GH is the most abundant anterior pituitary hormone and GH-secretion somatotrope
cells constitute up to 50% of the total anterior pituitary cell population.
The pituitary GH gene produces two alternatively products that give rise 22-kDa
GH(191 amino acids) and a less abundant, 20-kDa GH molecule, with similar
GH secretion is controlled by complex hypothalamic
and a peripheral factor:
► GHRH is stimulates GH synthesis and release
Ghrelin or gastric-derived peptide, as well as synthetic agonists of the GHRP
receptor stimulate GHRH and also directly stimulate GH release.
GHRH is secreted as discrete spikes that elicit GH pulses whereas SRIF sets
basal GH tone.
► Somatostain" Somatotropin Release Inhibiting
Factor (SRIF)" is synthesized in the medial preoptic area of the
and inhibits GH secretion.
► IGF-I, the peripheral target hormone for GH, feeds
back to inhibit GH, estrogen induces GH, whereas glucocorticoid excess
suppresses GH release.
GH secretion is pulsatile, with greatest levels at
night. Generally correlating with the onset of sleep. GH secretory rates decline
markedly with age so that hormone production in middle age is about 15% of production during puberty. These
changes are paralleled by an age-related decline in lean muscle mass.
GH secretion is also reduced in obese individuals,
though IGF-I levels are usually preserved, suggesting a change in the set point
for the feed back control. Elevated GH levels occur within an hour of deep sleep
onset as well as after exercise, physical stress, trauma and during sepsis.
Integrated 24-h GH secretion is higher in women and
is also enhanced by estrogen replacement. Using standard essays, random GH
measurements are undetectable in~50% of daytime samples obtained from healthy
subjects and are undetectable in most obese and elderly subjects. Thus, single
random GH measurements do not distinguish patients with adult GH deficiency from
GH secretion is profoundly influenced by
nutritional factors. Using newer ultra sensitive chemiluminescence's-based GH
assays with a sensitivity of 0.002 µg/L, a glucose load can be shown to suppress
GH to > 0.7µg/L in female and to > 0.07µg/L in male subjects. Increased
GH pulse frequency and peak amplitudes occur with chronic malnutrition or
prolonged fasting. GH is stimulated by high-protein meals and by L-arginine. GH
secretion is induced dopamine and apomorphine ( a dopamine receptor agonist), as
well as by α-adrenergic pathways, β-adrenergic
blockage induces basal GH and enhances GHRH- and insulin-evoked GH release.
GH induces protein synthesis and nitrogen retention
and impairs glucose tolerance by antagonizing insulin action. GH also stimulates
lipolysis, leading to increased circulating fatty acid levels, reduced omental
fat mass and enhanced lean body mass. GH promotes sodium, potassium and water
retention and elevates serum levels of inorganic phosphate. Linear bone growth
occurs as a result of complex hormonal and growth factor actions, including
those of IGF-I.
Insulin-like growth factors:
Through GH exerts direct effects in target tissues,
many of its physiological effects are mediated indirectly through IGF-I, a
potent growth and differentiation factor. The major source of circulating IGF-I
is hepatic in origin. Peripheral tissue IGF-I exerts local paracrine actions
that appear to be both dependent and independent of GH. Thus, GH administration
induces circulating IGF-I as well as stimulating IGF-I expression in multiple
IGF-I is not an approved drug. Investigational studies provide insight into its
physiologic effects. Injected IGF-I
(100µg/Kg) induces hypoglycemia and lower
doses improve insulin sensitivity in patients with severe insulin resistance
and diabetes. in IGF-I infusion enhances nitrogen retention and lowers cholesterol
levels. Bone turn over may also be
stimulated by IGF-I.
► IGF-I side effects are
dose-dependent, and overdose may result in hypoglycemia, hypotension, fluid
temporomandibular jaw pain and increased intracranial pressure. All
of which are reversible.
Disorders of growth and development:
Skeletal maturation and somatic growth:
The growth plate is dependent on a variety of hormonal stimuli including GH,
IGF-I, sex steroids, thyroid hormones, paracrine growth factors. The
growth-promoting process also requires caloric energy, amino acids, vitamins and
trace metals and consumers about 10% of normal energy production.
Bone age is delayed because of:
► GH deficiency
► Thyroid hormone deficiency
► Elevated pubertal sex steroid levels.
GH deficiency in children:
GH deficiency isolated GH deficiency is characterized by:
► Short stature
► Increased fat
► High-pitched voice
GHRH receptor mutations:
Recessive mutations of the GHRH receptor gene in subjects with severe
proportionate dwarfism are associated with low basal GH levels that can’t be
stimulated by exogenous GHRH, GHRP or insulin-induced hypoglycemia.
Growth hormone insensitivity:
This is caused by defects of GH receptor structure or signaling.
homozygous or heterozygous mutationsof the GH receptor are associated
with partial or complete GH insensitivity and growth failure (laron syndrome)
this diagnosis is based on normal or high GH levels.
Nutritional short stature:
Caloric deprivation and malnutrition, uncontrolled diabetes and
chronic renal failure represent secondary causes of GH receptor function.
Children with these conditions typically exhibit features of acquired short
stature with elevated GH and low IGF-I levels. Circulating GH receptor
antibodies may rarely cause peripheral GH insensitivity.
Psychosocial short stature:
Emotional and social deprivation lead to growth retardation
accompanied by delayed speech, discordant hyperphagia and attenuated response to