20-ALPHA-HYDROXYSTEROID DEHYDROGENASE-ACTIVITY IN RAT PLACENTA

20alpha-Hydroxysteroid dehydrogenase (20alpha-HSD) (EC.1.1.1.149) is t he enzyme which catabolizes progesterone to 20alpha-dihydroprogesteron e (20alpha-OHP), a biologically inactive steroid, and is distributed i n a variety of tissues including non-steroid-producing tissues. In the present study, changes in cytosolic 20alpha-HSD activity were investi gated in rat placental tissues and its relationship to embryonic morta lity was considered; the mesometrial endometrium (including the ectopl acental cone) on days 8-11 of pregnancy (day 0 = estrus), and the chor ioallantoic placenta and visceral yolk sac (vitelline membrane) on day s 12-21 were separately subjected to measurement of the enzyme activit y. 20alpha-HSD activity was not detected in the chorioallantoic placen ta until day 20 and then increased dramatically on day 21. Interesting ly, 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 c ontain two different types of 20alpha-HSD (HSD-1 and HSD-2). By an imm unohistochemical method, with polyclonal antiserum to rat 20alpha-HSD, decidual cells and trophoblastic giant cells adjacent to the ectoplac ental cone (day 10), spongiotrophoblasts and visceral yolk sac cells ( days 21) were positively stained. The number of fetuses on day 10 of p regnancy 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 pl acental tissues seems to lower the concentration of progesterone in th e fetal environment. Thus, 20alpha-HSD activity was found in the tissu es surrounding the fetus during pregnancy in the rat except for the sp ecific period (days 11 and 12) during which spontaneous fetal loss occ urs. 20alpha-HSD is therefore present in the decidual cells during pla centation and in the visceral yolk sac throughout pregnancy. These res ults support the hypothesis that 20alpha-HSD acts as a survival factor for fetuses, protecting them from the cytotoxic activity of progester one by metabolizing it to the inactive steroid.