Evidence for distinct glucocorticoid and guanine 3',5'-monophosphate-effected inhibition of stimulated adrenocorticotropin release in vitro.
Previous work has shown that corticosterone, cell-membrane permeant analogs of cGMP, as well as activators of guanylyl cyclase inhibit secretagogue-stimulated ACTH release. In the present study we have examined whether cGMP mediates the inhibitory effect of corticosterone in perifused isolated rat anterior pituitary cells. A brief 22.5-min exposure to corticosterone strongly inhibited ACTH secretion evoked by arginine vasopressin (AVP), 48 mM KC1, and two types of combined stimuli, i.e. 41-residue CRF and AVP (0.05 and 0.5 nM, respectively; CRF/AVP), or ionomycin and phorbol-dibutyrate (200 and 10 nM, respectively; PdBu/IM). The time course of inhibition by corticosterone was similar in all cases; a rapid approximately 30% reduction in ACTH was evident within 25 min, which increased to 60% by 50-70 min and will be referred to as the delayed effect. The corticosteroid inhibition of PdBu/IM-induced ACTH release was fully antagonized by the glucocorticoid/progestin antagonist RU 38486, indicating that it is exerted through type II glucocorticoid receptors. In contrast to corticosterone, the cGMP derivative 8-bromo-cGMP failed to suppress ACTH release evoked by PdBu/IM, whereas it effectively inhibited the action of CRF/AVP. Furthermore, ionomycin reversed the reduction of CRF/AVP-stimulated ACTH release by 8-bromo-cGMP, but had no effect on the delayed inhibition caused by corticosterone. These data indicate that there are two distinct cellular pathways of inhibiting stimulus-evoked ACTH secretion in vitro. One of these is activated by corticosterone, whereas the other involves cGMP as a cellular messenger.
Antoni
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FA
Department of Human Anatomy, University of Oxford, England.
Dayanithi
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G
D000324:Adrenocorticotropic Hormone / Q000037:antagonists & inhibitors*; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D003345:Corticosterone / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D005938:Glucocorticoids / Q000494:pharmacology*; D015759:Ionomycin / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology
D005938:Glucocorticoids; D001127:Arginine Vasopressin; C016276:8-bromocyclic GMP; D015240:Phorbol 12,13-Dibutyrate; D015759:Ionomycin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006152:Cyclic GMP; D011188:Potassium; D003345:Corticosterone