In vivo metabolism and binding of 6 alpha-methylprogesterone; a progestin with anti-androgenic and synandrogenic activities.

The synthetic progestin 6 alpha-methylprogesterone (6MP) was shown to have androgenic, synandrogenic and anti-androgenic actions on mouse kidney. In vitro studies indicated that 6MP competes with testosterone for binding sites on the androgen receptor in kidney cytosol and nuclei. The in vivo distribution of 6MP and testosterone differed following subcutaneous administration: Testosterone levels were 10 and 100-fold higher than those of 6MP in plasma and nuclei from prostate-seminal vesicle. In kidney nuclei, the concentrations of these two steroids were similar. In addition, kidney nuclei bound a hydroxylated metabolite of 6MP as well as the parent compound, whereas only 6MP was found in nuclei from prostate-seminal vesicle. In vivo competition studies indicated that nonradioactive 6MP and testosterone decreased the uptake of 3H-testosterone by nuclei of kidney and prostate-seminal vesicle. By contrast, 3H-6MP uptake in kidney nuclei was potentiated by the prior administration of 6MP or testosterone. These results suggest that factors in addition to the androgen receptor may be involved in the binding and mechanism of action of 6MP on mouse kidney.