Growth hormone

‘’’Growth hormone’’’ (GH) is a peptide hormone that is made in and secreted from the somatotroph cells of the anterior pituitary gland, and which is essential for regulating post-natal growth in all mammals. In somatrotrophs, GH is stored in large, dense-cored secretory granules, which are secreted by calcium-dependent exocytosis. GH secretion from the pituitary depends on many factors, including stress, exercise, and the stage of the menstrual cycle.

GH exerts its effects by interacting with the GH receptor – a G-protein coupled receptor that is expressed by many cell types. GH increases bone mineral density, especially in longitudinal bones, but also influences many other processes that influence body composition, such as lipid metabolism. Many of the actions of GH are mediated by insulin-like growth factor-I (IGF-I) secreted from the liver in response to GH. GH secretion declines progressively during adulthood, and this decline becomes especially marked in elderly subjects. In individuals with severe GH deficiency, muscle mass, muscle strength and bone mass are all decreased, and the relative proportion of total and visceral fat is increased. Thus, GH promotes skeletal growth, increases catabolic rate, and promotes muscle growth rather than fat deposition.

Growth hormone deficiency

Short stature can be caused by impairments of either GH secretion or GH receptor function. Short stature in children with Prader-Willi syndrome, which is explained in part, by a decreased GH secretory capacity, can be effectively treated with exogenous GH for one year. GH treatment to correct physical abnormality has to be continued indefinitely. In children with idiopathic short stature, the causes for growth failure are not definitely established. Plasma GH binding protein activity in children with idiopathic short stature has been reported to be significantly lower than in a control group. GH binding protein is a soluble form of GH receptor which can bind GH, and the decreased GH binding protein activity in children with idiopathic short stature suggests that they may present a degree of GH insensitivity due to a defect at the GH-receptor level.

GH secretion in dwarfism

Dwarfism can arise by defects in GH production and release, or by defects in downstream signalling, and there are several animal models that exemplify this. For example, in dwarf (dw/dw) chickens, the overall GH mean, amplitude, and baseline concentrations are significantly higher than those of control normal-sized (Dw/dw) chickens, and no differences in peak length or peak frequency between genotypes are observed. By contrast, in the dwarf mouse strain (lit/lit), anterior pituitaries do not release GH or accumulate cyclic adenosine 3’ monophosphate (cyclic AMP) in response to human or rat GH releasing hormone (GHRH), whereas dibutyryl cyclic AMP, as well as the adenylate cyclase stimulators forskolin and cholera toxin, markedly stimulate GH release. Thus the basis of the GH deficiency in the little mouse may be a defect in an early stage of GHRH-stimulated GH release, related either to receptor binding or to the function of the hormone-receptor complex, while the defect in the dwarf chickens is a failure to respond to GH.

Pulsatile GH secretion

In all species studied to date, GH is released episodically. This pulsatile pattern of secretion is particularly marked in male rats, which show large pulses of GH secretion at approximately 3-h intervals with peak values higher than 200 ng/ml and basal values lower than 1 ng/ml. More continuous secretion and substantially higher basal concentrations are evident in female rats. This difference is an important contributor to the higher growth rate in males of most mammalian species.

Pulsatile GH secretion is governed mainly by two hypothalamic peptides: a stimulatory factor, GHRH, and an inhibitory factor, somatostatin. These peptide factors reach the anterior pituitary gland via the hypophysial portal circulation after release from nerve endings in the median eminence. Measurement of immunoreactive GHRH and somatostatin concentrations in portal blood found episodic secretion of immunoreactive GHRH, with maximal concentrations during GH secretory episodes, and secretion of immunoreactive GHRH was accompanied by a moderate reduction in portal plasma concentrations of immunoreactive somatostatin.

Hypothalamic control of GH secretion

GHRH is synthesised by a sub-population of neuroendocrine neurones in the arcuate nucleus of the hypothalamus, and somatostatin by a sub-population of neurones in the periventricular nucleus. These peptides are transported along axons to neurosecretory nerve endings in the median eminence, and released from nerve terminals into the hypothalamo-hypophysial portal blood circulation to influence the anterior pituitary gland.