Proposed model for placental progesterone and estrogen synthesis. For detailed description, see text. Progestagens are shown in green, estrogens in red, and androgens in blue color. Solid arrows indicate enzymatic steps that have been demonstrated in human placenta; respective enzymes are shown in gray. Dashed arrows indicate hypothetic routes of transport of sulfate-conjugated compounds. Dashed purple circles highlight sulfate-conjugated compounds that require transporters for uptake into (SOAT, OAT4, and OATP2B1) and export (ABCG2) from cells. A-dione, androstenedione; ABC transporters, ATP-binding cassette transporters; BCRP, breast cancer resistance protein; DHEA, dehydroepiandrosterone; DHEA-S, dehydroepiandrosterone sulfate; CYPs, cytochrome P-450 enzymes; E1, estrone; E1-S, estrone sulfate; E2, Estradiol; E2-S, estradiol sulfate; E3, estriol; E3-S, estriol sulfate; ER, endoplasmatic reticulum; pFEC, placental-fetal endothelial cell; -OH-, -Hydroxy-; 17α-OHP, 17α-hydroxyprogesterone; HSD, hydroxysteroid dehydrogenase; OAT4, organic anion transporter 4; OATP2B1, organic anion transporting polypeptide 2B1; SOAT, sodium-dependent organic anion transporter; STS, steroid sulfatase; SULT, sulfotransferase; STB, syncytiotrophoblast; TES, testosterone.