This was the first of the hypothalamic releasing hormones to be identified; its tripeptide structure was determined in 1968. The hormone is elaborated by the anterior periventricular, paraventricular, arcuate, ventromedial, and dorsomedial neurons, but not by those of the posterior hypothalamic or thalamic nuclei. It stimulates the release of thyroid-stimulating hormone (TSH) from the pituitary gland. TSH, in turn, increases the activity of every step of the synthesis of thyroid hormone and stimulates the release of T4 (thyroxine) and T3 (triiodothyronine). T3 provides inhibitory feedback upon the secretion of TRH and TSH. TRH also stimulates pituitary cells to release dopamine and somatostatin to a slight degree; the latter has an inhibitory effect on TSH. Beyond the functions described above, it is notable that more than half the amount of TRH in the brain is found outside the hypothalamus—in brainstem raphe nuclei, tractus solitarius, and the anterior and lateral horn cells of spinal cord—suggesting that in addition to its role in stimulating the production of thyroid hormones, TRH may function as a central regulator of the autonomic nervous system.
This hormone and somatostatin are both secreted by specialized tuberoinfundibular neurons and released into the hypophyseal–portal circulation, by which they are carried to specific growth hormone (GH) secreting cells of the anterior pituitary gland (somatotropes). Immunohistochemical staining has shown the sources of growth hormone-releasing hormone (GHRH) and somatostatin to be neurons of the posterior part of the arcuate and ventromedian hypothalamic nuclei and other neurons of the median eminence and premammillary area.
Somatostatin, a 14-amino-acid peptide also known as growth hormone release-inhibiting hormone, is produced more anteriorly by neurons in the periventricular area and small cell part of the paraventricular nucleus. It inhibits the release of GH, opposing the effects of GHRH. In addition, it inhibits the release of TSH and prolactin. Somatostatin is also secreted by delta cells in the pyloric antrum, duodenum, and pancreatic islet; it functions to decrease the rate of gastric emptying by suppressing the release of hormones such as gastrin and secretin.
Somatomedin C, a basic peptide that is synthesized in the liver, exerts feedback control of GH by inhibiting the pituitary somatotropes and stimulating the release of somatostatin. Also, it has been demonstrated that all 4 biogenic amines (dopamine, norepinephrine, epinephrine, and serotonin) influence GH regulation, as does acetylcholine, either by direct action on pituitary somatotropic cells or on hypothalamic regulatory neurons. TRH also increases GH secretion from somatotropes. Sleepand stress-induced fluctuations of GH and somatostatin are well described, and relate to projections from the amygdala, hippocampus, and other limbic structures to the arcuate nuclei via the medial corticohypothalamic tract (in the stria terminalis).
Growth hormone enhances skeletal growth by stimulating the proliferation of cartilage and growth of muscle. It also regulates lipolysis, stimulates the uptake of amino acids in cells, and has anti-insulin effects. The blood concentrations of GH fluctuate from 1 or 2 ng/mL to more than 60 ng/mL, being highest within the first hour or two after the onset of sleep.