Conversion of Progesterone to 5α-Pregnane-3,20-dione and 3α-Hydroxy-5α-pregnan-20-one by Rat Medial Basal Hypothalami and the Effects of Estradiol and Stage of Estrous Cycle on the Conversion*

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Abstract
Tissue slices of rat medial basal hypothalami (MBH’s) from various stages of estrous cycle were incubated with 3H-progesterone. Regardless of the stage of the estrous cycle, most of the recovered tissue radioactivity was present in the 1000 × g pellet after subcellular fractionation. The radioactivity associated with the 1000 × g pelletafter subcellular fractionation. The radioactivity associated with the 1000 X g pellet was isolated and identified on the basis of reverse isotopic dilution techhniques by purification to a constant specific activity. With all incubations the 2 major metabolites identified were 5α-pregnane-3,20-dione and 3αhydroxy- 5α-pregnan-20-one. Other metabolites of progesterone, if any, appear to be present in very small amounts (2–3%). Although no qualitative changes in metabolism of progesterone were observed with respect to the stage of the estrous cycle, quantitative variations were evident. Higher accumulations of 3H-5αpregnane- 3,20-dione as compared to 3H-3α-hydroxy- 5α-pregnan-20-one were observed in all incubations. The highest accumulation of 3H-5apregnane- 3,20-dione was observed during the mornings of diestrus 2 and estrus. The lowest accumulation of 3H-5α-pregnane-3,20-dione occurred on the mornings of diestrus 1 and proestrus. 3H-3cthydroxy- Sa-pregnan-20-one accumulation followed a somewhat similar pattern except for the morning proestrus. The effects of estrogen on the metabolism of progesterone was studied by incubating MBH’s from ovariectomized rats treated with 17β-estradiol and compared with MBH’s from untreated castrates. Although a consistent trend toward a higher accumulation of 3H-5α-pregnane-3,20-dione was evident in the estradiol treated group, the p value is only 0.1. The results with the 3α-hydroxy- 5α-pregnan-20-one were inconsistent and not statistically different. (Endocrinology93: 1157, 1973)