Progesterone binding to mineralocorticoid receptors: in vitro and
in vivo studies.
Myles, K., and J. W. Funder.
Baker Medical Research Institute, Melbourne, Australia
APStracts 2:0234E, 1995.
In previous studies using expressed recombinant human
mineralocorticoid receptors (MR) progesterone was reported to have
widely divergent affinity, from 10 nM to <10 pM. In the present
studies cytosol preparations of colon or hippocampus were incubated
with [3H]aldosterone or [3H]progesterone, alone or with excess RU486,
and the ability of each steroid to compete for MR determined. In
guinea-pig, progesterone has equivalent affinity to aldosterone for
MR in vitro, and in rats 3x that of aldosterone, with no differences
between tissues. In vivo, in both epithelial (kidney, colon) and non
-epithelial tissues (heart, hippocampus) progesterone was 10-100-fold
less potent a competitor than aldosterone for MR, both in the absence
of transcortin (8-day old rats) and in adult mice. Bolus injection of
[3H]progesterone was not specifically bound in any of the four
tissues. Whether progesterone at steady state may bid for MR
occupancy under conditions of high circulating free levels (in utero,
luteal phase, pregnancy), presumably to act as an antagonist to
cortisol/corticosterone in unprotected non-epithelial receptors, thus
remains to be determined.
Received 10 July 1995; accepted in final form 10 November 1995.
APS Manuscript Number E322-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 December 95