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Proliferative responses of normal rat ventral prostate in organ culture: Effects of testosterone and its metabolites in chemically defined medium
Author(s) -
Buchanan Lynn J.,
Riches Andrew C.
Publication year - 1985
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.2990070410
Subject(s) - endocrinology , medicine , testosterone (patch) , dihydrotestosterone , androstenedione , organ culture , dna synthesis , androstane , prostate , androstenediol , androsterone , androgen , biology , chemistry , dna , hormone , steroid , in vitro , biochemistry , cancer
Proliferative responses of normal rat ventral prostate to testosterone were compared with that of its major metabolites, 5α‐dihydrotestosterone, androstenedione, androstanedione, and 5α‐androstane‐3β,17β‐diol in serum‐free organ culture medium using the incorporation of 5‐[ 125 I]‐iodo‐2′‐deoxyuridine ( 125 I‐UdR) to monitor DNA synthesis. With the exception of 5α‐androstane‐3β,17β‐diol, these androgens induced comparable increases in DNA synthesis at both 4 × 10 −9 and 4 × 10 −7 M, and at 4 × 10 −5 M they exerted a nonspecific cytotoxic effect, resulting in marked suppression of 125 I‐UdR uptake. In contrast, 5α‐androstane‐3β,17β‐diol was not stimulatory at 4 × 10 −9 M, whereas at both 4 × 10 −7 and 4 × 10 −5 M it stimulated marginal increases in DNA synthesis and effectively maintained the histology of the tissue in a state comparable to the intact gland. Unlike 5α‐dihydrotestosterone, its epimer 5β‐dihydrotestosterone was inactive at all concentrations used. These results support the hypothesis that testosterone action in the prostate is mediated by the formation of active 5α‐reduced metabolites.