Down-regulation of the mineralocorticoid receptor by dexamethasone in an amphibian kidney cell line (A6)

The A6 cell line, derived from Xenopus kidney, is an in vitro model of cortico-steroid mediated transepitheial Na+ transport stimulation. We report the apparent down-regulation of mineralocorticoid receptor levels in A6 cells, in response to the presence of the synthetic glucorticoid dexamethasone in the culture medium. Mineralocorticoid receptor binding was suppressed to approximately 25% of control following 24-hour exposure to 10nM dexamethasone. Scatchard analysis of concentration-binding experiments show down-regulation of maximum binding capacity by Dex exposure with no alteration of MR affinity, i.e. alteration of MR number only. The effect is dose-responsive with half-maximal down regulation at 1 nM. Maximal inhibition of binding occurred after 24-hours exposure to dexamethasone. The inhibitory effect of dexamethasone on MR binding was unique for the glucocorticoid, with no effect exhibited following similar treatment with an androgen, an estrogen, or a mineralocorticoid.