REGULATION OF ADRENAL 3-BETA-HYDROXYSTEROID DEHYDROGENASE DELTA-5-DELTA-4-ISOMERASE EXPRESSION AND ACTIVITY BY ADRENOCORTICOTROPIN AND CORTICOSTERONE IN THE RAT

This study describes the regulation of adrenal 3-beta-hydroxy-5-ene-steroid dehydrogenase/DELTA-5-DELTA-4-isomerase (3-beta-HSD) expression and activity by ACTH and corticosterone, alone or in combination, in intact male and female rats as well as the effect of ACTH on 3-beta-HSD expression and activity in the adrenals of hypophysectomized female animals. The effect of treatment on total 3-beta-HSD mRNA levels was measured by dot blot hybridization using rat 3-beta-HSD cDNA, while the specific regulation of type I and type II 3-beta-HSD mRNAs was analyzed by ribonuclease protection assay. The concentration of 3-beta-HSD protein was measured by Western blot, using cross-reacting antibodies raised against purified human placental 3-beta-HSD, while 3-beta-HSD enzymatic activity was measured by the conversion of [C-14]dehydroepiandrosterone into [C-14]androstenedione. The present data show that the trophic effect of ACTH on male and female rat adrenals is accompanied by increases in total 3-beta-HSD mRNA, enzymatic activity, and protein content. Hypophysectomy, on the other hand, causes a marked decrease in 3-beta-HSD mRNA levels and enzymatic activity, which is completely reversed by administration of ACTH. On the other hand, corticosterone treatment results in a marked inhibition of 3-beta-HSD mRNA levels, enzymatic activity, and protein content in intact animals; this effect is probably mediated by a decrease in ACTH secretion. The present data show that ACTH and corticosterone, via its inhibitory action on ACTH secretion, have potent and opposite effects on the expression of two 3-beta-HSD genes in the rat adrenal; a parallel effect is observed on both type I and II 3-beta-HSD. Such data suggest that 3-beta-HSD could well play a major role in the regulation of steroid formation in the adrenal cortex.