Growth hormone receptor deficiency results in blunted ghrelin feeding response, obesity, and hypolipidemia in mice

2006 ◽  
Vol 290 (2) ◽  
pp. E317-E325 ◽  
Author(s):  
Emil Egecioglu ◽  
Mikael Bjursell ◽  
Anna Ljungberg ◽  
Suzanne L. Dickson ◽  
John J. Kopchick ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Food Intake ◽  
Growth Hormone Receptor ◽  
Hdl Cholesterol ◽  
Serum Levels ◽  
High Plasma ◽  
Littermate Control ◽  
Apo B ◽  
Gh Secretion ◽  
Increase Food Intake

We have previously shown that growth hormone (GH) overexpression in the brain increased food intake, accompanied with increased hypothalamic agouti-related protein (AgRP) expression. Ghrelin, which stimulates both appetite and GH secretion, was injected intracerebroventricularly to GHR−/− and littermate control (+/+) mice to determine whether ghrelin's acute effects on appetite are dependent on GHR signaling. GHR−/− mice were also analyzed with respect to serum levels of lipoproteins, apolipoprotein (apo)B, leptin, glucose, and insulin as well as body composition. Central injection of ghrelin into the third dorsal ventricle increased food consumption in +/+ mice, whereas no change was observed in GHR−/− mice. After ghrelin injection, AgRP mRNA expression in the hypothalamus was higher in +/+ littermates than in GHR−/− mice, indicating a possible importance of AgRP in the GHR-mediated effect of ghrelin. Compared with controls, GHR−/− mice had increased food intake, leptin levels, and total and intra-abdominal fat mass per body weight and deceased lean mass. Moreover, serum levels of triglycerides, LDL and HDL cholesterol, and apoB, as well as glucose and insulin levels were lower in the GHR−/− mice. In summary, ghrelin's acute central action to increase food intake requires functionally intact GHR signaling. Long-term GHR deficiency in mice is associated with high plasma leptin levels, obesity, and increased food intake but a marked decrease in all lipoprotein fractions.

Disturbances of growth hormone-insulin-like growth factor axis and response to growth hormone in acidosis

1998 ◽  
Vol 275 (1) ◽  
pp. R120-R128
Author(s):  
Karina Jandziszak ◽  
Carlos Suarez ◽  
Ethan Wasserman ◽  
Ross Clark ◽  
Bonnie Baker ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Food Intake ◽  
Linear Growth ◽  
Growth Failure ◽  
Serum Levels ◽  
Igf Binding Proteins ◽  
Gh Secretion ◽  
Term Administration ◽  
Igf Binding ◽  
Final Length

Severe chronic metabolic acidosis (CMA) in rats is associated with poor food intake and downregulation of growth hormone (GH), insulin-like growth factors (IGFs), and liver receptors; the administration of recombinant GH (rGH) fails to improve the growth failure. In mice with carbonic anhydrase II deficiency (CAD), a model of moderate CMA with food intake close to normal, we studied serum levels of GH, IGFs, and IGF-binding proteins, and the growth response to rGH. CAD was associated with low serum levels of GH in males. Randomized administration of rGH from ∼5 to ∼12 wk to CAD mice improved food efficiency and increased serum IGF-I levels, final length, and weight compared with placebo without affecting blood pH. Although administration of rGH also increased linear growth in healthy animals, the effect was less than that in CAD mice and was only observed when started before 6 wk of life. Thus growth failure in CAD mice is associated with a decrease in GH secretion in males but not in females. Long-term administration of rGH increases linear growth in CAD mice despite persistent CMA.

scholarly journals 17α-Estradiol Modulates IGF1 and Hepatic Gene Expression in a Sex-Specific Manner

2020 ◽  
Author(s):  
Silvana Sidhom ◽  
Augusto Schneider ◽  
Yimin Fang ◽  
Samuel McFadden ◽  
Justin Darcy ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Insulin Sensitivity ◽  
Growth Hormone Receptor ◽  
Health Benefits ◽  
Male Mice ◽  
Wild Type ◽  
Somatotropic Axis ◽  
Gh Secretion ◽  
17Β Estradiol ◽  
Estradiol 17Β

