 0.017). Peak GH after a GHRH test was significantly inversely correlated to follow-up time (r(s) = -0.46, p < 0.0001) and to BED (R(s) = -0.28, p = 0.03), and both were found to be of significance in a multivariante regression analysis. We speculate that a significant number of patients developed hypothalamic radiation-induced damage to the GHRH secreting neurons, and secondary to this the pituitary gland developed decreased responsiveness to GHRH following CI in childhood.

  13. 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.

  14. 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.

  15. 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.

  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. 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

  18. 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

  19. 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

  20. 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. PMID:20224451

  1. Antagonists of growth hormone-releasing hormone inhibit growth of androgen-independent prostate cancer through inactivation of ERK and Akt kinases.

    PubMed

    Rick, Ferenc G; Schally, Andrew V; Szalontay, Luca; Block, Norman L; Szepeshazi, Karoly; Nadji, Mehrdad; Zarandi, Marta; Hohla, Florian; Buchholz, Stefan; Seitz, Stephan

    2012-01-31

    The management of castration-resistant prostate cancer (CRPC) presents a clinical challenge because of limitations in efficacy of current therapies. Novel therapeutic strategies for the treatment of CRPC are needed. Antagonists of hypothalamic growth hormone-releasing hormone (GHRH) inhibit growth of various malignancies, including androgen-dependent and independent prostate cancer, by suppressing diverse tumoral growth factors, especially GHRH itself, which acts as a potent autocrine/paracrine growth factor in many tumors. We evaluated the effects of the GHRH antagonist, JMR-132, on PC-3 human androgen-independent prostate cancer cells in vitro and in vivo. JMR-132 suppressed the proliferation of PC-3 cells in vitro in a dose-dependent manner and significantly inhibited growth of PC-3 tumors by 61% (P < 0.05). The expression of GHRH, GHRH receptors, and their main splice variant, SV1, in PC-3 cells and tumor xenografts was demonstrated by RT-PCR and Western blot. The content of GHRH protein in PC-3 xenografts was lowered markedly, by 66.3% (P < 0.01), after treatment with JMR-132. GHRH induced a significant increase in levels of ERK, but JMR-132 abolished this outcome. Our findings indicate that inhibition of PC-3 prostate cancer by JMR-132 involves inactivation of Akt and ERK. The inhibitory effect produced by GHRH antagonist can result in part from inactivation of the PI3K/Akt/mammalian target of rapamycin and Raf/MEK/ERK pathways and from the reduction in GHRH produced by cancer cells. Our findings support the role of GHRH as an autocrine growth factor in prostate cancer and suggest that antagonists of GHRH should be considered for further development as therapy for CRPC.

  2. Association of Turner Syndrome and Growth Hormone Deficiency: A Review.

    PubMed

    Marques, Jorge Sales; Aires, Sónia

    2015-09-01

    Turner syndrome (TS) is an important cause of short stature in girls. Patients with TS most often do not have growth hormone deficiency (GHD). Testing GH secretion is not indicated despite the presence of short stature. In the last 20 years only three cases were reported with this association in Pubmed. We describe a case of an 11 year old girl with short stature and karyotype confirmed TS: 45,X(16)46,X,i(X)(ql0)(13). Because her growth velocity was low (-3 SD), we evaluated the GH response with stimulating tests and the results were under the normal range. These findings were compatible with GHD. It is important to check for GHD in patients with TS whenever the growth velocity is low for age and sex.

  3. 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

  4. 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.

  5. Recombinant growth hormone treatment of amyotrophic lateral sclerosis.

    PubMed

    Smith, R A; Melmed, S; Sherman, B; Frane, J; Munsat, T L; Festoff, B W

    1993-06-01

    Based on the known trophic effects of growth hormone (GH) on nerve and muscle 75 patients with ALS were treated for up to 18 months with synthetic human growth hormone (Protropin) or a placebo. The course of ALS was assessed serially using a quantitative (TQNE) neuromuscular and manual exam (MRC) and laboratory chemistries. Average insulin-related growth factor (IGF-I) values increased from 1.2 to 2.3 U/mL in the treated group. Surprisingly, serum insulin levels did not increase. Hyperglycemia was noted in only 2 patients of the 38 patients receiving hGH, and this resolved with cessation of treatment. Over the 12 months of treatment there were 11 deaths (6 controls, 5 treated). Survival analysis, performed approximately 12 months following cessation of treatment, did not reveal a difference between the treatment and placebo group. The TQNE scores declined inexorably in both the control and treated group. Retrospective analysis of the TQNE data indicated a poor prognosis for patients who lost arm strength early. A correlation between the TQNE and MRC scores was evident at early stages of motor unit loss, less so when muscle weakness was advanced. PMID:8502260

  6. 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.

  7. [Growth hormone administered to non-growth hormone deficient, small girls: echographic aspect of the gonads and uterus].

    PubMed

    Colle, M; Broussin, B

    1993-09-01

    The effect of growth hormone (GH) treatment on prepubertal gonads is controversial especially with regard to the risk of precocious puberty. Ultrasound assessment of ovarian volume, follicle size, and uterine growth was performed in 20 premenarcheal girls (8.0 +/- 2.6 years) receiving growth hormone (GH) for short stature (-2.8 +/- 0.4 SD) not related to growth hormone deficiency or Turner syndrome. Mean GH dosage was 1.0 +/- 0.4 IU/kg/week and mean duration of treatment at evaluation was 16.3 +/- 8.9 months. All patients underwent real time ultrasonography of the pelvic organs and ten subjects also had color Doppler studies of the ovarian and uterine arteries. Ultrasound findings were similar to those reported in normal prepubertal girls. Mean uterine length (29.1 +/- 7.5 mm) and volume (1.23 +/- 0.86 ml) were correlated with age but not with dosage or duration of GH treatment. Ovarian volumes was within the normal age-specific range in all patients except a 7.9 year old girl with substantially enlarged ovaries (4.7 ml) but no evidence or precocious puberty. Ovarian follicles were found in five girls; they measured less than 9 mm in diameter in every case except one (13 mm follicle in an 11-year-old). Blood flow in the ovarian arteries was seen on 5 of the 10 color Doppler studies and was not correlated with dosage or duration of GH treatment. Administration of GH to non-GH-deficient girls did not substantially affect the internal genital organs. It remains uncertain whether the single case of ovarian enlargement seen was related to GH treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Growth factor signalling networks in breast cancer and resistance to endocrine agents: new therapeutic strategies.

    PubMed

    Nicholson, R I; Hutcheson, I R; Britton, D; Knowlden, J M; Jones, H E; Harper, M E; Hiscox, S E; Barrow, D; Gee, J M W

    2005-02-01

    Recent evidence demonstrates that growth factor networks are highly interactive with the estrogen receptor (ER) in the control of breast cancer growth and development. As such, tumor responses to anti-hormones are likely to be a composite of the ER and growth factor inhibitory activity of these agents, with alterations/aberrations in growth factor signalling providing a mechanism for the development of anti-hormone resistance. In this light, the current article focuses on illustrating the relationship between growth factor signalling and anti-hormone failure in our in-house tumor models of breast cancer and describes how we are now beginning to successfully target their actions to improve the effects of anti-hormonal drugs and to block aggressive disease progression.

  9. Perspective: Proteomic approach to detect biomarkers of human growth hormone

    PubMed Central

    Ding, Juan; List, Edward O.; Okada, Shigeru; Kopchick, John J.

    2009-01-01

    Several serum biomarkers for recombinant human growth hormone (rhGH) have been established, however, none alone or in combination have generate a specific, sensitive, and reproducible ‘kit’ for the detection of rhGH abuse. Thus, the search for additional GH specific biomarkers continues. In this review, we focus on the use of proteomics in general and 2-dimensional electrophoresis (2-DE) in particular for the discovery of new GH induced serum biomarkers. Also, we review some of the protocols involved in 2DE. Finally, the possibility of tissues other than blood for biomarker discovery is discussed. PMID:19501004

  10. 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.

  11. Algorithmic complexity of growth hormone release in humans.

    PubMed

    Prank, K; Wagner, M; Brabant, G

    1997-01-01

    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.

  12. 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.

  13. Glucocorticoids enhance stability of human growth hormone mRNA.

    PubMed Central

    Paek, I; Axel, R

    1987-01-01

    We have studied the control of expression of the human growth hormone (hGH) gene introduced into the chromosomes of mouse fibroblasts. Cell lines transformed with the hGH gene expressed low levels of intact hGH mRNA and secreted hGH protein into the medium. Although the level of expression of hGH mRNA was low, the gene remained responsive to induction by glucocorticoid hormones. To localize the sequences responsible for induction and to determine the mechanism by which these cis-acting sequences enhance gene expression, we have constructed a series of fusion genes between the hGH gene and the herpes simplex virus (HSV) thymidine kinase (tk) gene. We have demonstrated that a fusion gene in which hGH cDNA is flanked at its 5' terminus by an HSV tk promoter and is flanked at its 3' terminus by 3' HSV tk DNA remains inducible by glucocorticoids. Our studies indicate that the hGH exons contain sequences which are responsible for glucocorticoid hormone induction. Pulse-chase experiments, in vitro nuclear transcription, and approach to steady-state measurements indicate that the mechanisms responsible for induction of the hGH cDNA fusion gene operate posttranscriptionally to enhance the stability of hGH mRNA. Moreover, this increased stability was associated with an increase in the length of the 3' poly(A) tail on hGH mRNA. Images PMID:3037323

  14. 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.

  15. Role of growth hormone-releasing hormone in dyslipidemia associated with experimental type 1 diabetes

    PubMed Central

    Romero, Maritza J.; Lucas, Rudolf; Dou, Huijuan; Sridhar, Supriya; Czikora, Istvan; Mosieri, Eby M.; Rick, Ferenc G.; Block, Norman L.; Sridhar, Subbaramiah; Fulton, David; Weintraub, Neal L.; Bagi, Zsolt; Schally, Andrew V.

    2016-01-01

    Dyslipidemia associated with triglyceride-rich lipoproteins (TRLs) represents an important residual risk factor for cardiovascular and chronic kidney disease in patients with type 1 diabetes (T1D). Levels of growth hormone (GH) are elevated in T1D, which aggravates both hyperglycemia and dyslipidemia. The hypothalamic growth hormone-releasing hormone (GHRH) regulates the release of GH by the pituitary but also exerts separate actions on peripheral GHRH receptors, the functional role of which remains elusive in T1D. In a rat model of streptozotocin (STZ)-induced T1D, GHRH receptor expression was found to be up-regulated in the distal small intestine, a tissue involved in chylomicron synthesis. Treatment of T1D rats with a GHRH antagonist, MIA-602, at a dose that did not affect plasma GH levels, significantly reduced TRL, as well as markers of renal injury, and improved endothelial-dependent vasorelaxation. Glucagon-like peptide 1 (GLP-1) reduces hyperglucagonemia and postprandial TRL, the latter in part through a decreased synthesis of apolipoprotein B-48 (ApoB-48) by intestinal cells. Although plasma GLP-1 levels were elevated in diabetic animals, this was accompanied by increased rather than reduced glucagon levels, suggesting impaired GLP-1 signaling. Treatment with MIA-602 normalized GLP-1 and glucagon to control levels in T1D rats. MIA-602 also decreased secretion of ApoB-48 from rat intestinal epithelial cells in response to oleic acid stimulation in vitro, in part through a GLP-1–dependent mechanism. Our findings support the hypothesis that antagonizing the signaling of GHRH in T1D may improve GLP-1 function in the small intestine, which, in turn, diminishes TRL and reduces renal and vascular complications. PMID:26831066

  16. 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.

  17. Induction of sensitivity of fibroblast cultures to pituitary growth hormone by a thermostable serum factor

    SciTech Connect

    Bulatov, A.A.; Osipova, T.A.; Pankov, Y.A.; Terekhov, S.M.

    1985-05-01

    This paper presents data to show that highly purified pituitary growth hormone (GH) preparations, themselves unable to stimulate DNA biosynthesis in cultures of adult human skin fibroblasts, acquire this ability if the cells are treated simultaneously with a factor present in a thermostable and acid-resistant fraction of rat blood serum. Activity of this factor in rat blood serum has been shown to depend on the pituitary, and to increase after hypophysectomy. Human GH, while not exhibiting activity itself, if added to the medium simultaneously with serum fraction from hypophysectomized rats, stimulated DNA biosynthesis by fibroblasts significantly. The increase in tritium-thymidine incorporation under the influence of the hormone together with the serum fraction amounted to 233%. It is important to not that serum fraction of intact rats of the same age in a concentration of 1% was unable to induce sensitivity of the fibroblasts to human GH.

  18. Reduced growth hormone signaling and methionine restriction: interventions that improve metabolic health and extend life span.

    PubMed

    Brown-Borg, Holly M

    2016-01-01

    Interventions that improve health are often associated with longevity. Reduced growth hormone signaling has been shown to increase life span in mice by over 50%. Similarly, reductions in dietary intake of methionine, in rats and mice, result in life-span extension. Many factors affect metabolic health, mitochondrial function, and resistance to stressors, each of which influence aging and life span. This paper presents a comparison of these two interventions, as well as the results of a study combining these interventions, to understand potential mechanisms underlying their effectiveness in enhancing healthy aging.

  19. Growth of functional cranial components in rats with intrauterine growth retardation after treatment with growth hormone.

    PubMed

    Quintero, Fabián Anibal; Castro, Luis Eduardo; Luna, María Eugenia; Guimarey, Luis Manuel; Cesani, María Florencia; Fucini, María Cecilia; Villanueva, Myriam; Prio, Verónica; Oyhenart, Evelia Edith

    2012-12-01

    The goal of this study was to analyse the effect of growth hormone (GH) on catch-up growth of functional facial (splanchnocranial) and neurocranial components in rats with intrauterine growth retardation (IUGR). Wistar rats were divided into the following groups: control (C), sham-operated (SH), IUGR, and IUGR + GH. IUGR was surgically induced and GH was administered between 21 and 60 days of age. Radiographs were obtained at 1, 21, 42, 63, and 84 days of age in order to measure length, width, and height of neurocranium (NL, NW, and NH) and face length, width, and height (FL, FW, and FH). Analysis of variance was performed at 1 day of age and a principal components analysis (PCA) at 84 days of age. Neurocranial and facial volumetric indexes were calculated as NVI = (3)√NL × NW × NH and FVI = (3)√FL × FW × FH, respectively, and adjusted by non-linear regression analysis. On postnatal day 1, there were significant differences between SH and IUGR (P < 0.01). Also, in both genders, final neurocranial volume was similar between SH and IUGR + GH groups, while the IUGR group had the lower value (P < 0.01). Final facial volume was similar among the three groups. In both genders, facial growth rates were SH = IUGR > IUGR + GH (P < 0.01). The first axis of the PCA exhibited size effect and the second axis showed shape effect. Reductions of placental blood flow modify cranial growth. The functional neurocranial and facial components in rats with IUGR presented different recovery strategies through modular behaviour, mainly related to modifications of growth rate as response to GH administration.

  20. 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.

  1. 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

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

    PubMed

    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.

  3. Immunomodulation and hormonal disruption without compromised disease resistance in perfluorooctanoic acid (PFOA) exposed Japanese quail.

    PubMed

    Smits, Judit E G; Nain, Sukhbir

    2013-08-01

    This study evaluated the impact of oral perfluorooctanoic acid (PFOA) on Japanese quail at concentrations found in American and Belgian workers at PFOA manufacturing facilities. Three arms of the immune system were tested; T cell, B cell, and innate immunity. After 6 weeks exposure, quail were challenged with E. coli infection to test the ultimate measure of immunotoxicity, disease resistance. The T cell response was lower in the high exposure groups. Antibody mediated, and innate immune responses were not different. Growth rate was higher, whereas thyroid hormone levels were lower in PFOA-exposed birds. Morbidity/mortality from disease challenge was not different among the control and PFOA-exposed groups, and no overt PFOA toxicity was observed pre-disease challenge. Although PFOA at 'worst case scenario' levels caused T cell immunosuppression, this did not translate into increased disease susceptibility, demonstrating that immunotoxicity testing must be interpreted with caution since disease resistance is the ultimate concern. PMID:23639742

  4. Weight loss and wrestling training: effects on growth-related hormones.

    PubMed

    Roemmich, J N; Sinning, W E

    1997-06-01

    Adolescent wrestlers (n = 9, 15.4 yr) and recreationally active control males (n = 7, 15.7 yr) were measured before, at the end of, and 3.5-4 mo after a competitive wrestling season to assess the influence of dietary restriction on growth-related hormones. Wrestlers had significant elevations preseason to late season for morning serum concentrations (mean of 8 serial samples) of growth hormone (GH; 2.9 +/- 0.7 vs. 6.5 +/- 1.4 ng/ml) and sex hormone-binding globulin (SHBG; 16.1 +/- 2.3 vs. 27.9 +/- 6.9 nmol/l) and significant reductions in GH-binding protein (GHBP; 178 +/- 19 vs. 109 +/- 17 pmol/l), insulin-like growth factor I (IGF-I; 332 +/- 30 vs. 267 +/- 34 ng/ml), testosterone (T; 4.9 +/- 0.4 vs. 3.6 +/- 0.4 ng/ml), and free testosterone (Free-T; 22.4 +/- 3.6 vs. 15.7 +/- 2.8 pg/ml). Wrestlers had significant postseason reductions in GH (3.44 +/- 1.30 ng/ml) and SHBG (10.43 +/- 4.13 nmol/l) but elevations in GHBP (66.7 +/- 23.8 pmol/l), IGF-I (72.9 +/- 25.1 ng/ml), T (2.10 +/- 0.46 ng/ml), and Free-T (9.76 +/- 3.01 pg/ml). Concentrations of luteinizing hormone (LH), estradiol, prolactin, cortisol, insulin, and thyroid hormones did not differ because of exercise-dietary practices of wrestlers. In-season elevations in GH, with concomitant reductions in GHBP and IGF-I, that were reversed during the postseason suggest a reduction in GH receptor number and partial GH resistance during the season. Nonelevated LH with reduced T levels suggests a central hypothalamic-pituitary-gonadal (H-P-G) axis impairment. In conclusion, undernutrition may lead to altered H-P-G and GH-IGF-I axes function in adolescent wrestlers. However, only the wrestlers' late-season Free-T concentrations were outside the normal range, and the hormone axis impairments were quickly reversed. The present data do not address hormonal axis responses to several years of wrestling and weight loss.

  5. Growth-hormone-releasing factor immunoreactivity in human endocrine tumors.

    PubMed Central

    Bostwick, D. G.; Quan, R.; Hoffman, A. R.; Webber, R. J.; Chang, J. K.; Bensch, K. G.

    1984-01-01

    Seventy-three human tumors and adjacent nonneoplastic tissues were analyzed immunohistochemically for the presence of growth-hormone-releasing factor (GRF). Four of 9 pancreatic endocrine tumors, 2 of 3 appendiceal carcinoids, and 1 of 5 cecal carcinoids were immunoreactive for GRF. One of the GRF-containing pancreatic tumors was associated with acromegaly. Histologically, the growth patterns of these tumors were variable, and the distribution of immunoreactive cells was patchy and irregular. There were no normal cells that contained GRF. These results indicate that GRF production by human tumors is more common than previously thought, although clinical acromegaly may not be apparent in patients who harbor such neoplasms. Images Figure 1 PMID:6093542

  6. 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.

  7. Salivary hormonal values from high-speed resistive exercise workouts.

    PubMed

    Caruso, John F; Lutz, Brant M; Davidson, Mark E; Wilson, Kyle; Crane, Chris S; Craig, Chrsity E; Nissen, Tim E; Mason, Melissa L; Coday, Michael A; Sheaff, Robert J; Potter, William T

    2012-03-01

    Our study purpose examined salivary hormonal responses to high-speed resistive exercise. Healthy subjects (n = 45) performed 2 elbow flexor workouts on a novel (inertial kinetic exercise; Oconomowoc, WI, USA) strength training device. Our methods included saliva sample collection at both preexercise and immediately postexercise; workouts entailed two 60-second sets separated by a 90-second rest period. The samples were analyzed in duplicate for their testosterone and cortisol concentrations ([T], [C]). Average and maximum elbow flexor torque were measured from each exercise bout; they were later analyzed with a 2(gender) × 2(workout) analysis of variance (ANOVA) with repeated measures for workout. The [T] and [C] each underwent a 2(gender) × 2(time) ANOVA with repeated measures for time. A within-subject design was used to limit error variance. Average and maximum torque each had gender (men > women; p < 0.05) effects. The [T] elicited a 2-way interaction (p < 0.05), as men incurred a significant 14% increase over time, but women's values were unchanged. Yet multivariate regression revealed that 3 predictor variables (body mass and average and maximum torques) did not account for a significant amount of variance associated with the rise in male [T]. Changes in [C] were not significant. In conclusion, changes in [T] concur with the results from other studies that showed significant elevations in male [T], despite the brevity of current workouts and the rather modest volume of muscle mass engaged. Practical applications imply that salivary assays may be a viable alternative to blood draws from athletes, yet coaches and others who may administer this treatment should know that our results may have produced greater pre-post hormonal changes if postexercise sample collection had occurred at a later time point.

  8. Radioimmunoassay of human growth hormone: technique and application to plasma, cerebrospinal fluid, and pituitary extracts

    PubMed Central

    Thomas, Frances J.; Lloyd, H. M.; Thomas, M. J.

    1972-01-01

    A radioimmunoassay for human growth hormone using activated charcoal is described and its precision, accuracy, and sensitivity are defined. Results are presented for growth hormone measurements in plasma obtained during hypoglycaemia induced with insulin in patients of short stature and during glucose tolerance tests in patients with acromegaly. The method was used to measure growth hormone concentrations in cerebrospinal fluid and in extracts of pituitary tumours. No growth hormone was detected in the cerebrospinal fluid of patients without acromegaly. In patients with acromegaly, the concentration of growth hormone in cerebrospinal fluid was measurable and was considerably elevated in one patient with extrasellar extension of a pituitary tumour. Extracts of chromophobe pituitary tumours contained very small concentrations of growth hormone. In extracts of pituitary tumours removed from acromegalic patients, concentrations fell either below or within the normal range. PMID:5086220

  9. 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.

  10. Chronic [D-Ala2]-growth hormone-releasing hormone administration attenuates age-related deficits in spatial memory.

    PubMed

    Thornton, P L; Ingram, R L; Sonntag, W E

    2000-02-01

    The age-related decline in growth hormone is one of the most robust endocrine markers of biological aging and has been hypothesized to contribute to the physiological deficits observed in aged animals. However, there have been few studies of the impact of this hormonal decline on brain aging. In this study, the effect of long-term subcutaneous administration of [D-Ala2]-growth hormone-releasing hormone (GHRH) on one measure of brain function, memory, was investigated. Animals were injected daily with 2.3 microg of [D-Ala2]-GHRH or saline from 9 to 30 months of age, and the spatial learning and reference memory of animals were assessed by using the Morris water maze and compared with those of 6-month-old animals. Results indicated that spatial memory decreased with age and that chronic [D-Ala2]-GHRH prevented this age-related decrement (24% improvement in the annulus-40 time and 23% improvement in the number of platform crossings compared with saline treated, age-matched controls; p < .05 each). No changes were noted in sensorimotor performance. [D-Ala2]-GHRH attenuated the age-related decline in plasma concentrations of insulinlike growth factor-1 (IGF-1) (p <.05). These data suggest that growth hormone and IGF-1 have important effects on brain function, that the decline in growth hormone and IGF-1 with age contributes to impairments in reference memory, and that these changes can be reversed by the chronic administration of GHRH.

  11. 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

  12. Growth hormone deficiency and premature thelarche in a female infant with kabuki makeup syndrome.

    PubMed

    Devriendt, K; Lemli, L; Craen, M; de Zegher, F

    1995-01-01

    We report on a girl with the kabuki makeup syndrome, including short stature, premature thelarche and partial growth hormone deficiency of hypothalamic origin, without stalk interruption. Treatment with recombinant human growth hormone resulted in an increase of annualized growth velocity from 3.6 to 11.2 cm. The kabuki makeup syndrome may be associated with hypothalamopituitary dysfunction.

  13. 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. PMID:3243205

  14. 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.

  15. The inhibitory effects of interleukin-1 on growth hormone action during catabolic illness.

    PubMed

    Cooney, Robert N; Shumate, Margaret

    2006-01-01

    Growth hormone (GH) induces the expression of the anabolic genes responsible for growth, metabolism, and differentiation. Normally, GH stimulates the synthesis of circulating insulin-like growth factor-I (IGF-I) by liver, which upregulates protein synthesis in many tissues. The development of GH resistance during catabolic illness or inflammation contributes to loss of body protein, resulting in multiple complications that prolong recovery and cause death. In septic patients, increased levels of proinflammatory cytokines and GH resistance are commonly observed together. Numerous studies have provided evidence that the inhibitory effects of cytokines on skeletal muscle protein synthesis during sepsis and inflammation are mediated indirectly by changes in the GH/IGF-I system. Interleukin (IL)-1, a member of the family of proinflammatory cytokines, interacts with most cell types and is an important mediator of the inflammatory response. Infusion of a specific IL-1 receptor antagonist (IL-1Ra) ameliorates protein catabolism and GH resistance during systemic infection. This suggests that IL-1 is an important mediator of GH resistance during systemic infection or inflammation. Consequently, a better understanding of the interaction between GH, IL-1, and the regulation of protein metabolism is of great importance for the care of the patient.

  16. Growth hormone deficiency in 18q deletion syndrome

    SciTech Connect

    Ghidoni, P.D.; Cody, J.; Danney, J.

    1994-09-01

    The 18q- syndrome is one of the most common chromosomal deletion syndromes. Clinical characteristics are variable but may include: hypotonia, cleft palate, mental retardation and hearing impairment. Growth failure (GF) (<3% weight/height) is present in 80% of affected individuals. We evaluated growth hormone (GH) sufficiency in 15 patients with 18q- syndrome. Of these 15 patients, 10 have growth failure (<3% weight/height); of the remaining 5, 3 had normal growth parameters and 2 had growth along the 5%. Twelve patients failed to produce adequate GH following standard stimulation testing. Of these 12 patients with inadequate GH production, 2 had normal growth (above 3%). Of the 15, only 1 has normal GH production and normal growth parameters. Bone age was obtained on 1 patient with both GH deficiency and GF, and revealed significant delays. GH levels in response to GH releasing factor were normal in 3 out of 4 patients. MRI studies of GH-deficient patients indicated normal midline structures. Myelination in the few studied GH-deficient patients appeared delayed. The gene for myelin basic protein (MBP) is known to be located on the terminal portion of the long arm of chromosome 18. Neither the gene for GH, GH releasing factor nor GH releasing factor receptor is on chromosome 18. These genes are located on chromosomes 17, chromosome 20 and chromosome 7, respectively. Findings to date suggest that GH deficiency is common in individuals with 18q- syndrome. The etiology of this finding is unknown. We postulate that a gene(s) on chromosome 18q is involved in GH expression.

  17. 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. PMID:25874614

  18. 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

  19. Elevation of serum creatine phosphokinase during growth hormone treatment in patients with multiple pituitary hormone deficiency.

    PubMed

    Momoi, T; Yamanaka, C; Tanaka, R; Yoshida, A; Okumura, M; Yamakura, S; Takasaki, Y; Sasaki, H; Kawai, M

    1995-11-01

    Serum creatinine phosphokinase (s-CPK) increased to more than 500 U/l in 5 out of 21 patients with growth hormone (GH) deficiency during the 2 years of treatment with biosynthetic GH. In three of these five patients, s-CPK had elevated gradually after the start of GH treatment and remained high in one patient except in the period when GH injection was interrupted, and gradually decreased in the other two patients during treatment. These three patients had complete GH deficiency associated with multiple pituitary hormone deficiency due to pituitary stalk transection. One of the remaining two patients had Noonan syndrome and his s-CPK levels before therapy were relatively high. The fifth patient was a baseball athlete and the elevation of s-CPK seemed to be attributable to the strenuous exercise. Conclusion. s-CPK increases significantly in a certain group of patients with GH deficiency during GH replacement therapy. Measurement of s-CPK is to be included in the follow up laboratory tests at least in the 1st treatment year to evaluate the potential hazardous effects of GH on muscle.

  20. 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

  1. Growth hormone-releasing hormone (GHRH) polymorphisms associated with carcass traits of meat in Korean cattle

    PubMed Central

    Cheong, Hyun Sub; Yoon, Du-Hak; Kim, Lyoung Hyo; Park, Byung Lae; Choi, Yoo Hyun; Chung, Eui Ryong; Cho, Yong Min; Park, Eng Woo; Cheong, Il-Cheong; Oh, Sung-Jong; Yi, Sung-Gon; Park, Taesung; Shin, Hyoung Doo

    2006-01-01

    Background Cold carcass weight (CW) and longissimus muscle area (EMA) are the major quantitative traits in beef cattle. In this study, we found several polymorphisms of growth hormone-releasing hormone (GHRH) gene and examined the association of polymorphisms with carcass traits (CW and EMA) in Korean native cattle (Hanwoo). Results By direct DNA sequencing in 24 unrelated Korean cattle, we identified 12 single nucleotide polymorphisms within the 9 kb full gene region, including the 1.5 kb promoter region. Among them, six polymorphic sites were selected for genotyping in our beef cattle (n = 428) and five marker haplotypes (frequency > 0.1) were identified. Statistical analysis revealed that -4241A>T showed significant associations with CW and EMA. Conclusion Our findings suggest that polymorphisms in GHRH might be one of the important genetic factors that influence carcass yield in beef cattle. Sequence variation/haplotype information identified in this study would provide valuable information for the production of a commercial line of beef cattle. PMID:16749938

  2. Caloric Restriction Effect on Proinflammatory Cytokines, Growth Hormone, and Steroid Hormone Concentrations during Exercise in Judokas.

    PubMed

    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).

  3. 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…

  4. The effects of growth hormone deficiency and growth hormone replacement therapy on intellectual ability, personality and adjustment in children.

    PubMed

    Puga González, B; Ferrández Longás, A; Oyarzábal, M; Nosas, R

    2010-06-01

    Traditionally, it has been assumed that intellectual development in children with growth hormone deficiency (GHD) is distributed between ranges of a normal population based on the observation that it does not differ substantially from that of children of the same age. Nevertheless, few studies have investigated this assumption. This Spanish Collaborative study was prospectively planned with two main purposes: to study a possible influence of GHD on intelligence quotient (IQ), personality traits and adaptative capacity and to study the evolution of these parameters during substitution therapy with growth hormone (GH). Although the overall intellectual ability of children with GHD is comparable to that of a normal reference population, some areas such the motor-component scale (evaluated by McCarthy test) and performance IQ (evaluated by WISC-R) were below the mean at the beginning of the study, showing significant improvement during therapy. Emotional adjustment (normal at study start) also improved significantly during treatment. Females showed better adjustment capacity before and during GH therapy. Longer studies with an increased number of cases are needed to confirm these effects of GHD and its treatment in children.

  5. 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.

  6. Hormonal regulation of temperature-induced growth in Arabidopsis.

    PubMed

    Stavang, Jon A; Gallego-Bartolomé, Javier; Gómez, María D; Yoshida, Shigeo; Asami, Tadao; Olsen, Jorunn E; García-Martínez, José L; Alabadí, David; Blázquez, Miguel A

    2009-11-01

    Successful plant survival depends upon the proper integration of information from the environment with endogenous cues to regulate growth and development. We have investigated the interplay between ambient temperature and hormone action during the regulation of hypocotyl elongation, and we have found that gibberellins (GAs) and auxin are quickly and independently recruited by temperature to modulate growth rate, whereas activity of brassinosteroids (BRs) seems to be required later on. Impairment of GA biosynthesis blocked the increased elongation caused at higher temperatures, but hypocotyls of pentuple DELLA knockout mutants still reduced their response to higher temperatures when BR synthesis or auxin polar transport were blocked. The expression of several key genes involved in the biosynthesis of GAs and auxin was regulated by temperature, which indirectly resulted in coherent variations in the levels of accumulation of nuclear GFP-RGA (repressor of GA1) and in the activity of the DR5 reporter. DNA microarray and genetic analyses allowed the identification of the transcription factor PIF4 (phytochrome-interacting factor 4) as a major target in the promotion of growth at higher temperature. These results suggest that temperature regulates hypocotyl growth by individually impinging on several elements of a pre-existing network of signaling pathways involving auxin, BRs, GAs, and PIF4.

  7. Inhibitory effects of antagonists of growth hormone-releasing hormone on growth and invasiveness of PC3 human prostate cancer.

