STEROID TRANSFORMATIONS IN PREGNANT MARES - METABOLISM OF EXOGENOUS PROGESTINS AND UNUSUAL METABOLIC-ACTIVITY IN-VIVO AND IN-VITRO

The mare possesses unique steroid hormone metabolic activity during pr egnancy in that peripheral 4-pregnene-3,20-dione (progesterone; P4) is undetectable by 220 days gestation. This study examines in vivo metab olism of progestins by the pregnant mare and in vitro metabolic activi ty of maternal and fetal tissues. Pregnant mares (n = 3) received intr avenous infusions of 3 beta-hydroxy-5-pregnen-20-one (pregnenolone; P5 ), P4, 5 alpha-pregnane-3,20-dione (5 alpha-DHP), 3 beta-hydroxy-5 alp ha-pregnan-20-one (3 beta-5 alpha), deuterium labeled (D4)-P5, D4-3 be ta-5 alpha and vehicle. Anestrous mares (n = 2) were infused with P5, P4, and vehicle. Also, placenta, endometrium, fetal gonad, maternal an d fetal liver, and adrenal from 4 animals were incubated in D4-P5, D4- 5 alpha-DHP, or D4-3 beta-5 alpha. Pregnant mares (in vivo) converted infused P5 predominantly to 5-pregnene-3 beta,20 beta-diol (P5-beta be ta), 5 alpha-DHP, 20 alpha-hydroxy-5 alpha-pregnan-3-one (20 alpha-5 a lpha), and 3 beta-5 alpha while only minor concentrations of P4 were d etected. Infused P4 was converted primarily to 5 alpha-DHP and 20 alph a-hydroxypregnanes and when 5 alpha-DHP served as a substrate, other 5 alpha-pregnanes were formed Infused 3 beta-5 alpha was either reduced to pa-diol or oxidized to Sa-DHP. Regardless of treatment, anestrous mares were incapable of producing any 20 alpha-hydroxypregnanes but co uld convert PS to PS-beta beta and P4 in quantities similar to that of pregnant mares. In vitro, placenta converted D4-P5 to D4-P4 while D4- 3 beta-5 alpha was oxidized to D4-5 alpha-DHP. Endometrium converted s ubstrate primarily to D4-20 alpha- hydroxypregnanes. Both maternal and fetal liver produced D4-20 beta-hydroxy compounds regardless of subst rate. Maternal and fetal adrenal were capable of conversion of D4-P5 t o D4-P4 while fetal gonad did not perform any significant metabolism o f substrate, though it produced P5. These data explain the absence of P4 and presence of other progestin metabolites in maternal circulation during mid- and late pregnancy. Pregnenolone can be Sec-reduced to 3 beta-5 alpha, and 3 beta-5 alpha could be 3-oxidized to 5 alpha-DHP. I t is 5 alpha-DHP that may serve as substrate for other 5 alpha-pregnan es.