Abstract Aging is the greatest risk factor for most chronic diseases. The somatotropic axis is one of the most conserved biological pathways that regulates aging across species. 17α-Estradiol (17α-E2), a diastereomer of 17β-estradiol (17β-E2), was recently found to elicit health benefits, including improved insulin sensitivity and extend longevity exclusively in male mice. Given that 17β-E2 is known to modulate somatotropic signaling in females through actions in the pituitary and liver, we hypothesized that 17α-E2 may be modulating the somatotropic axis in males, thereby contributing to health benefits. Herein, we demonstrate that 17α-E2 increases hepatic insulin-like growth factor 1 (IGF1) production in male mice without inducing any changes in pulsatile growth hormone (GH) secretion. Using growth hormone receptor knockout (GHRKO) mice, we subsequently determined that the induction of hepatic IGF1 by 17α-E2 is dependent upon GH signaling in male mice, and that 17α-E2 elicits no effects on IGF1 production in female mice. We also determined that 17α-E2 failed to feminize the hepatic transcriptional profile in normal (N) male mice, as evidenced by a clear divergence between the sexes, regardless of treatment. Conversely, significant overlap in transcriptional profiles was observed between sexes in GHRKO mice, and this was unaffected by 17α-E2 treatment. Based on these findings, we propose that 17α-E2 acts as a pleiotropic pathway modulator in male mice by uncoupling IGF1 production from insulin sensitivity. In summary, 17α-E2 treatment upregulates IGF1 production in wild-type (and N) male mice in what appears to be a GH-dependent fashion, while no effects in female IGF1 production are observed following 17α-E2 treatment.

Serum levels of growth hormone during the stunted postnatal development of the vasopressin-deficient Brattleboro rat

1983 ◽  
Vol 98 (3) ◽  
pp. 351-356 ◽  
Author(s):  
G. J. Boer ◽  
M. Rieutort
Keyword(s):  
Growth Hormone ◽  
Postnatal Development ◽  
Serum Levels ◽  
Postnatal Growth ◽  
The Body ◽  
Rapid Decline ◽  
Brattleboro Rats ◽  
Brattleboro Rat ◽  
Gh Secretion ◽  
Constant Period

Levels of GH in serum were assayed during the development of heterozygous (HET) control and vasopressin-deficient homozygous (HOM) Brattleboro rats. In early postnatal growth no differences in GH concentrations were present between HET and HOM rats for the rapid decline in serum levels of GH in the first week and the constant period up to day 24 of age thereafter. However, higher values were found in 55-day-old HOM rats and lower values at the age of 9 months. It is concluded that the stunted development of the body and brain of HOM rats is not GH-related, and that changes or anomalies in GH secretion appear only after neurogenesis has been completed.

scholarly journals Differential Response to Aminergic Stimuli and Biological Behavior of Growth Hormone Secreting Pituitary Adenomas

1990 ◽  
Vol 17 (1) ◽  
pp. 78-82 ◽  
Author(s):  
Guillermo Fanghanel ◽  
Oscar Larraza ◽  
Martha Villalobos ◽  
Leticia Fanghanel ◽  
Marcos Velasco ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Growth Hormone ◽  
Oral Dose ◽  
Single Oral Dose ◽  
Clinical Course ◽  
Serum Levels ◽  
Biological Behavior ◽  
Treatment Results ◽  
Gh Secretion ◽  
Aggressive Tumor