    PubMed

    Muñoz-Moreno, Laura; Arenas, M Isabel; Schally, Andrew V; Fernández-Martínez, Ana B; Zarka, Elías; González-Santander, Marta; Carmena, María J; Vacas, Eva; Prieto, Juan C; Bajo, Ana M

    2013-02-15

    New approaches are needed to the therapy of advanced prostate cancer. This study determined the effect of growth hormone-releasing hormone (GHRH) antagonists, JMR-132 and JV-1-38 on growth of PC3 tumors as well as on angiogenesis and metastasis through the evaluation of various factors that contribute largely to the progression of prostate cancer. Human PC3 androgen-independent prostate cancer cells were injected subcutaneously into nude mice. The treatment with JMR-132 (10 μg/day) or JV-1-38 (20 μg/day) lasted 41 days. We also evaluated the effects of JMR-132 and JV-1-38 on proliferation, cell adhesion and migration in PC-3 cells in vitro. Several techniques (Western blot, reverse transcription polymerase chain reaction, immunohistochemistry, ELISA and zymography) were used to evaluate the expression levels of GHRH receptors and its splice variants, GHRH, vascular endothelial growth factor (VEGF), hypoxia inducible factor (HIF)-1α, metalloproteinases (MMPs) -2 and -9, β-catenin and E-cadherin. GHRH antagonists suppressed the proliferation of PC-3 cells in vitro and significantly inhibited growth of PC3 tumors. After treatment with these analogues, we found an increase in expression of GHRH receptor accompanied by a decrease of GHRH levels, a reduction in both VEGF and HIF-1α expression and in active forms of MMP-2 and MMP-9, a significant increase in levels of membrane-associated β-catenin and a significant decline in E-cadherin. These results support that the blockade of GHRH receptors can modulate elements involved in angiogenesis and metastasis. Consequently, GHRH antagonists could be considered as suitable candidates for therapeutic trials in the management of androgen-independent prostate cancer.

  8. Modulation of long-term memory and extinction responses induced by growth hormone (GH) and growth hormone releasing hormone (GHRH) in rats.

    PubMed

    Schneider-Rivas, S; Rivas-Arancibia, S; Vázquez-Pereyra, F; Vázquez-Sandoval, R; Borgonio-Pérez, G

    1995-01-01

    The purpose of this work is to study the participation of growth hormone (GH) and growth hormone releasing hormone (GHRH) in the modulation of long-term memory and the extinction response of a passive avoidance task in rats. However, the effect on memory vary according to the age of the animals due to plasma levels of either hormone being modified during the aging process. Male Wistar rats were divided according to age into two experimental blocks (young rats 3 months old and aged rats 24 months old at the start of the experiment) where each block received the same treatment. Each experimental block was then divided randomly into three groups where two were experimental and the other served as control. The animals were then submitted to a one-trial passive avoidance conditioning and tested for memory retention 24 hrs after as well as twice a week until the extinction response occurred. The control group received an isotonic saline solution and the other two groups received 0.8 U.I. of GH or 4 mcg of GHRH respectively. All substances were in a 0.08 ml volume and applied 24 hrs before training as well as 24 hrs before each retention session. The results indicate that GH and GHRH modulate long-term memory as well as the extinction response and in either case the response seems to vary with age. GH and GHRH facilitates long-term memory in young rats but not in aged rats. Finally, whereas GH delays the extinction response in both groups, GHRH retards the extinction only in aged rats.

  9. Ethanol, growth hormone and testosterone in peripubertal rats.

    PubMed

    Tentler, J J; LaPaglia, N; Steiner, J; Williams, D; Castelli, M; Kelley, M R; Emanuele, N V; Emanuele, M A

    1997-03-01

    The deleterious effects of ethanol on the hypothalamic pituitary growth hormone axis in adult male humans and animals have been well documented. It is also well established that ethanol has toxic effects on testicular function in adult humans and animals. Much less is known, however, about the effects of ethanol on the growth hormone (GH) axis and testicular function in adolescence. Recent studies have established that adolescent problem drinking is a widespread and growing threat to the health of young people in the United States. In the present study, therefore, we investigated if acute ethanol exposure in peripubertal male Sprague-Dawley rats altered normal pituitary and testicular function. Serum levels of GH and testosterone were measured at 1.5, 3, 6, and 24 h after a single i.p. injection of either saline or 3 g/kg body weight ethanol. Histologic analysis as well as serum testosterone levels allowed us to assign animals to either early puberty (35-day-old animals), mid-puberty (41-day-old animals), or young adult (51- and 66-day-old animals) status. Ethanol produced significant decrements in serum testosterone in the 51- and 66-day-old animals, with a trend toward suppression in the 41-day-old group. Furthermore acute ethanol administration significantly decreased serum GH (P < 0.0001 by 3 way ANOVA) demonstrating a significant effect of ethanol on serum GH in all age groups and at all time points studied when compared with saline injected controls (P < 0.01 by Turkey's studentized range test). Despite this significant fall in peripheral GH levels, there was no decrease in either GH mRNA or growth hormone-releasing factor (GRF) mRNA levels nor in hypothalamic concentration of GRF peptide. We conclude that, as in adult animals, acute exposure to ethanol causes a prolonged and severe decrement in serum GH which is possibly mediated at the level of secretion. In addition, there is attenuation in testosterone secretion. These data are all the more important

  10. 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...

  11. Estrogens regulate the hepatic effects of growth hormone, a hormonal interplay with multiple fates.

    PubMed

    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.

  12. Growth hormone assays: current methodologies and their limitations.

    PubMed

    Bidlingmaier, Martin; Strasburger, Christian J

    2007-01-01

    Measurement of circulating growth hormone (GH) concentrations is essential in diagnosis of either GH deficiency or GH excess. The invention of immunoassays for the measurement of peptide hormones was a major breakthrough, enabling the routine analysis of GH concentrations in larger series of samples. Over the last few decades, measurement technology has evolved from less sensitive, mainly radioactive assays based on polyclonal antisera to the latest generations of highly sensitive chemiluminescence methods employing monoclonal antibodies. Unfortunately, the development of newer assays did not lead to better agreement among the results obtained by different assay methods. On the contrary, the differences tended to increase when monoclonal antibody based assays became more popular. The actual value reported for the GH concentration in a specific patient's sample still mainly depends on the method used by the respective laboratory, limiting the applicability of international consensus guidelines in clinical practice. The heterogeneity of the analyte itself, the availability of different reference preparations for calibration and the interference from matrix components such as GH binding protein are among the reasons why standardizing GH assays is difficult. An additional challenge arose from the availability of a GH receptor antagonist for the treatment of acromegaly, which is basically a mutated form of GH and therefore interferes in many GH assays. This review provides an overview on GH assays used in clinical practice, their limitations and the potential next steps towards standardization.

  13. Pituitary function and growth hormone dynamics in acromegaloidism.

    PubMed

    Mims, R B

    1978-12-01

    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

  14. Ultrastructural study of mixed growth hormone & prolactin secreting pituitary adenomas.

    PubMed

    Sarkar, C; Dinda, A K; Roy, S; Kochupillai, N; Kharbanda, K; Tandon, P N

    1992-08-01

    An ultrastructural study was done on 15 mixed growth hormone (GH) and prolactin (PRL)-secreting pituitary adenomas surgically removed from acromegalic patients with hyper-prolactinaemia, in order to see whether the 2 hormones were present in the same cell or in different cells. Double labelling immunogold technique was used for simultaneous ultrastructural localization of GH and PRL. It was found that each neoplastic cell in these 15 tumours (30 to 50 cells were studied in each case) contained 4 populations of granules viz., (i) granules positive for only GH; (ii) granules positive for only PRL; (iii) granules positive for both GH and PRL; and (iv) granules negative for both GH and PRL (unlabelled). Though the relative percentage of these 4 types of granules varied from cell to cell even within the same tumour, the major population (49.9 to 96%) was constituted by the mixed granules showing labelling for both GH and PRL. Almost all the cells examined from each tumour appeared to be mammosomatotrophs. Thus, the study indicated that mammosomatotroph adenomas are perhaps more common among mixed GH and PRL--secreting pituitary adenomas than previously believed. It could be important to recognize these tumours from the therapeutic point of view.

  15. Emerging options in growth hormone therapy: an update

    PubMed Central

    Kemp, Stephen F; Frindik, J Paul

    2011-01-01

    Growth hormone (GH) was first used to treat a patient in 1958. For the next 25 years it was available only from cadaver sources, which was of concern because of safety considerations and short supply. In 1985, GH produced by recombinant DNA techniques became available, expanding its possible uses. Since that time there have been three indications approved by the US Food and Drug Administration (FDA) for GH-deficiency states and nine indications approved for non-GH-deficiency states. In 2003 the FDA approved GH for use in idiopathic short stature (ISS), which may indirectly cover other diagnoses that have short stature as a feature. However, coverage for GH therapy is usually more reliably obtainable for a specific indication, rather than the ISS indication. Possible future uses for GH therapy could include the treatment of syndromes such as Russell–Silver syndrome or chondrodystrophy. Other non-short-stature indications could include wound healing and burns. Other uses that have been poorly studied include aging and physical performance, in spite of the interest already shown by elite athletes in using GH. The safety profile of GH developed over the past 25 years has shown it to be a very safe hormone with few adverse events associated with it. The challenge for the future is to follow these patients into adulthood to determine whether GH therapy poses any long-term risks. PMID:21966214

  16. McCune-Albright syndrome: growth hormone and prolactin hypersecretion.

    PubMed

    Christoforidis, Athanasios; Maniadaki, Ilianna; Stanhope, Richard

    2006-05-01

    McCune-Albright syndrome (MAS) has a special interest for endocrinologists as its pathogenesis results in hypersecretion of hormones in peripheral endocrine tissues. This can be expressed as precocious puberty, mainly in girls, primary hyperthyroidism, growth hormone (GH) and/or prolactin excess, hyperparathyroidism and hypercortisolism. The incidence of GH excess among patients with MAS has been assessed as up to 21%. The pathogenesis of GH hypersecretion in MAS is not completely understood, whereas it seems to be different from the aetiology of acromegaly/gigantism in non-MAS patients. The clinical expression of GH excess can be masked because of precocious puberty or craniofacial fibrous dysplasia, indicating the necessity for screening. Medical treatment is usually the only option in MAS patients with GH excess, as transsphenoidal surgery is usually restricted due to massive thickening of the skull base, whereas radiotherapy is contraindicated due to probable higher predisposition to sarcomatous transformation. The use of bromocriptine, cabergoline and octreotide, or the combination of these, has shown variable results, whereas pegvisomant, a GH receptor antagonist, is a new promising option, although not yet used in patients with MAS. PMID:16789626

  17. Insulin resistance and delayed clearance of peptide hormones in cirrhotic rat liver.

    PubMed

    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 125I-insulin by hepatocytes isolated from cirrhotic and normal livers were also studied. The half-lives (t1/2) 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 (P less than 0.001). 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. PMID:3296781

  18. 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.

  19. 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.

  20. Skeletal effects of growth hormone and insulin-like growth factor-I therapy.

    PubMed

    Lindsey, Richard C; Mohan, Subburaman

    2016-09-01

    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.

  1. AIDS activists secure approval for human growth hormone (Serostim).

    PubMed

    1996-01-01

    The Food and Drug Administration (FDA) has given a verbal commitment to accelerated approval for recombinant human growth hormone (Serostim) for AIDS-associated wasting syndrome. The drug, manufactured by Serono Laboratories, is the first of its kind that directly affects the metabolic dysfunction of AIDS-related wasting. The approval came on the heels of a meeting with AIDS activists, Serono Laboratories, and the FDA. Serono committed, at the meeting's conclusion, to submit finalized documents to the FDA within a week. ACT UP Golden Gate won a victory when the wholesale price cap of the drug was set at $36,000.00 annually, despite the company's original demand of $75,000.00 or more.

  2. Biological effects of growth hormone and its antagonist.

    PubMed

    Okada, S; Kopchick, J J

    2001-03-01

    Serum levels of growth hormone (GH) can vary. Low levels of GH can result in a dwarf phenotype and have been positively correlated with an increased life expectancy. High levels of GH can lead to gigantism or a clinical syndrome termed acromegaly and has been implicated in diabetic eye and kidney damage. Additionally the GH/IGF-1 system has been postulated as a risk factor for several types of cancers. Thus both elevated and suppressed circulating levels of GH can have pronounced physiological effects. More than a decade ago the first drug of a new class, a GH antagonist, was discovered. This molecule is now being tested for its ability to combat the effects of high circulating levels of GH. Here, we discuss some of the detrimental actions of GH, and how a GH antagonist can be used to combat these effects. PMID:11286784

  3. 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.

  4. 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.

  5. Changes in plasma growth hormone (GH) and secretion patterns of GH and luteinizing hormone in buffaloes (Bubalus bubalis) during growth.

    PubMed

    Mondal, Mohan; Prakash, B S

    2004-08-01

    To assess the changes of plasma growth hormone (GH) and secretion patterns of GH and luteinizing hormone (LH) during growth in buffaloes, six growing female Murrah buffalo calves (mean age 6+/-0.9 months and body weight 66+/-6 kg) were selected. Plasma samples were collected twice a week for 52 weeks for GH and LH assay. To examine for pulsatile secretion samples were collected at 15 minutes interval for 9 hr at weeks 6 and 42 for GH and LH measurements. Plasma progesterone was also estimated in twice-a-week samples to assess whether any of the buffalo had begun ovarian cyclicity. The body weight of all animals was recorded at weekly interval. Plasma GH concentration decreased (P < 0.01) only up to week 29 and showed an increasing trend (P < 0.01) thereafter. The ratio of plasma GH to body weight declined (P < 0.01) throughout the entire experimental period. Plasma GH showed a declining trend only up to when the animals attained 155 kg body weight and thereafter showed an increasing trend (P < 0.01). Plasma GH revealed distinct pulsatile patterns of release, with a mean of 6 and 5 pulses in the 6-week and 42-week samples, respectively. The plasma LH concentrations around the 42-week time period were significantly higher (P < 0.01) than at the 6-week time period, and they exhibited pulsatility. No animal reached puberty until the end of the experiment. In summary, plasma GH levels have a definite pattern of change during growth and patterns of secretion of plasma GH and LH also have a relation with body weight in this species of animal. PMID:15554346

  6. A comparison of the growth responses following intramuscular GHRH plasmid administration versus daily growth hormone injections in young pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  7. 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. PMID:10392356

  8. Significance of the disulphide bonds of human growth hormone.

    PubMed

    Junnila, Riia K; Kopchick, John J

    2013-01-01

    Growth hormone (GH) structure is stabilised by two disulphide bonds, C53-C165 and C182-C189 in human GH. Researchers have investigatedthe role of these structural features since the late 1960s. Early studies implied that the disulphide bonds would not be importantfor biological activity of GH. However, more advanced techniques, as well as clues from patients carrying mutations in their GH1 gene,have demonstrated that the integrity of the disulphide bond between cysteines C53 and C165 is required for biological activity of GH.In contrast, disruption of the C-terminal disulphide bond (C182-C189) has only modest effects on the biological potency of GH, despitedecreased binding affinity to GH receptor and reduced stability as shown by a comprehensive in vitro study.To confirm these results, we generated transgenic mice that express a human GH analogue, C189A, and observed normal growth-promotingand lipolytic activities. In this article, we present new data and review old results concerning the disulphide bonds of GH. We also discussrelevant mutations found in patients with growth disorders. PMID:24002958

  9. Metabolic clearance and production rates of human growth hormone.

    PubMed

    Taylor, A L; Finster, J L; Mintz, D H

    1969-12-01

    The metabolic clearance rate (MCR) of human growth hormone (HGH) was determined by the constant infusion to equilibrium technique utilizing HGH-(125)I. 22 control subjects had a MCR of 229 +/-52 ml/min (mean +/-SD). No difference was evident between sexes, or between various age groups. Patients with acromegaly demonstrated normal MCR's. Moreover, acute elevations of plasma growth hormone concentrations in normal subjects did not alter the MCR of HGH. The MCR was relatively constant from day to day and within the day when subjects were evaluated in the supine position. In contrast, the assumption of the upright position was associated with a mean 24% decrease in the MCR. These results were contrasted with the MCR of HGH observed in a small number of patients with altered thyroid function or diabetes mellitus. In six patients with hypothyroidism the MCR (131 +/-36 ml/min) was significantly decreased (P < 0.001); whereas the MCR in eight patients with hyperthyroidism (240 +/-57 ml/min) did not differ from control subjects. The MCR in eight patients with insulin-independent diabetes mellitus (IID) (185 +/-41 ml/min) and in eight patients with insulin-dependent diabetes mellitus (IDD) (136 +/-31 ml/min) were significantly different from control subjects (P = < 0.05 and P = < 0.001, respectively). These data were interpreted to indicate that the plasma HGH-removing mechanism(s) is not saturated at physiologic plasma HGH levels, that plasma HGH levels alone may not permit distinction between variations in pituitary release of the hormone and its rate of clearance from the plasma, and that the estimation of the MCR of HGH may help clarify the mechanism of abnormal plasma HGH responses to various stimuli. Production rates of HGH (PR) in control subjects (347 +/-173 mmug/min) were contrasted with hyperthyroid patients (529 +/-242 mmug/min, P < 0.05), hypothyroid patients (160 +/-69 mmug/min, P < 0.02), IID (245 +/-100 mmug/min, NS), and IDD (363 +/-153 mmug/min, NS

  10. 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

  11. Isolation, cDNA cloning, and growth promoting activity of rabbitfish (Siganus guttatus) growth hormone.

    PubMed

    Ayson, F G; de Jesus, E G; Amemiya, Y; Moriyama, S; Hirano, T; Kawauchi, H

    2000-02-01

    We report the isolation, cDNA cloning, and growth promoting activity of rabbitfish (Siganus guttatus; Teleostei; Perciformes; Siganidae) growth hormone (GH). Rabbitfish GH was extracted from pituitary glands under alkaline conditions, fractionated by gel filtration chromatography on Sephadex G-100, and purified by high-performance liquid chromatography. The fractions containing GH were identified by immunoblotting with bonito GH antiserum. Under nonreducing conditions, the molecular weight of rabbitfish GH is about 19 kDa as estimated by SDS-PAGE. The purified hormone was potent in promoting growth in rabbitfish fry. Weekly intraperitoneal injections of the hormone significantly accelerated growth. This was evident 3 weeks after the start of the treatment, and its effect was still significant 2 weeks after the treatment was terminated. Rabbitfish GH cDNA was cloned to determine its nucleotide sequence. Excluding the poly (A) tail, rabbitfish GH cDNA is 860 base pairs (bp) long. It contained untranslated regions of 94 and 175 bp in the 5' and 3' ends, respectively. It has an open reading frame of 588 bp coding for a signal peptide of 18 amino acids and a mature protein of 178 amino acid residues. Rabbitfish GH has 4 cysteine residues. On the amino acid level, rabbitfish GH shows high identity (71-74%) with GHs of other perciforms, such as tuna, sea bass, yellow tail, bonito, and tilapia, and less (47-49%) identity with salmonid and carp GHs.

  12. Vaccine Therapy and Pembrolizumab in Treating Patients With Hormone-Resistant, Metastatic Prostate Cancer

    ClinicalTrials.gov

    2016-06-22

    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

  13. 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.

  14. 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

  15. Recurrent hormone-binding domain truncated ESR1 amplifications in primary endometrial cancers suggest their implication in hormone independent growth.

    PubMed

    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

  16. 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

  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. 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…

  19. Hypothalamic neuronal hamartoma associated with pituitary growth hormone cell adenoma and acromegaly.

    PubMed

    Asa, S L; Bilbao, J M; Kovacs, K; Linfoot, J A

    1980-01-01

    A hypothalamic neuronal hamartoma associated with a sparsely granulated growth hormone cell adenoma of the pituitary and acromegaly is reported. It is suggested that the patient had a primary neuronal tumor, whose neurosecretory activity promoted the development of the growth hormone secreting pituitary adenoma causing acromegaly.

  20. 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. PMID:25077093

  1. 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.

  2. 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

  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. 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.

  5. 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.

  6. JAK2 activation by growth hormone and other cytokines

    PubMed Central

    Waters, Michael J.; Brooks, Andrew J.

    2015-01-01

    Growth hormone (GH) and structurally related cytokines regulate a great number of physiological and pathological processes. They do this by coupling their single transmembrane domain (TMD) receptors to cytoplasmic tyrosine kinases, either as homodimers or heterodimers. Recent studies have revealed that many of these receptors exist as constitutive dimers rather than being dimerized as a consequence of ligand binding, which has necessitated a new paradigm for describing their activation process. In the present study, we describe a model for activation of the tyrosine kinase Janus kinase 2 (JAK2) by the GH receptor homodimer based on biochemical data and molecular dynamics simulations. Binding of the bivalent ligand reorientates and rotates the receptor subunits, resulting in a transition from a form with parallel TMDs to one where the TMDs separate at the point of entry into the cytoplasm. This movement slides the pseudokinase inhibitory domain of one JAK kinase away from the kinase domain of the other JAK within the receptor dimer–JAK complex, allowing the two kinase domains to interact and trans-activate. This results in phosphorylation and activation of STATs and other signalling pathways linked to this receptor which then regulate postnatal growth, metabolism and stem cell activation. We believe that this model will apply to most if not all members of the class I cytokine receptor family, and will be useful in the design of small antagonists and agonists of therapeutic value. PMID:25656053

  7. Growth hormone receptor antagonists: discovery and potential uses.

    PubMed

    Kopchick, J J; Okada, S

    2001-06-01

    Serum levels of growth hormone (GH) in the human body vary and can influence the levels of insulin-like growth factor I (IGF-1). Low levels of GH can result in a dwarf phenotype and have been positively correlated with an increased life expectancy. High levels of GH can lead to gigantism or a clinical syndrome termed acromegaly, and also have been implicated in diabetic eye and kidney damage. Additionally, it has been postulated that the GH-IGF-I system can be involved in several types of cancers. Overall, both elevated and suppressed circulating levels of GH can have pronounced physiological effects. More than a decade ago a new class of drug, a GH antagonist, was discovered. It is now being tested for its ability to combat the effects of high circulating levels of GH. In this review, we will discuss some of the detrimental actions of GH and how a GH antagonist may be used to combat these effects. PMID:11527080

  8. Increased secretion of growth hormone, prolactin, antidiuretic hormone, and cortisol induced by the stress of motion sickness.

    PubMed

    Eversmann, T; Gottsmann, M; Uhlich, E; Ulbrecht, G; von Werder, K; Scriba, P C

    1978-01-01

    The stress of motion sickness was experimentally provoked by Coriolis effect. Significant and reproducible increases from the basal serum level (delta mean +/- S.E.) of antidiuretic hormone delta - ADH: 48.2 +/- 4.6 pg/ml; p less than 0.0005), of growth hormone (delta - hGH: 10.0 +/- 1.2 ng/ml; p less than 0.0005), of prolactin (delta - hPRL: 186.5 +/- 29.9 muU/ml; p less than 0.0005), and of cortisol (delta - F; 12.3 +/- 0.9 microgram%; p less than 0.0005) were observed, whereas the luteinizing hormone levels did not change significantly. The stimulation of hormone secretion induced by different degrees of motion sickness seems to correlate with the severity of motion sickness. The secretion of antidiuretic hormones is the most sensitive indicator for the stress of motion sickness whereas growth hormone, prolactin, and cortisol responses to the stress of motion sickness are more delayed and less pronounced.

  9. 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. PMID:26194064

  10. 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.

  11. 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.

  12. 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.

  13. Metabolic response to human growth hormone during prolonged starvation

    PubMed Central

    Felig, Philip; Marliss, Errol B.; Cahill, George F.

    1971-01-01

    The metabolic response to human growth hormone (HGH) was studied in five obese subjects in the fed state and during prolonged (5-6 wk) starvation. In the fed state (three subjects), HGH induced an elevation in basal serum insulin concentration, a minimal increase in blood and urine ketone levels, and a marked reduction in urinary nitrogen and potassium excretion resulting in positive nitrogen and potassium balance. In prolonged fasting (four subjects), HGH administration resulted in a 2- to 3-fold increase in serum insulin which preceded a 50% elevation in blood glucose. Persistence of the lipolytic effects of HGH was indicated by a rise in free fatty acids and glycerol. The response differed markedly from the fed state in that blood β-hydroxybutyrate and acetoacetate levels rose by 20-40%, resulting in total blood ketone acid concentrations of 10-12 mmoles/liter, ketonuria of 150-320 mmoles/day, and increased urinary potassium loss. The subjects complained of nausea, vomiting, weakness, and myalgias. Despite a 50% reduction in urea excretion during HGH administration, total nitrogen loss remained unchanged as urinary ammonia excretion rose by 50% and correlated directly with the degree of ketonuria. It is concluded that in prolonged starvation (a) HGH may have a direct insulinotropic effect on the beta cell independent of alterations in blood glucose concentration, (b) persistence of the lipolytic action of HGH results in severe exaggeration of starvation ketosis and interferes with its anticatabolic action by necessitating increased urinary ammonia loss, and (c) failure of HGH to reduce net protein catabolism in starvation suggests that this hormone does not have a prime regulatory role in conserving body protein stores during prolonged fasting. PMID:5540176

  14. 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

  15. Growth hormone and drug metabolism. Acute effects on nuclear ribonucleic acid polymerase activity and chromatin.

    PubMed Central

    Spelsberg, T C; Wilson, J T

    1976-01-01

    Adult male rats, subjected either to sham operation or to hypophysectomy and adrenalectomy were maintained for 10 days before treatment with growth hormone. Results of the acute effects of growth hormone on the rat liver nuclear RNA polymerase I (nucleolar) and II (nucleoplasmic) activities as well as the chromatin template capacity were then studied and compared with the growth-hormone effects on the drug metabolism described in the preceding paper (Wilson & Spelsberg, 1976). 2. Conditions for isolation and storage of nuclei for maintenance of optimal polymerase activities are described. It is verified that the assays for polymerase activities require a DNA template, all four nucleoside triphosphates, and a bivalent cation, and that the acid-insoluble radioactive product represents RNA. Proof is presented that under high-salt conditions DNA-like RNA (polymerase II) is synthesized, and that under low-salt conditions in the presence of alpha-amanitin, rRNA (polymerase I) is synthesized. 3. In the livers of hypophysectomized/adrenalectomized rats, growth hormone increases the activity of both RNA polymerase enzymes and the chromatin template capacity within 1h after treatment. The effects last for 12h in the case of polymerase II but for only 6h in the case of polymerase I. Sham-operated rats respond to growth hormone in a manner somewhat similar to that shown by hypophysectomized/adrenalectomized rats. These results, which demonstrate an enhancement of RNA polymerase I activity in response to growth hormone, support those from other laboratories. 4. Growth-hormone enhancement of the chromatin template capacity in the liver of hypophysectomized/adrenalectomized rats contrasts with previous reports. The growth-hormone-induced de-repression of the chromatin DNA could represent the basis of the growth-hormone-induced enhancement of RNA polymerase II activity in the hypophysectomized/adrenalectomized rats, although some effect of growth-hormone on the polymerase enzymes

  16. The effects of stress hormones on growth of selected periodontitis related bacteria.

    PubMed

    Jentsch, H F R; März, Diana; Krüger, Monika

    2013-12-01

    The focus of this study was to examine in vitro the effects of stress hormones (catecholamines: epinephrine, norepinephrine, dopamine and hydrocortisone: cortisol) on the growth of four anaerobic species of periodontitis-related bacteria (Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia and Tannerella forsythia) and one facultative anaerobic species (Eikenella corrodens). Bacterial growth was determined by two different methods: fluorescence in situ hybridization (FISH), and the viable count by culture method. To simulate stress, each single strain was grown in a special growth medium with three different concentrations of each hormone, using an anaerobic chamber at 37 °C. Growth of F. nucleatum increased in the presence of all stress hormones. Growth of P. gingivalis was not significantly influenced by any hormone. Growth of P. intermedia and E. corrodens was inhibited by almost all stress hormones tested. Both methods of analysis revealed that the highest concentrations of norepinephrine and cortisol increased the growth of T. forsythia. Different hormones have a different effect on the growth of periodontitis-related bacteria in vitro. It appears that bacterial viability is more strongly influenced than is bacterial metabolic activity. The growth of F. nucleatum particularly and partially of T. forsythia is increased by several stress hormones and may have an additional negative impact on periodontal disease.

  17. 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.

  18. Lack of hormone binding in COS-7 cells expressing a mutated growth hormone receptor found in Laron dwarfism.

    PubMed Central

    Edery, M; Rozakis-Adcock, M; Goujon, L; Finidori, J; Lévi-Meyrueis, C; Paly, J; Djiane, J; Postel-Vinay, M C; Kelly, P A

    1993-01-01

    A single point mutation in the growth hormone (GH) receptor gene generating a Phe-->Ser substitution in the extracellular binding domain of the receptor has been identified in one family with Laron type dwarfism. The mutation was introduced by site-directed mutagenesis into cDNAs encoding the full-length rabbit GH receptor and the extracellular domain or binding protein (BP) of the human and rabbit GH receptor, and also in cDNAs encoding the full length and the extracellular domain of the related rabbit prolactin (PRL) receptor. All constructs were transiently expressed in COS-7 cells. Both wild type and mutant full-length rabbit GH and PRL receptors, as well as GH and prolactin BPs (wild type and mutant), were detected by Western blot in cell membranes and concentrated culture media, respectively. Immunofluorescence studies showed that wild type and mutant full-length GH receptors had the same cell surface and intracellular distribution and were expressed with comparable intensities. In contrast, all mutant forms (full-length receptors or BPs), completely lost their modify the synthesis ligand. These results clearly demonstrate that this point mutation (patients with Laron syndrome) does not modify the synthesis or the intracellular pathway of receptor proteins, but rather abolishes ability of the receptor or BP to bind GH and is thus responsible for the extreme GH resistance in these patients. Images PMID:8450064

  19. Facial morphometry of Ecuadorian patients with growth hormone receptor deficiency/Laron syndrome.

    PubMed Central

    Schaefer, G B; Rosenbloom, A L; Guevara-Aguirre, J; Campbell, E A; Ullrich, F; Patil, K; Frias, J L

    1994-01-01

    Facial morphometry using computerised image analysis was performed on patients with growth hormone receptor deficiency (Laron syndrome) from an inbred population of southern Ecuador. Morphometrics were compared for 49 patients, 70 unaffected relatives, and 14 unrelated persons. Patients with growth hormone receptor deficiency showed significant decreases in measures of vertical facial growth as compared to unaffected relatives and unrelated persons with short stature from other causes. This report validates and quantifies the clinical impression of foreshortened facies in growth hormone receptor deficiency. Images PMID:7815422

  20. Hormone-dependent Model on Seed Germination Sensitive to Growth Stage

    NASA Astrophysics Data System (ADS)

    Kawaguchi, Satoshi; Mimura, Masayasu; Ohya, Tomoyuki; Okabe, Hirotaka; Kai, Shoichi

    2000-04-01

    In the germination of seeds, there often observes cluster-formation of well-grown roots and the edge effect phenomenon.During germination and growth before starting photosynthesis, direct interaction such as competition for nutrition among hosts is rather weak because of self-supplying of nutrition.Instead, hormones play an important role and may cause the above experimental observations.In order to understand these aspects, we propose a growth model for root.The hormone effect and its growth-stage-dependent sensitivity are taken into consideration.It is discussed how the growth process of grouping roots is influenced by exogenous hormones secreted from roots.

  1. Protective Role of Growth Hormone against Hyperhomocysteinemia Induced Glomerular Injury

    PubMed Central

    Li, Caixia; Xia, Min; Abais, Justine M.; Liu, Xiaocheng; Li, Ningjun; Boini, Krishna M.; Li, Pin-Lan

    2013-01-01

    The present study investigated the protective role of growth hormone (GH) against hyperhomocysteinemia (hHcys)-induced activations of reactive oxygen species (ROS)/hypoxia-inducible factor (HIF)-1α, epithelial-mesenchymal transition (EMT) and consequent glomerular injury. A hyperhomocysteinemia (hHcys) model was induced by folate free (FF) diet in mice. The urine protein excretion significantly increased while plasma GH levels dramatically decreased in hHcys. Real time RT-PCR showed that GH receptor (GHR) level increased in the cortex of hHcys mice, which mainly occurred in podocytes as shown by confocal microscopy. Recombinant mouse growth hormone (rmGH) treatment (0.02 mg/kg, once a day for 6 weeks) significantly restored the plasma GH, inhibited GHR up-regulation and attenuated proteinuria. Correspondingly, rmGH treatment also blocked hHcys-induced decrease in the expression of podocin, a podocyte slit diaphragm molecule, and inhibited the increases in the expression of desmin, a podocyte injury marker. It was also demonstrated that in hHcys the expression of epithelial markers, p-cadherin and ZO-1, decreased, while the expression of mesenchymal markers, FSP-1 and α-SMA, increased in podocytes, which together suggest the activation of EMT in podocytes. NADPH oxidase (Nox)-dependent superoxide anion (O2·−) and HIF-1α level in the hHcys mice cortex was markedly enhanced. These hHcys-induced EMT enhancement and Nox-dependant O2·−/HIF-1α activation were significantly attenuated by rmGH treatment. HIF-1α level increased in Hcys-treated cultured podocytes, which were blocked by rmGH treatment. Meanwhile, Hcys-induced EMT in cultured podocytes was significantly reversed by HIF-1α siRNA. All these results support the view that GH ameliorates hHcys-induced glomerular injury by reducing Nox-dependent O2·−/HIF-1α signal pathway and EMT. PMID:23529346

  2. Egg size-dependent expression of growth hormone receptor accompanies compensatory growth in fish

    PubMed Central

    Segers, F. H. I. D.; Berishvili, G.; Taborsky, B.

