Growth Regulation

2011 ◽  
Author(s):  
Jyotsna Keni ◽  
Anna Pawlikowska – Haddal
Keyword(s):  
Growth Hormone ◽  
Growth Regulation ◽  
Somatic Growth ◽  
High Specificity ◽  
Regulatory Peptides ◽  
Postnatal Growth ◽  
Releasing Hormone ◽  
Gh Secretion ◽  
Stimulation Tests ◽  
Main Regulator

While multiple hormones influence somatic growth, the main regulator of postnatal growth is growth hormone. Growth hormone (GH) is secreted in a pulsatile manner from the anterior pituitary primarily as a 22-kilodalton molecule (although other forms may be found). The development of the pituitary gland as well as GH gene expression is regulated by the multiple pituitary transcription factors listed in Table11-1. The Pit-1 and Prop-1 genes encode proteins that are often mutated or deleted in cases of congenital hypopituitarism. Under normal waking conditions, GH levels are often low or undetectable, but several times during the day, and particularly at night during stage 3 of sleep, surges of GH secretion occur. The pulsatile pattern characteristic of GH secretion largely reflects the interaction of multiple regulators, including two hypothalamic regulatory peptides: GH-releasing hormone (GHRH), which stimulates GH secretion, and somatostatin (somatotropin release–inhibiting factor [SRIF]), which inhibits GH secretion. Multiple neurotransmitters and neuropeptides are involved in regulation of release of these hypothalamic factors, including, but not limited to, serotonin, histamine, norepinephrine, dopamine, acetylcholine, γ -aminobutyric acid (GABA), thyroid-releasing hormone, vasoactive intestinal peptide, gastrin, neurotensin, substance P, calcitonin, neuropeptide Y, vasopressin, corticotropinreleasing hormone, and galanin. Many factors influence GH secretion; notably, glucose that inhibits, and certain amino acids and Ghrelin that stimulate GH secretion. GH secretion is also impacted by a variety of nonpeptide hormones, including androgens, estrogens, thyroxine, and glucocorticoids. The precise mechanisms by which these hormones regulate GH secretion are complex, potentially involving actions at both the hypothalamic and pituitary levels. Exogenous physiological and pharmacological factors are known to stimulate GH secretion. Some of these agents, including clonidine, L-dopa, and exercise, are used in GH stimulation tests. In plasma, the majority of GH is bound with high specificity and affinity, but with relatively low capacity to a carrier protein termed GH binding protein (GHBP). The GHBP is a cleavage product of the extracellular domain of the GH receptor.

Genetic defects causing functional and structural isolated growth hormone deficiency

2011 ◽  
Vol 2 (2) ◽  
Author(s):  
Vibor Petkovic ◽  
Primus Mullis
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Somatic Growth ◽  
Human Growth ◽  
Postnatal Growth ◽  
Metabolic Effects ◽  
Hormone Deficiency ◽  
Height Velocity ◽  
Gh Secretion ◽  
Normal Standards

AbstractNormal somatic growth requires the integrated function of many of the hormonal, metabolic, and other growth factors involved in the hypothalamo-pituitary-somatotrope axis. Human growth hormone (hGH) causes a variety of physiological and metabolic effects in humans and its pivotal role in postnatal growth is undisputed. Disturbances that occur during this process often cause subnormal GH secretion and/or subnormal GH sensitivity/responsiveness resulting in short stature. Despite the complexity of this linear growth process, the growth pattern of children, if evaluated in the context of normal standards, is rather predictable. Children presenting with short stature (i.e out of normal standards) are treated with daily injections of recombinant human GH (rhGH), which leads in almost all cases to an increase of height velocity. Although it is becoming more and more evident that many genes are involved in controlling the regulation of growth, the main aim of this review is to focus on the GH-1 gene, the various gene alterations and their important physiological and pathophysiological role in growth.

scholarly journals Decreased galanin mRNA levels in growth hormone-releasing hormone neurons after perinatally induced growth retardation

