Figure 6.

Models of steroid hormone metabolism in mouse and human cervix during pregnancy. A, In the mouse, steroid 5α-reductase type 1 (5αR-1) is induced in cervical epithelial cells to inactivate progesterone locally. B, In the human cervix during pregnancy, circulating progesterone (P) and estradiol (E2) enter the cervical stroma, and are metabolized by 5α-reductase type 1 and 20α-HSDs (AKR1C1-C3) to 5α-dihydroprogesterone (5αDHP) and 20α-hydroxyprogesterone (20αP). Estradiol and 20α-hydroxyprogesterone are converted to estrone (E1) and progesterone, respectively, by high levels of 17βHSD type 2 (17βHSD2) in endocervical epithelial cells, resulting in inactivation of estradiol and the maintenance of progesterone levels in the surrounding stromal cells. Robust expression of 17βHSD type 2 in epithelial cells also counteracts 20α-reduction of progesterone by epithelial AKR1C enzymes. C, During cervical ripening and parturition, 17βHSD type 2 is decreased in endocervical epithelial cells. Conversion of estradiol to estrone and 20α-hydroxyprogesterone to progesterone is thereby compromised, resulting in increased estradiol and 20α-hydroxyprogesterone levels and inactivation of progesterone responses in the stroma.