J. Lipid Res. Neurobiology of Lipids (ISSN1683-5506)
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Journal of Lipid Research, Vol. 11, 346-354, July 1970
Copyright © 1970 by Lipid Research, Inc.

Inhibition of lipid synthesis and glucose-6-phosphate dehydrogenase in rat skin by dehydroepiandrosterone

Vincent A. Ziboh , M. A. Dreize , and S. L. Hsia

Departments of Dermatology and Biochemistry, University of Miami School of Medicine, Miami, Florida, 33136

Lipid synthesis from acetate-1-14C 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-14C and the formation of 14CO2 from glucose-1-14C, 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.

Supplementary key words 6-phospho-d-gluconate dehydrogenase • malic enzyme • polar lipids • neutral lipids • lipogenesis

Submitted on June 16, 1969
Accepted on April 13, 1970


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