Gamma 3-melanotropin promotes mitochondrial cholesterol accumulation in the rat adrenal cortex.
Gamma 3-melanotropin (gamma 3-MSH) facilitates a rapid, dose-dependent, and cycloheximide-insensitive increase in the concentration of mitochondrial free cholesterol in the adrenals of hypophysectomized rats. Physiological concentrations of various synthetic and native preparations of gamma 3-MSH are potent, while gamma-MSH is not. This cholesterol accumulation coincides with the activation of cholesteryl ester hydrolysis by gamma 3-MSH, while the rates of cholesterol esterification and of mitochondrial cholesterol side-chain cleavage are unaffected. Conversely, ACTH inhibits cholesterol ester esterification. Therefore, gamma 3-MSH and ACTH together may coordinate a substantial shift in the set-point of cholesteryl ester in equilibrium cholesterol cycling toward the right. Because ACTH also activates cholesterol side-chain cleavage, this coordinate effect on the flux of cholesterol substrate is manifest as a potentiation of corticosteroidogenesis by gamma 3-MSH. These data extend our previous studies demonstrating that pro-gamma-MSH polypeptides have an endocrine influence on the rat adrenal cortex.
D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002784:Cholesterol / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism; D003366:Cosyntropin / Q000494:pharmacology; D005260:Female; D007016:Hypophysectomy; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology*; D008928:Mitochondria / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D002787:Sterol Esterase / Q000378:metabolism; D002785:Sterol O-Acyltransferase / Q000378:metabolism
D002788:Cholesterol Esters; D003366:Cosyntropin; D009074:Melanocyte-Stimulating Hormones; D002784:Cholesterol; D002786:Cholesterol Side-Chain Cleavage Enzyme; D002785:Sterol O-Acyltransferase; D002787:Sterol Esterase