Chapter 3 Regulation of growth hormone gene expression

Publisher Summary In addition to its regulation by mechanisms, which include the precursor mRNA processing machinery, GH regulation is under the control of a variety of different factors, which act, essentially, on two tissues, i.e., the hypothalamus and somatotrophs in the pituitary. The hypothalamus produces two neuropeptides, which function to either stimulate (GHRF) or inhibit (somatostatin) the synthesis and release of GH. GHRF binds to a G-protein-coupled receptor on the surface of somatotrophs in the anterior pituitary. Binding triggers the activation of adenylate cyclase which causes an increase in intracellular cAMP and the subsequent activation of PK-A. Upon activation, the catalytic subunit of PK-A dissociates from the holoenzyme and enters the nucleus where it then activates CREB by phosphorylating it at serine 133. GH is also regulated by negative feedback mechanisms at the level of the hypothalamus by both IGF-I and GH itself. Studies have shown that GH and IGF-I both stimulate the release of somatostatin.