    2012-01-01

    Large egg size usually boosts offspring survival, but mothers have to trade off egg size against egg number. Therefore, females often produce smaller eggs when environmental conditions for offspring are favourable, which is subsequently compensated for by accelerated juvenile growth. How this rapid growth is modulated on a molecular level is still unclear. As the somatotropic axis is a key regulator of early growth in vertebrates, we investigated the effect of egg size on three key genes belonging to this axis, at different ontogenetic stages in a mouthbrooding cichlid (Simochromis pleurospilus). The expression levels of one of them, the growth hormone receptor (GHR), were significantly higher in large than in small eggs, but remarkably, this pattern was reversed after hatching: young originating from small eggs had significantly higher GHR expression levels as yolk sac larvae and as juveniles. GHR expression in yolk sac larvae was positively correlated with juvenile growth rate and correspondingly fish originating from small eggs grew faster. This enabled them to catch up fully in size within eight weeks with conspecifics from larger eggs. This is the first evidence for a potential link between egg size, an important maternal effect, and offspring gene expression, which mediates an adaptive adjustment in a relevant hormonal axis. PMID:21752823

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

    NASA Technical Reports Server (NTRS)

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

    1994-01-01

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

  4. Measuring growth hormone and insulin-like growth factor-I in infants: what is normal?

    PubMed

    Hawkes, Colin Patrick; Grimberg, Adda

    2013-12-01

    The role of growth hormone (GH) and insulinlike growth factor-I (IGF-I) change through early childhood. Whereas poor growth is a later presenting feature, infants with isolated GH deficiency have a normal birth weight and length, and often present with hypoglycemia. IGF-I plays an important role antenatally and post-natally in somatic and brain growth. In order to evaluate the GH/IGF-I axis in infancy, an understanding of the normal physiology is required. Measurements of GH and IGF-I in this population should be interpreted in the context of the assays used, as well as their limitations. In this review, we summarize our current understanding of normal GH and IGF-I secretion in children under 18 months of age, and describe variations in the reported assay-specific measurements.

  5. Measuring Growth Hormone and Insulin-like Growth Factor-I in Infants: What is Normal?

    PubMed Central

    Hawkes, Colin Patrick; Grimberg, Adda

    2014-01-01

    The role of growth hormone (GH) and insulin-like growth factor-I (IGF-I) change through early childhood. Whereas poor growth is a later presenting feature, infants with isolated GH deficiency have a normal birth weight and length, and often present with hypoglycemia. IGF-I plays an important role antenatally and post-natally in somatic and brain growth. In order to evaluate the GH/IGF-I axis in infancy, an understanding of the normal physiology is required. Measurements of GH and IGF-I in this population should be interpreted in the context of the assays used, as well as their limitations. In this review, we summarize our current understanding of normal GH and IGF-I secretion in children under 18 months of age, and describe variations in the reported assay-specific measurements. PMID:24575549

  6. LEPROT and LEPROTL1 cooperatively decrease hepatic growth hormone action in mice

    PubMed Central

    Touvier, Thierry; Conte-Auriol, Françoise; Briand, Olivier; Cudejko, Céline; Paumelle, Réjane; Caron, Sandrine; Baugé, Eric; Rouillé, Yves; Salles, Jean-Pierre; Staels, Bart; Bailleul, Bernard

    2009-01-01

    Growth hormone (GH) is a major metabolic regulator that functions by stimulating lipolysis, preventing protein catabolism, and decreasing insulin-dependent glucose disposal. Modulation of hepatic sensitivity to GH and the downstream effects on the GH/IGF1 axis are important events in the regulation of metabolism in response to variations in food availability. For example, during periods of reduced nutrient availability, the liver becomes resistant to GH actions. However, the mechanisms controlling hepatic GH resistance are currently unknown. Here, we investigated the role of 2 tetraspanning membrane proteins, leptin receptor overlapping transcript (LEPROT; also known as OB-RGRP) and LEPROT-like 1 (LEPROTL1), in controlling GH sensitivity. Transgenic mice expressing either human LEPROT or human LEPROTL1 displayed growth retardation, reduced plasma IGF1 levels, and impaired hepatic sensitivity to GH, as measured by STAT5 phosphorylation and Socs2 mRNA expression. These phenotypes were accentuated in transgenic mice expressing both proteins. Moreover, gene silencing of either endogenous Leprot or Leprotl1 in H4IIE hepatocytes increased GH signaling and enhanced cell-surface GH receptor. Importantly, we found that both LEPROT and LEPROTL1 expression were regulated in the mouse liver by physiologic and pathologic changes in glucose homeostasis. Together, these data provide evidence that LEPROT and LEPROTL1 influence liver GH signaling and that regulation of the genes encoding these proteins may constitute a molecular link between nutritional signals and GH actions on body growth and metabolism. PMID:19907080

  7. LEPROT and LEPROTL1 cooperatively decrease hepatic growth hormone action in mice.

    PubMed

    Touvier, Thierry; Conte-Auriol, Françoise; Briand, Olivier; Cudejko, Céline; Paumelle, Réjane; Caron, Sandrine; Baugé, Eric; Rouillé, Yves; Salles, Jean-Pierre; Staels, Bart; Bailleul, Bernard

    2009-12-01

    Growth hormone (GH) is a major metabolic regulator that functions by stimulating lipolysis, preventing protein catabolism, and decreasing insulin-dependent glucose disposal. Modulation of hepatic sensitivity to GH and the downstream effects on the GH/IGF1 axis are important events in the regulation of metabolism in response to variations in food availability. For example, during periods of reduced nutrient availability, the liver becomes resistant to GH actions. However, the mechanisms controlling hepatic GH resistance are currently unknown. Here, we investigated the role of 2 tetraspanning membrane proteins, leptin receptor overlapping transcript (LEPROT; also known as OB-RGRP) and LEPROT-like 1 (LEPROTL1), in controlling GH sensitivity. Transgenic mice expressing either human LEPROT or human LEPROTL1 displayed growth retardation, reduced plasma IGF1 levels, and impaired hepatic sensitivity to GH, as measured by STAT5 phosphorylation and Socs2 mRNA expression. These phenotypes were accentuated in transgenic mice expressing both proteins. Moreover, gene silencing of either endogenous Leprot or Leprotl1 in H4IIE hepatocytes increased GH signaling and enhanced cell-surface GH receptor. Importantly, we found that both LEPROT and LEPROTL1 expression were regulated in the mouse liver by physiologic and pathologic changes in glucose homeostasis. Together, these data provide evidence that LEPROT and LEPROTL1 influence liver GH signaling and that regulation of the genes encoding these proteins may constitute a molecular link between nutritional signals and GH actions on body growth and metabolism. PMID:19907080

  8. Dangers of growth hormone therapy in critically ill patients.

    PubMed

    Ruokonen, E; Takala, J

    2000-07-01

    Prolonged stay of patients is the major challenge for modern intensive care because of its effects on morbidity and resource utilization. Severe trauma or infection are associated with the catabolic response, characterized by increased protein turnover and negative nitrogen balance. Severe catabolism leads to end-organ dysfunction and muscular weakness prolonging the need for mechanical ventilation. Catabolism cannot be prevented with standard parenteral or enteral nutritional formulas. In order to prevent the complications of catabolism in intensive care patients, recombinant growth hormone (rhGH) has been applied during two decades as an experimental therapy for patients requiring parenteral nutrition and for those with respiratory failure. Administration of rhGH has resulted in positive nitrogen balance, and studies in mechanically ventilated patients suggest that it may shorten the need for ventilatory support. In contrast to the results of these relatively small studies, a recent multinational randomized controlled trial revealed that the administration of rhGH (with doses 10-20 times higher than those used for replacement therapy) increases the mortality of critically ill patients. This excessive mortality in patients treated with rhGH was related to infections and development of multiple organ failure. Administration of high doses of rhGH to critically ill patients cannot thus be recommended.

  9. Growth hormone prevents the development of autoimmune diabetes

    PubMed Central

    Villares, Ricardo; Kakabadse, Dimitri; Juarranz, Yasmina; Gomariz, Rosa P.; Martínez-A, Carlos; Mellado, Mario

    2013-01-01

    Evidence supports a relationship between the neuroendocrine and the immune systems. Data from mice that overexpress or are deficient in growth hormone (GH) indicate that GH stimulates T and B-cell proliferation and Ig synthesis, and enhances maturation of myeloid progenitor cells. The effect of GH on autoimmune pathologies has nonetheless been little studied. Using a murine model of type 1 diabetes, a T-cell–mediated autoimmune disease characterized by immune cell infiltration of pancreatic islets and destruction of insulin-producing β-cells, we observed that sustained GH expression reduced prodromal disease symptoms and eliminated progression to overt diabetes. The effect involves several GH-mediated mechanisms; GH altered the cytokine environment, triggered anti-inflammatory macrophage (M2) polarization, maintained activity of the suppressor T-cell population, and limited Th17 cell plasticity. In addition, GH reduced apoptosis and/or increased the proliferative rate of β-cells. These results support a role for GH in immune response regulation and identify a unique target for therapeutic intervention in type 1 diabetes. PMID:24218587

  10. Episodic molecular evolution of pituitary growth hormone in Cetartiodactyla.

    PubMed

    Maniou, Zoitsa; Wallis, O Caryl; Wallis, Michael

    2004-06-01

    The sequence of growth hormone (GH) is generally strongly conserved in mammals, but episodes of rapid change occurred during the evolution of primates and artiodactyls, when the rate of GH evolution apparently increased substantially. As a result the sequences of higher primate and ruminant GHs differ markedly from sequences of other mammalian GHs. In order to increase knowledge of GH evolution in Cetartiodactyla (Artiodactyla plus Cetacea) we have cloned and characterized GH genes from camel (Camelus dromedarius), hippopotamus (Hippopotamus amphibius), and giraffe (Giraffa camelopardalis), using genomic DNA and a polymerase chain reaction technique. As in other mammals, these GH genes comprise five exons and four introns. Two very similar GH gene sequences (encoding identical proteins) were found in each of hippopotamus and giraffe. The deduced sequence for the mature hippopotamus GH is identical to that of dolphin, in accord with current ideas of a close relationship between Cetacea and Hippopotamidae. The sequence of camel GH is identical to that reported previously for alpaca GH. The sequence of giraffe GH is very similar to that of other ruminants but differs from that of nonruminant cetartiodactyls at about 18 residues. The results demonstrate that the apparent burst of rapid evolution of GH occurred largely after the separation of the line leading to ruminants from other cetartiodactyls. PMID:15461431

  11. Mouse cellular cementum is highly dependent on growth hormone status.

    PubMed

    Smid, J R; Rowland, J E; Young, W G; Daley, T J; Coschigano, K T; Kopchick, J J; Waters, M J

    2004-01-01

    Cementum is known to be growth-hormone (GH)-responsive, but to what extent is unclear. This study examines the effects of extremes of GH status on cementogenesis in three lines of genetically modified mice; GH excess (giant), GH antagonist excess (dwarf), and GH receptor-deleted (GHR-KO) (dwarf). Age-matched mandibular molar tissues were processed for light microscope histology. Digital images of sections of first molar teeth were captured for morphometric analysis of lingual root cementum. Cross-sectional area of the cellular cementum was a sensitive guide to GH status, being reduced nearly 10-fold in GHR-KO mice, three-fold in GH antagonist mice, and increased almost two-fold in giant mice (p < 0.001). Cellular cementum length was similarly influenced by GH status, but to a lesser extent. Acellular cementum was generally unaffected. This study reveals cellular cementum to be a highly responsive GH target tissue, which may have therapeutic applications in assisting regeneration of the periodontium. PMID:14691110

  12. Gender Bias in U.S. Pediatric Growth Hormone Treatment.

    PubMed

    Grimberg, Adda; Huerta-Saenz, Lina; Grundmeier, Robert; Ramos, Mark Jason; Pati, Susmita; Cucchiara, Andrew J; Stallings, Virginia A

    2015-06-09

    Growth hormone (GH) treatment of idiopathic short stature (ISS), defined as height <-2.25 standard deviations (SD), is approved by U.S. FDA. This study determined the gender-specific prevalence of height <-2.25 SD in a pediatric primary care population, and compared it to demographics of U.S. pediatric GH recipients. Data were extracted from health records of all patients age 0.5-20 years with ≥ 1 recorded height measurement in 28 regional primary care practices and from the four U.S. GH registries. Height <-2.25 SD was modeled by multivariable logistic regression against gender and other characteristics. Of the 189,280 subjects, 2073 (1.1%) had height <-2.25 SD. No gender differences in prevalence of height <-2.25 SD or distribution of height Z-scores were found. In contrast, males comprised 74% of GH recipients for ISS and 66% for all indications. Short stature was associated (P < 0.0001) with history of prematurity, race/ethnicity, age and Medicaid insurance, and inversely related (P < 0.0001) with BMI Z-score. In conclusion, males outnumbered females almost 3:1 for ISS and 2:1 for all indications in U.S. pediatric GH registries despite no gender difference in height <-2.25 SD in a large primary care population. Treatment and/or referral bias was the likely cause of male predominance among GH recipients.

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

    SciTech Connect

    Norstedt, G.; Enberg, B.; Francis, S.

    1994-12-31

    The isolation of growth hormone receptor (GHR) cDNA clones has made possible the transfection of GHRs into cultured cells. Our aim in this minireview is to show how the application of such approaches have benefited GHR research. GH stimulation of cells expressing GHR cDNAs can cause an alteration of cellular function that mimic those of the endogenous GHR. GHR cDNA transfected cells also offer a system where the mechanism of GH action can be studied. Such a system has been used to demonstrate that the GHR itself becomes tyrosine phosphorylated and that further phosphorylation of downstream proteins is important in GH action. The GH signals are transmitted to the nucleus and GH regulated genes have now begun to be characterized. The ability to use cell transfection for mechanistic studies of GH action will be instrumental to define domains within the receptor that are of functional importance and to determined pathways whereby GH signals are conveyed within the cell. 33 refs., 2 tabs.

  14. Growth hormone receptor/binding protein: Physiology and function

    SciTech Connect

    Herington, A.C.; Ymer, S.I.; Stevenson, J.L.; Roupas, P.

    1994-12-31

    Soluble truncated forms of the growth hormone receptor (GHR) are present in the circulation of many species and are also produced by many tissues/cell types. The major high-affinity forms of these GH-binding proteins (GHBP) are derived by alternative splicing of GHR mRNA in rodents, but probably by proteolytic cleavage in other species. Questions still remain with respect to the origins, native molecular forms(s), physiology, and function of the GHBPs, however. The observation that GH induces dimerization of the soluble GHBP and a membrane GHR, and that dimerization of GHR appears to be critical for GH bioactivity suggests that the presentation of GH to target cells, in an unbound form or as a monomeric or dimeric complex with GHBP, may have significant implications for the ability of GH to activate specific postreceptor signaling pathways (tyrosine kinase, protein kinase C, G-protein pathways) known to be utilized by GH for its diverse biological effects. This minireview addresses some of these aspects and highlights several new questions which have arisen as a result of recent advances in our understanding of the structure, function, and signaling mechanisms of the membrane bound GHR. 43 refs.

  15. Stability of human growth hormone in supercritical carbon dioxide.

    PubMed

    Kelly, Catherine A; Howdle, Steven M; Naylor, Andrew; Coxhill, Graham; Tye, Laura C; Illum, Lisbeth; Lewis, Andrew L

    2012-01-01

    The instability of human growth hormone (hGH) to temperature and interfaces makes its formulation into injectable, sustained-release drug delivery systems challenging. A novel method of encapsulating hGH in polymeric microparticles has been developed using supercritical CO(2) (scCO(2)) technology, but there is limited understanding of the stability of hGH within this system. The aim of this study was to evaluate the stability of hGH in scCO(2) processing. The integrity of the protein was assessed following exposure to scCO(2) using a range of different analytical techniques. Mass spectrometry showed that no peptide cleavage occurred as a result of processing or exposure to scCO(2). Size-exclusion chromatography detected formation of aggregates at high temperatures, but not as a result of the encapsulation process. Reverse-phase chromatography demonstrated that the production of deamidation products occurred as a function of temperature, but only at temperatures higher than those used for the encapsulation process. Circular dichroism and infrared spectroscopy demonstrated that the use of scCO(2) was not detrimental to the secondary molecular structure of hGH. Together, these results show that the structural integrity of hGH is unaffected by scCO(2) processing and that hGH can be successfully encapsulated in polymer microparticles using this technique.

  16. Structural basis for cyclodextrins' suppression of human growth hormone aggregation

    PubMed Central

    Otzen, Daniel Erik; Knudsen, Benjamin Raerup; Aachmann, Finn; Larsen, Kim Lambertsen; Wimmer, Reinhard

    2002-01-01

    Many therapeutic proteins require storage at room temperature for extended periods of time. This can lead to aggregation and loss of function. Cyclodextrins (CDs) have been shown to function as aggregation suppressors for a wide range of proteins. Their potency is often ascribed to their affinity for aromatic amino acids, whose surface exposure would otherwise lead to protein association. However, no detailed structural studies are available. Here we investigate the interactions between human growth hormone (hGH) and different CDs at low pH. Although hGH aggregates readily at pH 2.5 in 1 M NaCl to form amorphous aggregates, the presence of 25 to 50 mM of various β-CD derivatives is sufficient to completely avoid this. α- and γ-CD are considerably less effective. Stopped-flow data on the aggregation reaction in the presence of β-CD are analyzed according to a minimalist association model to yield an apparent hGH-β-CD dissociation constant of ∼6 mM. This value is very similar to that obtained by simple fluorescence-based titration of hGH with β-CD. Nuclear magnetic resonance studies indicate that β-CD leads to a more unfolded conformation of hGH at low pH and predominantly binds to the aromatic side-chains. This indicates that aromatic amino acids are important components of regions of residual structure that may form nuclei for aggregation. PMID:12070330

  17. Exceptional Association Between Klinefelter Syndrome and Growth Hormone Deficiency

    PubMed Central

    Doubi, Sana; Amrani, Zoubida; Ouahabi, Hanan El; Boujraf, Saïd; Ajdi, Farida

    2015-01-01

    Klinefelter syndrome (KS) is characterized in adults by the combination of a tall stature, small testes, gynecomastia, and azoospermia. This case is described in a North African population of the Mediterranean region of North Africa. We report the case of a male 16 years old, of Arab ethnic origin, and diagnosed with this syndrome, who had a small height in relation to a growth hormone (GH) deficiency and a history of absence seizures (generalized myoclonic epilepsy). The patient's size was <−2.8 standard deviation (SD) with weight <−3 SD. GH deficiency was isolated and confirmed by two dynamic tests (insulin — hypoglycemia tolerance test and clonidine) with normal hypothalamic magnetic resonance imaging (MRI). GH supplementation using recombinant GH was advocated, while gonadotropin treatment was deferred. Small size in children or adolescents should not eliminate the diagnosis of Klinefelter syndrome — on the contrary, the presence of any associated sign (brain maturation, delay in puberty, aggressiveness) should encourage one to request a karyotype for the diagnosis and appropriate care of any case of KS that can be associated with GH deficiency, or which is in a variant form (isochromosome Xq, 49,XXXXY). PMID:27330737

  18. Dissolving Microneedle Patch for Transdermal Delivery of Human Growth Hormone

    PubMed Central

    Lee, Jeong Woo; Choi, Seong-O; Felner, Eric I.

    2014-01-01

    Clinical impact of biotechnology has been constrained by the limitations of traditional hypodermic injection of biopharmaceuticals. Microneedle patches have been proposed as a minimally invasive alternative. In this study, we assess the translation of a dissolving microneedle patch designed for simple, painless self-administration of biopharmacetucials that generates no sharp biohazardous waste. To study pharmacokinetics and safety of this approach, human growth hormone (hGH) was encapsulated in 600 μm long dissolving microneedles composed of carboxymethylcellulose and trehalose using an aqueous, moderate-temperature process that maintained complete hGH activity after encapsulation and retained most activity after storage for up to 15 months at room temperature and humidity. After manual insertion into the skin of hairless rats, hGH pharmacokinetics were similar to conventional subcutaneous injection. After patch removal, the microneedles had almost completely dissolved, leaving behind only blunt stubs. The dissolving microneedle patch was well tolerated, causing only slight, transient erythema. This study suggests that a dissolving microneedle patch can deliver hGH and other biopharmaceuticals in a manner suitable for self-administration without sharp biohazardous waste. PMID:21360810

  19. Growth hormone and risk for cardiac tumors in Carney complex.

    PubMed

    Bandettini, W Patricia; Karageorgiadis, Alexander S; Sinaii, Ninet; Rosing, Douglas R; Sachdev, Vandana; Schernthaner-Reiter, Marie Helene; Gourgari, Evgenia; Papadakis, Georgios Z; Keil, Meg F; Lyssikatos, Charalampos; Carney, J Aidan; Arai, Andrew E; Lodish, Maya; Stratakis, Constantine A

    2016-09-01

    Carney complex (CNC) is a multiple neoplasia syndrome that is caused mostly by PRKAR1A mutations. Cardiac myxomas are the leading cause of mortality in CNC patients who, in addition, often develop growth hormone (GH) excess. We studied patients with CNC, who were observed for over a period of 20 years (1995-2015) for the development of both GH excess and cardiac myxomas. GH secretion was evaluated by standard testing; dedicated cardiovascular imaging was used to detect cardiac abnormalities. Four excised cardiac myxomas were tested for the expression of insulin-like growth factor-1 (IGF-1). A total of 99 CNC patients (97 with a PRKAR1A mutation) were included in the study with a mean age of 25.8 ± 16.6 years at presentation. Over an observed mean follow-up of 25.8 years, 60% of patients with GH excess (n = 46) developed a cardiac myxoma compared with only 36% of those without GH excess (n = 54) (P = 0.016). Overall, patients with GH excess were also more likely to have a tumor vs those with normal GH secretion (OR: 2.78, 95% CI: 1.23-6.29; P = 0.014). IGF-1 mRNA and protein were higher in CNC myxomas than in normal heart tissue. We conclude that the development of cardiac myxomas in CNC may be associated with increased GH secretion, in a manner analogous to the association between fibrous dysplasia and GH excess in McCune-Albright syndrome, a condition similar to CNC. We speculate that treatment of GH excess in patients with CNC may reduce the likelihood of cardiac myxoma formation and/or recurrence of this tumor.

  20. Growth hormone and risk for cardiac tumors in Carney complex.

    PubMed

    Bandettini, W Patricia; Karageorgiadis, Alexander S; Sinaii, Ninet; Rosing, Douglas R; Sachdev, Vandana; Schernthaner-Reiter, Marie Helene; Gourgari, Evgenia; Papadakis, Georgios Z; Keil, Meg F; Lyssikatos, Charalampos; Carney, J Aidan; Arai, Andrew E; Lodish, Maya; Stratakis, Constantine A

    2016-09-01

    Carney complex (CNC) is a multiple neoplasia syndrome that is caused mostly by PRKAR1A mutations. Cardiac myxomas are the leading cause of mortality in CNC patients who, in addition, often develop growth hormone (GH) excess. We studied patients with CNC, who were observed for over a period of 20 years (1995-2015) for the development of both GH excess and cardiac myxomas. GH secretion was evaluated by standard testing; dedicated cardiovascular imaging was used to detect cardiac abnormalities. Four excised cardiac myxomas were tested for the expression of insulin-like growth factor-1 (IGF-1). A total of 99 CNC patients (97 with a PRKAR1A mutation) were included in the study with a mean age of 25.8 ± 16.6 years at presentation. Over an observed mean follow-up of 25.8 years, 60% of patients with GH excess (n = 46) developed a cardiac myxoma compared with only 36% of those without GH excess (n = 54) (P = 0.016). Overall, patients with GH excess were also more likely to have a tumor vs those with normal GH secretion (OR: 2.78, 95% CI: 1.23-6.29; P = 0.014). IGF-1 mRNA and protein were higher in CNC myxomas than in normal heart tissue. We conclude that the development of cardiac myxomas in CNC may be associated with increased GH secretion, in a manner analogous to the association between fibrous dysplasia and GH excess in McCune-Albright syndrome, a condition similar to CNC. We speculate that treatment of GH excess in patients with CNC may reduce the likelihood of cardiac myxoma formation and/or recurrence of this tumor. PMID:27535175

  1. Further studies on phosphorylated pituitary somatotropin (growth hormone)

    SciTech Connect

    Kornberg, L.J.; Liberti, J.P.

    1987-05-01

    This laboratory made the original observation that naturally-occurring ovine growth hormone (GH) is phosphorylated and that slices of pituitary glands from male rats synthesize and secrete /sup 32/P-GH. This observation has been extended to explore the generality of this process. After incubation in PO/sub 4/-free Ham's F-10 medium (PFH) or in saline/Hepes (SH) containing 300..mu..Ci /sup 32/Pi/mL, tissue and medium were separated and a cell extract was prepared. GH in the medium and extract was recovered by immunoprecipitation using rat GH antiserum. The samples were electrophoresed under denaturating conditions and processed for autoradiography. /sup 32/P-GH was characterized by the presence of a protein-staining band and radioactive area which migrated the same as authentic GH and /sup 125/I-GH. Slices of glands from male rats incubated for 2h in PFH secreted /sup 32/P-GH. Similar results were found upon incubation of slices from female rats in the presence of SH. Short-term incubations of acutely dispersed pituitary cells obtained from young and old male rats also synthesized and secreted /sup 32/P-GH. Thus, the production of /sup 32/P-GH occurs (a) in simple and complex incubaton media, (b) in slices and cells from glands from older and younger rats and (c) in female as well as male rats. Therefore, phosphorylation of GH appears to be a general phenomenon. The physiological action(s) of phosphorylated GH in growth and development is under study.

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

    PubMed Central

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

    1991-01-01

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

  3. Pentadecapeptide BPC 157 enhances the growth hormone receptor expression in tendon fibroblasts.

    PubMed

    Chang, Chung-Hsun; Tsai, Wen-Chung; Hsu, Ya-Hui; Pang, Jong-Hwei Su

    2014-01-01

    BPC 157, a pentadecapeptide derived from human gastric juice, has been demonstrated to promote the healing of different tissues, including skin, muscle, bone, ligament and tendon in many animal studies. However, the underlying mechanism has not been fully clarified. The present study aimed to explore the effect of BPC 157 on tendon fibroblasts isolated from Achilles tendon of male Sprague-Dawley rat. From the result of cDNA microarray analysis, growth hormone receptor was revealed as one of the most abundantly up-regulated genes in tendon fibroblasts by BPC 157. BPC 157 dose- and time-dependently increased the expression of growth hormone receptor in tendon fibroblasts at both the mRNA and protein levels as measured by RT/real-time PCR and Western blot, respectively. The addition of growth hormone to BPC 157-treated tendon fibroblasts dose- and time-dependently increased the cell proliferation as determined by MTT assay and PCNA expression by RT/real-time PCR. Janus kinase 2, the downstream signal pathway of growth hormone receptor, was activated time-dependently by stimulating the BPC 157-treated tendon fibroblasts with growth hormone. In conclusion, the BPC 157-induced increase of growth hormone receptor in tendon fibroblasts may potentiate the proliferation-promoting effect of growth hormone and contribute to the healing of tendon. PMID:25415472

  4. Diacylglycerol production induced by growth hormone in Ob1771 preadipocytes arises from phosphatidylcholine breakdown

    SciTech Connect

    Catalioto, R.M.; Ailhaud, G.; Negrel, R. )

    1990-12-31

    Growth Hormone has recently been shown to stimulate the formation of diacylglycerol in Ob1771 mouse preadipocyte cells without increasing inositol lipid turnover. Addition of growth hormone to Ob1771 cells prelabelled with ({sup 3}H)glycerol or ({sup 3}H)choline led to a rapid, transient and stoechiometric formation of labelled diacylglycerol and phosphocholine, respectively. In contrast, no change was observed in the level of choline and phosphatidic acid whereas the release of water-soluble metabolites in ({sup 3}H)ethanolamine prelabelled cells exposed to growth hormone was hardly detectable. Stimulation by growth hormone of cells prelabelled with (2-palmitoyl 9, 10 ({sup 3}H))phosphatidylcholine also induced the production of labelled diacyglycerol. Pertussis toxin abolished both diacylglycerol and phosphocholine formation induced by growth hormone. It is concluded that growth hormone mediates diacylglycerol production in Ob1771 cells by means of phosphatidylcholine breakdown involving a phospholipase C which is likely coupled to the growth hormone receptor via a pertussis toxin-sensitive G-protein.

  5. The relationship between growth hormone polymorphism and growth hormone receptor genes with milk yield and reproductive performance in Holstein dairy cows

    PubMed Central

    Hadi, Z; Atashi, H; Dadpasand, M; Derakhshandeh, A; Ghahramani Seno, M. M

    2015-01-01

    The aim of this study was to investigate the potential association between growth hormone GH/AluI and growth hormone receptor GHR/AluI polymorphisms with milk yield and reproductive performances in Holstein dairy cows in Iran. Blood samples of 150 Holstein cows were collected and their genomic DNA was extracted using Gene-Fanavaran DNA extracting kit. Fragments of the 428 bp of exon 5 growth hormone (GH) gene and the 342 bp of exon 10 growth hormone receptor (GHR) gene were amplified using the polymerase chain reaction (PCR) method. PCR products were digested by the AluI restriction enzyme and electrophoresed on 3% agarose gel. Continuous and categorical data were analyzed using linear mixed models through Proc MIXED and logistic regression models through Proc GENMOD of SAS software, respectively. The results showed no relationship between the examined traits and GH/AluI or GHR/AluI genes. A significant relationship was found between GH/AluI polymorphism and dystocia, but the presence of the GH-L allele reduced the incidence of dystocia. The results suggest that the GH-LL genotype reduces dystocia probably by affecting the release of growth hormone; nevertheless, further studies will be needed to examine the relationship between dystocia and GH genotypes. PMID:27175183

  6. Intimate associations between the endogenous opiate systems and the growth hormone-releasing hormone system in the human hypothalamus.

    PubMed

    Olsen, J; Peroski, M; Kiczek, M; Grignol, G; Merchenthaler, I; Dudas, B

    2014-01-31

    Although it is a general consensus that opioids modulate growth, the mechanism of this phenomenon is largely unknown. Since endogenous opiates use the same receptor family as morphine, these peptides may be one of the key regulators of growth in humans by impacting growth hormone (GH) secretion, either directly, or indirectly, via growth hormone-releasing hormone (GHRH) release. However, the exact mechanism of this regulation has not been elucidated yet. In the present study we identified close juxtapositions between the enkephalinergic/endorphinergic/dynorphinergic axonal varicosities and GHRH-immunoreactive (IR) perikarya in the human hypothalamus. Due to the long post mortem period electron microscopy could not be utilized to detect the presence of synapses between the enkephalinergic/endorphinergic/dynorphinergic and GHRH neurons. Therefore, we used light microscopic double-label immunocytochemistry to identify putative juxtapositions between these systems. Our findings revealed that the majority of the GHRH-IR perikarya formed intimate associations with enkephalinergic axonal varicosities in the infundibular nucleus/median eminence, while endorphinergic-GHRH juxtapositions were much less frequent. In contrast, no significant dynorphinergic-GHRH associations were detected. The density of the abutting enkephalinergic fibers on the surface of the GHRH perikarya suggests that these juxtapositions may be functional synapses and may represent the morphological substrate of the impact of enkephalin on growth. The small number of GHRH neurons innervated by the endorphin and dynorphin systems indicates significant differences between the regulatory roles of endogenous opiates on growth in humans. PMID:24239719

  7. [Effect of growth hormone and calcitriol on the growth plate in uremic rats].

    PubMed

    Amil, B; Fernández-Fuente, M; Santos, F; Rodríguez, J; Díaz-Tejón, L; García, E; Carbajo, E

    2003-01-01

    This study analyzed the modifications induced by growth hormone (GH) and/or calcitriol treatments in the growth plate of growth retarded uremic rats. Four groups of 5/6 nephrectomized rats were studied: untreated (U), treated with GH (U + GH), treated with calcitriol (U + D), treated with GH and calcitriol (U + GH + D). Treatments were given intraperitoneally during the second week of renal failure. Uremic groups were compared with sham-operated rats fed ad libitum (C) or pair-fed with U (CP). In comparison with C and CP, histomorphometric analysis of tibial proximal ends of U group showed decreased bone formation, as estimated by osseous front advance (OFA), elongation of growth cartilage and its hypertrophic zone, and decreased size of most distal chondrocytes. The U + D group tended to normalize growth cartilage height, and that of its hypertrophic zone, as well as the size of chondrocytes. In U + GH group OFA improved and chondrocyte size became normal, but growth cartilage remained elongated. Similar results were found in the U + GH + D group. These findings indicate that, in chronic renal insufficiency, the beneficial effect of GH on growth is not associated with normalization of growth cartilage morphology and that calcitriol facilitates chondrocyte maturation. When given together the effect of GH prevails.