ABSTRACT:Growth hormone (GH) serum levels in response to the administration of aminergic drugs and thyroliberine (TRH) were determined in a group of 34 acromegalics. Administration of bromocriptine (10 mg single oral dose) was followed by a decrease in GH below 60% control values in 35% of the cases. Administration of diazepam (10 mg single oral dose) to those cases not responding to bromocriptine induced a decrease in GH in 58% of the cases and an increase in GH in 42%. Administration of cyproheptadine (24 mg/day for one month) to those cases not responding to bromocriptine or with increased GH after the administration of diazepam, decreased GH in 75%, while increased GH in 25% of the cases. TRH 200 (Xg single I.V. dose induced increase of 128% GH basal level in 65% of cases (TRH positive) which correlated with more benign clinical course, decreased GH levels in response to bromocriptine, increased PRL levels, PRL-GH mixed secreting adenomas in immunohistochemistry studies, presence of granulated cells in electron microscopy studies and normalization of GH in the majority of surgically treated cases. By contrast, TRH negative cells correlated with aggressive tumor growth, lack of response to bromocriptine, normal PRL levels, pure GH secreting adenomas by immunohistochemistry, poorly granulated cells and lack of response to surgical treatment. Results suggest that there is more than one type of acromegaly that might be distinguished by the aminergic control on GH secretion.

Effect of chronic hyperghrelinemia on ingestive action of ghrelin

2006 ◽  
Vol 290 (3) ◽  
pp. R803-R808 ◽  
Author(s):  
Wei Wei ◽  
Xiang Qi ◽  
Jason Reed ◽  
Jeff Ceci ◽  
Hui-Qun Wang ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Food Intake ◽  
Transgenic Mice ◽  
Growth Response ◽  
Fat Pad ◽  
Endogenous Ligand ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Gh Secretion ◽  
Ghrelin Gene

The stomach hormone ghrelin is the endogenous ligand for the growth hormone secretagogue receptor (GHS-R). Systemic administration of ghrelin will cause elevations in growth hormone (GH) secretion, food intake, adiposity, and body growth. Ghrelin also affects insulin secretion, gastric acid secretion, and gastric motility. Several reports indicate that repeated or continuous activation of GHS-R by exogenous GHSs or ghrelin results in a diminished GH secretory response. The purpose of this study was to examine the extent to which the acute stimulation of food intake by exogenous ghrelin is altered by chronic hyperghrelinemia in transgenic mice that overexpress the human ghrelin gene. The present findings show that the orexigenic action of exogenous ghrelin is not diminished by a chronic hyperghrelinemia and indicate that the food ingestive pathway of the GHS-R is not susceptible to desensitization. In contrast, the epididymal fat pad growth response, like the GH response, to exogenous ghrelin is blunted in ghrelin transgenic mice with chronic hyperghrelinemia.

Reduced food intake is the main cause of low growth hormone receptor expression in uremic rats

1994 ◽  
Vol 106 (1-2) ◽  
pp. 51-56 ◽  
Author(s):  
Sandra Mara F. Villares ◽  
Laure Goujon ◽  
Saâd Maniar ◽  
Marie-C. Delehaye-Zervas ◽  
Jean-François Martini ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Food Intake ◽  
Hormone Receptor ◽  
Growth Hormone Receptor ◽  
Receptor Expression ◽  
Hormone Receptor Expression

Regulation by catecholamines of spontaneous growth hormone secretion in the baboon

1981 ◽  
Vol 241 (3) ◽  
pp. E196-E199
Author(s):  
J. K. Stewart ◽  
D. J. Koerker ◽  
C. J. Goodner ◽  
C. C. Gale ◽  
M. F. Minton ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Serum Levels ◽  
Adolescent Male ◽  
Serum Prolactin ◽  
Base Line ◽  
Spontaneous Growth ◽  
Fourfold Increase ◽  
Gh Secretion

To gain an increased understanding of the role of central neurotransmitters in the regulation of spontaneous growth hormone (GH) secretion in the primate, we investigated the effects of peripheral intravenous infusion of the alpha-adrenergic receptor-blocking agent, phentolamine (5.0-mg bolus and 1.5 mg . kg-1 . 12 h-1), and the tyrosine hydroxylase inhibitor, alpha-methyl-p-tyrosine (MPT, 300 mg . kg-1 . 24 h-1), on the pattern of GH secretion in five adolescent male baboons. Serum GH concentrations were measured in blood samples taken at 20-min intervals over 12 h (0530–1730) after an overnight fast. In nontreatment control studies, GH secretion exhibited a predictable rhythmic oscillation with a mean period of 5.7 +/- 0.4 (SE) h. Phentolamine significantly decreased the 12-h mean and integrated GH concentrations compared to control values, but the small peaks of GH, which could be distinguished from base-line concentrations in three of the animals, occurred at the same time as during control studies. Whereas alpha-methyl-p-tyrosine slightly reduced serum levels of GH, it significantly increased the GH pulse frequency in the baboons. A two- to fourfold increase in serum prolactin levels occurred in all animals treated with MPT. These findings suggest that alpha-adrenergic pathways play a stimulatory role in maintaining spontaneous daytime GH secretion in the baboon and that one or more catecholamines are involved in the generation of rhythmic GH release.

