Estrogen and Progesterone Metabolism in the Cervix during Pregnancy and Parturition

Abstract

Experimental and clinical studies in a variety of nonprimate species demonstrate that progesterone withdrawal leads to changes in gene expression that initiate parturition at term. Mice deficient in 5alpha-reductase type I fail to undergo cervical ripening at term despite the timely onset of luteolysis and progesterone withdrawal in blood. Our objective was to test the hypothesis that estrogen and progesterone metabolism is regulated in cervical tissues during pregnancy, even in species in which parturition is not characterized by progesterone withdrawal in blood. Estradiol and progesterone metabolism was quantified in intact cervical tissues from nonpregnant and pregnant women at term before or after labor. The study was conducted at a university hospital. Tissues were obtained from five nonpregnant and 21 pregnant women (nine before labor and 12 in labor). Enzyme activity measurements, Northern blot analysis, quantitative real-time RT-PCR, and immunohistochemistry were used to quantify steroid hormone metabolizing enzymes in cervical and myometrial tissues. During pregnancy, 17beta-hydroxysteroid dehydrogenase type 2 was induced in glandular epithelial cells to catalyze the conversion of estradiol to estrone and stroma-derived 20alpha-hydroxyprogesterone to progesterone. During parturition, 17beta-hydroxysteroid dehydrogenase type 2 was down-regulated in endocervical cells, thereby creating a microenvironment favorable for cervical ripening. Together, the data indicate that cervical ripening during parturition involves localized regulation of estrogen and progesterone metabolism through a complex relationship between cervical epithelium and stroma, and that steroid hormone metabolism in cervical tissues from pregnant women is unique from that in mice.