The Expression of Placental 17β-Hydroxysteroid Dehydrogenase Genes Is Associated with the Elevation of Active Androgens and Estrogens in Pregnant Women, but Does Not Affect 11-Oxygenated C19 Steroids

The placenta produces a variety of steroid hormones through the catalytic activity of steroidogenic enzymes, including cytochrome P450 (CYP) hydroxylases and hydroxysteroid dehydrogenases (HSD). Large amounts of progesterone produced by the placenta are essential for the maintenance of pregnancy. Although androgens and estrogens are also elevated in maternal circulation during gestation, there are conflicting reports on whether de novo synthesis of these steroids occurs in the human placenta. To address this issue, we performed a comprehensive analysis of steroidogenic gene expression in early and term placenta. While none of the genes examined showed binary expression changes, 17β-HSDs, including HSD17B1 and AKR1C3, were markedly upregulated in the term placenta. CYP19A1 and HSD11B2 genes were also markedly upregulated. In contrast, CYP17A1, CYP21A2, CYP11B1, CYP11B2, and HSD17B3 were almost undetectable. Consistent with these findings, the plasma ratios of active to precursor sex steroids (estradiol/estrone and testosterone/androstenedione) were higher in pregnant than in non-pregnant women, although concentrations of all steroids increased. In contrast, plasma levels and profiles of 11-oxygenated androgens were unchanged. These results indicate that the human placenta does not significantly contribute to circulating levels of either classical or novel classes of androgens. Therefore, this study provides new insights into the tissue of origin and the physiological significance of sex steroids during gestation.