Molecular and cell biology of the growth hormone-releasing hormone receptor.

The GHRH receptor is a seven transmembrane G-protein-linked receptor found predominantly in the pituitary gland. It is essential for normal somatotroph proliferation and for the synthesis and secretion of GH. Significant amounts of GHRH receptor are also found in the hypothalamus, kidney and placenta. Transcription of the GHRH receptor gene promoter is enhanced by Pit-1 and by glucocorticoids but is inhibited by oestrogen. Recently, mutations involving severe GHRH receptor truncations have been associated with human type 1 GHD. Studies of chimeric receptors and of GHRH receptor cross-linking sites have shown that the N-terminal extracellular domain of the GHRH receptor is required for hormone binding, but that key sites for ligand specificity and signalling are associated with the transmembrane helices and intervening loops. Evidence from the ovine GHRH receptor suggests that the C-terminus has an inhibitory function and may be involved in down-regulation via internalization and phosphorylation. A better understanding of the GHRH receptor may lead to new therapies for the treatment of GH disorders.