2001 ◽  
Vol 170 (3) ◽  
pp. 521-528 ◽  
Author(s):  
CT Huizinga ◽  
CB Oudejans ◽  
HA Delemarre-Van de Waal
Keyword(s):  
Growth Hormone ◽  
Growth Retardation ◽  
Adult Stage ◽  
Postnatal Growth ◽  
Hybridization Technique ◽  
Mrna Levels ◽  
Adult Rats ◽  
Double Labeling ◽  
Releasing Hormone ◽  
Gh Secretion

Intrauterine growth retardation (IUGR) is associated with persistent postnatal growth retardation accompanied by dysfunction of the hypothalamic components of the growth hormone (GH) axis. At the adult stage, this is reflected by increased somatostatin (SS) and decreased neuropeptide Y (NPY) mRNA levels, whereas the GH-releasing hormone (GHRH) mRNA levels are normal and the output of GH remains unchanged. To extend our insight into the hypothalamic control of GH secretion in growth retarded rats, we determined galanin (GAL) mRNA levels at the adult stage of perinatally malnourished (i.e. IUGR and early postnatally food restricted) rats. Analyses included comparison of GAL mRNA levels in GHRH neurons in perinatally malnourished adult rats using a semi-quantitative double labeling in situ hybridization technique. We report that IUGR is accompanied by a 60% decrease in GAL mRNA levels in all GHRH neurons in the male IUGR group whereas a tendency towards a decrease was observed in the male early postnatally food restricted (FR) group. These effects became more pronounced when the analysis was restricted to GHRH neurons coexpressing GAL mRNA i.e. decreased GAL mRNA levels were seen in both male and female IUGR rats and in FR males. These data show that GAL mRNA levels in GHRH neurons are persistently decreased after perinatal malnutrition. Taking these results together with our previous data on SS, NPY and GHRH mRNA levels, we can conclude that IUGR leads to a reprogramming of the hypothalamic regulation of GH secretion.

scholarly journals Growth Hormone-Releasing Peptide-2 Stimulates GH Secretion in GH-Deficient Patients with Mutated GH-Releasing Hormone Receptor1

2001 ◽  
Vol 86 (7) ◽  
pp. 3279-3283
Author(s):  
Rogério G. Gondo ◽  
Manuel H. Aguiar-Oliveira ◽  
César Y. Hayashida ◽  
Sergio P. A. Toledo ◽  
Neusa Abelin ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Releasing Hormone ◽  
Gh Secretion

scholarly journals From growth hormone-releasing peptides to ghrelin: discovery of new modulators of GH secretion

2006 ◽  
Vol 50 (1) ◽  
pp. 17-24 ◽  
Author(s):  
Ana Maria J. Lengyel
Keyword(s):  
Growth Hormone ◽  
Protein Kinase ◽  
C Protein ◽  
Releasing Hormone ◽  
Gh Secretagogues ◽  
Main Site ◽  
Gh Secretion ◽  
Kinase C ◽  
Growth Hormone Releasing Peptides

Growth hormone (GH)-releasing hormone and somatostatin modulate GH secretion. A third mechanism has been discovered in the last decade, involving the action of GH secretagogues. Ghrelin is a new acylated peptide produced mainly by the stomach, but also synthesized in the hypothalamus. This compound increases both GH release and food intake. The relative roles of hypothalamic and circulating ghrelin on GH secretion are still unknown. Endogenous ghrelin might amplify the basic pattern of GH secretion, optimizing somatotroph responsiveness to GH-releasing hormone. This peptide activates multiple interdependent intracellular pathways at the somatotroph, involving protein kinase C, protein kinase A and extracellular calcium systems. However, as ghrelin induces a greater release of GH in vivo, its main site of action is the hypothalamus. In this paper we review the available data on the discovery of ghrelin, the mechanisms of action and possible physiological roles of GH secretagogues and ghrelin on GH secretion, and, finally, the regulation of GH release in man after intravenous administration of these peptides.

