Molecular interactions of Levonorgestrel and its 5α-reduced derivative with androgen receptors in hamster flanking organs

Abstract

The 5α-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 5α-reduced metabolite in the flank organ test and on [U- 14C]glucose incorporation into lipids by this tissue were determined. Homogenates from female hamster flank organs were incubated in the presence of [ 3H]LNG at pH 7.4. The radioactive 5α-LNG metabolite was isolated and its purity was assessed. Competition experiments for androgen binding receptors were carried out with 1.38 nM [ 3H-7α-17α]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- 14C]glucose incorporation into lipids was determined under organ culture conditions. The 5α-LNG had the same binding capacity to androgen receptors (AR) as LNG in male flank organs. The flank organ test demonstrated that 5α-LNG activity was similar to that observed for levonorgestrel and testosterone (T) on gonadectomized male hamster flank organs. Topical applications of LNG or 5α-LNG increased [U- 14C]glucose incorporation into lipids in a way similar to that of T. The overall data indicate that LNG and 5α-LNG produced androgenic activity in the lipid pathway of male flank organs, and that 5α-reduction is not essential for the LNG effect on this tissue.