Different binding of testosterone, 19-nortestosterone and their 5 alpha-reduced derivatives to the androgen receptor of the rat seminal vesicle: a step toward the understanding of the anabolic action of nortesterone.

Abstract

Binding to the androgen receptor of rat seminal vesicle was studied in vitro using cell-free extract or minced tissue. Relative binding affinities of 5 alpha-dihydrotestosterone (DHT), 5 alpha-dihydro-19-nortestosterone (DHN), nortestosterone and testosterone were estimated from their competition with [3H]-DHT for the binding sites. In contrast with the conflicting results obtained with cell-free systems incubated at 0-15 degrees C, studies performed with vesicular mince at 37 degrees C proved to be useful to demonstrate characteristic differences in binding affinity and to gain information about binding both to cytosol and nuclear receptors. Competition data were graphically analyzed, and after correction for steroid metabolism the following relative competition indices were obtained: DHT = 1.00; nortestosterone = 0.32-0.4; testosterone = 0.1-0.2; DHN = 0.12. However, binding to cytosolic and nuclear receptors did not differ significantly. It is concluded that testosterone and 19-nortestosterone (which are equally good substrates for 5 alpha-reductase) are converted in the seminal vesicles to metabolites, of which DHT exhibits an affinity to the androgen receptor nearly one order of magnitude higher than that of DHN. On the other hand, in skeletal muscles that are practically devoid of 5 alpha-reductase activity, the 3-fold higher affinity of nortestosterone to the receptor, expectedly, results in a myotropic activity that is superior to that of testosterone.