Effect of urocortin on ACTH secretion from rat anterior pituitary in vitro and in vivo: comparison with corticotropin-releasing hormone.
Both urocortin (UCN) and corticotropin-releasing hormone (CRH) are known to stimulate secretion of adrenocorticotropic hormone (ACTH) by corticotroph cells via type-1 corticotropin-releasing hormone receptor (CRHR-1). We extensively examined UCN effects on the anterior pituitary (AP), particularly on proopiomelanocortin (POMC) mRNA and CRHR-1 mRNA as well as ACTH secretion in vivo. Moreover, signal transduction with UCN exposure was assessed in AP cell cultures in comparison with transduction following CRH exposure. Intravenously administered of UCN (5 microg/kg) increased ACTH and corticosterone secretion. Similarly, intravenous administration of UCN increased POMC mRNA and decreased CRHR-1 mRNA in the AP. These UCN effects were more potent and long-lasting than those of CRH. The prominent effect of UCN on ACTH secretion in vivo was confirmed in AP cell cultures, where application of UCN stimulated ACTH release approximately 7 times more strongly than CRH. The effect of UCN on ACTH release was enhanced by phorbol esters which activate protein kinase C, but was reduced by the selective cAMP-dependent protein kinase inhibitor, H-89. These results suggest that, as with CRH, UCN stimulates ACTH production and/or release through cAMP-dependent mechanisms, and that protein kinase C-dependent mechanism has a synergistic effect upon UCN-induced ACTH release. The more potent effects of UCN relative to CRH may be attributable to UCN's higher affinity for CRHR-1.
Asaba
K
K
Second Department of Internal Medicine, Kochi Medical School, Okoh-cho, Nankoku-city, Kochi 783-8505, Japan.
Makino
S
S
Hashimoto
K
K
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D008297:Male; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics; D054832:Urocortins
D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone