20-ALPHA-HYDROXYSTEROID DEHYDROGENASE-ACTIVITY IN RAT PLACENTA

20alpha-Hydroxysteroid dehydrogenase (20alpha-HSD) (EC.1.1.1.149) is the enzyme which catabolizes progesterone to 20alpha-dihydroprogesterone (20alpha-OHP), a biologically inactive steroid, and is distributed in a variety of tissues including non-steroid-producing tissues. In the present study, changes in cytosolic 20alpha-HSD activity were investigated in rat placental tissues and its relationship to embryonic mortality was considered; the mesometrial endometrium (including the ectoplacental cone) on days 8-11 of pregnancy (day 0 = estrus), and the chorioallantoic placenta and visceral yolk sac (vitelline membrane) on days 12-21 were separately subjected to measurement of the enzyme activity. 20alpha-HSD activity was not detected in the chorioallantoic placenta until day 20 and then increased dramatically on day 21. Interestingly, considerable activity of the enzyme was found in the visceral yolk sac from days 14 to 21 and in the mesometrial endometrium from days 8 to 10, whereas it was undetectable in these tissues on days 11 and 12. Analysis of DEAE column chromatography revealed that these tissues contain two different types of 20alpha-HSD (HSD-1 and HSD-2). By an immunohistochemical method, with polyclonal antiserum to rat 20alpha-HSD, decidual cells and trophoblastic giant cells adjacent to the ectoplacental cone (day 10), spongiotrophoblasts and visceral yolk sac cells (days 21) were positively stained. The number of fetuses on day 10 of pregnancy was 15.4 and decreased significantly to 12.9 on day 12. Since the progesterone concentration in the amniotic fluid was only 3-4% of the maternal serum concentration, expression of 20alpha-HSD in the placental tissues seems to lower the concentration of progesterone in the fetal environment. Thus, 20alpha-HSD activity was found in the tissues surrounding the fetus during pregnancy in the rat except for the specific period (days 11 and 12) during which spontaneous fetal loss occurs. 20alpha-HSD is therefore present in the decidual cells during placentation and in the visceral yolk sac throughout pregnancy. These results support the hypothesis that 20alpha-HSD acts as a survival factor for fetuses, protecting them from the cytotoxic activity of progesterone by metabolizing it to the inactive steroid.