Pyridostigmine enhances, but does not normalise, the GH response to GH-releasing hormone in obese subjects

1990 ◽  
Vol 122 (3) ◽  
pp. 385-390 ◽  
Author(s):  
R. C. Castro ◽  
J. G. H. Vieira ◽  
A. R. Chacra ◽  
G. M. Besser ◽  
A. B. Grossman ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Acetylcholinesterase Inhibitor ◽  
Random Order ◽  
Normal Subjects ◽  
Obese Patients ◽  
Releasing Hormone ◽  
Gh Secretion ◽  
Obese Subjects ◽  
Higher Doses ◽  
Hormone Responsiveness

Abstract Obese patients are characterised by several neuroendocrine abnormalities, including characteristically a decrease in growth hormone responsiveness to GH-releasing hormone. In normal subjects, the GH response to GHRH is enhanced by the acetylcholinesterase inhibitor, pyridostigmine. We have studied the effect of this drug on GH secretion in gross obesity. Twelve obese patients were studied (mean weight 156% of ideal) and compared with a group of 8 normal volunteers. Each subject was initially studied on two occasions, in random order, with GHRH (1–29) NH2 100 μg iv alone and following pretreatment with pyridostigmine 120 mg orally one hour prior to GHRH. In obese patients, the GH response to GHRH was significantly blunted when compared to controls (GH peak: 20 ± 4 vs 44 ± 16 μg/l; mean ± sem). After pyridostigmine, the response to GHRH was enhanced in the obese subjects, but remained significantly reduced compared to non-obese subjects treated with GHRH and pyridostigmine (GH peak: 30 ± 5 vs 77 ± 20 μg/l, respectively). In 6 subjects, higher doses of GHRH or pyridostigmine did not further increase GH responsiveness in obese patients. Our results suggest that obese patients have a disturbed cholinergic control of GH release, probably resulting from increased somatostatinergic tone. This disturbed regulation may be responsible, at least in part, for the blunted GH responses to provocative stimuli.

The influence of insulin on circulating ghrelin

2003 ◽  
Vol 284 (2) ◽  
pp. E313-E316 ◽  
Author(s):  
Daniel E. Flanagan ◽  
Mark L. Evans ◽  
Teresa P. Monsod ◽  
Frances Rife ◽  
Rubina A. Heptulla ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Energy Homeostasis ◽  
Insulin Infusion ◽  
Significant Rise ◽  
Releasing Hormone ◽  
Gh Secretion ◽  
Physiological Regulator ◽  
Underlying Mechanisms ◽  
Mean Glucose

Ghrelin is a novel peptide that acts on the growth hormone (GH) secretagogue receptor in the pituitary and hypothalamus. It may function as a third physiological regulator of GH secretion, along with GH-releasing hormone and somatostatin. In addition to the action of ghrelin on the GH axis, it appears to have a role in the determination of energy homeostasis. Although feeding suppresses ghrelin production and fasting stimulates ghrelin release, the underlying mechanisms controlling this process remain unclear. The purpose of this study was to test the hypotheses, by use of a stepped hyperinsulinemic eu- hypo- hyperglycemic glucose clamp, that either hyperinsulinemia or hypoglycemia may influence ghrelin production. Having been stable in the period before the clamp, ghrelin levels rapidly fell in response to insulin infusion during euglycemia (baseline ghrelin 207 ± 12 vs. 169 ± 10 fmol/ml at t = 30 min, P < 0.001). Ghrelin remained suppressed during subsequent periods of hypoglycemia (mean glucose 53 ± 2 mg/dl) and hyperglycemia (mean glucose 163 ± 6 mg/dl). Despite suppression of ghrelin, GH showed a significant rise during hypoglycemia (baseline 4.1 ± 1.3 vs. 28.2 ± 3.9 μg/l at t = 120 min, P < 0.001). Our data suggest that insulin may suppress circulating ghrelin independently of glucose, although glucose may have an additional effect. We conclude that the GH response seen during hypoglycemia is not regulated by circulating ghrelin.

