MOLECULAR-INTERACTIONS OF LEVONORGESTREL AND ITS 5-ALPHA-REDUCED DERIVATIVE WITH ANDROGEN RECEPTORS IN HAMSTER FLANKING ORGANS

The 5 alpha-reduction of levonorgestrel (LNG) as well as its binding c apacity to the androgen receptors of the hamster flank organ were inve stigated. Furthermore, the effects of LNG and its 5 alpha-reduced meta bolite in the flank organ test and on [U-C-14]glucose incorporation in to lipids by this tissue were determined, Homogenates from female hams ter flank organs were incubated in the presence of [H-3]LNG at pH 7.4. The radioactive 5 alpha-LNG metabolite was isolated and its purity wa s assessed. Competition experiments for androgen binding receptors wer e carried out with 1.38 nM [H-3-7 alpha-17 alpha]dimethyl-19-nortestos terone (DMNT), K-d, plus a range of increasing concentrations of the d ifferent unlabeled steroid hormones, The flank organ test was performe d in vivo, and [U-C-14]glucose incorporation into lipids was determine d under organ culture conditions. The 5 alpha-LNG had the same binding capacity to androgen receptors (AR) as LNG in male flank organs. The flank organ test demonstrated that 5 alpha-LNG activity was similar to that observed for levonorgestrel and testosterone (T) on gonadectomiz ed male hamster flank organs. Topical applications of LNG or 5 alpha-L NG increased [U-C-14]glucose incorporation into lipids in a way simila r to that of T. The overall data indicate that LNG and 5 alpha-LNG pro duced androgenic activity in the lipid pathway of male flank organs, a nd that 5 alpha-reduction is not essential for the LNG effect on this tissue.