Inhibition of cholesterol side-chain cleavage by intermediates of an alternative steroid biosynthetic pathway.
Mitochondrial preparations from endocrine tissues were incubated with radioactive cholesterol and the effect of hydroxylated metabolites of 23,24-dinor-5-cholen-3 beta-ol (23,24-dinor-5-cholene-3 beta,20-diol and 23,24-dinor-5-cholene-3 beta,21-diol) on the production of pregnenolone was measured. These compounds are intermediates in an alternative, sesterterpene pathway for steroid hormone biosynthesis. It was found that these materials, like the analogous side-chain-hydroxylated derivatives of cholesterol (20 alpha-hydroxycholesterol and 22S-hydroxycholesterol), inhibit cholesterol side-chain cleavage. The possibility that there could be a control mechanism whereby metabolites of 23,24-dinor-5-cholen-3 beta-ol inhibit steroidogenesis occurring by the cholesterol pathway is discussed.
van Haren
E J
EJ
Department of Medicine, University of Cambridge, Addenbrookes Hospital, England.
Tait
A D
AD
D000311:Adrenal Glands / Q000378:metabolism; D000818:Animals; D002417:Cattle; D002784:Cholesterol / Q000378:metabolism*; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000037:antagonists & inhibitors*; D004702:Endocrine Glands / Q000378:metabolism*; D005260:Female; D006801:Humans; D006900:Hydroxylation; D008928:Mitochondria / Q000201:enzymology; D010053:Ovary / Q000378:metabolism; D011283:Pregnenes / Q000378:metabolism / Q000494:pharmacology; D011284:Pregnenolone / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D013256:Steroids / Q000096:biosynthesis*
C007502:23,24-dinor-5-cholene-3,21-diol; D011283:Pregnenes; D013256:Steroids; C007501:20-methylpregn-5-ene-3,20-diol; C012507:5-pregnen-3 beta-ol; D011284:Pregnenolone; D002784:Cholesterol; D002786:Cholesterol Side-Chain Cleavage Enzyme