Effect of adrenalectomy and aldosterone on the modulation of mineralocorticoid receptors in rat kidney.
Adrenalectomized rat kidney is commonly used for the study of mineralocorticoid mechanism of action in mammals. In this model, aldosterone is known to bind to two classes of binding sites: type I (mineralocorticoid) and type II (glucocorticoid). The study of the aldosterone binding in normal rat kidney requires the elimination of endogenous hormones bound to each type of receptor. Thus, a suitable technique was developed using in situ perfusion of the kidneys. The efficacy of this method was of about 85 to 90% at the level of both cytoplasm and nucleus. Aldosterone binding capacity was checked in normal rat kidney after in situ perfusion and was found to be 300 to 500% lower than in adrenalectomized rat kidney, both in cytoplasm and nuclei. Computer analysis of aldosterone binding parameters in the cytoplasm (30,000 X g supernatant) of rat kidney suggested that adrenalectomy might induce an important rise in the number of mineralocorticoid receptors (congruent to 260%). An increase in the number of glucocorticoid receptors was also observed but appeared to be lower. Aldosterone, when perfused during 24 h in adrenalectomized rats, lowered the number of type I sites to the same level as observed in normal rat kidney. This effect was fully reversible after interruption of aldosterone perfusion. These results suggested an aldosterone-induced down regulation of mineralocorticoid receptors.
D000315:Adrenalectomy; D000450:Aldosterone / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D007668:Kidney / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D010477:Perfusion; D051381:Rats; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid / Q000187:drug effects / Q000378:metabolism*
D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid; D000450:Aldosterone