Inhibition of lipid synthesis and glucose-6-phosphate dehydrogenase in rat skin by dehydroepiandrosterone.
Lipid synthesis from acetate-1-(14)C by rat skin was inhibited 44-56% by 2.5 x 10(-4) m dehydroepiandrosterone (DHA) in vitro with or without addition of glucose in the incubation medium. This inhibition affected all the lipid fractions examined (hydrocarbons, sterols, sterol esters, tri-, di- and monoglycerides, fatty acids, and polar lipids) and could be reversed by NADPH. DHA also inhibited lipid synthesis from glucose-U-(14)C and the formation of (14)CO(2) from glucose-1-(14)C, indicating interference with pentose cycle activity. Experiments with the 105,000 g supernatant fluid of rat skin homogenates demonstrated considerable activities of malic enzyme (ME) (12.6 nmoles of NADPH generated per min per mg of protein), of glucose-6-phosphate dehydrogenase (G6PD), and of 6-phosphogluconate dehydrogenase (6PGD) (17.5 nmoles of NADPH generated per min per mg of protein). G6PD was inhibited 98% by 2.5 x 10(-4) m dehydroepiandrosterone, while 6PGD and ME were not affected. It can be estimated from these data that the pentose cycle may contribute 41-57% of the NADPH needed for lipid synthesis in rat skin; the remainder of the necessary NADPH is presumably supplied by malic enzyme.
D000085:Acetates / Q000378:metabolism; D000818:Animals; D002247:Carbon Isotopes; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D004952:Esters / Q000378:metabolism; D005227:Fatty Acids / Q000096:biosynthesis; D005947:Glucose / Q000378:metabolism; D005954:Glucosephosphate Dehydrogenase / Q000037:antagonists & inhibitors*; D005989:Glycerides / Q000096:biosynthesis; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008055:Lipids / Q000096:biosynthesis*; D008291:Malate Dehydrogenase / Q000378:metabolism; D008297:Male; D008660:Metabolism / Q000187:drug effects; D009249:NADP; D051381:Rats; D012867:Skin / Q000201:enzymology / Q000378:metabolism*
D000085:Acetates; D002247:Carbon Isotopes; D004952:Esters; D005227:Fatty Acids; D005989:Glycerides; D008055:Lipids; D003687:Dehydroepiandrosterone; D009249:NADP; D008291:Malate Dehydrogenase; D005954:Glucosephosphate Dehydrogenase; D005947:Glucose