Role of exogenous cholesterol in regulation of adrenal steroidogenesis in the rat.
Rat steroidogenic tissues take up cholesterol, and it has been suggested that this process plays a regulatory role in steroid hormone synthesis. To provide evidence for this hypothesis, we carried out studies in lipoprotein-deficient rats. Lipoprotein deficiency, achieved by treating male rats with pharmacological amounts of estradiol, led to profound lowering of plasma cholesterol (8 +/- 2 versus 54 +/- 4 mg/dl) and adrenal cholesteryl ester content (113 +/- 57 versus 747 +/- 108 micrograms/organ). Basal serum corticosterone levels were decreased by 50%, and the response to adrenocorticotropic hormone (ACTH) was totally abolished. Injection of high density lipoprotein (HDL) to estradiol-treated animals restored the response of corticosterone to ACTH. Comparable in vitro studies with adrenal cell suspensions obtained from lipoprotein-deficient rats confirmed the in vivo data. Measurement of [14C]acetate incorporation and uptake of both HDL- and low density lipoprotein (LDL)-cholesterol in these adrenal cells showed a progressive increase with the duration of estradiol treatment, and neither of these two phenomena was altered by ACTH. These results provide in vitro and in vivo evidence for the hypothesis that normal adrenal steroidogenesis depends upon cholesterol delivery from plasma. Furthermore, under the conditions studied, ACTH does not stimulate adrenal de novo cholesterol biosynthesis nor the uptake of either HDL- or LDL-cholesterol.
D000085:Acetates / Q000378:metabolism; D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D002784:Cholesterol / Q000096:biosynthesis / Q000378:metabolism*; D002788:Cholesterol Esters / Q000096:biosynthesis; D003345:Corticosterone / Q000097:blood; D004958:Estradiol / Q000494:pharmacology; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013256:Steroids / Q000096:biosynthesis*
D000085:Acetates; D002788:Cholesterol Esters; D008075:Lipoproteins, HDL; D013256:Steroids; D004958:Estradiol; D000324:Adrenocorticotropic Hormone; D002784:Cholesterol; D003345:Corticosterone