Inhibition of DNA synthesis in mouse epidermis and breast epithelium by dehydroepiandrosterone and related steroids.
Long-term treatment of C3H mice with the adrenal steroid, dehydroepiandrosterone (DHEA), has previously been shown to suppress spontaneous breast cancer development. A single i.p. injection of DHEA into C3H or ICR mice inhibits the rate of [3H]thymidine incorporation in breast epithelium and in 12-0-tetradecanoylphorbol-13-acetate (TPA)-stimulated epidermis. DHEA is a potent non-competitive inhibitor of mammalian glucose-6-phosphate dehydrogenase (G6PDH). 16 alpha-Br-epiandrosterone (Br-Epi), which is 60 times more active than DHEA is an inhibitor of G6PDH, is also much more active in reducing the rate of [3H]thymidine incorporation into mouse breast epithelium and epidermis. Synthetically prepared DHEA-sulfatide also inhibits G6PDH activity and [3H]thymidine incorporation in TPA-stimulated mouse epidermis. On the contrary, DHEA-sulfate, which is virtually inactive as an inhibitor of G6PDH, is also inactive as an inhibitor of [3H]thymidine incorporation in mouse epidermis.
D000818:Animals; D001940:Breast / Q000378:metabolism*; D004247:DNA / Q000096:biosynthesis*; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004817:Epidermis / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008813:Mice, Inbred ICR; D013256:Steroids / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors
D013256:Steroids; D003687:Dehydroepiandrosterone; D004247:DNA; D005954:Glucosephosphate Dehydrogenase; D013936:Thymidine