In vitro binding and metabolism of androgens in various organs: a comparative study

Abstract

A comparative study of in vitro binding and metabolism of 5α-dihydrotestosterone (5α-DHT), testosterone (T) and 19-nortestosterone (19-Nor-T) in the prostate (PR), bulbocavernosus/levator ani (BCLA) and skeletal muscle (SM) of the rat was performed. After the homogenate of the organs was incubated at 0°C for 2 h, the 100,000 g cytosol was processed. Binding was analyzed by agargel electrophoresis at low temperature and androgen metabolism by t.l.c. The overall physico-chemical characteristics of the androgen receptor are similar if not identical in the PR, BCLA, and SM. The dissociation constants being within the organs different, in the prostate K D(19-Nor-T) < K D(5α-DHT) < K D(T) and in the BCLA K D(5α-DHT) < K D(19-Nor-T) < K D(T). The range being 7 × l0 -10 M-4 × l0 -9 M. Significant differences were found between the available androgen binding sites expressed as fmol/mg cytosol protein: being 170 in PR, 24 in BCLA and 2 in SM. In the PR after 5α-DHT incubation at 0°C, 26% of the extracted radioactivity was found as 5α-androstanediols, while after T incubation 10% was converted to 5α-DHT and 6% to 5α-androstanediols. In the BCLA and SM only small amounts of 5α-DHT were metabolized to 5α-androstanediols (5–8%), and no conversion of T to 5α-DHT was measurable. In conclusion, no different physico-chemical characteristics of the androgen receptor of the PR, BCLA and SM, but rather differences in the affinity of the receptor to various steroids, differences in metabolism of the steroids and especially differences in the amount of available androgen binding sites might be responsible for the different androgen dependency of PR, BCLA and SM.