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-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 5 alpha-LNG metabolite was isolated and its purity was assessed. Competition experiments for androgen binding receptors were carried out with 1.38 nM [3H-7 alpha-17 alpha]dimethyl-19- nortestosterone (DMNT), Kd, 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 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-14C]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.
Department of Biological Systems, Metropolitan University-Xochimilco and Iztapalapa, Mexico City, Mexico.
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Vilchis
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Pérez-Palacios
D000818:Animals; D001667:Binding, Competitive; D002369:Castration; D006224:Cricetinae; D005260:Female; D005947:Glucose / Q000378:metabolism; D066298:In Vitro Techniques; D016912:Levonorgestrel / Q000737:chemistry / Q000378:metabolism*; D050356:Lipid Metabolism; D008297:Male; D010084:Oxidation-Reduction; D011944:Receptors, Androgen / Q000378:metabolism*; D012627:Sebaceous Glands / Q000187:drug effects / Q000378:metabolism*; D013739:Testosterone / Q000494:pharmacology
D011944:Receptors, Androgen; D013739:Testosterone; D016912:Levonorgestrel; D005947:Glucose