Effect of Adrenocorticotropin on Production Rates and Metabolic Clearance Rates of Testosterone and Estradiol*

Abstract

Using the constant infusion technique, [7-3H]testosterone and [4-l4C]estradiol were infused into six men and two women and [7-3H]androstenedione and [4-l4C]estrone were infused into two men before and after the administration of 60 U ACTH every 12 h for four doses. Measurements of the MCRs, plasma levels of endogenous hormones, and blood production rates (PBs) were performed before and after ACTH. The fraction of infused androgen converted to and measured as estrogen ([ρ]AND,ESTBB) was also determined before and after ACTH. In all six men, ACTH caused a significant rise in the mean value for the MCR of testosterone from 900 ± 80 to 1250 ± 80 (SE) liters/day, a significant decrease in the mean value for levels of testosterone from 5.2 ± 0.9 to 2.0 ± 0.6 ng/ml, and a significant decrease in the PB of testosterone from 4.5 ± 0.5 to 2.3 ± 0.6 mg/day. In both women, MCR of testosterone rose, the plasma levels remained essentially unchanged, and the PBS increased. In the men, ACTH administration resulted in a nonsignificant rise in the MCR of estradiol from 1760 ± 50 to 2010 ± 120 liters/day, and no change in the circulating level (30 ± 2 to 26 ± 2 pg/ml) or the PB (53 ± 4 to 54 ± 6 μg/day). The fractional conversion of testosterone to estradiol, [ρ]T,2BB, did not change (0.0032 ± 0.0006 to 0.0032 ± 0.0004). In both women, the MCR for estradiol rose, but the changes in levels and estradiol PB were divergent. In both men, although the MCRs for androstenedione and estrone did not change appreciably, the circulating levels and PBS rose. The mean level of LH in six men did not change under these conditions (51 ± 11 before and 57 ± 11 ng/ml after ACTH). We conclude that in men, ACTH increases the metabolism of testosterone and decreases its circulating level, synthesis, and production rate. During the course of the study, LH levels did not rise in response to the fall in testosterone. The circulating level and PB of estradiol remain unchanged because ACTH results in increased production of androstenedione and estrone, both of which are converted to estradiol. In women, the PB of testosterone does not fall after ACTH, presumably because of the increased PB of androstenedione.