Figure 1
Estrogen biosynthesis and metabolism in breast tissue. In breast tissue, estrogens come directly from ovaries or they are synthesized from androgens secreted by the adrenals. (1) The first metabolic pathway of estrogen involves the transformation of estradiol (E2) to estrone (E1) by 17β-hydroxysteroid dehydrogenase (17βHSD) and its subsequent conjugation to estrone sulfate (E1S) by estrogen sulfotransferase. (2) Both E2 and E1 can be oxidized by the action of different cytochromes P450 (CYPs) to generate 2- and 4-hydroxy-catecholestrogen (OHCE). (3) These metabolites can be further methoxylated by catechol-O-methyltransferase (COMT). (4) UDP-glucuronosyltransferases (UGTs) are able to conjugate parent estrogens E2 and E1, as well as there derivatives 2/4-OHCE and 2/4-methoxy-catecholestrogen (MeOCE). The resulting estrogen glucuronides are devoid of biologic activities. AR, androgen receptor; 3β-HSD, 3β-hydroxysteroid dehydrogenase; CYP19, aromatase; Δ5-diol, androstenediol; DHT, dihydrotestosterone; ER, estrogen receptor; MeO, methoxy; OH, hydroxy; testo, testosterone.