Corticosterone inhibition of osmotically stimulated vasopressin from hypothalamic-neurohypophysial explants.
Glucocorticoids inhibit and glucocorticoid deficiency increases vasopressin (AVP) release in vivo. To determine whether the effect of glucocorticoids is hypothalamic and mediated via a glucocorticoid receptor, explants of the hypothalamic-neurohypophysial system were used to measure AVP release during agonist and antagonist exposure. Explants from adult rats, which contained AVP neurons of the supraoptic nucleus with axonal projections terminating in the neural lobe but excluded the paraventricular nucleus, were perifused with an osmotic stimulus (increase of 5 mosmol/h over 6 h) in the absence or presence of corticosterone (100 micrograms/dl) or with corticosterone (100 micrograms/dl) in the absence or presence of the glucocorticoid antagonist RU-486 (10 microM). AVP release was not increased during osmotic stimulation in the presence of corticosterone (Cort) and was 20-30% lower than osmotically stimulated release observed in the absence of Cort. RU-486 reversed the inhibitory effect of corticosterone on AVP release. No changes in AVP mRNA content were detected. These results suggest that Cort inhibits osmotically stimulated AVP release by a direct effect within the hypothalamus and/or neurohypophysis. This effect is mediated by the glucocorticoid receptor through either genomic or nongenomic mechanisms.
Papanek
P E
PE
Department of Physiology, Chicago Medical School, Illinois 60064, USA.
Sladek
C D
CD
Raff
H
H
D000818:Animals; D001127:Arginine Vasopressin / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D003345:Corticosterone / Q000494:pharmacology*; D006727:Hormone Antagonists / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D009995:Osmosis; D010904:Pituitary Gland, Posterior / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D006727:Hormone Antagonists; D012333:RNA, Messenger; D001127:Arginine Vasopressin; D015735:Mifepristone; D003345:Corticosterone