Growth Regulation

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.