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 [14C]dehydroepiandrosterone into [14C]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.
Trudel
C
C
Medical Research Council Group in Molecular Endocrinology, CHUL Research Center, Ste-Foy, Quebec, Canada.
Couët
J
J
Martel
C
C
Labrie
C
C
Labrie
F
F
D000311:Adrenal Glands / Q000033:anatomy & histology / Q000201:enzymology* / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D003345:Corticosterone / Q000097:blood / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D005260:Female; D007016:Hypophysectomy; D008297:Male; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D011375:Progesterone Reductase / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013251:Steroid Isomerases / Q000235:genetics / Q000378:metabolism*
C021425:3 beta-hydroxysteroid oxidoreductase-delta(5) 3-ketosteroid isomerase; D009097:Multienzyme Complexes; D012333:RNA, Messenger; D000324:Adrenocorticotropic Hormone; D004247:DNA; D011375:Progesterone Reductase; D013251:Steroid Isomerases; C022660:steroid delta-isomerase; D003345:Corticosterone