Thyroid hormone-mediated transcriptional activation of the rat liver malic enzyme gene by dehydroepiandrosterone.
Dehydroepiandrosterone (DHEA), a naturally occurring steroid secreted from the adrenal, has been reported to decrease the body weight gain in rodents without suppressing food intake and to stimulate malic enzyme activity in liver (Tepperman, H. M., de la Garza, S. A., and Tepperman, J. (1968) Am. J. Physiol. 214, 1126-1132). Herrin, we demonstrate that DHEA induces hepatic malic enzyme activity by increasing the rate of transcription of the malic enzyme gene. This transcriptional activation of the malic enzyme gene is dose dependent, i.e. the treatment of euthyroid male rats with daily doses of 17.5 and 35 mg of DHEA/100 g of body weight for 7 days elevated the rate of malic enzyme gene transcription in liver above the basal levels 4-5- and 8-9-fold, respectively. The levels of nuclear malic enzyme RNA, cytoplasmic malic enzyme mRNA, and enzyme activity were increased correspondingly. Malic enzyme stimulation by DHEA was liver specific, i.e. malic enzyme activity in brain, heart, kidney, and testis was unchanged. Thyroid hormone is required for the induction of hepatic malic enzyme activity by DHEA since in hypothyroid animals, DHEA was without effect. However, stimulatory effects of thyroid hormone and DHEA on malic enzyme expression are additive in euthyroid rat livers at both levels of gene transcription and enzyme activity.
Song
M K
MK
Clinical Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892.
Grieco
D
D
Rall
J E
JE
Nikodem
V M
VM
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D005796:Genes / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008291:Malate Dehydrogenase / Q000235:genetics*; D008297:Male; D009206:Myocardium / Q000201:enzymology; D009928:Organ Specificity; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013737:Testis / Q000187:drug effects / Q000201:enzymology; D013961:Thyroid Gland / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects*; D014284:Triiodothyronine / Q000494:pharmacology*
D014284:Triiodothyronine; D003687:Dehydroepiandrosterone; D008291:Malate Dehydrogenase