EXPRESSION OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE DURING DECIDUALIZATION OF HUMAN ENDOMETRIAL STROMAL CELLS

This study evaluated the expression of the corticosteroid-metabolizing enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) during in v itro decidualization of human endometrial stromal cells. The cultured stromal cells displayed both NADP(+)-dependent (type 1) and NAD(+)-dep endent (type 2) 11 beta HSD activities under basal conditions. Althoug h the cells did not respond to estradiol (E(2)) added alone, catalytic levels of both isoforms were enhanced by medroxyprogesterone acetate (MPA) and further enhanced by E(2) plus MPA. Type I messenger RNA (mRN A) was undetected by Northern analysis of total RNA, but was evident a s a 1.5-kilobase band in polyadenylated selected RNA from E(2)- plus M PA-treated cultures. Use of RT-PCR to augment the sensitivity of mRNA detection revealed the presence of type I mRNA as a faint band in the MPA-treated cultures and as an intense band in the E(2)- plus MPA-trea ted cultures. Thus, type I mRNA is present as a low abundance message in the cultured stromal cells whose steady state levels parallel proge stin-enhanced enzyme activity. As the expression of several progestin- regulated decidualization markers is also augmented by E(2), the resul ts of the present study reveal a correlation between enhanced 11 beta HSD expression and the decidualization reaction. Time-course measureme nts indicated that elevated 11 beta HSD expression is an early event i n the decidualization response, which precedes E(2)- plus MPA-enhanced PRL production by several days. Clear dose-response effects on both t ype 1 and type 2 11 beta HSD activities were obtained in cells incubat ed with 10(-8) mol/liter E(2) added together with MPA at concentration s that approximated circulating progesterone levels from the luteal ph ase (10(-9) mol/liter) through pregnancy (10(-7) mol/liter). Corticost eroids are thought to exert toxic and teratogenic effects on the impla nting embryo and could influence trophoblast invasion by regulating ex tracellular matrix turnover. Therefore, the novel finding that decidua lization involves marked enhancement of the corticosteroid-metabolizin g capacity of stromal cells suggests a mechanism by which decidual cel ls could affect the health and invasiveness of implanting trophoblasti c cells.