Corticotrophin-releasing hormone does not inhibit growth hormone-releasing hormone-induced release of growth hormone in control subjects but is effective in patients with eating disorders

1994 ◽  
Vol 140 (2) ◽  
pp. 327-332 ◽  
Author(s):  
M Rolla ◽  
A Andreoni ◽  
D Bellitti ◽  
M Ferdeghini ◽  
E Ghigo ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Eating Disorders ◽  
Young Women ◽  
Animal Studies ◽  
Area Under The Curve ◽  
Inhibitory Influence ◽  
Releasing Hormone ◽  
Gh Secretion ◽  
Not Otherwise Specified ◽  
Normal Women

Abstract Previous studies have shown that corticotrophin-releasing hormone (CRH) inhibits GH secretion in response to GH-releasing hormone (GHRH) in normal women and men, and animal studies suggest that this effect is mediated by an increased release of somatostatin from the hypothalamus. It has been reported that there are abnormalities in the neuroendocrine regulation of the hypothalamo-pituitary-somatotrophic axis and the hypothalamo-pituitary-adrenocortical axis in patients with eating disorders. The present study therefore investigated the ability of CRH to inhibit the GH response to GHRH in eight young women with anorexia nervosa (AN) and in seven young women with eating disorders which were not otherwise specified (NOS). We also compared the effect of CRH in the patients with the response it caused in ten control women. In contrast to a previous report, combined i.v. administration of 50 μg human CRH (hCRH) and 50 μg GHRH(1–29) caused a GH response in control women which was higher, although not significantly so, than that induced by GHRH alone (area under the curve (AUC) 988·5 ±506·0 compared with 1568·4 ±795·6 (s.e.m.) ng/ml per 120 min for GHRH alone and GHRH plus hCRH respectively). Conversely, the administration of hCRH given together with GHRH markedly inhibited the GH response induced by the latter in both AN patients (AUC 2253·0 ±385·7 compared with 1224·4 ±265·7 ng/ml per 120 min for GHRH and GHRH plus hCRH respectively; P<0·005 and NOS patients (AUC 2827·4±281·1 compared with 308·5 ± 183·4 ng/ml per 120 min for GHRH and GHRH plus hCRH respectively; P<0·0001). These results (1) refute the suggestion that there is an inhibitory influence of CRH over GH secretion under normal conditions, (2) indicate that this inhibitory influence exists in patients with eating disorders, and (3) imply that, in the latter, hypothalamic somatostatinergic function is, at least in part, preserved. Journal of Endocrinology (1994) 140, 327–332

Induction of growth hormone (GH) mRNA by pulsatile GH-releasing hormone in rats is pattern specific

2000 ◽  
Vol 278 (5) ◽  
pp. E885-E891 ◽  
Author(s):  
Russell J. Borski ◽  
Wellington Tsai ◽  
Roberta Demott-Friberg ◽  
Ariel L. Barkan
Keyword(s):  
Growth Hormone ◽  
Weight Gain ◽  
Body Weight Gain ◽  
Somatic Growth ◽  
Pulse Amplitude ◽  
Female Rats ◽  
Mrna Levels ◽  
Female Rat ◽  
Constant Frequency ◽  
Releasing Hormone

Growth hormone-releasing hormone (GHRH) is a main inducer of growth hormone (GH) pulses in most species studied to date. There is no information regarding the pattern of GHRH secretion as a regulator of GH gene expression. We investigated the roles of the parameters of exogenous GHRH administration (frequency, amplitude, and total amount) upon induction of pituitary GH mRNA, GH content, and somatic growth in the female rat. Continuous GHRH infusions were ineffective in altering GH mRNA levels, GH stores, or weight gain. Changing GHRH pulse amplitude between 4, 8, and 16 μg/kg at a constant frequency (Q3.0 h) was only moderately effective in augmenting GH mRNA levels, whereas the 8 μg/kg and 16 μg/kg dosages stimulated weight gain by as much as 60%. When given at a 1.5-h frequency, GHRH doubled the amount of GH mRNA, elevated pituitary GH stores, and stimulated body weight gain. In the rat model, pulsatile but not continuous GHRH administration is effective in inducing pituitary GH mRNA and GH content as well as somatic growth. These studies suggest that the greater growth rate, pituitary mRNA levels, and GH stores seen in male compared with female rats are likely mediated, in part, by the endogenous episodic GHRH secretory pattern present in males.

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