  8. Effects of long-term growth hormone-releasing factor administration on plasma growth hormone, luteinizing hormone and progesterone profiles in growing female buffaloes (Bubalus bubalis).

    PubMed

    Mondal, M; Prakash, B S

    2004-10-01

    To investigate the effects of long-term growth hormone-releasing factor (GRF) administration on plasma growth hormone (GH), LH and progesterone and body weight gain in growing buffalo calves, 12 female Murrah buffaloes within the age group of 6-8 months of age were divided into two groups (treatment and control groups) of six each in such a way so that average body weights between the groups did not differ (p > 0.05). Control buffaloes were not given any hormonal treatment and treatment group buffaloes were treated with synthetic bovine GRF [bGRF (1-44)-NH(2)] at the rate of 10 microg/100 kg body weight intravenously at an interval of 15 days from week 6 (5-week pre-treatment period) till 18 injections were completed (week 6-42 treatment period) and thereafter, effect of exogenous GRF were observed for 10-week post-treatment period. Jugular blood samples were drawn twice a week at 3-4-day intervals for plasma GH, LH and progesterone quantification. Body weight of all animals was recorded twice a week. During pre-treatment period, mean plasma GH, LH and progesterone did not differ (p > 0.05) between the groups. But during treatment as well as post-treatment period, mean plasma GH levels were found to be significantly (p < 0.01) higher in treatment than control group of buffaloes. Administration of GRF for longer term sustained a higher level of plasma GH even after cessation of treatment. GRF-treated buffaloes attained higher (p < 0.01) body weight than the controls. Repeated GRF administration for long-term significantly (p < 0.01) increased plasma LH and progesterone. In conclusion, repeated long-term exogenous GRF administration induces and even enhances GH release without any sign of refractoriness. GRF may, therefore, be used to induce daily GH release without loss of responsiveness over an extended period of time in young growing female buffaloes and it may assist these animals to grow faster. PMID:15367266

  9. Synthesis of the Growth Hormone Secretion Mechanism Using Nonlinear Analysis and CAD Tools.

    PubMed

    Shell, J R

    2005-01-01

    The goal of this paper is to present a hardware realization of the feed-forward and feedback hypothalamic-pituitary growth hormone (GH) secretion mechanism based on a bio-mathematical nonlinear delay differential equation model developed by Farhy et al. (2003) and Veldhuis et al. (2001). Behavioral modeling is implemented through Verilog hardware descriptive language (HDL) to simulate the antagonistic and stimulatory interaction of growth hormone, growth hormone releasing hormone (GHRH) and somatotropin release inhibiting factor (SRIF). The model is synthesized using computer aided design (CAD) tools and is promulgated through a combinational complex programmable logic device (CPLD)/field programmable grid array (FPGA) Xilinx XSA-50 microchip. The microchip sequentially displays the decimal equivalents of the time changing hormonal concentration levels of the biomathematical model.

  10. Alterations of growth plate and abnormal insulin-like growth factor I metabolism in growth-retarded hypokalemic rats: effect of growth hormone treatment.

    PubMed

    Gil-Peña, Helena; Garcia-Lopez, Enrique; Alvarez-Garcia, Oscar; Loredo, Vanessa; Carbajo-Perez, Eduardo; Ordoñez, Flor A; Rodriguez-Suarez, Julian; Santos, Fernando

    2009-09-01

    Hypokalemic tubular disorders may lead to growth retardation which is resistant to growth hormone (GH) treatment. The mechanism of these alterations is unknown. Weaning female rats were grouped (n = 10) in control, potassium-depleted (KD), KD treated with intraperitoneal GH at 3.3 mg x kg(-1) x day(-1) during the last week (KDGH), and control pair-fed with KD (CPF). After 2 wk, KD rats were growth retarded compared with CPF rats, the osseous front advance (+/-SD) being 67.07 +/- 10.44 and 81.56 +/- 12.70 microm/day, respectively. GH treatment did not accelerate growth rate. The tibial growth plate of KD rats had marked morphological alterations: lower heights of growth cartilage (228.26 +/- 23.58 microm), hypertrophic zone (123.68 +/- 13.49 microm), and terminal chondrocytes (20.8 +/- 2.39 microm) than normokalemic CPF (264.21 +/- 21.77, 153.18 +/- 15.80, and 24.21 +/- 5.86 microm). GH administration normalized these changes except for the distal chondrocyte height. Quantitative PCR of insulin-like growth factor I (IGF-I), IGF-I receptor, and GH receptor genes in KD growth plates showed downregulation of IGF-I and upregulation of IGF-I receptor mRNAs, without changes in their distribution as analyzed by immunohistochemistry and in situ hybridization. GH did not further modify IGF-I mRNA expression. KD rats had normal hepatic IGF-I mRNA levels and low serum IGF-I values. GH increased liver IGF-I mRNA, but circulating IGF-I levels remained reduced. This study discloses the structural and molecular alterations induced by potassium depletion on the growth plate and shows that the lack of response to GH administration is associated with persistence of the disturbed process of chondrocyte hypertrophy and depressed mRNA expression of local IGF-I in the growth plate.

  11. Multiple Hürthle cell adenomas in a patient with thyroid hormone resistance

    PubMed Central

    Xifra, Gemma; Mauri, Silvia; Gironès, Jordi; Rodríguez Hermosa, José Ignacio; Oriola, Josep; Ricart, Wifredo; Fernández-Real, José Manuel

    2013-01-01

    Summary Background: Thyroid hormone resistance (RTH) is a rare cause of thyroid dysfunction. High TSH levels, as described in RTH syndrome, are known to be associated with an increased risk of developing thyroid nodules with subsequent growth and malignancy. Patient findings: In 2006, a 29-year-old Caucasian man presented with a palpable mass in the neck. Increased free thyroxine and triiodothyronine levels were found in the context of unsuppressed TSH levels, despite no signs or symptoms of hyperthyroidism. Ultrasonography revealed a multinodular and enlarged goitre, and fine-needle aspiration cytology revealed suspicious features of malignancy. After excluding pituitary tumour and levothyroxine (l-T4) treatment, the patient was diagnosed with generalized RTH. Screening for all the known mutations in thyroid hormone receptor-β (TR β (THRB)) was negative. Thyroidectomy disclosed five Hürthle adenomas and three hyperplasic nodules. Euthyroidism was achieved after surgery with 6.1 μg/kg per day of l-T4. Conclusion: RTH may be a risk factor that predisposes to the development of multiple Hürthle cell adenomas. To our knowledge, this is the first case of multiple Hürthle cell adenomas in a patient with RTH. Learning points High TSH levels, as described in RTH syndrome, are known to be associated with an increased risk of developing thyroid nodules, with subsequent growth and malignancy.The exact role of TR β mutants in thyroid carcinogenesis is still undefined.We report the first case of multiple Hürthle cell adenomas associated with RTH. PMID:24683474

  12. Protective effect of Growth Hormone-Releasing Hormone agonist in bacterial toxin-induced pulmonary barrier dysfunction

    PubMed Central

    Czikora, Istvan; Sridhar, Supriya; Gorshkov, Boris; Alieva, Irina B.; Kasa, Anita; Gonzales, Joyce; Potapenko, Olena; Umapathy, Nagavedi S.; Pillich, Helena; Rick, Ferenc G.; Block, Norman L.; Verin, Alexander D.; Chakraborty, Trinad; Matthay, Michael A.; Schally, Andrew V.; Lucas, Rudolf

    2014-01-01

    Rationale: Antibiotic treatment of patients infected with G− or G+ bacteria promotes release of the toxins lipopolysaccharide (LPS) and pneumolysin (PLY) in their lungs. Growth Hormone-releasing Hormone (GHRH) agonist JI-34 protects human lung microvascular endothelial cells (HL-MVEC), expressing splice variant 1 (SV-1) of the receptor, from PLY-induced barrier dysfunction. We investigated whether JI-34 also blunts LPS-induced hyperpermeability. Since GHRH receptor (GHRH-R) signaling can potentially stimulate both cAMP-dependent barrier-protective pathways as well as barrier-disruptive protein kinase C pathways, we studied their interaction in GHRH agonist-treated HL-MVEC, in the presence of PLY, by means of siRNA-mediated protein kinase A (PKA) depletion. Methods: Barrier function measurements were done in HL-MVEC monolayers using Electrical Cell substrate Impedance Sensing (ECIS) and VE-cadherin expression by Western blotting. Capillary leak was assessed by Evans Blue dye (EBD) incorporation. Cytokine generation in broncho-alveolar lavage fluid (BALF) was measured by multiplex analysis. PKA and PKC-α activity were assessed by Western blotting. Results: GHRH agonist JI-34 significantly blunts LPS-induced barrier dysfunction, at least in part by preserving VE-cadherin expression, while not affecting inflammation. In addition to activating PKA, GHRH agonist also increases PKC-α activity in PLY-treated HL-MVEC. Treatment with PLY significantly decreases resistance in control siRNA-treated HL-MVEC, but does so even more in PKA-depleted monolayers. Pretreatment with GHRH agonist blunts PLY-induced permeability in control siRNA-treated HL-MVEC, but fails to improve barrier function in PKA-depleted PLY-treated monolayers. Conclusions: GHRH signaling in HL-MVEC protects from both LPS and PLY-mediated endothelial barrier dysfunction and concurrently induces a barrier-protective PKA-mediated and a barrier-disruptive PKC-α-induced pathway in the presence of PLY, the

  13. Oxidative stress impact on growth hormone secretion in the eye

    PubMed Central

    Šarić, Borna; Šarić, Vlatka Brzović; Barberić, Monika; Predović, Jurica; Rumenjak, Vlatko; Cerovski, Branimir

    2015-01-01

    Aim To evaluate the influence of oxidative stress on extrapituitary growth hormone (GH) secretion in the eye and to analyze the interdependence between eye and serum GH levels under normal and hypoxic conditions. Methods Pars plana vitrectomy (PPV) was performed in 32 patients with developed proliferative diabetic retinopathy (PDR) and 49 non-diabetic controls, both of whom required this procedure as part of their regular treatment in the period from April 2013 to December 2014. During PPV, vitreous samples were taken and blood was simultaneously collected from the cubital vein. GH levels in serum and vitreous samples were measured by electrochemical luminescence assay. Oxidative stress was measured by enzyme-linked immunosorbent assay of advanced oxidation protein products (AOPP) and lipid hydroperoxide (LPO) in serum and vitreous. Results Serum AOPP levels were significantly higher than vitreous levels in both groups (P < 0.001 for each group) and LPO levels were significantly higher only in PDR group (P < 0.001). There was a significant positive correlation between serum and vitreous LPO levels in PDR group (r = 0.909; P < 0.001). Serum GH levels were significantly higher than vitreous levels in both groups (P < 0.001 for each group). Serum GH levels were significantly higher in PDR group than in controls (P = 0.012). Vitreous GH values were slightly higher in PDR group, but the difference was not significant. Conclusion Our study confirms that GH production in the eye is autonomous and independent of oxidative stress or pituitary GH influence. PMID:26321025

  14. Responses of growth hormone aggregates to different intermittent exercise intensities.

    PubMed

    Rubin, Martyn R; Kraemer, William J; Kraemer, Robert R; Durand, Robert J; Acevedo, Edmund O; Johnson, Lisa G; Castracane, V D; Scheett, Timothy P; French, Duncan N; Volek, Jeff S

    2003-04-01

    The purpose of this study was to determine the impact of high-intensity intermittent exercise on the presence of circulating growth hormone (GH) aggregates measured using two different assay techniques. Six male subjects with endurance training background participated in this study under both exercise and no-exercise control conditions. After resting blood sampling, subjects completed an intermittent treadmill exercise protocol at four speeds predicted to elicit a specific VO(2):60% VO(2max) for 10 min, 75% for 10 min, 90% for 5 min, and 100% for 2 min. After each exercise intensity was completed treadmill speed was reduced to a walk (3.5-4 min) for blood sampling. Sampling continued every 15 min for 1 h into recovery. All samples were then measured for GH concentrations using Nichols immunoradiometric assay (IRMA) and Diagnostic Systems Laboratory's immunofunctional assay (IFA). A second set of samples was chemically reduced using reduced glutathione (GSH; 10 mM for 18 h at room temperature) to break disulfide bonds between possible oligomeric GH complexes, and subsequently assayed using the same GH assays. With the IRMA, GH was significantly elevated ( P<0.05) after the 75% workload and remained elevated through 30 min post-exercise. After adding GSH to the sample, the IRMA indicated significant increases in GH as early as the 60% exercise intensity and remained elevated through 45 min into recovery. At 75%, the GSH assay run was significantly higher than the non-GSH assay run. With the IFA, GH was significantly elevated at 60% in the non-GSH condition, whereas the GSH assay run indicated significant elevations at 75%. Both GSH and non-GSH conditions remained elevated through 30 min into recovery. These data indicate that the addition of GSH to serum samples prior to assay via an IRMA may break existing disulfide bonds between aggregated GH molecules, thus altering the apparent assay signal to reveal greater total GH in the sample.

  15. Gender Bias in U.S. Pediatric Growth Hormone Treatment

    PubMed Central

    Grimberg, Adda; Huerta-Saenz, Lina; Grundmeier, Robert; Ramos, Mark Jason; Pati, Susmita; Cucchiara, Andrew J.; Stallings, Virginia A.

    2015-01-01

    Growth hormone (GH) treatment of idiopathic short stature (ISS), defined as height <−2.25 standard deviations (SD), is approved by U.S. FDA. This study determined the gender-specific prevalence of height <−2.25 SD in a pediatric primary care population, and compared it to demographics of U.S. pediatric GH recipients. Data were extracted from health records of all patients age 0.5–20 years with ≥ 1 recorded height measurement in 28 regional primary care practices and from the four U.S. GH registries. Height <−2.25 SD was modeled by multivariable logistic regression against gender and other characteristics. Of the 189,280 subjects, 2073 (1.1%) had height <−2.25 SD. No gender differences in prevalence of height <−2.25 SD or distribution of height Z-scores were found. In contrast, males comprised 74% of GH recipients for ISS and 66% for all indications. Short stature was associated (P < 0.0001) with history of prematurity, race/ethnicity, age and Medicaid insurance, and inversely related (P < 0.0001) with BMI Z-score. In conclusion, males outnumbered females almost 3:1 for ISS and 2:1 for all indications in U.S. pediatric GH registries despite no gender difference in height <−2.25 SD in a large primary care population. Treatment and/or referral bias was the likely cause of male predominance among GH recipients. PMID:26057697

  16. Growth hormone STAT5-mediated signaling and its modulation in mice liver during the growth period.

    PubMed

    Martinez, Carolina S; Piazza, Verónica G; Ratner, Laura D; Matos, Marina N; González, Lorena; Rulli, Susana B; Miquet, Johanna G; Sotelo, Ana I

    2013-01-01

    Postnatal growth exhibits two instances of rapid growth in mice: the first is perinatal and independent of growth hormone (GH), the second is peripuberal and GH-dependent. Signal transducer and activator of transcription 5b (STAT5b) is the main GH-signaling mediator and it is related to IGF1 synthesis and somatic growth. The aim of this work was to assess differential STAT5 sensitivity to GH during the growth period in mouse liver of both sexes. Three representative ages were selected: 1-week-old animals, in the GH-independent phase of growth; 2.5-week-old mice, at the onset of the GH-dependent phase of growth; and 9-week-old young adults. GH-signaling mediators were assessed by immunoblotting, quantitative RT-PCR and immunohistochemistry. GH-induced STAT5 phosphorylation is low at one-week and maximal at 2.5-weeks of age when compared to young adults, accompanied by higher protein content at the onset of growth. Suppressor CIS and phosphatase PTP1B exhibit high levels in one-week animals, which gradually decline, while SOCS2 and SOCS3 display higher levels at adulthood. Nuclear phosphorylated STAT5 is low in one-week animals while in 2.5-week animals it is similar to 9-week control; expression of SOCS3, an early response GH-target gene, mimics this pattern. STAT5 coactivators glucocorticoid receptor (GR) and hepatic nuclear factor 1 (HNF1) abundance is higher in adulthood. Therefore, GH-induced STAT5 signaling presents age-dependent activity in liver, with its maximum coinciding with the onset of GH-dependent phase of growth, accompanied by an age-dependent variation of modulating factors. This work contributes to elucidate the molecular mechanisms implicated in GH responsiveness during growth.

  17. Growth hormone in the brain: characteristics of specific brain targets for the hormone and their functional significance.

    PubMed

    Nyberg, F

    2000-10-01

    During the past decade studies have shown that growth hormone (GH) may exert profound effects on the central nervous system (CNS). For instance, GH replacement therapy was found to improve the psychological capabilities in adult GH deficient (GHD) patients. Furthermore, beneficial effects of the hormone on certain functions, including memory, mental alertness, motivation, and working capacity, have been reported. Likewise, GH treatment of GHD children has been observed to produce significant improvement in many behavioral problems seen in these individuals. Studies also indicated that GH therapy affects the cerebrospinal fluid levels of various hormones and neurotransmitters. Further support that the CNS is a target for GH emerges from observations indicating that the hormone may cross the blood-brain barrier (BBB) and from studies confirming the presence of GH receptors in the brain. It was previously shown that specific binding sites for GH are present in discrete areas in the CNS of both humans and rats. Among these regions are the choroid plexus, hippocampus, hypothalamus, and spinal cord. The density of GH binding in the various brain regions was found to decline with increasing age. More recently, we were able to clone and determine the structure of several GH receptors in the rat and human brain. Although the brain receptor proteins for the hormone were shown to differ in molecular size compared to those present in peripheral tissues the corresponding transcripts did not seem to differ from their peripheral congeners. GH receptors in the hypothalamus are likely to be involved in the regulatory mechanism for hormone secretion and those located in the choroid plexus have been suggested to have a role in the receptor-mediated transport of GH across the BBB. The functions mediated by the GH receptors identified in the hippocampus are not yet known but recently it was speculated that they may be involved in the hormone's action on memory and cognitive functions.

  18. Growth in Boys with 45,X/46,XY Mosaicism: Effect of Growth Hormone Treatment on Statural Growth.

    PubMed

    Bertelloni, Silvano; Baroncelli, Giampiero I; Massart, Francesco; Toschi, Benedetta

    2015-01-01

    45,X/46,XY mosaicism is a rare sex chromosome disorder of sex development. Short stature is a main feature of boys with this condition. Different causes likely contribute to growth impairment. Growth hormone (GH) has been administered to treat short stature in boys with 45,X/46,XY mosaicism, but conflicting data are available. Here, spontaneous growth patterns as well as short- and long-term follow-up studies during GH therapy in these patients are reviewed. Short- and mid-term data showed an improvement of the growth pattern in GH-treated boys, mainly when hormonal therapy was started early, while long-term follow-up demonstrated similar adult heights in GH-treated and untreated patients. Individual biological factors (e.g. different chromosome constitution, different mosaicism among various tissues, impaired pubertal growth spurt), non-homogeneous GH doses and different ages at start of therapy may contribute to the variable results. Thus, early GH therapy at pharmacological doses may improve the growth pattern of short boys with 45,X/46,XY mosaicism, but data on adult height are disappointing. Evaluation of larger patient samples treated by homogeneous doses and long-term follow-up studies assessing adult height and safety are needed to reach definitive conclusions on GH therapy in boys with 45,X/46,XY mosaicism.

  19. Growth in Boys with 45,X/46,XY Mosaicism: Effect of Growth Hormone Treatment on Statural Growth.

    PubMed

    Bertelloni, Silvano; Baroncelli, Giampiero I; Massart, Francesco; Toschi, Benedetta

    2015-01-01

    45,X/46,XY mosaicism is a rare sex chromosome disorder of sex development. Short stature is a main feature of boys with this condition. Different causes likely contribute to growth impairment. Growth hormone (GH) has been administered to treat short stature in boys with 45,X/46,XY mosaicism, but conflicting data are available. Here, spontaneous growth patterns as well as short- and long-term follow-up studies during GH therapy in these patients are reviewed. Short- and mid-term data showed an improvement of the growth pattern in GH-treated boys, mainly when hormonal therapy was started early, while long-term follow-up demonstrated similar adult heights in GH-treated and untreated patients. Individual biological factors (e.g. different chromosome constitution, different mosaicism among various tissues, impaired pubertal growth spurt), non-homogeneous GH doses and different ages at start of therapy may contribute to the variable results. Thus, early GH therapy at pharmacological doses may improve the growth pattern of short boys with 45,X/46,XY mosaicism, but data on adult height are disappointing. Evaluation of larger patient samples treated by homogeneous doses and long-term follow-up studies assessing adult height and safety are needed to reach definitive conclusions on GH therapy in boys with 45,X/46,XY mosaicism. PMID:26529521

  20. Parathyroid hormone secretory pattern, circulating activity, and effect on bone turnover in adult growth hormone deficiency.

    PubMed

    Ahmad, A M; Hopkins, M T; Fraser, W D; Ooi, C G; Durham, B H; Vora, J P

    2003-02-01

    Adult growth hormone deficiency (AGHD) is associated with osteoporosis. Reports have associated parathyroid hormone (PTH) circadian rhythm abnormalities with osteoporosis. Furthermore, there is evidence of relative PTH insensitivity in AGHD patients. Factors regulating PTH circadian rhythm are not fully understood. There is evidence that serum phosphate is a likely determinant of PTH rhythm. The aim of this study was to investigate PTH circadian rhythm and its circulating activity and association with bone turnover in untreated AGHD patients compared to healthy individuals. We sampled peripheral venous blood at 30-min and urine at 3-h intervals during the day over a 24-h period from 1400 h in 14 untreated AGHD patients (7 M, 7 W; mean age, 49.5 +/- 10.7 years) and 14 age (48.6 +/- 11.4 years; P = NS) and gender-matched controls. Cosinor analysis was performed to analyze rhythm parameters. Cross-correlational analysis was used to determine the relationship between variables. Serum PTH (1-84), phosphate, total calcium, urea, creatinine, albumin, type I collagen C-telopeptides (CT(x)), a bone resorption marker, and procollagen type I amino-terminal propeptide (PINP), a bone formation marker, were measured on all samples. Nephrogenous cyclic adenosine monophosphate (NcAMP), which reflects the renal activity of PTH, was calculated from plasma and urinary cAMP. Urinary calcium and phosphate were measured on all urine samples. Significant circadian rhythms were observed for serum PTH, phosphate, CT(x), and PINP in AGHD and healthy subjects (P < 0.001). No significant rhythm was observed for serum-adjusted calcium. PTH MESOR (rhythm-adjusted mean) was significantly higher (P < 0.05), whereas the MESOR values for phosphate, CT(x) (P < 0.05), and PINP (P < 0.001) were lower in AGHD patients than in controls. AGHD patients had significantly lower 24-h NcAMP (P < 0.001) and higher urinary calcium excretion (P < 0.05). Maximum cross-correlation between PTH and phosphate (r = 0

  1. A Rare Corticotroph-Secreting Tumor with Coexisting Prolactin and Growth Hormone Staining Cells

    PubMed Central

    Kannan, Subramanian; Staugaitis, Susan M.; Weil, Robert J.; Hatipoglu, Betul

    2012-01-01

    Pituitary adenomas can express and secrete different hormones. Expression of pituitary hormones in nonneoplastic pituitary cells is regulated by different transcription factors. Some pituitary adenomas show plurihormonal expression. The most commonly reported plurihormonal adenomas are composed of somatotrophs, lactotrophs, thyrotrophs and gonadotrophs. Pituitary adenomas composed of both corticotroph and somatolactotroph secreting cells are not common because transcription factors regulating the expression of these hormones are different. We report a rare case of pituitary adenoma with concomitant corticotroph, prolactin, and growth hormone staining cells, review literature on similar cases, and discuss possible biological mechanisms underlying these plurihormonal tumors. PMID:23320206

  2. Exercise‐Induced growth hormone during acute sleep deprivation

    PubMed Central

    Ritsche, Kevin; Nindl, Bradly C.; Wideman, Laurie

    2014-01-01

    Abstract The effect of acute (24‐h) sleep deprivation on exercise‐induced growth hormone (GH) and insulin‐like growth factor‐1 (IGF‐1) was examined. Ten men (20.6 ± 1.4 years) completed two randomized 24‐h sessions including a brief, high‐intensity exercise bout following either a night of sleep (SLEEP) or (24‐h) sleep deprivation (SLD). Anaerobic performance (mean power [MP], peak power [PP], minimum power [MinP], time to peak power [TTPP], fatigue index, [FI]) and total work per sprint [TWPS]) was determined from four maximal 30‐sec Wingate sprints on a cycle ergometer. Self‐reported sleep 7 days prior to each session was similar between SLEEP and SLD sessions (7.92 ± 0.33 vs. 7.98 ± 0.39 h, P =0.656, respectively) and during the actual SLEEP session in the lab, the total amount of sleep was similar to the 7 days leading up to the lab session (7.72 ± 0.14 h vs. 7.92 ± 0.33 h, respectively) (P =0.166). No differences existed in MP, PP, MinP, TTPP, FI, TWPS, resting GH concentrations, time to reach exercise‐induced peak GH concentration (TTP), or free IGF‐1 between sessions. GH area under the curve (AUC) (825.0 ± 199.8 vs. 2212.9 ± 441.9 μg/L*min, P <0.01), exercise‐induced peak GH concentration (17.8 ± 3.7 vs. 39.6 ± 7.1 μg/L, P <0.01) and ΔGH (peak GH – resting GH) (17.2 ± 3.7 vs. 38.2 ± 7.3 μg/L, P <0.01) were significantly lower during the SLEEP versus SLD session. Our results indicate that the exercise‐induced GH response was significantly augmented in sleep‐deprived individuals. PMID:25281616

  3. Protective actions of melatonin and growth hormone on the aged cardiovascular system.

    PubMed

    Paredes, Sergio D; Forman, Katherine A; García, Cruz; Vara, Elena; Escames, Germaine; Tresguerres, Jesús A F

    2014-05-01

    Epidemiological studies indicate that certain aspects of lifestyle and genetics act as risk factors for a variety of cardiovascular disorders, including coronary disease, hypertension, heart failure and stroke. Aging, however, appears to be the major contributor for morbidity and mortality of the impaired cardiovascular system. Growth hormone (GH) and melatonin seem to prevent cardiac aging, as they contribute to the recovery of several physiological parameters affected by age. These hormones exhibit antioxidant properties and decrease oxidative stress and apoptosis. This paper summarizes a set of studies related to the potential role that therapy with GH and melatonin may play in the protection of the altered cardiac function due to aging, with a focus on experiments performed in our laboratory using the senescence-accelerated mouse as an aging model. In general, we observed significantly increased inflammation, oxidative stress and apoptosis markers in hearts from senescence-accelerated prone 10-month-old animals compared to 2-month-old controls, while anti-inflammatory and antiapoptotic markers as well as endothelial nitric oxide synthase were decreased. Senescence-accelerated resistant animals showed no significant changes with age. GH or melatonin treatment prevented the age-dependent cardiac alterations observed in the senescence-accelerated prone group. Combined administration of GH plus melatonin reduced the age-related changes in senescence-accelerated prone hearts in an additive fashion that was different to that displayed when administered alone. GH and melatonin may be potential agents for counteracting oxidative stress, apoptosis and inflammation in the aging heart.

  4. Effects of growth hormone (GH) transgene and nutrition on growth and bone development in common carp.

    PubMed

    Zhu, Tingbing; Zhang, Tanglin; Wang, Yaping; Chen, Yushun; Hu, Wei; Zhu, Zuoyan

    2013-10-01

    Limited information is available on effects of growth hormone transgene and nutrition on growth and development of aquatic animals. Here, we present a study to test these effects with growth-enhanced transgenic common carp under two nutritional conditions or feeding rations (i.e., 5% and 10% of fish body weight per day). Compared with the nontransgenic fish, the growth rates of the transgenic fish increased significantly in both feeding rations. The shape of the pharyngeal bone was similar among treatments, but the transgenic fish had relatively smaller and lighter pharyngeal bone compared with the nontransgenic fish. Calcium content of the pharyngeal bone of the transgenic fish was significantly lower than that of the nontransgenic fish. Feeding ration also affected growth rate but less of an effect on bone development. By manipulating intrinsic growth and controlling for both environment (e.g., feeding ration) and genetic background or genotype (e.g., transgenic or not), this study provides empirical evidence that the genotype has a stronger effect than the environment on pharyngeal bone development. The pharyngeal bone strength could be reduced by decreased calcium content and calcification in the transgenic carp.

  5. Effects of microgravity on growth hormone concentration and distribution in plants

    NASA Technical Reports Server (NTRS)

    Schulze, Aga; Jensen, Philip; Desrosiers, Mark; Bandurski, Robert S.

    1989-01-01

    On earth, gravity affects the distribution of the plant growth hormone, indole-3-acetic acid (IAA), in a manner such that the plant grows into a normal vertical orientation (shoots up, roots down). How the plant controls the amount and distribution of IAA is only partially understood and is currently under investigation in this laboratory. The question to be answered in the flight experiment concerns the effect of gravity on the concentration, turn over, and distribution of the growth hormone. The answer to this question will aid in understanding the mechanism by which plants control the amount and distribution of growth hormone. Such knowledge of a plant's hormonal metabolism may aid in the growth of plants in space and will lead to agronomic advances.

  6. Restriction fragment length polymorphisms in dairy and beef cattle at the growth hormone and prolactin loci.

    PubMed

    Hallerman, E M; Nave, A; Kashi, Y; Holzer, Z; Soller, M; Beckmann, J S

    1987-01-01

    Two bovine populations, a Holstein-Friesian dairy stock and a synthetic (Baladi X Hereford X Simmental X Charolais) beef stock, were screened for restriction fragment length polymorphisms (RFLPs) at the growth hormone and prolactin genes. Most RFLPs at the growth hormone gene are apparently the consequence of an insertion/deletion event which was localized to a region downstream of the structural gene. The restriction map for the genomic region including the growth hormone gene was extended. Two HindIII RFLPs at the growth hormone locus, as well as several RFLPs at the prolactin gene, seemed to be the consequence of a series of point mutations. The results are discussed in terms of the possibility that minor genomic variability underlies quantitative genetic variation.

  7. Hormone resistant prostatic adenocarcinoma. An evaluation of prognostic factors in pre- and post-treatment specimens.

    PubMed Central

    Berner, A.; Nesland, J. M.; Waehre, H.; Silde, J.; Fosså, S. D.

    1993-01-01

    Pre- and post-treatment specimens from 47 patients with hormone resistant prostatic carcinoma were compared with each other regarding histological grade and immunoreactivity for p53 protein, neuron specific enolase and c-erbB-2 protein. Significantly more specimens expressed a high malignancy grade when the tumour had become hormone resistant than at the time of initial diagnosis (Gleason P: < 0.0001, WHO P:0.0003). p53 protein immunoreactivity increased significantly with disease progression (P:0.006), while tissue PSA immunoreactivity was reduced in post-treatment specimens (P:0.011). p53 protein expression did not correlate with histological grade or PSA expression and seems to be an independent parameter which participates late in the neoplastic transformation. Thirty-two percent of the tumours were neuron specific enolase positive, but this parameter did not correlate with development of hormone resistance. c-erbB-2 protein reactivity was not recognised. Images Figure 1 PMID:7688548

  8. A 66-bp deletion in growth hormone releasing hormone gene 5'-flanking region with largemouth bass recessive embryonic lethal.

    PubMed

    Ma, D M; Han, L Q; Bai, J J; Li, S J; Fan, J J; Yu, L Y; Quan, Y C

    2014-06-01

    Growth hormone releasing hormone (GHRH) regulates the secretion of growth hormone (GH) in the pituitary gland. A 66-bp deletion (c.-923_-858del) was detected in the 5'-flanking sequence of the largemouth bass (Micropterus salmoides) GHRH gene. In two cultured random populations of adult individuals (A: n = 170 and B: n = 150), the genotype ratios of +/+:+/- were 2.5:1 and 2.8:1 respectively. Only one -/- fish was detected. A Largemouth bass family was constructed with two heterozygous individuals (+/-) as parents. The genotype ratio of +/+:+/-:-/- in the filial generation embryos was 1:1.6:0.1 at the neurula and 1:2:0 at hatched larvae stages. This indicated that the 66-bp deletion was a recessive lethal site and that homozygous individuals (-/-) died off in embryonic development. The growth traits (body weight, body length and body depth) were measured, and the GHRH mRNA expression levels in brain tissue were detected using real-time PCR. The effects of genotype (+/-) on growth traits and GHRH mRNA expression were not significant. Although the cause of death was not clear, the results hint that the 66-bp deletion site in GHRH 5'-flanking sequence significantly affects the livability in largemouth bass embryonic development. PMID:24697798

  9. A 66-bp deletion in growth hormone releasing hormone gene 5'-flanking region with largemouth bass recessive embryonic lethal.

