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 capacity to the androgen receptors of the hamster flank organ were investigated. Furthermore, the effects of LNG and its 5 alpha-reduced metabolite in the flank organ test and on [U-C-14]glucose incorporation into lipids by this tissue were determined, Homogenates from female hamster 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 was assessed. Competition experiments for androgen binding receptors were carried out with 1.38 nM [H-3-7 alpha-17 alpha]dimethyl-19-nortestosterone (DMNT), K-d, plus a range of increasing concentrations of the different unlabeled steroid hormones, The flank organ test was performed in vivo, and [U-C-14]glucose incorporation into lipids was determined 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 gonadectomized male hamster flank organs. Topical applications of LNG or 5 alpha-LNG increased [U-C-14]glucose incorporation into lipids in a way similar to that of T. The overall data indicate that LNG and 5 alpha-LNG produced androgenic activity in the lipid pathway of male flank organs, and that 5 alpha-reduction is not essential for the LNG effect on this tissue.