The metabolism of androstenedione in human pregnancy: the use of constant infusion of unlabeled steroid to assess its metabolic clearance rate, its production rate, and its conversion into androgens and estrogens.

Using constant infusion of unlabeled steroid, we have studied the metabolic clearance rate (MCR), half-life (T 1/2), and conversion ratio of androstenedione (A) into androgens and estrogens throughout human pregnancy. In nonpregnant women, results obtained by infusion of unlabeled A were identical to those obtained by the infusion of either labeled steroid or a mixture of labeled and unlabeled steroid. A twofold increase in the infusion rate did not change any of these results, indicating that enzyme availability was not a limiting step. When compared to the nonpregnant state, pregnancy was associated with a twofold rise in plasma A production rate (PR) (p less than 0.05) but with minimal changes in its MCR or its T 1/2, thus leading to a twofold increase in the plasma concentration of A (p less than 0.05). The conversion of A into testosterone (T) rose twofold at term pregnancy (p less than 0.05), whereas that of A into estrone (E1) rose fivefold (p less than 0.01) and that of A into estradiol (E2) rose 16 fold (p less than 0.001). It is concluded that constant infusions of unlabeled A can be used successfully to study the kinetics of A when one is reluctant to infuse isotopic steroid.