    PubMed

    Ma, D M; Han, L Q; Bai, J J; Li, S J; Fan, J J; Yu, L Y; Quan, Y C

    2014-06-01

    Growth hormone releasing hormone (GHRH) regulates the secretion of growth hormone (GH) in the pituitary gland. A 66-bp deletion (c.-923_-858del) was detected in the 5'-flanking sequence of the largemouth bass (Micropterus salmoides) GHRH gene. In two cultured random populations of adult individuals (A: n = 170 and B: n = 150), the genotype ratios of +/+:+/- were 2.5:1 and 2.8:1 respectively. Only one -/- fish was detected. A Largemouth bass family was constructed with two heterozygous individuals (+/-) as parents. The genotype ratio of +/+:+/-:-/- in the filial generation embryos was 1:1.6:0.1 at the neurula and 1:2:0 at hatched larvae stages. This indicated that the 66-bp deletion was a recessive lethal site and that homozygous individuals (-/-) died off in embryonic development. The growth traits (body weight, body length and body depth) were measured, and the GHRH mRNA expression levels in brain tissue were detected using real-time PCR. The effects of genotype (+/-) on growth traits and GHRH mRNA expression were not significant. Although the cause of death was not clear, the results hint that the 66-bp deletion site in GHRH 5'-flanking sequence significantly affects the livability in largemouth bass embryonic development.

  10. Growth hormone and anabolic steroids: athletes are the tip of the iceberg.

    PubMed

    Perls, Thomas T

    2009-09-01

    Professional Athletes' misuse of anabolic steroids, growth hormone and other drugs are the tip of a very large, mostly ignored iceberg, made up of people who receive these drugs for such non-medical uses as body-building, school sports and "anti-aging". Although these drugs are often used in combination, this article focuses on growth hormone. Fuelling the demand for these drugs are drug manufacturers, pharmacies, websites, clinics and their doctors. PMID:20355224

  11. Growth hormone and anabolic steroids: athletes are the tip of the iceberg.

    PubMed

    Perls, Thomas T

    2009-09-01

    Professional Athletes' misuse of anabolic steroids, growth hormone and other drugs are the tip of a very large, mostly ignored iceberg, made up of people who receive these drugs for such non-medical uses as body-building, school sports and "anti-aging". Although these drugs are often used in combination, this article focuses on growth hormone. Fuelling the demand for these drugs are drug manufacturers, pharmacies, websites, clinics and their doctors.

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

    NASA Technical Reports Server (NTRS)

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

    1974-01-01

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

  13. Why Treat girls with Turner Syndrome with Growth Hormone? Growth and Beyond.

    PubMed

    Ranke, Michael B

    2015-06-01

    Turner Syndrome (TS) is a rare disorder, characterized by numerous signs and symptoms, which are also highly variable in their expression in individuals. The understanding of the genetic basis of the phenotype has advanced greatly during the past decades. The most consistent features, which negatively affect the quality of life in these individuals, are short stature and impaired gonadal function. After recombinant human growth hormone (rhGH) became available and was shown to improve height, it was then approved and has been used widely. Yet it remains a challenge to decide on the optimal treatment modality for individuals with TS and to evaluate the benefits and risks also in terms of karyotype of GH on growth and on other organ systems. This article reviews some of the major aspects related to these issues.

  14. Growth hormone, insulin-like growth factor-1 and the aging brain.

    PubMed

    Ashpole, Nicole M; Sanders, Jessica E; Hodges, Erik L; Yan, Han; Sonntag, William E

    2015-08-01

    Growth hormone (GH) and insulin-like growth factor (IGF)-1 regulate the development and function of cells throughout the body. Several clinical diseases that result in a decline in physical and mental functions are marked by mutations that disrupt GH or IGF-1 signaling. During the lifespan there is a robust decrease in both GH and IGF-1. Because GH and IGF-1 are master regulators of cellular function, impaired GH and IGF-1 signaling in aging/disease states leads to significant alterations in tissue structure and function, especially within the brain. This review is intended to highlight the effects of the GH and IGF-1 on neuronal structure, function, and plasticity. Furthermore, we address several potential mechanisms through which the age-related reductions in GH and IGF-1 affect cognition. Together, the studies reviewed here highlight the importance of maintaining GH and IGF-1 signaling in order to sustain proper brain function throughout the lifespan. PMID:25300732

  15. Growth hormone and insulin-like growth factor I in a Sydney Olympic gold medallist.

    PubMed

    Armanini, D; Faggian, D; Scaroni, C; Plebani, M

    2002-04-01

    An Italian athlete who won a gold medal at the Sydney Olympic Games was studied. She was accused of doping after the finding of high levels of plasma growth hormone (GH) before the Games. She was studied firstly under stressed and then under unstressed conditions. In the first study, GH was measured every 20 minutes for one hour; it was above the normal range in all blood samples, whereas insulin-like growth factor I (IGF-I) was normal. In the second study, GH progressively returned to accepted normal levels; IGF-I was again normal. It was concluded that the normal range for GH in athletes must be reconsidered for doping purposes, because athletes are subject to stress and thus to wide variations in GH levels. PMID:11916901

  16. Growth hormone, insulin-like growth factor-1 and the aging brain.

    PubMed

    Ashpole, Nicole M; Sanders, Jessica E; Hodges, Erik L; Yan, Han; Sonntag, William E

    2015-08-01

    Growth hormone (GH) and insulin-like growth factor (IGF)-1 regulate the development and function of cells throughout the body. Several clinical diseases that result in a decline in physical and mental functions are marked by mutations that disrupt GH or IGF-1 signaling. During the lifespan there is a robust decrease in both GH and IGF-1. Because GH and IGF-1 are master regulators of cellular function, impaired GH and IGF-1 signaling in aging/disease states leads to significant alterations in tissue structure and function, especially within the brain. This review is intended to highlight the effects of the GH and IGF-1 on neuronal structure, function, and plasticity. Furthermore, we address several potential mechanisms through which the age-related reductions in GH and IGF-1 affect cognition. Together, the studies reviewed here highlight the importance of maintaining GH and IGF-1 signaling in order to sustain proper brain function throughout the lifespan.

  17. Why Treat girls with Turner Syndrome with Growth Hormone? Growth and Beyond.

    PubMed

    Ranke, Michael B

    2015-06-01

    Turner Syndrome (TS) is a rare disorder, characterized by numerous signs and symptoms, which are also highly variable in their expression in individuals. The understanding of the genetic basis of the phenotype has advanced greatly during the past decades. The most consistent features, which negatively affect the quality of life in these individuals, are short stature and impaired gonadal function. After recombinant human growth hormone (rhGH) became available and was shown to improve height, it was then approved and has been used widely. Yet it remains a challenge to decide on the optimal treatment modality for individuals with TS and to evaluate the benefits and risks also in terms of karyotype of GH on growth and on other organ systems. This article reviews some of the major aspects related to these issues. PMID:26182480

  18. Microarchitecture, but not bone mechanical properties, is rescued with growth hormone treatment in a mouse model of growth hormone deficiency.

    PubMed

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

    2012-01-01

    Growth hormone (GH) deficiency is related to an increased fracture risk although it is not clear if this is due to compromised bone quality or a small bone size. We investigated the relationship between bone macrostructure, microarchitecture and mechanical properties in a GH-deficient (GHD) mouse model undergoing GH treatment commencing at an early (prepubertal) or late (postpubertal) time point. Microcomputed tomography images of the femur and L4 vertebra were obtained to quantify macrostructure and vertebral trabecular microarchitecture, and mechanical properties were determined using finite element analyses. In the GHD animals, bone macrostructure was 25 to 43% smaller as compared to the GH-sufficient (GHS) controls (P < 0.001). GHD animals had 20% and 19% reductions in bone volume ratio (BV/TV) and trabecular thickness (Tb.Th), respectively. Whole bone mechanical properties of the GHD mice were lower at the femur and vertebra (67% and 45% resp.) than the GHS controls (P < 0.001). Both early and late GH treatment partially recovered the bone macrostructure (15 to 32 % smaller than GHS controls) and the whole bone mechanical properties (24 to 43% larger than GHD animals) although there remained a sustained 27-52% net deficit compared to normal mice (P < 0.05). Importantly, early treatment with GH led to a recovery of BV/TV and Tb.Th with a concomitant improvement of trabecular mechanical properties. Therefore, the results suggest that GH treatment should start early, and that measurements of microarchitecture should be considered in the management of GHD. PMID:22505889

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

    SciTech Connect

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

    1990-09-01

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

  20. Characterization of growth hormone and prolactin produced by human pituitary in culture.

    PubMed

    Skyler, J S; Rogol, A D; Lovenberg, W; Knazek, R A

    1977-02-01

    Fragments of a pituitary tumor from a patient with acromegaly were grown in tissue culture. The tumor secreted both growth hormone and prolactin,which were recovered in high concentrations. The nonpurified hormones were characterized and compared to their respective counterparts obtained by extraction from normal pituitaries obtained at autopsy. The tissue culture and pituitary extracted hormones were eluted from Sephadex G-100 with the same partition coefficients. Growth hormone from both sources showed parallel dose-response displacement curves, by logit-log transformation, in both specific immunoassay and in a specific lymphocyte binding assay. Prolactin from both sources was compared in specific immunoassay using three different antisera. Parallel logit-log displacement curves were seen with one antiserum, while the other two antisera yielded non-parallel curves, indicating structural differences between prolactin from the two sources. Quantitative polyacrylamide gel electrophoresis was performed using multiphasic buffer systems previously developed for characterization of each hormone. By the criteria of joint 95% confidence envelopes of retardation co-efficient and relative free mobility, tissue culture growth hormone and prolactin were indistinguishable from their pituitary-extracted counterparts. This study demonstrates that, prior to purification, tissue culture derived hormone can be characterized by multiple criteria and compared to a standard preparation. Structural differences can be detected, as in the case of prolactin. When the hormones are indistinguishable, as in the case of growth hormone, it becomes worthwhile to increase the scale of tissue cultured production, with the prospect that tissue culture may serve as a source of hormone for both experimental and therapeutic use.

  1. Markers of Bone Metabolism Are Affected by Renal Function and Growth Hormone Therapy in Children with Chronic Kidney Disease

    PubMed Central

    Doyon, Anke; Fischer, Dagmar-Christiane; Bayazit, Aysun Karabay; Canpolat, Nur; Duzova, Ali; Sözeri, Betül; Bacchetta, Justine; Balat, Ayse; Büscher, Anja; Candan, Cengiz; Cakar, Nilgun; Donmez, Osman; Dusek, Jiri; Heckel, Martina; Klaus, Günter; Mir, Sevgi; Özcelik, Gül; Sever, Lale; Shroff, Rukshana; Vidal, Enrico; Wühl, Elke; Gondan, Matthias; Melk, Anette; Querfeld, Uwe; Haffner, Dieter; Schaefer, Franz

    2015-01-01

    Objectives The extent and relevance of altered bone metabolism for statural growth in children with chronic kidney disease is controversial. We analyzed the impact of renal dysfunction and recombinant growth hormone therapy on a panel of serum markers of bone metabolism in a large pediatric chronic kidney disease cohort. Methods Bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase 5b (TRAP5b), sclerostin and C-terminal FGF-23 (cFGF23) normalized for age and sex were analyzed in 556 children aged 6–18 years with an estimated glomerular filtration rate (eGFR) of 10–60 ml/min/1.73m2. 41 children receiving recombinant growth hormone therapy were compared to an untreated matched control group. Results Standardized levels of BAP, TRAP5b and cFGF-23 were increased whereas sclerostin was reduced. BAP was correlated positively and cFGF-23 inversely with eGFR. Intact serum parathormone was an independent positive predictor of BAP and TRAP5b and negatively associated with sclerostin. BAP and TRAP5B were negatively affected by increased C-reactive protein levels. In children receiving recombinant growth hormone, BAP was higher and TRAP5b lower than in untreated controls. Sclerostin levels were in the normal range and higher than in untreated controls. Serum sclerostin and cFGF-23 independently predicted height standard deviation score, and BAP and TRAP5b the prospective change in height standard deviation score. Conclusion Markers of bone metabolism indicate a high-bone turnover state in children with chronic kidney disease. Growth hormone induces an osteoanabolic pattern and normalizes osteocyte activity. The osteocyte markers cFGF23 and sclerostin are associated with standardized height, and the markers of bone turnover predict height velocity. PMID:25659076

  2. Modulation of Mammary Gland Development and Milk Production by Growth Hormone Expression in GH Transgenic Goats.

    PubMed

    Bao, Zekun; Lin, Jian; Ye, Lulu; Zhang, Qiang; Chen, Jianquan; Yang, Qian; Yu, Qinghua

    2016-01-01

    Mammary gland development during puberty and reconstruction during pregnancy and lactation is under the control of circulating endocrine hormones, such as growth hormone, which are released from the pituitary. In this study, we explored the influence of overexpression of growth hormone in the mammary gland on breast development and milk production in goats. Using transcriptome sequencing, we found that the number of highly expressed genes was greater in GH transgenic goats than non-transgenic goats. Furthermore, KEGG pathway analysis showed that the majority of the genes belonged to the MAPK signaling pathway and the ECM-receptor interaction pathway. The expression of genes related to breast development was further confirmed using qRT-PCR. Interestingly, both milk production and milk quality were increased. The results of these experiments imply that overexpression of growth hormone in the breast may stimulate breast development and enhances milk production by modulating alveolar cell proliferation or branching through the MAPK signaling pathway. PMID:27445863

  3. Modulation of Mammary Gland Development and Milk Production by Growth Hormone Expression in GH Transgenic Goats

    PubMed Central

    Bao, Zekun; Lin, Jian; Ye, Lulu; Zhang, Qiang; Chen, Jianquan; Yang, Qian; Yu, Qinghua

    2016-01-01

    Mammary gland development during puberty and reconstruction during pregnancy and lactation is under the control of circulating endocrine hormones, such as growth hormone, which are released from the pituitary. In this study, we explored the influence of overexpression of growth hormone in the mammary gland on breast development and milk production in goats. Using transcriptome sequencing, we found that the number of highly expressed genes was greater in GH transgenic goats than non-transgenic goats. Furthermore, KEGG pathway analysis showed that the majority of the genes belonged to the MAPK signaling pathway and the ECM-receptor interaction pathway. The expression of genes related to breast development was further confirmed using qRT-PCR. Interestingly, both milk production and milk quality were increased. The results of these experiments imply that overexpression of growth hormone in the breast may stimulate breast development and enhances milk production by modulating alveolar cell proliferation or branching through the MAPK signaling pathway. PMID:27445863

  4. Modulation of Mammary Gland Development and Milk Production by Growth Hormone Expression in GH Transgenic Goats.

    PubMed

    Bao, Zekun; Lin, Jian; Ye, Lulu; Zhang, Qiang; Chen, Jianquan; Yang, Qian; Yu, Qinghua

    2016-01-01

    Mammary gland development during puberty and reconstruction during pregnancy and lactation is under the control of circulating endocrine hormones, such as growth hormone, which are released from the pituitary. In this study, we explored the influence of overexpression of growth hormone in the mammary gland on breast development and milk production in goats. Using transcriptome sequencing, we found that the number of highly expressed genes was greater in GH transgenic goats than non-transgenic goats. Furthermore, KEGG pathway analysis showed that the majority of the genes belonged to the MAPK signaling pathway and the ECM-receptor interaction pathway. The expression of genes related to breast development was further confirmed using qRT-PCR. Interestingly, both milk production and milk quality were increased. The results of these experiments imply that overexpression of growth hormone in the breast may stimulate breast development and enhances milk production by modulating alveolar cell proliferation or branching through the MAPK signaling pathway.

  5. Growth and endocrine effect of growth hormone transgene dosage in diploid and triploid coho salmon.

    PubMed

    Devlin, Robert H; Sakhrani, Dionne; Biagi, Carlo A; Smith, Jack L; Fujimoto, Takafumi; Beckman, Brian

    2014-01-15

    Growth-hormone transgene dosage, polyploidy, and parental effects on growth and endocrine responses have been assessed in coho salmon. Diploid fry with one or two transgene doses grew equally, whereas later-stage juvenile homozygotes grew faster than hemizygotes. In contrast, homozygotes and hemizygotes grew equally after smoltification, both in sea water and fresh water. Triploid transgenic salmon showed impaired growth which could not be fully overcome with additional transgene copies. Levels of muscle GH mRNA were elevated in two vs. one transgene dose diploids, but in triploids, a dosage effect was observed in muscle but not for animals carrying three transgene doses. IGF-I mRNA levels were elevated in transgenic vs. non-transgenic animals, but a dosage effect was not observed. Diploids and triploids with two transgenes had higher plasma GH levels than one-dose animals, but three-dose triploids showed no further elevation. Circulating IGF-I levels also showed a dosage effect in diploids, but not among any transgene doses in triploids. The present study reveals complex interactions among transgene dosage, maternal effects, developmental stage, and ploidy on growth and endocrine parameters in GH transgenic coho salmon. Specifically, GH transgenes do not always express nor have effects on growth that are directly correlated with the number of transgenes. Further, the reduced growth rate seen in triploid transgenic animals could not be fully overcome by increasing transgene dosage. The findings have relevance for understanding growth physiology, transgene function, and for environmental risk assessments that require understanding phenotypes of hemizygous vs. homozygous transgenic animals in populations.

  6. Development of gonadotropes may involve cyclic transdifferentiation of growth hormone cells.

    PubMed

    Childs, G V

    2002-04-01

    The cyclic rise in expression of anterior pituitary gonadotropins coincides with the appearance of cells sharing gonadotropic and somatotropic phenotypes. To learn more about possible factors that regulate the origin of this cell type, we studied the time of appearance of cells that co-expressed growth hormone (GH) and gonadotropins and estrogen receptors during the estrous cycle and compared this timing with known changes in regulatory hormones or their receptors. The first event in this cell population is an increase in expression of estrogen receptor (ER)beta by GH cells from estrus to metestrus suggesting that estrogen may mediate this early change. Expression of GH mRNA rises rapidly from metestrus to mid-cycle. The rise is seen first in GH cells and then in cells with luteinizing hormone (LH) antigens. These data suggest that, early in the cycle, cells bearing GH and growth hormone releasing hormone (GHRH) receptors begin to produce LH and gonadotropin releasing hormone (GnRH) receptors. Early in proestrus, there is an increase in cells with GH and follicle-stimulating hormone (FSH) suggesting that this set of multipotential cells develops later than GH-LH cells. This fits with earlier studies showing the later rise in expression of FSH mRNA. Collectively these data suggest that the anterior pituitary contains a subset of GH cells that have the capacity to respond to multiple releasing hormones and support more than one system.

  7. Rooster feathering, androgenic alopecia, and hormone dependent tumor growth: What is in common?

    PubMed Central

    Mayer, Julie Ann; Chuong, Cheng-Ming; Widelitz, Randall

    2015-01-01

    Different epithelial organs form as a result of epithelial - mesenchymal interactions and share a common theme modulated by variations (Chuong edit. In Molecular Basis of Epithelial Appendage Morphogenesis, 1998). One of the major modulators is the sex hormone pathway that acts on the prototype signaling pathway to alter organ phenotypes. Here we focus on how the sex hormone pathway interfaces with epithelia morphogenesis related signaling pathways. We first survey these sex hormone regulated morphogenetic processes in various epithelial organs. Sexual dimorphism of hairs and feathers has implications in sexual selection. Diseases of these pathways result in androgenic alopecia, hirsutism, henny feathering, etc. The growth and development of mammary glands, prostate glands and external genitalia essential for reproductive function are also dependent on sex hormones. Diseases affecting these organs include congenital anomalies and hormone dependent type of breast and prostate cancers. To study the role of sex hormones in new growth in the context of system biology / pathology, an in vivo model in which organ formation starts from stem cells is essential. With recent developments (Yu et al., The morphogenesis of feathers. Nature 420:308–312, 2002), the growth of tail feathers in roosters and hens has become a testable model in which experimental manipulations are possible. We show exemplary data of differences in their growth rate, proliferative cell population and signaling molecule expression. Working hypotheses are proposed on how the sex hormone pathways may interact with growth pathways. It is now possible to test these hypotheses using the chicken model to learn fundamental mechanisms on how sex hormones affect organogenesis, epithelial organ cycling, and growth related tumorigenesis. PMID:15617560

  8. Effect of growth hormone on protein phosphorylation in isolated rat hepatocytes

    SciTech Connect

    Yamada, K.; Lipson, K.E.; Marino, M.W.; Donner, D.B.

    1987-02-10

    Hepatocytes from male rats were incubated with (/sup 32/P)P/sub i/ for 40 min at 37/sup 0/C, thereby equilibrating the cellular ATP pool with /sup 32/P. Subsequent exposure to bovine growth hormone for 10 additional min did not change the specific activity of cellular (..gamma..-/sup 32/P)ATP. Two-dimensional gel electrophoresis or chromatofocusing followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used to fractionate phosphoproteins solubilized from control or hormone-stimulated cells. Stimulation of hepatocytes with 5 nM growth hormone for 10 min at 37/sup 0/C affected the phosphorylation of a number of proteins including an M/sub r/ 46,000 species of pI 4.7 whose phosphorylation was augmented (2.65 +/- 0.50)-fold. A significant fraction of the maximal effect of growth hormone on phosphorylation of the M/sub r/ 46,000 species was elicited by 1-5% receptor occupancy. Bovine growth hormone, which binds to somatogenic receptors with great specificity, or recombinant human growth hormone, which is not contaminated with other hormones, affected phosphorylation of hepatic proteins similarly. The M/sub r/ 46,000 phosphoprotein was isolated in a fraction enriched in cytosol after centrifugation of cellular homogenates. Phosphorylation of the M/sub r/ 46,000 phosphoprotein was also increased (1.75 +/- 0.35)-fold and (2.15 +/- 0.50)-fold by insulin and glucagon, respectively. These observations are consistent with the possibility that selective changes in the phosphorylation state of cellular proteins may mediate growth hormone actions in cells.

  9. Levels of hormones and cytokines associated with growth in Honamlı and native hair goats.

    PubMed

    Devrim, A K; Elmaz, O; Mamak, N; Sudagidan, M

    2015-01-01

    This study was designed to assess alterations of hormone and cytokine levels associated with growth period during puberty in Honamlı goats which were identified as a new goat breed and had one of the highest meat production potential among the other goat breeds in Turkey. Honamlı goats are originated from native hair goats, so parallel studies of sampling and analyzing were conducted also in native hair goats which have moderate meat production. Blood serum samples of Honamlı (n=90) and native hair goats (n=90) were obtained from the pure herds in Korkuteli and Ka districts of Anatolia. Concentrations of growth hormone (GH), myostatin (MSTN), insulin-like growth factor (IGF), growth hormone releasing hormone (GHRH), growth hormone releasing peptide (GHRP), leptin, transforming growth factor-betal (TGF-β1) and vascular endothelial cell growth factor (VEGF) levels were measured by ELISA in each breed in the age groups of 4, 8 and 12 months. The present results indicate interesting correlations among the age groups and all the examined hormone and cytokine parameters exhibited significant (P<0.05 and P<0.001) differences. The parameters investigated were usually begun to increase after 4 months of age in the both breeds and sexes. Therefore, this paper supported the view that the beginning of hormonal alterations of goats could occur at 4th month of age. The results reported here emphasize the primary role played by GH, MSTN, IGF-1, leptin, GHRH, GHRP, TGF-βi and VEGF in the first year growth period of goats.

  10. Puberty, statural growth, and growth hormone release in children with cerebral palsy

    PubMed Central

    Kuperminc, Michelle N.; Gurka, Matthew J.; Houlihan, Christine M.; Henderson, Richard C.; Roemmich, James N.; Rogol, Alan D.

    2010-01-01

    Objective Children with cerebral palsy (CP) are smaller than normally growing children.. The association between the growth hormone (GH) axis and growth in children with CP during puberty is unknown. We compared growth and markers of the GH axis in pre-pubertal and pubertal children with moderate to severe CP and without CP over a three-year period. Study design Twenty children with CP, ages 6–18, Gross Motor Function Classification System levels III–V, were compared to a group of sixty-three normally growing children of similar age. Anthropometry, Tanner stage, bone age, and laboratory analyses were performed every six months for three years. Laboratory values included spontaneous overnight GH release, fasting IGF-1 and IGFBP-3. Repeated measures models were used to evaluate interactions among Tanner stage and group (children with CP vs. reference children), taking into account gender, age, and nutritional status. Results Children with CP grew more slowly than those without CP at all Tanner stages (p<0.01). Patterns of IGF-1 and GH secretion in children with CP were similar to those of the reference group; however, the concentrations of IGF-1 (p<0.01) and GH (p<0.01) were lower in girls with CP, with a similar trend for boys (p=0.10 and 0.14, respectively). Conclusions Diminished circulating IGF-1 and GH concentrations may explain the differences in growth between the two groups. PMID:20216931

  11. Cortical bone growth and maturational changes in dwarf rats induced by recombinant human growth hormone

    NASA Technical Reports Server (NTRS)

    Martinez, D. A.; Orth, M. W.; Carr, K. E.; Vanderby, R. Jr; Vailas, A. C.

    1996-01-01

    The growth hormone (GH)-deficient dwarf rat was used to investigate recombinant human (rh) GH-induced bone formation and to determine whether rhGH facilitates simultaneous increases in bone formation and bone maturation during rapid growth. Twenty dwarf rats, 37 days of age, were randomly assigned to dwarf plus rhGH (GH; n = 10) and dwarf plus vehicle (n = 10) groups. The GH group received 1.25 mg rhGH/kg body wt two times daily for 14 days. Biochemical, morphological, and X-ray diffraction measurements were performed on the femur middiaphysis. rhGH stimulated new bone growth in the GH group, as demonstrated by significant increases (P < 0.05) in longitudinal bone length (6%), middiaphyseal cross-sectional area (20%), and the amount of newly accreted bone collagen (28%) in the total pool of middiaphyseal bone collagen. Cortical bone density, mean hydroxyapatite crystal size, and the calcium and collagen contents (microgram/mm3) were significantly smaller in the GH group (P < 0.05). Our findings suggest that the processes regulating new collagen accretion, bone collagen maturation, and mean hydroxyapatite crystal size may be independently regulated during rapid growth.

  12. Growth hormone and insulin-like growth factors in fish: Where we are and where to go

    USGS Publications Warehouse

    Reinecke, M.; Bjornsson, Bjorn Thrandur; Dickhoff, Walton W.; McCormick, S.D.; Navarro, I.; Power, D.M.; Gutierrez, J.

    2005-01-01

    This communication summarizes viewpoints, discussion, perspectives, and questions, put forward at a workshop on "Growth hormone and insulin-like growth factors in fish" held on September 7th, 2004, at the 5th International Symposium on Fish Endocrinology in Castello??n, Spain. ?? 2005 Elsevier Inc. All rights reserved.

  13. Ontogeny and pituitary regulation of testicular growth hormone-releasing hormone-like messenger ribonucleic acid.

    PubMed

    Berry, S A; Pescovitz, O H

    1990-09-01

    The testis is rich in central nervous system-type neuropeptides, including a GH-releasing hormone (GHRH)-like substance. We examined the ontogeny and pituitary regulation of testicular GHRH-like mRNA (t-GHRH mRNA) and compared this to expression of insulin-like growth factor-I (IGF-I) and IGF-II mRNA in developing testis. t-GHRH mRNA was measured by dot blot hybridization and quantitated using a hypothalamic GHRH cRNA standard. t-GHRH mRNA was not detectable in Northern blots in fetal testis on day 19 of gestation, but was present in low but detectable amounts in testicular dot blots on day 2 of life (0.44 pg/micrograms total RNA). Levels of the RNA increased beginning on day 21 (1.72 +/- 0.23 pg/micrograms total RNA) and reached adult levels by day 30 (4.96 +/- 0.84 pg/micrograms total RNA). The GHRH species on Northern analysis was about 1750 nucleotides at all ages examined; there was a larger species of about 3350 nucleotides seen on days 65 and 90. There was no correlation between the ontogeny of t-GHRH mRNA and either IGF-I or IGF-II mRNAs, which were maximally expressed in the testes of day 2 animals and decreased with age. To examine the influence of the pituitary gland on t-GHRH mRNA, levels of the mRNA were measured in the tests of hypophysectomized animals and age-matched controls. In animals hypophysectomized on day 21 and killed on day 42 and in animals hypophysectomized on day 42 and killed on day 63, there was marked diminution of t-GHRH mRNA (19 +/- 5% and 9 +/- 2% of age-matched controls, respectively). In contrast, in animals hypophysectomized on day 65 and killed on either day 80 or 90, there was a much smaller difference in levels of t-GHRH mRNA compared to values in control animals (73 +/- 20%). This was unlike the effect of hypophysectomy on testicular IGF-I mRNA, where uniform diminution was seen in all three groups. Because GH is important in the regulation of hypothalamic GHRH mRNA, we examined the effects of administration of recombinant

  14. [Therapeutic possibilities in patients with selective pituitary resistance to thyroid hormones].

    PubMed

    Iglesias, Pedro; Díez, Juan José

    2008-03-15

    Selective pituitary resistance to thyroid hormones (SPRTH) is a non-neoplastic form of inappropriate secretion of thyrotropin (TSH). The etiology of this hormonal resistance is linked to inactivating mutations in the thyroid hormone receptor beta (TR-beta) gene. These mutations affect critical portions of the receptor's triiodothyronine (T3)-binding domain. Clinically, SPRTH is characterized by hyperthyroidism with goiter and absence of pituitary mass in the morphologic study. Laboratory data show an elevation of free T3 and free thyroxine concentrations without suppression of TSH, with normal molar subunit alpha/TSH ratio. At this time, there is no specific therapy for SPRHT. Beta blockers, such as atenolol, and benzodiazepines have been used as a symptomatic therapy. Among the drugs with the capacity for reducing TSH secretion are TR agonists, such as triiodothyroacetic acid, D-thyroxine, triiodothyropropionic acid, and L-T3. PMID:18373914

  15. Galactopoiesis/Effects of hormones and growth factors

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The term galactopoiesis was originally coined to describe the enhancement of an established lactation. In this sense, only exogenous somatotropin and thyroid hormones are clearly demonstrated galactopoietic agents in dairy animals. However, in a more inclusive sense, galactopoiesis has been used t...

  16. Effects of growth hormone and feeding level on endocrine measurements, hormone receptors, muscle growth and performance of prepubertal heifers.

    PubMed

    Vestergaard, M; Purup, S; Frystyk, J; Løvendahl, P; Sørensen, M T; Riis, P M; Flint, D J; Sejrsen, K

    2003-09-01

    Prepubertal Friesian heifer calves (n = 24, initial BW = 195 +/- 5 kg) were assigned to a 2 x 2 factorial block design and used to evaluate the effects of daily GH treatment (0 or 15 mg/d) at either a low or a high feeding level in a 5-wk treatment period on endocrine measurements, hormone receptors, muscle growth, and overall performance. In the pretreatment period, a low feeding level was employed for all calves. During the treatment period, animals at the low feeding level had free access to a roughage-based mixture, whereas animals at the high feeding level had free access to a concentrate mixture and were offered 2 kg/d of the roughage-based mixture. Blood samples were collected weekly starting 3 wk before treatment. Longissimus (LM) and supraspinatus (SS) muscles were obtained at slaughter. Metabolizable energy intake was 81% higher, digestible CP intake was 140% higher, and ADG was 115% higher (all P < 0.001) at the high vs. low feeding level. Feed (DMI, ME, and protein) intake was not affected by GH treatment, but ADG was 18% higher (P < 0.13) in GH-treated than in control heifers at both feeding levels. Although of different magnitudes, the muscle anabolic effects of GH treatment and high vs. low feeding level were additive, and both treatments increased carcass weights (P < 0.02 and P < 0.001, respectively), LM (P < 0.05 and P < 0.001), and SS (P < 0.06 and P < 0.003). The anabolic effect of GH treatment was similar in both muscles, whereas the effect of feeding level was most pronounced in LM. Overall, GH treatment increased plasma GH, IGF-I (both P < 0.001), and IGFBP-3 (P < 0.02); however, GH treatment increased total IGF-I, free IGF-I, and IGFBP-3, and decreased IGFBP-2 mainly at the high feeding level (GH x feeding level interaction; P < 0.02, 0.01, 0.03, and 0.10, respectively). The high feeding level increased insulin, free and total IGF-I, and IGFBP-3 (all P < 0.001), but decreased GH and IGFBP-2 (both P < 0.001). High feeding increased type-1 IGF

  17. Growth Hormone plus Childhood Low-Dose Estrogen in Turner’s Syndrome

    PubMed Central

    Ross, Judith L.; Quigley, Charmian A.; Cao, Dachuang; Feuillan, Penelope; Kowal, Karen; Chipman, John J.; Cutler, Gordon B.

