Clinical Information

Estrogens are involved in development and maintenance of the female phenotype, germ cell maturation, and pregnancy. There are 3 major biologically active estrogens in humans: estrone (E1), estradiol (E2), and estriol (E3). Like all members of the steroid hormone family, they diffuse into cells and bind to specific nuclear receptors, which in turn alter gene transcription in a tissue specific manner. E2 is the most potent natural human estrogen, closely followed by E1, while E3 possess only 20% of the E2 affinity for the estrogen receptor. In men and nonpregnant women, E1 and E2 are formed from the androgenic steroids, androstenedione and testosterone, respectively. E3 is derived largely through conversion of E2, and to a lesser degree from 16a-metabolites of E1. E2 and E1 can also be converted into each other, and both can be inactivated via hydroxylation and conjugation.

During pregnancy E3 becomes the dominant estrogen. The fetal adrenal gland secretes dehydroepiandrosterone-sulfate, which is converted to E3 in the placenta and diffuses into the maternal circulation. The half-life of unconjugated E3 (uE3) in the maternal blood system is 20 to 30 minutes since the maternal liver quickly conjugates E3 to make it more water soluble for urinary excretion. E3 levels increase throughout the course of pregnancy, peaking at term.