Journal of Clinical Endocrinology & Metabolism, Vol 76, 1522-1528, Copyright © 1993 by Endocrine Society

ARTICLES

Vasopressin stimulates cortisol secretion from human adrenocortical tissue through activation of V1 receptors

V Perraudin, C Delarue, H Lefebvre, V Contesse, JM Kuhn and H Vaudry
European Institute for Peptide Research, Centre National de la Recherche Scientifique URA650, Mont-Saint-Aignan, France.

It has previously been shown that arginine vasopressin (AVP) exerts a direct stimulatory action on rat adrenocortical cells. In the present study, we have investigated the possible effect of AVP on cortisol secretion by normal human adrenocortical tissue. The occurrence of endogenous AVP in the human adrenal gland has been studied by means of the indirect immunofluorescence technique. The presence of AVP- containing cells was observed in both cortex and medulla. The action of AVP on corticosteroidogenesis has been investigated in vitro using a perifusion system technique coupled to a specific RIA for cortisol. Graded doses of AVP (from 10(-11)-10(-9) M) increased cortisol secretion in a dose-dependent manner (ED50, 4.5 x 10(-11) M). AVP also induced a significant stimulation of cortisol release from acutely dispersed adrenocortical cells. Prolonged administration of AVP (3 h) induced a rapid and transient increase in cortisol output, followed by a gradual decline in cortisol secretion. Repeated pulses of AVP, given at 90-min intervals, resulted in reproducible stimulations of cortisol output. Selective agonists and antagonists have been used to determine the type of receptor involved in the response of adrenocortical cells to AVP. Oxytocin at doses up to 10(-7) M had virtually no effect on cortisol secretion. The stimulatory effect of AVP was blocked by the V1 antagonist [beta-mercapto-beta,beta-cyclopentamethylene propionyl 1, OMe-Tyr2, Arg8]AVP. In contrast, the V2 antagonist [d(CH2)5D- Phe2,Ile4,Ala9-NH2]AVP did not affect the response of the adrenal gland to AVP. The selective V2 agonist [deamino-Cys1,D-Arg8]AVP did not mimic the stimulatory effect of AVP on cortisol secretion. Taken together, these results suggest that AVP, locally released by intracortical cells, may act as a paracrine factor to stimulate adrenal steroidogenesis in man. The effect of AVP on cortisol secretion appears to be mediated through activation of typical V1 receptors.

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