    2011-01-01

    BACKGROUND Short stature and ovarian failure are characteristic features of Turner’s syndrome. Although recombinant human growth hormone is commonly used to treat the short stature associated with this syndrome, a randomized, placebo-controlled trial is needed to document whether such treatment increases adult height. Furthermore, it is not known whether childhood estrogen replacement combined with growth hormone therapy provides additional benefit. We examined the independent and combined effects of growth hormone and early, ultra-low-dose estrogen on adult height in girls with Turner’s syndrome. METHODS In this double-blind, placebo-controlled trial, we randomly assigned 149 girls, 5.0 to 12.5 years of age, to four groups: double placebo (placebo injection plus childhood oral placebo, 39 patients), estrogen alone (placebo injection plus childhood oral low-dose estrogen, 40), growth hormone alone (growth hormone injection plus childhood oral placebo, 35), and growth hormone–estrogen (growth hormone injection plus childhood oral low-dose estrogen, 35). The dose of growth hormone was 0.1 mg per kilogram of body weight three times per week. The doses of ethinyl estradiol (or placebo) were adjusted for chronologic age and pubertal status. At the first visit after the age of 12.0 years, patients in all treatment groups received escalating doses of ethinyl estradiol. Growth hormone injections were terminated when adult height was reached. RESULTS The mean standard-deviation scores for adult height, attained at an average age of 17.0±1.0 years, after an average study period of 7.2±2.5 years were −2.81±0.85, −3.39±0.74, −2.29±1.10, and −2.10±1.02 for the double-placebo, estrogen-alone, growth hormone–alone, and growth hormone–estrogen groups, respectively (P<0.001). The overall effect of growth hormone treatment (vs. placebo) on adult height was a 0.78±0.13 increase in the height standard-deviation score (5.0 cm) (P<0.001); adult height was

  18. Sex steroid induced apoptosis as a rational strategy to treat anti-hormone resistant breast and prostate cancer.

    PubMed

    Jordan, V Craig; Fan, Ping; Abderrahman, Balkees; Maximov, Philipp Y; Hawsawi, Yousef M; Bhattacharya, Poulomi; Pokharel, Niranjana

    2016-05-01

    The combined incidence and the extended disease course of breast and prostate cancer is a major challenge for health care systems. The solution for society requires an economically viable treatment strategy to maintain individuals disease free and productive, so as to avoid the fracture of the family unit. Forty years ago, translational research using the antiestrogen tamoxifen was targeted to estrogen receptor (ER) positive micrometastatic tumor cells and established the long-term antihormone adjuvant treatment strategy used universally today. The antihormone strategy was the accepted structure of cancer biology. Sex steroid deprivation therapy remains the orthodox strategy for the treatment of both breast and prostate cancer. Despite major initial therapeutic success, the strategies of long term anti-hormone therapies with either tamoxifen or aromatase inhibitors (AI) or antiandrogens or abiraterone for breast and prostate cancer, respectively, eventually lead to a significant proportion of anti-hormone resistant or stimulated tumor growth. Remarkably, a general principle of anti-hormone resistance has emerged for both breast and prostate cancer based primarily on clinical and supportive laboratory data. Paradoxically, anti-hormone resistant cell populations emerge and grow but are vulnerable to the cytotoxicity of estrogen or androgen-induced apoptosis for both breast and prostate cancer, respectively. These consistent anticancer actions of sex steroids appear to recapitulate the more complex mechanism of bone remodeling in elderly men and women during sex steroid deprivation. Estrogen is the key hormone in both sexes because in men androgen is first converted to estrogen. Estrogen regulates and triggers apoptosis in osteoclasts that develop during estrogen deprivation and destroy bone to cause osteoporosis. Sex steroid deprived breast and prostate cancer has recruited a streamlined natural apoptotic program from the human genome, but this is suppressed in the

  19. Evaluation of DNA polymorphisms involving growth hormone relative to growth and carcass characteristics in Brahman steers.

    PubMed

    Beauchemin, V R; Thomas, M G; Franke, D E; Silver, G A

    2006-01-01

    Associations of DNA polymorphisms in growth hormone (GH) relative to growth and carcass characteristics in growing Brahman steers (N = 324 from 68 sires) were evaluated. Polymorphisms were an Msp-I RFLP and a leucine/valine SNP in the GH gene as well as a Hinf-I RFLP and a histidine/arginine SNP in transcriptional regulators of the GH gene, Pit-1 and Prop-1. Genotypic frequencies of the GH SNP, Pit-1 RFLP, and Prop-1 SNP were greater than 88% for one of the bi-allelic homozygous genotypes. Genotypic frequencies for the GH Msp-I RFLP genotypes were more evenly distributed with frequencies of 0.43, 0.42, and 0.15 for the genotypes of +/+, +/-, and -/-, respectively. Mixed model analyses of growth and carcass traits with genotype and contemporary group serving as fixed effects and sire fitted as a random effect suggested that sire was a significant source of variation (P < 0.05) in average daily gain, carcass yield, and marbling score. However, measures of growth and carcass traits were similar across GH Msp-I genotypes as steers were slaughtered when fat thickness was estimated to be approximately 1.0 cm. These polymorphisms within the GH gene and/or its transcriptional regulators do not appear to be informative predictors of growth and carcass characteristics in Brahman steers. This is partly due to the high level of homozygosity of genotypes. These findings do not eliminate the potential importance of these polymorphisms as predictors of growth and carcass traits in Bos taurus or Bos taurus x Bos indicus composite cattle. PMID:17117358

  20. Evaluation of DNA polymorphisms involving growth hormone relative to growth and carcass characteristics in Brahman steers.

    PubMed

    Beauchemin, V R; Thomas, M G; Franke, D E; Silver, G A

    2006-07-31

    Associations of DNA polymorphisms in growth hormone (GH) relative to growth and carcass characteristics in growing Brahman steers (N = 324 from 68 sires) were evaluated. Polymorphisms were an Msp-I RFLP and a leucine/valine SNP in the GH gene as well as a Hinf-I RFLP and a histidine/arginine SNP in transcriptional regulators of the GH gene, Pit-1 and Prop-1. Genotypic frequencies of the GH SNP, Pit-1 RFLP, and Prop-1 SNP were greater than 88% for one of the bi-allelic homozygous genotypes. Genotypic frequencies for the GH Msp-I RFLP genotypes were more evenly distributed with frequencies of 0.43, 0.42, and 0.15 for the genotypes of +/+, +/-, and -/-, respectively. Mixed model analyses of growth and carcass traits with genotype and contemporary group serving as fixed effects and sire fitted as a random effect suggested that sire was a significant source of variation (P < 0.05) in average daily gain, carcass yield, and marbling score. However, measures of growth and carcass traits were similar across GH Msp-I genotypes as steers were slaughtered when fat thickness was estimated to be approximately 1.0 cm. These polymorphisms within the GH gene and/or its transcriptional regulators do not appear to be informative predictors of growth and carcass characteristics in Brahman steers. This is partly due to the high level of homozygosity of genotypes. These findings do not eliminate the potential importance of these polymorphisms as predictors of growth and carcass traits in Bos taurus or Bos taurus x Bos indicus composite cattle.

  1. Hypergravity and estrogen effects on avian anterior pituitary growth hormone and prolactin levels

    NASA Technical Reports Server (NTRS)

    Fiorindo, R. P.; Negulesco, J. A.

    1980-01-01

    Developing female chicks with fractured right radii were maintained for 14 d at either earth gravity (1 g) or a hypergravity state (2 g). The birds at 1 g were divided into groups which received daily injections of (1) saline, (2) 200 micrograms estrone, and (3) 400 micrograms estrone for 14 d. The 2-g birds were divided into three similarly treated groups. All 2-g birds showed significantly lower body weights than did 1-g birds. Anterior pituitary (AP) glands were excised and analyzed for growth hormone and prolactin content by analytical electrophoresis. The 1-g chicks receiving either dose of daily estrogen showed increased AP growth hormone levels, whereas hypergravity alone did not affect growth hormone content. Chicks exposed to daily estrogen and hypergravity displayed reduced growth hormone levels. AP prolactin levels were slightly increased by the lower daily estrogen dose in 1-g birds, but markedly reduced in birds exposed only to hypergravity. Doubly-treated chicks displayed normal prolactin levels. Reduced growth in 2-g birds might be due, in part, to reduced AP levels of prolactin and/or growth hormone.

  2. Auxin, the organizer of the hormonal/environmental signals for root hair growth.

    PubMed

    Lee, Richard D-W; Cho, Hyung-Taeg

    2013-01-01

    The root hair development is controlled by diverse factors such as fate-determining developmental cues, auxin-related environmental factors, and hormones. In particular, the soil environmental factors are important as they maximize their absorption by modulating root hair development. These environmental factors affect the root hair developmental process by making use of diverse hormones. These hormonal factors interact with each other to modulate root hair development in which auxin appears to form the most intensive networks with the pathways from environmental factors and hormones. Moreover, auxin action for root hair development is genetically located immediately upstream of the root hair-morphogenetic genes. These observations suggest that auxin plays as an organizing node for environmental/hormonal pathways to modulate root hair growth. PMID:24273547

  3. Auxin, the organizer of the hormonal/environmental signals for root hair growth

    PubMed Central

    Lee, Richard D.-W.; Cho, Hyung-Taeg

    2013-01-01

    The root hair development is controlled by diverse factors such as fate-determining developmental cues, auxin-related environmental factors, and hormones. In particular, the soil environmental factors are important as they maximize their absorption by modulating root hair development. These environmental factors affect the root hair developmental process by making use of diverse hormones. These hormonal factors interact with each other to modulate root hair development in which auxin appears to form the most intensive networks with the pathways from environmental factors and hormones. Moreover, auxin action for root hair development is genetically located immediately upstream of the root hair-morphogenetic genes. These observations suggest that auxin plays as an organizing node for environmental/hormonal pathways to modulate root hair growth. PMID:24273547

  4. Hormonal therapy and chemotherapy in hormone-naive and castration resistant prostate cancer

    PubMed Central

    Sternberg, Cora N.

    2015-01-01

    The management of advanced castration resistant prostate cancer (CRPC) has been rapidly changing and is still evolving. In the last years, there has been an increasing knowledge of prostate cancer biology. New therapeutic agents and approaches have been evaluated demonstrating benefits in survival and quality of life in patients with metastatic prostate cancer. PMID:26816835

  5. Effects of spaceflight on hypothalamic peptide systems controlling pituitary growth hormone dynamics

    NASA Technical Reports Server (NTRS)

    Sawchenko, P. E.; Arias, C.; Krasnov, I.; Grindeland, R. E.; Vale, W.

    1992-01-01

    Possible effects of reduced gravity on central hypophysiotropic systems controlling growth hormone (GH) secretion were investigated in rats flown on Cosmos 1887 and 2044 biosatellites. Immunohistochemical (IHC)staining for the growth hormone-releasing factor (GRF), somatostatin (SS), and other hypothalamic hormones was performed on hypothalami obtained from rats. IHC analysis was complemented by quantitative in situ assessments of mRNAs encoding the precursors for these hormones. Data obtained suggest that exposure to microgravity causes a preferential reduction in GRF peptide and mRNA levels in hypophysiotropic neurons, which may contribute to impared GH secretion in animals subjected to spaceflight. Effects of weightlessness are not mimicked by hindlimb suspension in this system.

  6. Melanin concentrating hormone (MCH) is involved in the regulation of growth hormone in Cichlasoma dimerus (Cichlidae, Teleostei).

    PubMed

    Pérez Sirkin, D I; Cánepa, M M; Fossati, M; Fernandino, J I; Delgadin, T; Canosa, L F; Somoza, G M; Vissio, P G

    2012-03-01

    Growth hormone (GH) is the main pituitary hormone involved in somatic growth. In fish, the neuroendocrine control of GH is multifactorial due to the interaction of multiple inhibitors and stimulators. Melanin-concentrating hormone (MCH) is a cyclic peptide involved in skin color regulation of fish. In addition, MCH has been related to the regulation of food intake in both mammals and fish. There is only one report presenting evidences on the GH release stimulation by MCH in mammals in experiments in vitro, but there are no data on non-mammals. In the present work, we report for the first time the sequence of MCH and GH cDNA in Cichlasoma dimerus, a freshwater South American cichlid fish. We detected contacts between MCH fibers and GH cells in the proximal pars distalis region of the pituitary gland by double label confocal immunofluorescence indicating a possible functional relationship. Besides, we found that MCH increased GH transcript levels and stimulated GH release in pituitary cultures. Additionally, C. dimerus exposed to a white background had a greater number of MCH neurons with a larger nuclear area and higher levels of MCH transcript than those fish exposed to a black background. Furthermore, fish reared for 3 months in a white background showed a greater body weight and total length compared to those from black background suggesting that MCH might be related to somatic growth in C. dimerus. Our results report for the first time, that MCH is involved in the regulation of the synthesis and release of GH in vitro in C. dimerus, and probably in the fish growth rate.

  7. Gravity-induced asymmetric distribution of a plant growth hormone

    NASA Technical Reports Server (NTRS)

    Bandurski, R. S.; Schulze, A.; Momonoki, Y.

    1984-01-01

    Dolk (1936) demonstrated that gravistimulation induced an asymmetric distribution of auxin in a horizontally-placed shoot. An attempt is made to determine where and how that asymmetry arises, and to demonstrate that the endogenous auxin, indole-3-acetic acid, becomes asymmetrically distributed in the cortical cells of the Zea mays mesocotyl during 3 min of geostimulation. Further, indole-3-acetic acid derived by hydrolysis of an applied transport form of the hormone, indole-3-acetyl-myo-inositol, becomes asymmetrically distributed within 15 min of geostimulus time. From these and prior data is developed a working theory that the gravitational stimulus induces a selective leakage, or secretion, of the hormone from the vascular tissue to the cortical cells of the mesocotyl.

  8. Effects of growth hormone-releasing factor on growth hormone response, growth and feed conversion efficiency in buffalo heifers (Bubalus bubalis).

    PubMed

    Haldar, A; Prakash, B S

    2007-09-01

    The aim of this study was to determine the benefits of growth hormone-releasing factor (GRF) on growth and feed conversion efficiency (FCE) in buffaloes. Twelve Murrah buffalo heifers (Bubalus bubalis) of mean age 24.8 months and mean body weight 302.4kg were divided into two groups (treatment and control) with six animals in each group. The buffaloes were given intravenous injections of bovine GRF (bGRF) at a dose rate of 10microg/100kg body weight or an equal volume of saline at 15-day intervals for a period of 9 months. Plasma growth hormone (GH) responses to bGRF challenge were measured in blood samples collected at 90-day intervals on days 1, 90, 180 and 270 and samples were taken at -60, -30, 0, +10, +20, +30, +60, +120 and +180min relative to bGRF injection. Blood samples were also collected weekly by jugular venepuncture for the quantification of plasma GH. The average growth rate (AGR) and FCE of all animals were recorded at 15-day intervals. Plasma GH concentrations increased (P=0.001) steadily following bGRF challenge, peaking 10-20min after challenge and declining to baseline by 180min. In the treatment group, there were no significant differences (P>0.05) in either the peak heights of the GH response or the area under the curve (AUC) of the GH response after bGRF challenge on any of the four occasions of intensive bleeding. There were overall increases in plasma GH concentrations (P<0.01), AGR (P<0.01) and FCE (P=0.05) in the treatment group compared with the control animals. The study showed that GH responsiveness to administration of bGRF at 15-day intervals over 9 months of treatment remained unchanged in buffalo heifers. Exogenous bGRF treatment for a long period can therefore enhance GH release leading to higher growth rates and better feed conversion efficiency in buffalo heifers. PMID:17113797

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

    PubMed

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

    2015-04-01

    In the present study, we examined the trout gill cell line RTgill-W1 as a possible tool for in vitro investigation of epithelial gill function in fish. After seeding in transwells, transepithelial resistance (TER) increased until reaching a plateau after 1-2 days (20-80Ω⋅cm(2)), which was then maintained for more than 6 days. Tetrabromocinnamic acid, a known stimulator of TER via casein kinase II inhibition, elevated TER in the cell line to 125% of control values after 2 and 6h. Treatment with ethylenediaminetetraacetic acid induced a decrease in TER to <15% of pre-treatment level. Cortisol elevated TER after 12-72 h in a concentration-dependent manner, and this increase was antagonized by growth hormone (Gh). The effects of three osmoregulatory hormones, Gh, prolactin, and cortisol, on the mRNA expression of three tight junction proteins were examined: claudin-10e (Cldn-10e), Cldn-30, and zonula occludens-1 (Zo-1). The expression of cldn-10e was stimulated by all three hormones but with the strongest effect of Gh (50-fold). cldn-30 expression was stimulated especially by cortisol (20-fold) and also by Gh (4-fold). Finally, zo-1 was unresponsive to hormone treatment. Western blot analysis detected Cldn-10e and Cldn-30 immunoreactive proteins of expected molecular weight in samples from rainbow trout gills but not from RTgill-W1 cultures, possibly due to low expression levels. Collectively, these results show that the RTgill-W1 cell layers have tight junctions between cells, are sensitive to hormone treatments, and may provide a useful model for in vitro study of some in vivo gill phenomena.

  10. Evolutionary aspects of growth hormones and prolactins and their receptors

    SciTech Connect

    Tarpey, J.F.

    1986-01-01

    The interactions of GH's, PRL's and PL's with receptors for GH and PRL were examined from a comparative and evolutionary viewpoint. The binding of /sup 125/I-bGH to membrane preparations from liver of representatives of the major classes of non-mammalian vertebrates was also studied. Only hepatic membranes from sturgeon and Gillichthys had significant bGH binding and were further characterized and compared with male rabbit liver membranes in terms of time, temperature, pH, and membrane concentration to optimize binding conditions. The binding of several members of the GH, PRL, PL family of hormones to GH receptors from liver of sturgeon, Gillichthys, rabbit, mouse and rat was investigated. in terms of hormonal specificity, the mammalian receptors and the sturgeon binding sites were similar, while Gillichthys receptors had a different pattern of hormonal specificity. The binding of /sup 125/I-oPRL to renal membranes of the turtle, Pseudemys scripta elegans, was characterized and compared to PRL binding sites of kidney membranes of the bullfrog, Rana catesbeiana, and the tiger salamander, Ambystoma tigrinum.

  11. Response to three years of growth hormone therapy in girls with Turner syndrome

    PubMed Central

    Park, Hong Kyu; Lee, Hae Sang; Ko, Jung Hee; Hwang, Il Tae

    2013-01-01

    Purpose Short stature is the most common finding in patients with Turner syndrome. Improving the final adult height in these patients is a challenge both for the patients and physicians. We investigated the clinical response of patients to growth hormone treatment for height improvement over the period of three years. Methods Review of medical records from 27 patients with Turner syndrome treated with recombinant human growth hormone for more than 3 years was done. Differences in the changes of height standard deviation scores according to karyotype were measured and factors influencing the height changes were analyzed. Results The response to recombinant human growth hormone was an increase in the height of the subjects to a mean value of 1.1 standard deviation for subjects with Turner syndrome at the end of the 3-year treatment. The height increment in the first year was highest. The height standard deviation score in the third year was negatively correlated with the age at the beginning of the recombinant human growth hormone treatment. Different karyotypes in subjects did not seem to affect the height changes. Conclusion Early growth hormone administration in subjects with Turner syndrome is helpful to improve height response to the treatment. PMID:24904845

  12. Response to long-term growth hormone therapy in patients affected by RASopathies and growth hormone deficiency: Patterns of growth, puberty and final height data.

    PubMed

    Tamburrino, Federica; Gibertoni, Dino; Rossi, Cesare; Scarano, Emanuela; Perri, Annamaria; Montanari, Francesca; Fantini, Maria Pia; Pession, Andrea; Tartaglia, Marco; Mazzanti, Laura

    2015-11-01

    RASopathies are developmental disorders caused by heterozygous germline mutations in genes encoding proteins in the RAS-MAPK signaling pathway. Reduced growth is a common feature. Several studies generated data on growth, final height (FH), and height velocity (HV) after growth hormone (GH) treatment in patients with these disorders, particularly in Noonan syndrome, the most common RASopathy. These studies, however, refer to heterogeneous cohorts in terms of molecular information, GH status, age at start and length of therapy, and GH dosage. This work reports growth data in 88 patients affected by RASopathies with molecularly confirmed diagnosis, together with statistics on body proportions, pubertal pattern, and FH in 33, including 16 treated with GH therapy for proven GH deficiency. Thirty-three patients showed GH deficiency after pharmacological tests, and were GH-treated for an average period of 6.8 ± 4.8 years. Before starting therapy, HV was -2.6 ± 1.3 SDS, and mean basal IGF1 levels were -2.0 ± 1.1 SDS. Long-term GH therapy, starting early during childhood, resulted in a positive height response compared with untreated patients (1.3 SDS in terms of height-gain), normalizing FH for Ranke standards but not for general population and Target Height. Pubertal timing negatively affected pubertal growth spurt and FH, with IGF1 standardized score increased from -2.43 to -0.27 SDS. During GH treatment, no significant change in bone age velocity, body proportions, or cardiovascular function was observed.

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

    PubMed

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

    2015-01-01

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

  14. Chronic uremia attenuates growth hormone-induced signal transduction in skeletal muscle.

    PubMed

    Sun, Di Fei; Zheng, Zhilan; Tummala, Padmaja; Oh, Jun; Schaefer, Franz; Rabkin, Ralph

    2004-10-01

    Malnutrition and muscle wasting are common in chronic renal failure (CRF) and adversely affect morbidity and mortality. Contributing to the muscle wasting is resistance to growth hormone (GH). For testing whether impaired GH signaling is a cause of the skeletal muscle GH resistance and for elucidating its mechanisms, muscle GH signaling and action were studied in GH-deficient rats with surgically induced CRF and sham-operated pairfed control rats. GH treatment increased gastrocnemius muscle IGF-1 mRNA levels significantly in control but not in CRF rats. GH-activated Janus-associated kinase 2 (JAK2)-signal transducers and activators of transcription 5 (STAT5) signaling was impaired in CRF rats, despite normal GH receptor (GHR), JAK2, and STAT5 protein levels. Phosphorylation of the GHR, JAK2, and STAT5 in response to GH was depressed by nearly half in CRF (P < 0.05), and nuclear phospho-STAT5 levels were depressed by approximately one third (P < 0.01). GH-stimulated suppressors of cytokine signaling 2 mRNA levels were significantly higher in CRF. This may be related to inflammatory cytokine activity because C-reactive protein levels were elevated. Muscle protein-tyrosine phosphatase activity was also increased significantly by twofold. In conclusion, rats with CRF acquire skeletal muscle resistance to GH that is caused at least in part by impaired JAK2-GHR-STAT5 phosphorylation and nuclear STAT5 translocation. Furthermore, it seems that the attenuated JAK2-STAT5 phosphorylation may be caused by at least two different processes. One involves depressed phosphorylation of the signaling proteins because of increased suppressors of cytokine signaling 2 expression that may be linked to low-grade inflammation. The other may involve increased signaling protein dephosphorylation because of heightened protein-tyrosine phosphatase activity.

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

    PubMed

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

    2015-01-01

    Performing aerobics and resistance exercise at exactly the same time has not been available although combining both types of exercise in one training program has been attempted. The hybrid training system (HTS) is a resistance exercise that combines voluntary concentric muscle contractions with electrically stimulated eccentric muscle contractions. We devised an exercise technique using HTS on a cycle ergometer (HCE). Growth hormone (GH) and lactate are indicators of adequate training intensity. Interleukin-6 (IL-6) reflects enhancing lipid metabolism. The purpose of this study was to show that HCE provides sufficient exercise to stimulate the secretion of GH, lactate and IL-6. We compared an HCE test with cycle ergometer alone (CE). Ten healthy male subjects performed HCE and CE tests for 30 minutes each. The workload of both tests was set the same at 40% of each subject's peak oxygen uptake. For HCE, 2-minute HTS and 1-minute rest intervals were repeated. GH, lactate, and IL-6 were evaluated before and immediately after exercise, and at 15, 30 and 60 minutes. GH and lactate increased immediately after HCE. Moreover, the degree of the increases in GH after HCE (0 and 15 minutes) was higher than that after CE. IL-6 increased after HCE at 30 min, and the rate of change was higher than for CE. These results showed that HCE was more efficient in stimulating acute increases in GH, lactate and IL-6 than CE at the same workload. We may be able to combine electrically stimulated resistance exercise with aerobic exercise using HCE. PMID:26522057

  16. Effects of Growth Hormone Releasing Hormone on Visceral Fat, Metabolic and Cardiovascular Indices in Human Studies

    PubMed Central

    Stanley, Takara L.; Grinspoon, Steven K.

    2014-01-01

    Increased visceral adipose tissue (VAT) is associated with reductions in endogenous GH secretion, possibly as a result of hyperinsulinemia, increased circulating free fatty acid, increased somatostatin tone, and reduced ghrelin. Reduced GH may, in turn, further exacerbate visceral fat accumulation because of decreased hormone sensitive lipolysis in this depot. Data from multiple populations demonstrate that both reduced GH and increased VAT appear to contribute independently to dyslipidemia, increased systemic inflammation, and increased cardiovascular risk. The reductions in GH in states of visceral adiposity are characterized by reduced basal and pulsatile GH secretion with intact pulse frequency. Treatment with GH releasing hormone (GHRH) provides a means to reverse these abnormalities, increasing endogenous basal and pulsatile GH secretion without altering pulse frequency. This review describes data from HIV-infected individuals and individuals with general obesity showing that treatment with GHRH significantly reduces visceral fat, ameliorates dyslipidemia, and reduces markers of cardiovascular risk. Further research is needed regarding long term efficacy and safety of this treatment modality. PMID:25555516

  17. Hepatic growth hormone and glucocorticoid receptor signaling in body growth, steatosis and metabolic liver cancer development.

    PubMed

    Mueller, Kristina M; Themanns, Madeleine; Friedbichler, Katrin; Kornfeld, Jan-Wilhelm; Esterbauer, Harald; Tuckermann, Jan P; Moriggl, Richard

    2012-09-25

    Growth hormone (GH) and glucocorticoids (GCs) are involved in the control of processes that are essential for the maintenance of vital body functions including energy supply and growth control. GH and GCs have been well characterized to regulate systemic energy homeostasis, particular during certain conditions of physical stress. However, dysfunctional signaling in both pathways is linked to various metabolic disorders associated with aberrant carbohydrate and lipid metabolism. In liver, GH-dependent activation of the transcription factor signal transducer and activator of transcription (STAT) 5 controls a variety of physiologic functions within hepatocytes. Similarly, GCs, through activation of the glucocorticoid receptor (GR), influence many important liver functions such as gluconeogenesis. Studies in hepatic Stat5 or GR knockout mice have revealed that they similarly control liver function on their target gene level and indeed, the GR functions often as a cofactor of STAT5 for GH-induced genes. Gene sets, which require physical STAT5-GR interaction, include those controlling body growth and maturation. More recently, it has become evident that impairment of GH-STAT5 signaling in different experimental models correlates with metabolic liver disease, ranging from hepatic steatosis to hepatocellular carcinoma (HCC). While GH-activated STAT5 has a protective role in chronic liver disease, experimental disruption of GC-GR signaling rather seems to ameliorate metabolic disorders under metabolic challenge. In this review, we focus on the current knowledge about hepatic GH-STAT5 and GC-GR signaling in body growth, metabolism, and protection from fatty liver disease and HCC development.

  18. Deciphering the hormonal signalling network behind the systemic resistance induced by Trichoderma harzianum in tomato

    PubMed Central

    Martínez-Medina, Ainhoa; Fernández, Iván; Sánchez-Guzmán, María J.; Jung, Sabine C.; Pascual, Jose A.; Pozo, María J.

    2013-01-01

    Root colonization by selected Trichoderma isolates can activate in the plant a systemic defense response that is effective against a broad-spectrum of plant pathogens. Diverse plant hormones play pivotal roles in the regulation of the defense signaling network that leads to the induction of systemic resistance triggered by beneficial organisms [induced systemic resistance (ISR)]. Among them, jasmonic acid (JA) and ethylene (ET) signaling pathways are generally essential for ISR. However, Trichoderma ISR (TISR) is believed to involve a wider variety of signaling routes, interconnected in a complex network of cross-communicating hormone pathways. Using tomato as a model, an integrative analysis of the main mechanisms involved in the systemic resistance induced by Trichoderma harzianum against the necrotrophic leaf pathogen Botrytis cinerea was performed. Root colonization by T. harzianum rendered the leaves more resistant to B. cinerea independently of major effects on plant nutrition. The analysis of disease development in shoots of tomato mutant lines impaired in the synthesis of the key defense-related hormones JA, ET, salicylic acid (SA), and abscisic acid (ABA), and the peptide prosystemin (PS) evidenced the requirement of intact JA, SA, and ABA signaling pathways for a functional TISR. Expression analysis of several hormone-related marker genes point to the role of priming for enhanced JA-dependent defense responses upon pathogen infection. Together, our results indicate that although TISR induced in tomato against necrotrophs is mainly based on boosted JA-dependent responses, the pathways regulated by the plant hormones SA- and ABA are also required for successful TISR development. PMID:23805146

  19. General seizures revealing macro-adenomas secreting prolactin or prolactin and growth hormone in men

    PubMed Central

    Chentli, Farida; Akkache, Lina; Daffeur, Katia; Azzoug, Said

    2014-01-01

    Background: Epilepsy is a heterogeneous condition with numerous etiologies. Pituitary tumors are rarely responsible for generalized convulsions except when they are very large. Apart from anecdotic cases, only one study concerning epilepsy frequency in male macroprolactinomas is available in Medline. Our aim was to analyze epilepsy frequency and conditions under which seizures appear and disappear in men harboring macroprolactinomas or somatolactotroph adenomas. Materials and Methods: We retrospectively analyzed 90 men with macro-adenomas (>1 cm) secreting prolactin (PRL) (n = 82) or both PRL and growth hormone (n = 8) to look for generalized seizures. We took into account familial and personal medical history, clinical examination, routine and hormonal analyzes, and radiological assessment based on cerebral magnetic resonance imaging. Results: Between 1992 and 2012, we collected eight cases (8.9%): Seven were hospitalized for recent generalized seizures; one had epilepsy after conventional radiotherapy given in 1992 because of neurosurgery failure and resistance to bromocriptine. Their median age was 33.75 years (22-58), median PRL was 9,198 ng/ml and median tumor height was 74 mm (41-110). The temporal lobe was invaded in six cases. After tumor reduction, epilepsy disappeared and never relapsed after a follow-up varying between 1 and 20 years. Conclusion: Epilepsy, which is a life-threatening condition, can be the first presentation in men with prolactinomas or somatolactotroph adenomas, especially those involving the supra sellar area, and the brain. Convulsions can also appear after radiotherapy. That one should be avoided, if possible, before tumor reduction by surgery or medical treatment. PMID:24944932

  20. Growth hormone modulates hypothalamic inflammation in long-lived pituitary dwarf mice.

    PubMed

    Sadagurski, Marianna; Landeryou, Taylor; Cady, Gillian; Kopchick, John J; List, Edward O; Berryman, Darlene E; Bartke, Andrzej; Miller, Richard A

    2015-12-01

    Mice in which the genes for growth hormone (GH) or GH receptor (GHR(-/-) ) are disrupted from conception are dwarfs, possess low levels of IGF-1 and insulin, have low rates of cancer and diabetes, and are extremely long-lived. Median longevity is also increased in mice with deletion of hypothalamic GH-releasing hormone (GHRH), which leads to isolated GH deficiency. The remarkable extension of longevity in hypopituitary Ames dwarf mice can be reversed by a 6-week course of GH injections started at the age of 2 weeks. Here, we demonstrate that mutations that interfere with GH production or response, in the Snell dwarf, Ames dwarf, or GHR(-/-) mice lead to reduced formation of both orexigenic agouti-related peptide (AgRP) and anorexigenic proopiomelanocortin (POMC) projections to the main hypothalamic projection areas: the arcuate nucleus (ARH), paraventricular nucleus (PVH), and dorsomedial nucleus (DMH). These mutations also reduce hypothalamic inflammation in 18-month-old mice. GH injections, between 2 and 8 weeks of age, reversed both effects in Ames dwarf mice. Disruption of GHR specifically in liver (LiGHRKO), a mutation that reduces circulating IGF-1 but does not lead to lifespan extension, had no effect on hypothalamic projections or inflammation, suggesting an effect of GH, rather than peripheral IGF-1, on hypothalamic development. Hypothalamic leptin signaling, as monitored by induction of pStat3, is not impaired by GHR deficiency. Together, these results suggest that early-life disruption of GH signaling produces long-term hypothalamic changes that may contribute to the longevity of GH-deficient and GH-resistant mice.

