Estrogen and androgen dynamics in the cynomolgus monkey.

Abstract

We studied the dynamics of androgen, estrogen, and cortisol (F) production, metabolism, and protein binding in cynomolgus monkeys (M. fascicularis) to provide baseline data and to compare these parameters with those obtained in other primates. Constant infusions of 3H-labeled androgens, 14C-labeled estrogens, and [3H]F were administered to 11 male cynomolgus monkeys (M. fascicularis) for 3.5 h. Blood samples were obtained from a peripheral vein during the infusion, and all urine was collected for 96 h. In each of 3 monkeys, a catheter was inserted into the hepatic vein, and during the infusions blood samples were obtained from the hepatic and peripheral veins and the femoral artery. All blood and urine samples were analyzed for radioactivity as testosterone (T), androstenedione (A), dihydrotestosterone (DHT), estradiol (E2), and estrone (E1). When indicated, blood samples were also analyzed for radioactivity as F. Blood samples taken before the infusions were analyzed for endogenous T, A, DHT, E1, E2, and F concentrations; percent free T, free E2, and free F; and sex hormone-binding globulin and F-binding globulin capacities. The mean +/- SE MCRs for T, A, E2, E1, and F were 44 +/- 4, 407 +/- 40, 175 +/- 17, 315 +/- 28, and 57 +/- 6 liters/day, respectively. The mean blood production rates were 128 +/- 19, 91 +/- 14, 3.3 +/- 0.5, and 9.2 +/- 1.1 micrograms/day and 13.4 +/- 1.9 mg/day for T, A, E2, E1, and F, respectively. The aromatization of androgens was 1.30 +/- 0.10% for A to E1 and 0.28 +/- 0.03% for T to E2. The percent free F (4.34 +/- 0.42%) was greater than the percent free T (1.73 +/- 0.16%) or free E2 (2.75 +/- 0.22%), and the concentration of F-binding globulin was greater than that of sex hormone-binding globulin (227 +/- 35 vs. 60 +/- 7 nM). In the three monkeys who had hepatic venous catheterization, the mean extraction, across the splanchnic bed of T was 32 +/- 3%, that of E was 62 +/- 2%, and that of cortisol was 12 +/- 5%. Across peripheral tissues (leg) the mean extractions were 13 +/- 1%, 18 +/- 1%, and 6 +/- 4%, respectively. In general, the dynamics of androgen, estrogen, and F production and metabolism are similar in male cynomolgus and rhesus monkeys and in man. The similarity is especially close for peripheral aromatization despite differences in adipose tissue content between man and nonhuman primates.