Antihyperglycemic effect of dehydroepiandrosterone analogue 16 alpha-fluoro-5-androsten-17-one in diabetic mice.
The adrenocortical steroid, dehydroepiandrosterone, has been shown previously to produce an antidiabetic effect in C57BL/KsJ db/db mice. Preliminary clinical data suggest that this steroid may enhance insulin sensitivity in humans. The therapeutic use of dehydroepiandrosterone may be limited by its androgenic action. In a previous study, high-dose dehydroepiandrosterone therapy to postmenopausal women produced marked elevations in plasma testosterone (9-fold) and dihydrotestosterone (20-fold) levels. We previously developed the synthetic steroid, 16 alpha-fluoro-5-androsten-17-one, which lacks the androgenic action of dehydroepiandrosterone yet has retained other biological activities of the native steroid. In this study, administration of 16 alpha-fluoro-5-androsten-17-one in the diet (0.2 and 0.3%) to male C57BL/KsJ db/db mice markedly reduced plasma glucose levels. In contrast, treatment with dehydroepiandrosterone was effective in reducing plasma glucose levels at the 0.2% dose but had no effect at the 0.3% dose, possibly as a result of the androgenic state induced at the higher dose. Dehydroepiandrosterone treatment also produced a 25-fold elevation in plasma testosterone levels and a significant increase in seminal vesicle weights, whereas treatment with 16 alpha-fluoro-5-androsten-17-one had no apparent effect on the weight of the seminal vesicle glands.
Pashko
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LL
Fels Institute for Cancer Research and Molecular Biology, Temple University Medical School, Philadelphia, PA 19140.
Schwartz
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AG
D000736:Androstenes / Q000494:pharmacology*; D000818:Animals; D003687:Dehydroepiandrosterone / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D012669:Seminal Vesicles / Q000187:drug effects; D013739:Testosterone / Q000097:blood
D000736:Androstenes; D007004:Hypoglycemic Agents; C066783:16-fluoro-5-androsten-17-one; D013739:Testosterone; D003687:Dehydroepiandrosterone