  1. Growth hormone modulates hypothalamic inflammation in long-lived pituitary dwarf mice.

    PubMed

    Sadagurski, Marianna; Landeryou, Taylor; Cady, Gillian; Kopchick, John J; List, Edward O; Berryman, Darlene E; Bartke, Andrzej; Miller, Richard A

    2015-12-01

    Mice in which the genes for growth hormone (GH) or GH receptor (GHR(-/-) ) are disrupted from conception are dwarfs, possess low levels of IGF-1 and insulin, have low rates of cancer and diabetes, and are extremely long-lived. Median longevity is also increased in mice with deletion of hypothalamic GH-releasing hormone (GHRH), which leads to isolated GH deficiency. The remarkable extension of longevity in hypopituitary Ames dwarf mice can be reversed by a 6-week course of GH injections started at the age of 2 weeks. Here, we demonstrate that mutations that interfere with GH production or response, in the Snell dwarf, Ames dwarf, or GHR(-/-) mice lead to reduced formation of both orexigenic agouti-related peptide (AgRP) and anorexigenic proopiomelanocortin (POMC) projections to the main hypothalamic projection areas: the arcuate nucleus (ARH), paraventricular nucleus (PVH), and dorsomedial nucleus (DMH). These mutations also reduce hypothalamic inflammation in 18-month-old mice. GH injections, between 2 and 8 weeks of age, reversed both effects in Ames dwarf mice. Disruption of GHR specifically in liver (LiGHRKO), a mutation that reduces circulating IGF-1 but does not lead to lifespan extension, had no effect on hypothalamic projections or inflammation, suggesting an effect of GH, rather than peripheral IGF-1, on hypothalamic development. Hypothalamic leptin signaling, as monitored by induction of pStat3, is not impaired by GHR deficiency. Together, these results suggest that early-life disruption of GH signaling produces long-term hypothalamic changes that may contribute to the longevity of GH-deficient and GH-resistant mice. PMID:26268661

  2. Effects of growth hormone and insulin-like growth factor I on muscle in mouse models of human growth disorders.

    PubMed

    Clark, Ryan P; Schuenke, Mark; Keeton, Stephanie M; Staron, Robert S; Kopchick, John J

    2006-01-01

    The precise effects of growth hormone (GH) and insulin-like growth factor I (IGF-I) on muscle development and physiology are relatively unknown. Furthermore, there have been conflicting reports on the effects of GH/IGF-I on muscle. Distinguishing the direct effects of GH versus those of IGF-I is problematic, but animal models with altered GH/IGF-I action could help to alleviate some of the conflicting results and help to determine the independent actions of GH and IGF-I. The phenotypes of several mouse models, namely the GH receptor-gene-disrupted (GHR -/-) mouse and a variety of IGF-I -/- mice, are summarized, which ultimately will aid our understanding of this complex area. PMID:17259718

  3. Growth hormone receptor exon 3 isoforms and their implication in growth disorders and treatment.

    PubMed

    Jorge, Alexander A L; Arnhold, Ivo J P

    2009-04-01

    Human recombinant growth hormone (hGH) has been used to treat short stature in several different conditions, but considerable inter-individual variation in short- and long-term growth response exists. Pharmacogenomics can provide important insights into hGH therapy. The GH receptor (GHR) is the first key molecule mediating GH action. In the past 3 years, a common GHR polymorphism reflecting the presence (GHRfl) or absence (GHRd3) of exon 3 has been under intensive investigation regarding its influence on the response to hGH therapy. Studies that evaluated response to GH treatment determined by these two GHR isoforms in children with GH deficiency, girls with Turner syndrome, children born small for gestational age and patients with acromegaly showed that patients carrying the GHRd3 allele demonstrated a greater GH sensitivity than patients homozygous for the GHRfl allele. Other studies presented contradictory data, however, which may be caused by confounding factors such as small sample sizes and differences in experimental design. This GHR exon 3 genotype is the first identified genetic factor found to modulate the individual response to GH therapy. This article reviews the historical aspects and pharmacogenetic studies published to date in relation to this GHR polymorphism. The analyses of present and future validation studies may define the use of this and other polymorphisms in clinical practice, moving from pharmacogenetics to routine application and allowing individualization of hGH doses to optimize final outcome.

  4. Clinical and humanistic aspects of growth hormone deficiency and growth-related disorders.

    PubMed

    Rogol, Alan D

    2011-12-01

    Growth hormone (GH) therapy has evolved rapidly since the introduction of recombinant human GH (rhGH). The increase in the availability and safety of GH therapy has also increased the number of US Food and Drug Administration (FDA) indications for use in both children and adults. FDA indications in children include GH deficiency (GHD), Turner syndrome, idiopathic short stature, small for gestational age with failure to attain normal growth percentiles, Prader-Willi syndrome (PWS), chronic renal insufficiency, Noonan syndrome, and short stature due to short stature homeobox gene haploinsufficiency. Children and adolescents with GHD have demonstrated the greatest response to GHD therapy. The primary objective of rhGH therapy in children is to increase height velocity; however, the therapy also has benefits related to improved body composition, especially in children with conditions like PWS. Treatment of adult GHD primarily targets improvements in body composition, quality of life, and surrogate markers for cardiovascular disease. The safety reports of rhGH in children are generally good, but there have been a small number of cases of raised intracranial pressure, scoliosis, and muscle and joint discomfort. In adults, many side effects can be managed with dose titration at the initiation of treatment and dose reduction if side effects occur. PMID:22590765

  5. Role of insulin-like growth factor monitoring in optimizing growth hormone therapy.

    PubMed

    Wetterau, L; Cohen, P

    2000-01-01

    Much has been learned over the past two decades regarding the management of growth hormone (GH) deficiency in children and adolescents. Current GH therapy under ideal circumstances enables children to attain a final height within the normal range and close to their target height. However, such a successful outcome is not always achieved and the necessity to individualize treatment according to the specific needs of each GH-deficient child is now well recognized. Consensus does not currently exist as to how to formulate individualized treatment plans. Nonetheless, a clear role for a biochemical, as well as an auxological, monitoring approach has been established. Accurate determinations of height velocity and interval height increase (expressed as the change in height Z-score) continue to be the most important parameters in monitoring the response to treatment. The importance of routinely monitoring serum levels of insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 is an emerging paradigm. Firm roles have been established for this approach in the assurance of compliance and safety (particularly to avoid long-term theoretical risks). IGF monitoring also has important potential utility as a tool to assess and optimize the response to GH therapy through dose adjustments. In years to come, we expect the development of multiple GH treatment optimization strategies, including approaches such as prediction modeling, as well as serum IGF monitoring and dose adjustments, to evolve and improve. PMID:11202212

  6. Effect of single-dose radiation on cell survival and growth hormone secretion by rat anterior pituitary cells

    SciTech Connect

    Hochberg, Z.; Kuten, A.; Hertz, P.; Tatcher, M.; Kedar, A.; Benderly, A.

    1983-06-01

    Cranial irradiation has been shown to impair growth hormone secretion in children. In this study a cell culture of dispersed rat anterior pituitary cells was exposed to single doses of radiation in the range of 100 to 1500 rad. Survival curves were obtained for the different anterior pituitary cell lines, and growth hormone secretion was measured in the tissue culture medium. Both survival and growth hormone secretion curves showed an initial shoulder in the range of 0 to 300 rad, followed by a decline between 300 to 750 rad. It is concluded that growth hormone secreting acidophilic pituicytes are sensitive to radiation at single doses greater than 300 rad.

  7. Growth Control and Biophoton Radiation by Plant Hormones in Red Bean

    NASA Astrophysics Data System (ADS)

    Kai, Shoichi; Moriya, Tomoyuki; Fujimoto, Tokio

    1995-12-01

    The growth kinetics of seeds of red beans ( Phaseolus angularis ) was investigated by externally adding various hormones (gibberellin (GA3)), abscisic acid (ABA) and indole acetic acid (IAA)) during germination. For root growth of red beans, GA3 always acted as an activator while ABA as an inhibitor. IAA was both an activator and an inhibitor depending on its concentration. Root growth could be described by a stochastic logistic equation. The hormone concentration dependences of coefficients of the equation were determined. The hormone influences on biophoton radiation were also investgated. With GA3, the intensity of spontaneous bioluminescence increased with time and showed two strong radiation periods, in which strong localization of bioluminescence was induced. However with ABA and IAA, weaker bioluminescences were observed. The location of the strong radiation induced by GA3 was determined as the growing point near a root cap, by use of a two-dimensional photon counting system.

  8. A Child with Local Lipohypertrophy following Recombinant Human Growth Hormone Administration

    PubMed Central

    Koppen, Ilan J. N.; de Kruiff, Chris C.

    2016-01-01

    Local lipohypertrophy due to recombinant human growth hormone (rhGH) administration is a rare phenomenon. Here, we report a case of an 11-year-old girl who presented with a paraumbilical swelling, approximately one year after the start of rhGH treatment for short stature due to the presumed diagnosis of partial growth hormone insensitivity. Ultrasound imaging revealed an asymmetric distribution of subcutaneous fat tissue at the rhGH administration site, indicating local lipohypertrophy. After sparing her routine injection site and alternating other sites, the swelling disappeared within 6 months. Although the precise cause of local lipohypertrophy resulting from rhGH administration is still unclear, it might be related to the presumed diagnosis of partial growth hormone insensitivity. PMID:27803832

  9. Defective minor spliceosome mRNA processing results in isolated familial growth hormone deficiency

    PubMed Central

    Argente, Jesús; Flores, Raquel; Gutiérrez-Arumí, Armand; Verma, Bhupendra; Martos-Moreno, Gabriel Á; Cuscó, Ivon; Oghabian, Ali; Chowen, Julie A; Frilander, Mikko J; Pérez-Jurado, Luis A

    2014-01-01

    The molecular basis of a significant number of cases of isolated growth hormone deficiency remains unknown. We describe three sisters affected with severe isolated growth hormone deficiency and pituitary hypoplasia caused by biallelic mutations in the RNPC3 gene, which codes for a minor spliceosome protein required for U11/U12 small nuclear ribonucleoprotein (snRNP) formation and splicing of U12-type introns. We found anomalies in U11/U12 di-snRNP formation and in splicing of multiple U12-type introns in patient cells. Defective transcripts include preprohormone convertases SPCS2 and SPCS3 and actin-related ARPC5L genes, which are candidates for the somatotroph-restricted dysfunction. The reported novel mechanism for familial growth hormone deficiency demonstrates that general mRNA processing defects of the minor spliceosome can lead to very narrow tissue-specific consequences. Subject Categories Genetics, Gene Therapy ' Genetic Disease; Metabolism PMID:24480542

  10. Environmental estrogens inhibit growth of rainbow trout (Oncorhynchus mykiss) by modulating the growth hormone-insulin-like growth factor system.

    PubMed

    Hanson, Andrea M; Kittilson, Jeffrey D; Martin, Lincoln E; Sheridan, Mark A

    2014-01-15

    Although environmental estrogens (EE) have been found to disrupt a wide variety of developmental and reproductive processes in vertebrates, there is a paucity of information concerning their effects on organismal growth, particularly postembryonic growth. In this study, we exposed juvenile rainbow trout (Oncorhynchus mykiss) to 17β-estradiol (E2) β-sitosterol (βS), or 4-n-nonylphenol (NP) to assess the effects of EE on overall organismal growth and on the growth hormone-insulin-like-growth factor (GH-IGF) system. EE treatment significantly reduced food conversion, body condition, and body growth. EE-inhibited growth resulted from alterations in peripheral elements of the GH-IGF system, which includes multiple GH receptors (GHRs), IGFs, and IGF receptors (IGFRs). In general, E2, βS, and NP reduced the expression of GHRs, IGFs, and IGFRs; however, the effects varied in an EE-, tissue-, element type-specific manner. For example, in liver, E2 was more efficacious than either βS, and NP in reducing GHR expression, and the effect of E2 was greater on GHR 1 than GHR2 mRNA. By contrast, in gill, all EEs affected GHR expression in a similar manner and there was no difference in the effect on GHR1 and GHR 2 mRNA. With regard to IGF expression, all EEs reduced hepatic IGF1 and IGF2 mRNA levels, whereas as in gill, only E2 and NP significantly reduced IGF1 and IGF2 expression. Lastly, E2 and NP reduced the expression of IGFR1A and IGFR1B mRNA expression similarly in gill and red and white muscle, whereas βS had no effect on expression of IGFR mRNAs. These findings indicate that EEs disrupt post-embryonic growth by reducing GH sensitivity, IGF production, and IGF sensitivity.

  11. Invasive Growth Hormone Producing Pituitary Adenoma With Lymphocytic Infiltration: A Case Report and Literature Review

    PubMed Central

    Bidari-Zerehpoosh, Farahnaz; Sharifi, Gieve; Novin, Kambiz; Mortazavi, Nafiseh

    2015-01-01

    Introduction: We have presented a rare case of growth hormone (GH) producing pituitary adenoma with lymphocytic infiltration and brain parenchyma invasion. Case Presentation: A 37-year-old woman has presented with complaints of headache, amenorrhea and acromegalic features. Her laboratory studies showed markedly elevated levels of Insulin-like Growth Factor 1 (IGF-1), and low levels of follicle stimulating hormone and luteinizing hormone. Computerized tomography has revealed a pituitary mass without extra-sellar extension. The tumor has completely excised via trans-nasal endoscopic approach. Histologically, the tumor has diagnosed as a pituitary adenoma with GH positive cells. The serum IGF1 levels have gradually decreased to the normal range and the patient was symptom free for three and a half years when she has returned with complaint of visual impairment. The brain MRI that time has shown a supra-sellar mass growing independently into the remaining sellar part. Subsequently, surgical operation has performed via trans-nasal endoscopic approach. Histopathological and immunohistochemistry examination have revealed a rare case of growth hormone producing pituitary adenoma with brain invasion and lymphocytic infiltration. Conclusions: The aim of this publication was to present a rare case of growth hormone producing pituitary adenoma with brain invasion and lymphocytic infiltration. PMID:26855718

  12. Growth hormone analysis and treatment in Ellis-van Creveld syndrome.

    PubMed

    Versteegh, Florens G A; Buma, Sannine A; Costin, Gertrude; de Jong, Wilfried C; Hennekam, Raoul C M

    2007-09-15

    Little is known on growth, growth hormone (GH) levels and GH treatment in patients with Ellis-van Creveld syndrome (EvC). The aim of the present study was to assess growth, growth hormone status and the possible effectiveness of GH treatment in literature and in a small series of EvC patients. A review of literature indicated retarded growth for most EvC patients (-2 to -4.5 SDS) and minimal data on GH levels or treatment which did not allow any conclusion. We studied eight EvC patients, seven of whom were treated with GH. Four were GH deficient (GHD) and four were GH sufficient. In all patients treated with GH, first year growth velocity increased. In three of the four GHD and in one GH-sufficient patient a gain in height SDS was noted. In the present small EvC series GHD occurred more often than expected. Patient acquisition through the Growth Hormone Database will have caused a significant bias, but the present results indicate that GH treatment may improve growth in at least some patients with EvC. Therefore we conclude that EvC patients may benefit from being tested for GHD and, if indicated, treated. In addition a prospective study to evaluate GH status and linear growth in patients with EvC as well as the potential effectiveness of GH treatment is warranted.

  13. Growth hormone-releasing hormone (GHRH) antagonists inhibit the proliferation of androgen-dependent and -independent prostate cancers

    PubMed Central

    Letsch, Markus; Schally, Andrew V.; Busto, Rebeca; Bajo, Ana M.; Varga, Jozsef L.

    2003-01-01

    The antiproliferative effects of an antagonist of growth hormone-releasing hormone (GHRH) JV-1-38 were evaluated in nude mice bearing s.c. xenografts of LNCaP and MDA-PCa-2b human androgen-sensitive and DU-145 androgen-independent prostate cancers. In the androgen-sensitive models, JV-1-38 greatly potentiated the antitumor effect of androgen deprivation induced by surgical castration, but was ineffective when given alone. Thus, in castrated animals bearing MDA-PCa-2b cancers, the administration of JV-1-38 for 35 days virtually arrested tumor growth (94% inhibition vs. intact control, P < 0.01; and 75% vs. castrated control, P < 0.05). The growth of LNCaP tumors was also powerfully suppressed by JV-1-38 combined with castration (83% inhibition vs. intact control, P < 0.01; and 68% vs. castrated control, P < 0.05). However, in androgen-independent DU-145 cancers, JV-1-38 alone could inhibit tumor growth by 57% (P < 0.05) after 45 days. In animals bearing MDA-PCa-2b and LNCaP tumors, the reduction in serum prostate-specific antigen levels, after therapy with JV-1-38, paralleled the decrease in tumor volume. Inhibition of MDA-PCa-2b and DU-145 cancers was associated with the reduction in the expression of mRNA and protein levels of vascular endothelial growth factor. The mRNA expression for GHRH receptor splice variants was found in all these models of prostate cancer. Our results demonstrate that GHRH antagonists inhibit androgen-independent prostate cancers and, after combination with androgen deprivation, also androgen-sensitive tumors. Thus, the therapy with GHRH antagonist could be considered for the management of both androgen-dependent or -independent prostate cancers. PMID:12538852

  14. Parathyroid cell resistance to fibroblast growth factor 23 in secondary hyperparathyroidism of chronic kidney disease.

    PubMed

    Galitzer, H; Ben-Dov, I Z; Silver, Justin; Naveh-Many, Tally

    2010-02-01

    Although fibroblast growth factor 23 (FGF23) acting through its receptor Klotho-FGFR1c decreases parathyroid hormone expression, this hormone is increased in chronic kidney disease despite an elevated serum FGF23. We measured possible factors that might contribute to the resistance of parathyroid glands to FGF23 in rats with the dietary adenine-induced model of chronic kidney disease. Quantitative immunohistochemical and reverse transcription-PCR analysis using laser capture microscopy showed that both Klotho and FGFR1 protein and mRNA levels were decreased in histological sections of the parathyroid glands. Recombinant FGF23 failed to decrease serum parathyroid hormone levels or activate the mitogen-activated protein kinase signaling pathway in the glands of rats with advanced experimental chronic kidney disease. In parathyroid gland organ culture, the addition of FGF23 decreased parathyroid hormone secretion and mRNA levels in control animals or rats with early but not advanced chronic kidney disease. Our results show that because of a downregulation of the Klotho-FGFR1c receptor complex, an increase of circulating FGF23 does not decrease parathyroid hormone levels in established chronic kidney disease. This in vivo resistance is sustained in parathyroid organ culture in vitro.

  15. Absence of a growth hormone effect on rat soleus atrophy during a 4-day spaceflight

    NASA Technical Reports Server (NTRS)

    Jiang, Bian; Roy, Roland R.; Navarro, Christine; Edgerton, V. R.

    1993-01-01

    The effect of a 4-day-long spaceflight on the size and the enzyme properties of soleus fibers of rats and the effects of exogenous growth hormone (GH) on the atrophic response of the soleus muscle were investigated in four groups of rats: (1) control, (2) control plus GH treatment, (3) flight, and (4) flight plus GH treatment. Results showed that the fiber size and the type of myosin heavy chain expressed fibers (but not the metabolic properties) of the soleus were affected by four days of weightlessness and that the effects were not ameliorated by the administration of growth hormone.

  16. Infarction of a growth hormone-secreting macroadenoma during a TRH test.

    PubMed

    Lever, E G; Butler, J; Moore, P; Cox, T C; Maccabe, J J

    1986-06-01

    Pituitary infarction occurring immediately after TRH injection (200 micrograms) is reported in a patient with gigantism due to a growth hormone-secreting pituitary macroadenoma. Evidence of infarction was seen in CSF and in serial CT scans. Regression of symptoms and sign of acromegaly, abolition of abnormal growth hormone secretion, and virtually complete anterior and partial posterior pituitary failure rapidly followed. The infarction was probably initiated by a hypertensive response to TRH. TRH testing in acromegalic subjects may require smaller doses of TRH to avoid unwanted pressor responses. PMID:3090811

  17. Regulation of skeletal muscle growth in fish by the growth hormone--insulin-like growth factor system.

    PubMed

    Fuentes, Eduardo N; Valdés, Juan Antonio; Molina, Alfredo; Björnsson, Björn Thrandur

    2013-10-01

    The growth hormone (GH)-insulin-like growth factor (IGF) system is the key promoter of growth in vertebrates; however, how this system modulates muscle mass in fish is just recently becoming elucidated. In fish, the GH induces muscle growth by modulating the expression of several genes belonging to the myostatin (MSTN), atrophy, GH, and IGF systems as well as myogenic regulatory factors (MRFs). The GH controls the expression of igf1 via Janus kinase 2 (JAK2)/signal transducers and activators of the transcription 5 (STAT5) signaling pathway, but it seems that it is not the major regulator. These mild effects of the GH on igf1 expression in fish muscle seem to be related with the presence of higher contents of truncated GH receptor1 (tGHR1) than full length GHR (flGHR1). IGFs in fish stimulate myogenic cell proliferation, differentiation, and protein synthesis through the MAPK/ERK and PI3K/AKT/TOR signaling pathways, concomitant with abolishing protein degradation and atrophy via the PI3K/AKT/FOXO signaling pathway. Besides these signaling pathways control the expression of several genes belonging to the atrophy and IGF systems. Particularly, IGFs and amino acid control the expression of igf1, thus, suggesting other of alternative signaling pathways regulating the transcription of this growth factor. The possible role of IGF binding proteins (IGFBPs) and the contribution of muscle-derived versus hepatic-produced IGF1 on fish muscle growth is also addressed. Thus, a comprehensive overview on the GH-IGF system regulating fish skeletal muscle growth is presented, as well as perspectives for future research in this field.

  18. Differential petiole growth in Arabidopsis thaliana: photocontrol and hormonal regulation.

    PubMed

    Millenaar, Frank F; van Zanten, Martijn; Cox, Marjolein C H; Pierik, Ronald; Voesenek, Laurentius A C J; Peeters, Anton J M

    2009-01-01

    Environmental challenges such as low light intensity induce differential growth-driven upward leaf movement (hyponastic growth) in Arabidopsis thaliana. However, little is known about the physiological regulation of this response. Here, we studied how low light intensity is perceived and translated into a differential growth response in Arabidopsis. We used mutants defective in light, ethylene and auxin signaling, and in polar auxin transport, as well as chemical inhibitors, to analyze the mechanisms of low light intensity-induced differential growth. Our data indicate that photosynthesis-derived signals and blue light wavelengths affect petiole movements and that rapid induction of hyponasty by low light intensity involves functional cryptochromes 1 and 2, phytochrome-A and phytochrome-B photoreceptor proteins. The response is independent of ethylene signaling. Auxin and polar auxin transport, by contrast, play a role in low light intensity-induced differential petiole growth. We conclude that low light intensity-induced differential petiole growth requires blue light, auxin signaling and polar auxin transport and is, at least in part, genetically separate from well-characterized ethylene-induced differential growth.

  19. Molecular interactions between light and hormone signaling to control plant growth.

    PubMed

    Alabadí, David; Blázquez, Miguel A

    2009-03-01

    As sessile organisms, plants modulate their growth rate and development according to the continuous variation in the conditions of their surrounding environment, an ability referred to as plasticity. This ability relies on a web of interactions between signaling pathways triggered by endogenous and environmental cues. How changes in environmental factors are interpreted by the plant in terms of developmental or growth cues or, in other words, how they contribute to plant plasticity is a current, major question in plant biology. Light stands out among the environmental factors that shape plant development. Plants have evolved systems that allow them to monitor both quantitative and qualitative differences in the light that they perceive, that render important changes in their growth habit. In this review we focus on recent findings about how information from this environmental cue is integrated during de-etiolation and in the shade-avoidance syndrome, and modulated by several hormone pathways-the endogenous cues. In some cases the interaction between a hormone and the light signaling pathways is reciprocal, as is the case of the gibberellin pathway, whereas in other cases hormone pathways act downstream of the environmental cue to regulate growth. Moreover, the circadian clock adds an additional layer of regulation, which has been proposed to integrate the information provided by light with that provided by hormone pathways, to regulate daily growth.

  20. Impaired hair growth and wound healing in mice lacking thyroid hormone receptors.

    PubMed

    Contreras-Jurado, Constanza; García-Serrano, Laura; Martínez-Fernández, Mónica; Ruiz-Llorente, Lidia; Paramio, Jesus M; Aranda, Ana

    2014-01-01

    Both clinical and experimental observations show that the skin is affected by the thyroidal status. In hypothyroid patients the epidermis is thin and alopecia is common, indicating that thyroidal status might influence not only skin proliferation but also hair growth. We demonstrate here that the thyroid hormone receptors (TRs) mediate these effects of the thyroid hormones on the skin. Mice lacking TRα1 and TRβ (the main thyroid hormone binding isoforms) display impaired hair cycling associated to a decrease in follicular hair cell proliferation. This was also observed in hypothyroid mice, indicating the important role of the hormone-bound receptors in hair growth. In contrast, the individual deletion of either TRα1 or TRβ did not impair hair cycling, revealing an overlapping or compensatory role of the receptors in follicular cell proliferation. In support of the role of the receptors in hair growth, TRα1/TRβ-deficient mice developed alopecia after serial depilation. These mice also presented a wound-healing defect, with retarded re-epithelialization and wound gaping, associated to impaired keratinocyte proliferation. These results reinforce the idea that the thyroid hormone nuclear receptors play an important role on skin homeostasis and suggest that they could be targets for the treatment of cutaneous pathologies.

  1. Effects of growth hormone over-expression on reproduction in the common carp Cyprinus carpio L.

    PubMed

    Cao, Mengxi; Chen, Ji; Peng, Wei; Wang, Yaping; Liao, Lanjie; Li, Yongming; Trudeau, Vance L; Zhu, Zuoyan; Hu, Wei

    2014-01-01

    To study the complex interaction between growth and reproduction we have established lines of transgenic common carp (Cyprinus carpio) carrying a grass carp (Ctenopharyngodon idellus) growth hormone (GH) transgene. The GH-transgenic fish showed delayed gonadal development compared with non-transgenic common carp. To gain a better understanding of the phenomenon, we studied body growth, gonad development, changes of reproduction related genes and hormones of GH-transgenic common carp for 2years. Over-expression of GH elevated peripheral gh transcription, serum GH levels, and inhibited endogenous GH expression in the pituitary. Hormone analyses indicated that GH-transgenic common carp had reduced pituitary and serum level of luteinizing hormone (LH). Among the tested genes, pituitary lhβ was inhibited in GH-transgenic fish. Further analyses in vitro showed that GH inhibited lhβ expression. Localization of ghr with LH indicates the possibility of direct regulation of GH on gonadotrophs. We also found that GH-transgenic common carp had reduced pituitary sensitivity to stimulation by co-treatments with a salmon gonadotropin-releasing hormone (GnRH) agonist and a dopamine antagonist. Together these results suggest that the main cause of delayed reproductive development in GH transgenic common carp is reduced LH production and release.

  2. Energy intake and appetite-related hormones following acute aerobic and resistance exercise.

    PubMed

    Balaguera-Cortes, Liliana; Wallman, Karen E; Fairchild, Timothy J; Guelfi, Kym J

    2011-12-01

    Previous research has shown that resistance and aerobic exercise have differing effects on perceived hunger and circulating levels of appetite-related hormones. However, the effect of resistance and aerobic exercise on actual energy intake has never been compared. This study investigated the effect of an acute bout of resistance exercise, compared with aerobic exercise, on subsequent energy intake and appetite-regulating hormones. Ten active men completed 3 trials in a counterbalanced design: 45 min of resistance exercise (RES; free and machine weights), aerobic exercise (AER; running), or a resting control trial (CON). Following exercise or CON, participants had access to a buffet-style array of breakfast foods and drinks to consume ad libitum. Plasma concentrations of a range of appetite-regulating hormones were measured throughout each trial. Despite significantly higher energy expenditure with AER compared with RES (p < 0.05), there was no difference in total energy intake from the postexercise meal between trials (p = 0.779). Pancreatic polypeptide was significantly higher prior to the meal after both RES and AER compared with CON. In contrast, active ghrelin was lower following RES compared with both CON and AER (p ≤ 0.05), while insulin was higher following RES compared with CON (p = 0.013). In summary, the differential response of appetite-regulating hormones to AER and RES does not appear to influence energy intake in the postexercise meal. However, given the greater energy expenditure associated with AER compared with RES, AER modes of exercise may be preferable for achieving short-term negative energy balance. PMID:22111518

  3. Model for growth hormone receptor activation based on subunit rotation within a receptor dimer

    SciTech Connect

    Brown, Richard J.; Adams, Julian J.; Pelekanos, Rebecca A.; Wan, Yu; McKinstry, William J.; Palethorpe, Kathryn; Seeber, Ruth M.; Monks, Thea A.; Eidne, Karin A.; Parker, Michael W.; Waters, Michael J.

    2010-07-13

    Growth hormone is believed to activate the growth hormone receptor (GHR) by dimerizing two identical receptor subunits, leading to activation of JAK2 kinase associated with the cytoplasmic domain. However, we have reported previously that dimerization alone is insufficient to activate full-length GHR. By comparing the crystal structure of the liganded and unliganded human GHR extracellular domain, we show here that there is no substantial change in its conformation on ligand binding. However, the receptor can be activated by rotation without ligand by inserting a defined number of alanine residues within the transmembrane domain. Fluorescence resonance energy transfer (FRET), bioluminescence resonance energy transfer (BRET) and coimmunoprecipitation studies suggest that receptor subunits undergo specific transmembrane interactions independent of hormone binding. We propose an activation mechanism involving a relative rotation of subunits within a dimeric receptor as a result of asymmetric placement of the receptor-binding sites on the ligand.

  4. Interleukin-6 inhibits hepatic growth hormone signaling via upregulation of Cis and Socs-3.

    PubMed

    Denson, Lee A; Held, Matthew A; Menon, Ram K; Frank, Stuart J; Parlow, Albert F; Arnold, Dodie L

    2003-04-01

    Cytokines may cause an acquired growth hormone (GH) resistance in patients with inflammatory diseases. Anabolic effects of GH are mediated through activation of STAT5 transcription factors. We have reported that TNF-alpha suppresses hepatic GH receptor (GHR) gene expression, whereas the cytokine-inducible SH2-containing protein 1 (Cis)/suppressors of cytokine signaling (Socs) genes are upregulated by TNF-alpha and IL-6 and inhibit GH activation of STAT5. However, the relative importance of these mechanisms in inflammatory GH resistance was not known. We hypothesized that IL-6 would prevent GH activation of STAT5 and that this would involve Cis/Socs protein upregulation. GH +/- LPS was administered to TNF receptor 1 (TNFR1) or IL-6 null mice and wild-type (WT) controls. STAT5, STAT3, GHR, Socs 1-3, and Cis phosphorylation and abundance were assessed by using immunoblots, EMSA, and/or real time RT-PCR. TNF-alpha and IL-6 abundance were assessed by using ELISA. GH activated STAT5 in WT and TNFR1 or IL-6 null mice. LPS pretreatment prevented STAT5 activation in WT and TNFR1 null mice; however, STAT5 activation was preserved in IL-6 null mice. GHR abundance did not change with LPS administration. Inhibition of STAT5 activation by LPS was temporally associated with phosphorylation of STAT3 and upregulation of Cis and Socs-3 protein in WT and TNFR1 null mice; STAT3, Cis, and Socs-3 were not induced in IL-6 null mice. IL-6 inhibits hepatic GH signaling by upregulating Cis and Socs-3, which may involve activation of STAT3. Therapies that block IL-6 may enhance GH signaling in inflammatory diseases.

  5. Postnatal growth of broilers in response to in ovo administration of chicken growth hormone.

    PubMed

    Kocamis, H; Yeni, Y N; Kirkpatrick-Keller, D C; Killefer, J

    1999-08-01

    The effect of in ovo administration of chicken growth hormone (cGH) on growth rate and efficiency of gain, organ, and long bone growth of 42-d-old broiler chickens was investigated. Eggs were injected once with 100 microL vehicle (0.03 M NaHCO3, 0.15 M NaCl, pH 8.3) per embryo or vehicle containing 100 ng cGH/100 microL per embryo (n = 630 eggs total) on one of the following Days: 1, 4, or 7 through 18 of embryogenesis. There was no significant difference in hatchability between control and cGH treatment groups on any given injection day. Cumulative feed conversion of all treatment groups was improved relative to their respective control groups (P < 0.05). In ovo administration of cGH on Day 15 or 16 of incubation increased body weights (P < 0.01) of female broilers. On the other hand, body weights of male broilers were significantly increased by treatment on Day 1 (P < 0.04). Breast weights of female broilers from treatment groups Day 15 or 16 were increased (P < 0.01, P < 0.05, respectively). Liver weights of female broilers from treatment groups Day 1 and 15 were increased (P < 0.05, P < 0.01, respectively). In contrast, in ovo administration of cGH on Day 11 of incubation increased liver weights of male broilers (P < 0.03). There was no significant difference between control and treatment groups, in terms of heart or leg weights, or in Warner-Bratzler shear force of Pectoralis profundus muscle. Hydroxyproline concentration and cross-sectional area of female broiler tibias from treatment groups Day 11 or Day 16 were increased (P < 0.05), and ultimate breaking strength (stress) of tibias from the same groups was reduced (P < 0.05). In ovo administration of cGH altered growth and tissue development of broiler chickens in a time by sex dependent fashion.

