The role of intracellular messengers in adrenocorticotropin secretion in vitro.
Adrenocorticotropin (ACTH), an opiomelanocortin peptide, is secreted from anterior pituitary corticotrophs upon stimulation with corticotropin-releasing hormone (CRH), arginine vasopressin (AVP) and several other neuropeptides. CRH, the most potent secretagogue of ACTH, stimulates ACTH secretion and biosynthesis by increasing the production of cyclic adenosine 3',5'-monophosphate (cAMP) within corticotrophs. AVP, which is a weak secretagogue of ACTH but strongly potentiates CRH-stimulated ACTH secretion, operates through the phosphatidylinositol (PI) transduction pathway. Both CRH and AVP increase cytosolic free [Ca2+] within normal corticotrophs indicating a role for Ca2+ in ACTH secretion. Glucocorticoids inhibit ACTH synthesis by suppressing transcription of the proopiomelanocortin (POMC) gene and attenuate ACTH release by decreasing cAMP accumulation stimulated by CRH. This review focuses on the roles of these intracellular messengers in ACTH secretion from normal anterior pituitary cells in vitro, and discusses the possible interactions between the cAMP, calcium and PI transduction pathways. Future areas of research are suggested such as identification of protein substrates of cAMP-dependent and Ca2(+)-dependent kinases within normal corticotrophs and evaluation of their role in ACTH biosynthesis and secretion.
King
M S
MS
Department of Physiology, Neuroscience Program and Cancer Center, University of Virginia School of Medicine, Charlottesville 22908.
Baertschi
A J
AJ
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000502:physiology; D000242:Cyclic AMP / Q000502:physiology; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D007031:Hypothalamus / Q000502:physiology; D010716:Phosphatidylinositols / Q000502:physiology; D010902:Pituitary Gland / Q000502:physiology; D015290:Second Messenger Systems; D015398:Signal Transduction
D005938:Glucocorticoids; D010716:Phosphatidylinositols; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D002118:Calcium