Mechanism of inhibition of growth of 3T3-L1 fibroblasts and their differentiation to adipocytes by dehydroepiandrosterone and related steroids: Role of glucose-6-phosphate dehydrogenase

L. M. Shantz, P. Talalay, G. B. Gordon

Research output: Contribution to journalArticle

Abstract

Dehydroepiandrosterone (DHEA) and certain structural analogues block the differentiation of 3T3-L1 mouse embryo fibroblasts to adipocytes. These steroids also are potent uncompetitive inhibitors of mammalian glucose-6-phosphate dehydrogenases (G6PDs). We provide direct evidence that treatment of the 3T3-L1 cells with DHEA and its analogues results in intracellular inhibition of G6PD, which is associated with the block of differentiation: (i) Levels of 6-phosphogluconate and other products of the pentose phosphate pathway are decreased; (ii) the magnitude of these decreases depends on the potency of steroids as inhibitors of G6PD and on concentration and duration of exposure, and it is accompanied by a proportionate block of differentiation; (iii) in cells exposed to 16α-bromoepiandrosterone (a more potent inhibitor of G6PD than DHEA) at concentrations that block differentiation, introduction of exogenous 6-phosphogluconate in liposomes raises the levels of 6-phosphogluconate and other products of the pentose phosphate pathway and partially relieves the steroid block of cell growth and differentiation.

Original languageEnglish (US)
Pages (from-to)3852-3856
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume86
Issue number10
DOIs
StatePublished - 1989

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