Lack of growth hormone response to acute administration of dexamethasone in anorexia nervosa

1995 ◽  
Vol 132 (2) ◽  
pp. 152-158 ◽  
Author(s):  
Massimo Scacchi ◽  
Cecilia Invitti ◽  
Angela I Pincelli ◽  
Claudio Pandolfi ◽  
Antonella Dubini ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Anorexia Nervosa ◽  
Normal Subjects ◽  
High Plasma ◽  
Normal Weight ◽  
Growth Hormone Response ◽  
Acute Administration ◽  
Hormone Response ◽  
Gh Secretion ◽  
Plasma Gh

Scacchi M, Invitti C, Pincelli AI, Pandolfi C, Dubini A, Cavagnini F. Lack of growth hormone response to acute administration of dexamethasone in anorexia nervosa. Eur J Endocrinol 1995;132:152–8. ISSN 0804–4643 High plasma growth hormone (GH) levels, associated with abnormal hormone responses to provocative stimuli, point to an altered GH secretion in anorexia nervosa. The GH-releasing effect of acutely administered glucocorticoids, firmly established in normal subjects, has not been reported in these patients. In this study, acute iv administration of 4 mg of dexamethasone, compared with saline, increased plasma GH in nine normal-weight women (AUC 848.2 ± 127.95 vs 242.8 ± 55.35 μg·l−1·min−1, p < 0.05, respectively) but was ineffective in 11 anorectic patients (AUC 3271.8 ± 1407.11 vs 2780.0 ± 1162.04 μg·l−1·min−1, NS). After dexamethasone, a significant lowering of plasma cortisol was observed in normal women (AUC 25367.0 ± 3128.43 vs 47347.1 ± 4456.61 nmol·l−1·min−1, after dexamethasone and saline, respectively, p < 0.05), but not in anorectic patients (AUC 77809.3 ± 8499.92 vs 78454.9 ± 7603.62 nmol·l−1·min−1, NS). In both groups, plasma adrenocorticotrophin (ACTH) displayed a significant decrease after dexamethasone (AUC 523.6 ± 92.08 vs 874.2 ± 115.03 pmol·l−1·min−1, p < 0.05, after dexamethasone and saline, respectively, in anorectic patients and 377.5 ± 38.41 vs 1004.9 ± 200.51 pmol·l−1·min−1, p < 0.05, in controls). However, when considering the hormonal decremental areas, a significant dexamethasone-induced ACTH inhibition, compared to saline, was evidenced in normal (ΔAUC –414.4 ± 65.75 vs 222.9 ± 42.40 pmol·l−1·min−1, p < 0.05) but not in anorectic women (ΔAUC –254.2 ± 96.92 vs 2.9 ± 132.32 pmol·l−1·min−1, NS). In conclusion, compared to normal subjects, anorectic patients do not display an increase of plasma GH levels and show a lower degree of inhibition of the hypothalamic–pituitary–adrenal axis following acute iv administration of dexamethasone. This observation broadens the array of the abnormal GH responses to provocative stimuli in anorexia nervosa and supports the existence, in these patients, of a decreased hypothalamic somatostatin secretion, although the possibility of a reduced tissue sensitivity to glucocorticoids cannot be excluded. Francesco Cavagnini, 2nd Chair of Endocrinology, University of Milan, Istituto Scientifico Ospedale San Luca, Centro Auxologico Italiano, via Spagnoletto 3, 20149 Milano, Italy

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