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Shantz LM, Talalay P, Gordon GB. 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. Proc Natl Acad Sci U S A. 1989;86(10):3852-6doi: 10.1073/pnas.86.10.3852.
Shantz, L. M., Talalay, P., & Gordon, G. B. (1989). 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. Proceedings of the National Academy of Sciences of the United States of America, 86(10), 3852-6. https://doi.org/10.1073/pnas.86.10.3852
Shantz, L M, et al. "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." Proceedings of the National Academy of Sciences of the United States of America vol. 86,10 (1989): 3852-6. doi: https://doi.org/10.1073/pnas.86.10.3852
Shantz LM, Talalay P, Gordon GB. 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. Proc Natl Acad Sci U S A. 1989 May;86(10):3852-6. doi: 10.1073/pnas.86.10.3852. PMID: 2524835; PMCID: PMC287239.
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Proc Natl Acad Sci U S A. 1989 May;86(10):3852-6. doi: 10.1073/pnas.86.10.3852.

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.

Proceedings of the National Academy of Sciences of the United States of America

L M Shantz, P Talalay, G B Gordon

Affiliations

  1. Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205.

PMID: 2524835 PMCID: PMC287239 DOI: 10.1073/pnas.86.10.3852
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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 16 alpha-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.

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