Splanchnic Extraction and Conversion of Testosteroneand Dihydrotestosterone inMan*

Abstract

The splanchnic extraction and interconversion of testosterone and dihydrotestosterone (DHT) were studied in 7 healthy men (ages 29-46 years) undergoing cardiac catheterization. During a constant infusion of [1,2-3H]testosterone and [4-14C]DHT, the arterial and hepatic vein blood samples were taken and radioactive and non-radioactive testosterone and DHT were determined. Metabolic clearance rate (MCR), splanchnic extraction (SE), splanchnic clearance (SC), extrasplanchnic clearance (ESC), transfer constant in blood (T-DHT rhoBB) and transfer constant across the liver (T-DHT rhoSB) were calculated. The MCRT was 952 +- 172 (mean +- SD) 1/day and MCRDHT was 764 +/- 67 1/day in agreement with data from non-catheterized subjects. SET was 68.8 +/- 7.1% (mean +/- SD) and SEDHT was 37.6 +/- 5.9%. SET was significantly greater than SEDHT (P less than 0.001). The calculated SCT and ESCT were 638 +/- 112 (mean +/- SD) 1/day and 314 +/- 190 1/day, respectively. SCDHT and ESCDHT were 343 +/- 95 (mean +/-SD) 1/day and 421 +/-105 1/day, suggesting that a major fraction of testosterone is metabolized in the splanchnic organs and a higher fraction of DHT is metabolized in extrasplanchnic organs. In the interconversion study, overall conversion of testosterone to DHT in blood (T-DHT rhoBB) was 4.0 +/- 0.6% (mean +/- SD). No evidence for a net appearance of DHT by either mass or specific activity analysis in hepatic vein blood was observed in any infusion leading to the conclusion that the overall contribution of testosterone to circulating DHT from the liver (T-DHTrhoSB) was undetectable. This work indicates that conversion of testosterone to DHT occurs entirely in extrasplanchnic tissue in man.

Benign Prostatic Hyperplasia: a Disorder of Androgen Metabolism in the Male

“…Despite the the oretical predictions, we have studied the mass of DHT and the conversion of testosterone to DHT across splanchnic tissue by comparing aortic and hepatic vein concentration. The data indicates that neither by mass, radioactivity or specific activity is there any evidence for production of DHT by gut, liver, or splanchnic fat from testosterone or any other steroid entering or produced by splanchnic tissue [32,33]. This conclusion is similar to those reached by us for androstanediol [34].…”

Alteration in the metabolism of dihydrotestosterone in elderly men with prostate hyperplasia.

“…The importance of these observations was increased when it became clear that DHT conversion did not occur in muscle (13), and we have demonstrated that both DHT and 3adiol are derived from conversion in extrasplanchnic tissue (14). This work indicates that DHT and 3adiol production measured in the circulation may be a reflection of events occurring in sexual target tissue.…”

“…[14C]testosterone and [3H]3adiol were given by constant infusion over a 2-h period as described (11,12 for correction of losses and the plasma extracted with solvent as described (14). The dried extracts were then chromatographed on a celite column (18), collecting testosterone, DHT, and 3adiol fractions.…”

5α-Metabolism in Finasteride-Treated Subjects and Male Pseudohermaphrodites with Inherited 5α-Reductase Deficiency

“…For all variables except testoster one, a log conversion was done to normalize distribution. Paired comparisons were made following ANOVA using the Neuman-Keuls test [1], circulating DHT concentration is exclusively a reflection of peripheral conversion [6]. Thus, the low plasma DHT concentration and the elevated plasma testosterone -DHT ratios in subjects with inherited 5a-reductase defi ciency are due to diminished conversion of testosterone to DHT in peripheral tissues.…”