  6. Exercise and the growth hormone-insulin-like growth factor axis.

    PubMed

    Frystyk, Jan

    2010-01-01

    Exercise is a robust physiological stimulator of the pituitary secretion of growth hormone (GH), and within approximately 15 min after the onset of exercise, plasma GH starts to increase. GH and its primary downstream mediator, insulin-like growth factor I (IGF-I), play a critical role in formation, maintenance, and regeneration of skeletal muscles. Consequently, it seems logical to link the exercise-induced stimulation of GH with the hypertrophy observed in exercising muscles. GH stimulates circulating (endocrine) as well as locally produced (peripheral) IGF-I, which acts through autocrine/paracrine mechanisms. However, it remains to be clarified whether skeletal muscle hypertrophy after exercise is stimulated primarily by endocrine or paracrine/autocrine IGF-I. Early cross-sectional studies have observed positive correlations between circulating IGF-I levels and GH secretion, respectively, and indices of fitness. However, longitudinal exercise studies have shown that it is possible to increase muscle strength, performance, and VO2max without concomitant and robust changes in circulating IGF-I, indicating that the effect of exercise on skeletal muscles is mediated via paracrine/autocrine IGF-I rather than endocrine IGF-I. So far, most exercise studies have investigated the concentration of immunoreactive IGF-I in serum or plasma, obtained after extraction of the IGF-binding proteins (i.e., total IGF-I). However, several of the newer exercise studies have included measurement of free IGF-I as well as bioactive IGF-I. The aim of this review was to discuss whether measurement of free and/or bioactive IGF-I have increased our knowledge on the processes that link exercise, muscle hypertrophy, and GH/IGF-I axis. Thus, the current review will discuss (i) the different IGF-I assay methodologies and (ii) the current literature on free, bioactive, and immunoreactive (total) IGF-I in exercising subjects.

  7. Effect of season on milk temperature, milk growth hormone, prolactin, and somatic cell counts of lactating cattle

    NASA Astrophysics Data System (ADS)

    Igono, M. O.; Johnson, H. D.; Steevens, B. J.; Hainen, W. A.; Shanklin, M. D.

    1988-09-01

    Monthly fluctuations in milk temperature, somatic cell counts, milk growth hormone and prolactin of lactating cows were measured in milk samples over a 1 year period. The seasonal patterns in milk temperature, somatic cell count and milk prolactin concentration showed a positive trend with increasing environmental temperatures. Milk growth hormone concentration increased with lactation level and declined significantly during summer heat. Milk temperature and the measured hormonal levels may serve as indicators of the impact of the climatic environment on lactating cattle.

  8. Doping with growth hormone/IGF-1, anabolic steroids or erythropoietin: is there a cancer risk?

    PubMed

    Tentori, Lucio; Graziani, Grazia

    2007-05-01

    Anabolic steroid and peptide hormones or growth factors are utilized to increase the performance of athletes of professional or amateur sports. Despite their well-documented adverse effects, the use of some of these agents has significantly grown and has been extended also to non-athletes with the aim to improve appearance or to counteract ageing. Pre-clinical studies and epidemiological observations in patients with an excess of hormone production or in patients chronically treated with hormones/growth factors for various pathologies have warned about the potential risk of cancer development and progression which may be also associated to the use of certain doping agents. Anabolic steroids have been described to provoke liver tumours; growth hormone or high levels of its mediator insulin-like growth factor-1 (IGF-1) have been associated with colon, breast, and prostate cancers. Actually, IGF-1 promotes cell cycle progression and inhibits apoptosis either by triggering other growth factors or by interacting with pathways which have an established role in carcinogenesis and cancer promotion. More recently, the finding that erythropoietin (Epo) may promote angiogenesis and inhibit apoptosis or modulate chemo- or radiosensitivity in cancer cells expressing the Epo receptor, raised the concern that the use of recombinant Epo to increase tissue oxygenation might favour tumour survival and aggressiveness. Cancer risk associated to doping might be higher than that of patients using hormones/growth factors as replacement therapy, since enormous doses are taken by the athletes often for a long period of time. Moreover, these substances are often used in combination with other licit or illicit drugs and this renders almost unpredictable all the possible adverse effects including cancer. Anyway, athletes should be made aware that long-term treatment with doping agents might increase the risk of developing cancer.

  9. [Relationship between drought resistance and endogenous hormone content in different citrus species].

    PubMed

    Ma, Wen-Tao; Fan, Wei-Guo

    2014-01-01

    Eight plant seedlings of citrus species, Citrus tangerina, C. erythrosa, C. chuana, Poncirus trifoliate, C. sinensis x P. trifoliate, C. grandis, C. sinensis and C. vessucosa were used to investigate the effects of drought stress on plant biomass, drought resistance coefficient and leaf hormone (ABA, GA1+3 , ZR, IAA) changes. The results showed that, on the condition of precipitation less than 1200 mm, the biomass of different citrus species reduced obviously, and drought-resistance index and drought resistance showed in order of C. erythrosa > C. tangerina > P. trifoliate > C. chuana > C. sinensis x P. trifoliate > C. grandis > C. sinensis > C. vessucosa. The leaf ABA contents of the eight species increased whereas GA1+3 , ZR and IAA decreased, under the condition of drought stress. The ratios of ABA/GA1+3 and ABA/ZR in the species of C. erythrosa and C. tangerina increased drastically, yet there was no significant correlation between the ratio of ABA/IAA and the drought tolerance. The drought-resistance index was significantly positively related to the relative content of ABA (P < 0.01), while significantly negatively related to the relative content of GA1+3. The function to enhance drought resistance by those endogenous hormones in the citrus species showed in order of ABA > GA1+3, ZR > IAA. PMID:24765854

  10. Short-term effects of recombinant human growth hormone and feeding on gluconeogenesis in humans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    After a short-term fast, lactating women have increased rates of glucose production but not gluconeogenesis (GNG) despite relative hypoinsulinemia. We explored the effects of non-insulin-dependent increase in glucose utilization and recombinant human growth hormone (rhGH) on glucose production, glyc...

  11. Growth Hormone Effects in Immune Stress: AKT/eNOS Signaling Module in the Cellular Response

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The activation of the constitutive endothelial nitric-oxide synthase (eNOS) and expression of inducible NOS (iNOS) with subsequent nitric oxide production are among the early cellular responses that follow in a systemic exposure of animals to lipopolysaccharide (LPS). Growth hormone (GH) has been sh...

  12. Increased daylength stimulates plasma growth hormone and gill Na+, K+ and -ATPase Atlantic salmon (Salmo salar )

    USGS Publications Warehouse

    McCormick, S.D.; Bjornsson, Bjorn Thrandur; Sheridan, M.; Eilertson, C.; Carey, J.B.; O'Dea, M.

    1995-01-01

    Atlantic salmon juveniles reared at constant temperature (9–10°C) were exposed to four photoperiod treatment and sampled every 2 weeks from January through May. Fish reared under normal photoperiod exhibited eight-and three fold increases in plasma growth hormone and gill Na+, K+-ATPase activity, respectively, between January and April. Fish exposed to abrupt increases in daylength (LD 15:9) in February or March responded with earlier increases in plasma growth hormone and gill Na+, K+-ATPase activity, and earlier decreases in condition factor relative to fish in the normal photoperiod group. Fish maintained under short daylength (LD 9:15) from January to May exhibited delayed and muted increases in plasma growth hormone and gill Na+, K+-ATPase activity. Plasma thyroxine exhibited a 2.5-fold increase from February to late March in the normal photoperiod group, was generally lower in the LD 9:15 group, but exhibited no obvious response to abrupt increases in daylength. There was an increase in plasma 3,5,3′-triiodo-l-thyronine with time in all groups (43–80%) but no significant response to photoperiod. Plasma levels of somatostatin-25 were highest in the LD 9:15 group, but there was no detectable response to increased daylength in any of the photoperiod treatments. The results indicate that plasma growth hormone is responsive to increased daylength and may be causally related to subsequent increases in gill Na+, K+-ATPase.

  13. Effects of sericin on the testicular growth hormone/insulin-like growth factor-1 axis in a rat model of type 2 diabetes

    PubMed Central

    Song, Cheng-Jun; Yang, Zhen-Jun; Tang, Qi-Feng; Chen, Zhi-Hong

    2015-01-01

    This study investigated the effects of sericin on the testicular growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis in rats with type 2 diabetes mellitus. Forty rats were randomly assigned to normal control, type 2 diabetes mellitus, sericin and metformin treated groups. Type 2 diabetes was established by repeated intraperitoneal injection of streptozotocin, and identified by blood glucose ≥16.7 mmol/L at 1 week. The diabetic rats were given no other treatment, these rats in the sericin group were intragastrically perfused with 2.4 g/kg sericin and the metformin treated rats were intragastrically perfused with 55.33 mg/kg Metformin daily for 35 consecutive days. Enzyme-linked immunosorbent assays were used to determine serum testosterone, growth hormone and IGF-1 levels. Immunohistochemical staining, western blotting and reverse transcription-PCR were used to determine testicular growth hormone, growth hormone receptor and IGF-1 expression. The sericin significantly reduced serum growth hormone levels, downregulated growth hormone expression, increased serum testosterone and IGF-1 levels, and upregulated testicular growth hormone receptor and IGF-1 expression. Moreover, there were no significant differences in any of the parameters between the sericin and metformin treated groups. These findings indicated that sericin improved spermatogenic function through regulating the growth hormone/IGF-1 axis, thereby protecting reproductive function against diabetes-induced damage. PMID:26379831

  14. Hormone replacement therapy in children: The use of growth hormone and IGF-I.

    PubMed

    Pfäffle, Roland

    2015-06-01

    Recombinant human GH (rhGH) has been available since 1985. This article gives an overview, what has been achieved over the past 30 years in respect to optimization of rhGH treatment for the individual child with GH deficiency and what are the safety issues concerned with this treatment. In the last twenty years significant scientific progress has been made in the diagnosis of GH deficiency, the genetic disorders that are associated with pituitary GH deficiency and the genetics that influence growth in general. On the other hand rhGH is not only used in states of GH deficiency but also various conditions without a proven GH deficiency by classical standards. Clinical studies that investigated both the genetics of growth and the individual responses to rhGH therapy in these patient populations were able to refine our concept about the physiology of normal growth. In most patients under rhGH treatment there is a considerable short-term effect, however the overall gain in growth obtained by a long-term treatment until final height still remains a matter of debate in some of the conditions treated. Also first studies on the long-term safety risks of rhGH treatment have raised the question whether this treatment is similarly safe for all the patient groups eligible for such a treatment. Therefore even in the face of a longstanding safety record of this drug replacement therapy the discussion about the right cost and risk to benefit ratio is continuing. Consequently there is still a need for carefully conducted long-term studies that use modern anthropometric, genetic, and laboratory techniques in order to provide the necessary information for clinicians to select the patients that will benefit best from this valuable treatment without any long term risk.

  15. Hormone replacement therapy in children: The use of growth hormone and IGF-I.

    PubMed

    Pfäffle, Roland

    2015-06-01

    Recombinant human GH (rhGH) has been available since 1985. This article gives an overview, what has been achieved over the past 30 years in respect to optimization of rhGH treatment for the individual child with GH deficiency and what are the safety issues concerned with this treatment. In the last twenty years significant scientific progress has been made in the diagnosis of GH deficiency, the genetic disorders that are associated with pituitary GH deficiency and the genetics that influence growth in general. On the other hand rhGH is not only used in states of GH deficiency but also various conditions without a proven GH deficiency by classical standards. Clinical studies that investigated both the genetics of growth and the individual responses to rhGH therapy in these patient populations were able to refine our concept about the physiology of normal growth. In most patients under rhGH treatment there is a considerable short-term effect, however the overall gain in growth obtained by a long-term treatment until final height still remains a matter of debate in some of the conditions treated. Also first studies on the long-term safety risks of rhGH treatment have raised the question whether this treatment is similarly safe for all the patient groups eligible for such a treatment. Therefore even in the face of a longstanding safety record of this drug replacement therapy the discussion about the right cost and risk to benefit ratio is continuing. Consequently there is still a need for carefully conducted long-term studies that use modern anthropometric, genetic, and laboratory techniques in order to provide the necessary information for clinicians to select the patients that will benefit best from this valuable treatment without any long term risk. PMID:26051295

  16. Contribution of Estrone Sulfate to Cell Proliferation in Aromatase Inhibitor (AI) -Resistant, Hormone Receptor-Positive Breast Cancer

    PubMed Central

    Hanamura, Toru; Gohno, Tatsuyuki; Niwa, Toshifumi; Yamaguchi, Yuri; Horiguchi, Jun; Hayashi, Shin-ichi

    2016-01-01

    Aromatase inhibitors (AIs) effectively treat hormone receptor-positive postmenopausal breast cancer, but some patients do not respond to treatment or experience recurrence. Mechanisms of AI resistance include ligand-independent activation of the estrogen receptor (ER) and signaling via other growth factor receptors; however, these do not account for all forms of resistance. Here we present an alternative mechanism of AI resistance. We ectopically expressed aromatase in MCF-7 cells expressing green fluorescent protein as an index of ER activity. Aromatase-overexpressing MCF-7 cells were cultured in estrogen-depleted medium supplemented with testosterone and the AI, letrozole, to establish letrozole-resistant (LR) cell lines. Compared with parental cells, LR cells had higher mRNA levels of steroid sulfatase (STS), which converts estrone sulfate (E1S) to estrone, and the organic anion transporter peptides (OATPs), which mediate the uptake of E1S into cells. LR cells proliferated more in E1S-supplemented medium than did parental cells, and LR proliferation was effectively inhibited by an STS inhibitor in combination with letrozole and by ER-targeting drugs. Analysis of ER-positive primary breast cancer tissues showed a significant correlation between the increases in the mRNA levels of STS and the OATPs in the LR cell lines, which supports the validity of this AI-resistant model. This is the first study to demonstrate the contribution of STS and OATPs in E1S metabolism to the proliferation of AI-resistant breast cancer cells. We suggest that E1S metabolism represents a new target in AI-resistant breast cancer treatment. PMID:27228187

  17. The expression of growth hormone-releasing hormone (GHRH) and splice variants of its receptor in human gastroenteropancreatic carcinomas

    PubMed Central

    Busto, Rebeca; Schally, Andrew V.; Varga, Jozsef L.; Garcia-Fernandez, M. Olga; Groot, Kate; Armatis, Patricia; Szepeshazi, Karoly

    2002-01-01

    Splice variants (SVs) of receptors for growth hormone-releasing hormone (GHRH) have been found in primary human prostate cancers and diverse human cancer cell lines. GHRH antagonists inhibit growth of various experimental human cancers, including pancreatic and colorectal, xenografted into nude mice or cultured in vitro, and their antiproliferative action could be mediated in part through SVs of GHRH receptors. In this study we examined the expression of mRNA for GHRH and for SVs of its receptors in tumors of human pancreatic, colorectal, and gastric cancer cell lines grown in nude mice. mRNA for both GHRH and SV1 isoform of GHRH receptors was expressed in tumors of pancreatic (SW1990, PANC-1, MIA PaCa-2, Capan-1, Capan-2, and CFPAC1), colonic (COLO 320DM and HT-29), and gastric (NCI-N87, HS746T, and AGS) cancer cell lines; mRNA for SV2 was also present in Capan-1, Capan-2, CFPAC1, HT-29, and NCI-N87 tumors. In proliferation studies in vitro, the growth of pancreatic, colonic, and gastric cancer cells was stimulated by GHRH(1–29)NH2 and inhibited by GHRH antagonist JV-1–38. The stimulation of some gastroenteropancreatic cancer cells by GHRH was followed by an increase in cAMP production, and GHRH antagonist JV-1–38 competitively inhibited this effect. Our study indicates the presence of an autocrine/paracrine stimulatory loop based on GHRH and SV1 of GHRH receptors in human pancreatic, colorectal, and gastric cancers. The finding of SV1 receptor in human cancers provides an approach to an antitumor therapy based on the blockade of this receptor by specific GHRH antagonists. PMID:12186980

  18. Information for People Treated with Human Growth Hormone (Comprehensive Report)

    MedlinePlus

    ... org ) is a nonprofit organization concerned with children's growth disorders and adult GH deficiency. The HGF has information available online and through its toll-free number, 1–800–451–6434. The HGF also supports an Internet mailing list to help the exchange of information ...

  19. Hypothalamic hamartoma associated with central precocious puberty and growth hormone deficiency.

    PubMed

    Rousseau-Nepton, Isabelle; Kaduri, Sagi; Garfield, Natasha; Krishnamoorthy, Preetha

    2014-01-01

    Hypothalamic hamartomas (HHs) are tumors generally associated with isolated central precocious puberty (CPP). To our knowledge, we report a unique case of a girl with HH associated with CPP and growth hormone deficiency. This case highlights the complex interaction between HHs and the hypothalamic-pituitary-gonadal axis. It also emphasizes the value of close follow-up of growth velocity in these patients even after treatment of the CPP.

  20. Effects of intravenous corticotropin-releasing hormone upon sleep-related growth hormone surge and sleep EEG in man.

    PubMed

    Holsboer, F; von Bardeleben, U; Steiger, A

    1988-07-01

    Corticotropin-releasing hormone (CRH) plays a key role in coordinating neuroendocrine, metabolic and behavioral responses in stress and affective disorders. To further investigate the effects of enhanced pituitary-adrenocortical activity upon sleep-related phenomena we administered four intravenous injections of 50 micrograms human (h)-CRH or saline to 11 normal males at 10 p.m., 11 p.m., 12 p.m. and 1 a.m. and measured plasma levels of cortisol and growth hormone (GH) as well as sleep EEG recordings throughout the night. Treatment with h-CRH resulted in a significant increase of mean (+/- SEM) cortisol secretion between 11 p.m. and 3 a.m. (h-CRH: 100.6 +/- 9.5 ng/ml; saline: 39.0 +/- 1.5 ng/ml; p less than 0.01). This initial cortisol increase after repeated h-CRH stimulations was followed by a period of attenuated plasma cortisol between 3 and 7 a.m. (h-CRH: 70.3 +/- 7.0 ng/ml; saline: 115.5 +/- 8.0 ng/ml; p less than 0.01). Cortisol surges after h-CRH were associated with a significant blunting of sleep-related GH release expressed as areas under concentration curves (h-CRH: 1.245 +/- 0.32 ng/ml/min.10(3); saline: 2.462 +/- 0.92 ng/ml/min.10(3), p less than 0.01). In addition to these hormonal effects, h-CRH induced a decrease of REM and slow wave sleep (stages III and IV) while the amount of more shallow sleep (stages I and II) increased. These effects upon sleep structure were more pronounced during the second part of the night.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. [Study on exogenous hormones inducing parthenocarpy fruit growth and development and quality of Siraitia grosvenorii].

    PubMed

    Huang, Jie; Tu, Dong-ping; Ma, Xiao-jun; Mo, Chang-ming; Pan, Li-mei; Bai, Long-hua; Feng, Shi-xin

    2015-09-01

    To explore the growth and development and analyze the quality of the parthenocarpy fruit induced by exogenous hormones of Siraitia grosvenorii. the horizontal and vertical diameter, volume of the fruit were respectively measured by morphological and the content of endogenous hormones were determined by ELISA. The size and seed and content of mogrosides of mature fruit were determined. The results showed that the fruit of parthenocarpy was seedless and its growth and development is similar to the diploid fruit by hand pollination and triploid fruit by hand pollination or hormones. But the absolute value of horizontal and vertical diameter, volume of parthenocarpy fruit was less than those of fruit by hand pollination, while triploid was opposite. The content of IAA, ABA and ratio of ABA/GA was obviously wavy. At 0-30 d the content of IAA and ABA of parthenocarpy fruit first reduced then increased, content of IAA and GA parthenocarpy fruit was higher than that of fruit by hand pollination. Mogrosides of parthenocarpy fruit was close to pollination fruit. Hormones can induce S. grosvenorii parthenocarpy to get seedless fruit and the fruit shape and size and quality is close to normal diploid fruit by hand pollination and better than triploid fruit by hormone or hand pollination. PMID:26983201

  2. [Study on exogenous hormones inducing parthenocarpy fruit growth and development and quality of Siraitia grosvenorii].

    PubMed

    Huang, Jie; Tu, Dong-ping; Ma, Xiao-jun; Mo, Chang-ming; Pan, Li-mei; Bai, Long-hua; Feng, Shi-xin

    2015-09-01

    To explore the growth and development and analyze the quality of the parthenocarpy fruit induced by exogenous hormones of Siraitia grosvenorii. the horizontal and vertical diameter, volume of the fruit were respectively measured by morphological and the content of endogenous hormones were determined by ELISA. The size and seed and content of mogrosides of mature fruit were determined. The results showed that the fruit of parthenocarpy was seedless and its growth and development is similar to the diploid fruit by hand pollination and triploid fruit by hand pollination or hormones. But the absolute value of horizontal and vertical diameter, volume of parthenocarpy fruit was less than those of fruit by hand pollination, while triploid was opposite. The content of IAA, ABA and ratio of ABA/GA was obviously wavy. At 0-30 d the content of IAA and ABA of parthenocarpy fruit first reduced then increased, content of IAA and GA parthenocarpy fruit was higher than that of fruit by hand pollination. Mogrosides of parthenocarpy fruit was close to pollination fruit. Hormones can induce S. grosvenorii parthenocarpy to get seedless fruit and the fruit shape and size and quality is close to normal diploid fruit by hand pollination and better than triploid fruit by hormone or hand pollination.

  3. Correlating electrical resistance to growth conditions for multiwalled carbon nanotubes

    SciTech Connect

    Lan, Chun; Amama, Placidus B.; Fisher, Timothy S.; Reifenberger, Ronald G.

    2007-08-27

    A correlation between growth temperature and electrical resistance of multiwalled carbon nanotubes (MWNTs) has been established by measuring the resistance of individual MWNTs grown by microwave plasma-enhanced chemical vapor deposition (PECVD) at 800, 900, and 950 deg. C. The lowest resistances were obtained mainly from MWNTs grown at 900 deg. C. The MWNT resistance is larger on average at lower (800 deg. C) and higher (950 deg. C) growth temperatures. The resistance of MWNTs correlated well with other MWNT quality indices obtained from Raman spectra. This study identifies a temperature window for growing higher-quality MWNTs with fewer defects and lower resistance by PECVD.

  4. Correlating electrical resistance to growth conditions for multiwalled carbon nanotubes

    NASA Astrophysics Data System (ADS)

    Lan, Chun; Amama, Placidus B.; Fisher, Timothy S.; Reifenberger, Ronald G.

    2007-08-01

    A correlation between growth temperature and electrical resistance of multiwalled carbon nanotubes (MWNTs) has been established by measuring the resistance of individual MWNTs grown by microwave plasma-enhanced chemical vapor deposition (PECVD) at 800, 900, and 950°C. The lowest resistances were obtained mainly from MWNTs grown at 900°C. The MWNT resistance is larger on average at lower (800°C) and higher (950°C) growth temperatures. The resistance of MWNTs correlated well with other MWNT quality indices obtained from Raman spectra. This study identifies a temperature window for growing higher-quality MWNTs with fewer defects and lower resistance by PECVD.

  5. Effects of a growth hormone-releasing hormone antagonist on telomerase activity, oxidative stress, longevity, and aging in mice

    PubMed Central

    Banks, William A.; Morley, John E.; Farr, Susan A.; Price, Tulin O.; Ercal, Nuran; Vidaurre, Irving; Schally, Andrew V.

    2010-01-01

    Both deficiency and excess of growth hormone (GH) are associated with increased mortality and morbidity. GH replacement in otherwise healthy subjects leads to complications, whereas individuals with isolated GH deficiency such as Laron dwarfs show increased life span. Here, we determined the effects of treatment with the GH-releasing hormone (GHRH) receptor antagonist MZ-5-156 on aging in SAMP8 mice, a strain that develops with aging cognitive deficits and has a shortened life expectancy. Starting at age 10 mo, mice received daily s.c. injections of 10 μg/mouse of MZ-5-156. Mice treated for 4 mo with MZ-5-156 showed increased telomerase activity, improvement in some measures of oxidative stress in brain, and improved pole balance, but no change in muscle strength. MZ-5-156 improved cognition after 2 mo and 4 mo, but not after 7 mo of treatment (ages 12, 14 mo, and 17 mo, respectively). Mean life expectancy increased by 8 wk with no increase in maximal life span, and tumor incidence decreased from 10 to 1.7%. These results show that treatment with a GHRH antagonist has positive effects on some aspects of aging, including an increase in telomerase activity. PMID:21135231

  6. Structural and functional divergence of growth hormone-releasing hormone receptors in early sarcopterygians: lungfish and Xenopus.

    PubMed

    Tam, Janice K V; Chow, Billy K C; Lee, Leo T O

    2013-01-01

    The evolutionary trajectories of growth hormone-releasing hormone (GHRH) receptor remain enigmatic since the discovery of physiologically functional GHRH-GHRH receptor (GHRHR) in non-mammalian vertebrates in 2007. Interestingly, subsequent studies have described the identification of a GHRHR(2) in chicken in addition to the GHRHR and the closely related paralogous receptor, PACAP-related peptide (PRP) receptor (PRPR). In this article, we provide information, for the first time, on the GHRHR in sarcopterygian fish and amphibians by the cloning and characterization of GHRHRs from lungfish (P. dolloi) and X. laevis. Sequence alignment and phylogenetic analyses demonstrated structural resemblance of lungfish GHRHR to their mammalian orthologs, while the X. laevis GHRHR showed the highest homology to GHRHR(2) in zebrafish and chicken. Functionally, lungfish GHRHR displayed high affinity towards GHRH in triggering intracellular cAMP and calcium accumulation, while X. laevis GHRHR(2) was able to react with both endogenous GHRH and PRP. Tissue distribution analyses showed that both lungfish GHRHR and X. laevis GHRHR(2) had the highest expression in brain, and interestingly, X. laevis(GHRHR2) also had high abundance in the reproductive organs. These findings, together with previous reports, suggest that early in the Sarcopterygii lineage, GHRHR and PRPR have already established diverged and specific affinities towards their cognate ligands. GHRHR(2), which has only been found in xenopus, zebrafish and chicken hitherto, accommodates both GHRH and PRP.

  7. Older individuals heterozygous for a growth hormone-releasing hormone receptor gene mutation are shorter than normal subjects.

    PubMed

    Aguiar-Oliveira, Manuel H; Cardoso-Filho, Marco A; Pereira, Rossana M C; Oliveira, Carla R P; Souza, Anita H O; Santos, Elenilde G; Campos, Viviane C; Valença, Eugênia H O; de Oliveira, Francielle T; Oliveira-Neto, Luiz A; Gois-Junior, Miburge B; Oliveira-Santos, Alecia A; Salvatori, Roberto

    2015-06-01

    Growth hormone (GH)-releasing hormone (GHRH) is the most important stimulus for GH secretion by the pituitary gland. Subjects homozygous for GHRH receptor (GHRHR) gene (GHRHR) inactivating mutations have severe GH deficiency, resulting in severe short stature if not treated. We previously reported that young adults heterozygous for the c.57+1G>A null GHRHR mutation (MUT/N) have reduced weight and body mass index (BMI) but normal stature. Here we have studied whether older MUT/N have an additional phenotype. In a cross-sectional study, we measured height, weight and blood pressure, and calculated BMI in two groups (young, 20-40 years of age) and old (60-80 years) of individuals heterozygous for the same GHRHR mutation, and compared with a large number of individuals of normal genotype residing in the same geographical area. Standard deviation score (SDS) of weight was lower, and BMI had a trend toward reduction in young heterozygous compared with young normals, without significant difference in stature. Conversely, SDS of height was lower in older heterozygous individuals than in controls, corresponding to a reduction of 4.2 cm. These data show a reduced stature in older subjects heterozygous for the c.57+1G>A GHRHR mutation, indicating different effects of heterozygosis through lifespan. PMID:25761575

  8. MEAT SCIENCE AND MUSCLE BIOLOGY SYMPOSIUM--mechanism of growth hormone stimulation of skeletal muscle growth in cattle.

    PubMed

    Jiang, H; Ge, X

    2014-01-01

    Growth hormone, also called somatotropin (ST), is a polypeptide hormone produced by the anterior pituitary. The major functions of GH include stimulating bone and skeletal muscle growth, lipolysis, milk production, and expression of the IGF-I gene in the liver. Based on these functions, recombinant bovine ST (bST) and recombinant porcine ST (pST) have been used to improve milk production in dairy cows and lean tissue growth in pigs, respectively. However, despite these applications, the mechanisms of action of GH are not fully understood. Indeed, there has been a lot of controversy over the role of liver-derived circulating IGF-I and locally produced IGF-I in mediating the growth-stimulatory effect of GH during the last 15 yr. It is in this context that we have conducted studies to further understand how GH stimulates skeletal muscle growth in cattle. Our results do not support a role of skeletal muscle-derived IGF-I in GH-stimulated skeletal muscle growth in cattle. Our results indicate that GH stimulates skeletal muscle growth in cattle, in part, by stimulating protein synthesis in muscle through a GH receptor-mediated, IGF-I-independent mechanism. In this review, besides discussing these results, we also argue that liver-derived circulating IGF-I should be still considered as the major mechanism that mediates the growth-stimulatory effect of GH on skeletal muscle in cattle and other domestic animals.

  9. A comparison of fasting plasma insulin and growth hormone concentrations in marasmic, kwashiorkor, marasmic-kwashiorkor and underweight children.

    PubMed

    Robinson, H; Picou, D

    1977-05-01

    Fasting plasma insulin and growth hormone concentrations were measured in 24 marasmic, 11 kwashiorkor, 16 marasmic-kwashiorkor, and 4 underweight children. Hormone measurements were made by a special modification of the Hales and Randle double antibody immunoassay with increased sensitivity in the concentration range 0-25 micronU/ml. Fasting plasma insulin was low in marasmus, kwashiorkor, and marasmic-kwashiorkor children, and increased to normal levels after recovery. Fasting plasma growth hormone was elevated in all groups during malnutrition and was significantly decreased to normal levels after recovery. There were no significant differences in plasma insulin or growth hormone levels between the different clinical types of severe protein energy malnutrition. These hormonal changes in severe protein energy malnutrition are of complex and not fully understood etiology. However, recovered children appear to have a hormonal pattern similar to that described in normal control infants and children.

  10. Peptide T bolus normalizes the growth hormone secretion pattern in two children with AIDS.

    PubMed

    Barbey-Morel, Charlotte; McDonnell, Kevin; Pert, Candace B; Adams, MerriBeth; Farrand, Dean; Ruff, Michael R; Lumpkin, Michael D

    2002-12-01

    In humans, HIV infection reduces growth hormone (GH) secretion contributing to AIDS wasting. In rats, the HIV envelope protein gp120 alone blocks GH secretion both in vitro and in vivo through GH-releasing hormone receptors. Peptide T, a modified octapeptide derived from gp120, normalizes GH secretion. We now report that an intravenous bolus of peptide T normalizes nocturnal GH secretion in two out of three children with AIDS. These results, coupled with the lack of toxicity of this experimental AIDS therapeutic, justify clinical trials for AIDS wasting and pediatric AIDS. A clinical and basic science update on peptide T appears in Current HIV Research. PMID:12535709

  11. Effects of growth hormone and low dose estrogen on bone growth and turnover in long bones of hypophysectomized rats

    NASA Technical Reports Server (NTRS)

    Kidder, L. S.; Schmidt, I. U.; Evans, G. L.; Turner, R. T.

    1997-01-01

    Pituitary hormones are recognized as critical to longitudinal growth, but their role in the radial growth of bone and in maintaining cancellous bone balance are less clear. This investigation examines the histomorphometric effects of hypophysectomy (Hx) and ovariectomy (OVX) and the subsequent replacement of growth hormone (GH) and estrogen (E), in order to determine the effects and possible interactions between these two hormones on cortical and cancellous bone growth and turnover. The replacement of estrogen is of interest since Hx results in both pituitary and gonadal hormone insufficiencies, with the latter being caused by the Hx-associated reduction in follicle stimulating hormone (FSH). All hypophysectomized animals received daily supplements of hydrocortisone (500 microg/kg) and L-thyroxine (10 microg/kg), whereas intact animals received daily saline injections. One week following surgery, hypophysectomized animals received either daily injections of low-dose 17 beta-estradiol (4.8 microg/kg s.c.), 3 X/d recombinant human GH (2 U/kg s.c.), both, or saline for a period of two weeks. Flurochromes were administered at weekly intervals to label bone matrix undergoing mineralization. Whereas Hx resulted in reductions in body weight, uterine weight, and tibial length, OVX significantly increased body weight and tibial length, while reducing uterine weight. The combination of OVX and Hx resulted in values similar to Hx alone