TY - JOUR
T1 - Inhibition of testosterone 5α-reductase by and antiandrogenicity of allenic 3-keto-5,10-secosteroids
AU - Voigt, W.
AU - Castro, A.
AU - Covey, D. F.
AU - Robinson, C. H.
PY - 1978
Y1 - 1978
N2 - (4R)-5,10-seco-19-norpregna-4,5-diene-3,10,20-trione(II), a 3-keto-5,10-secosteroid which is an irreversible inhibitor of Δ5-3-ketosteroid isomerase was tested for its possible antiandrogenicity in the hamster flank organ test. The organs of female animals topically treated with 4 μg of testosterone propionate (TP) for 4 weeks enlarged in size and showed pigmentation resembling adult males. When compound II was applied concomitantly with TP, androgenic stimulation was completely blocked and the flank organs remained small like those of female animals. These results suggest that compound II may be a useful anti-androgen when applied topically. It may well act mainly by inhibition of the formation of 5α-reduced metabolites of testosterone, as judged by its effect on rat prostatic 5α-reductase. Thus, incubation of a rat prostatic homogenate with [4-14C]testosterone produced 5α-dihydrotestosterone and 5α- androstane-3α,17β-diol as the main products. However, when compound II was included in the incubation mixture, the production of these 5α-reduced metabolites was markedly inhibited.
AB - (4R)-5,10-seco-19-norpregna-4,5-diene-3,10,20-trione(II), a 3-keto-5,10-secosteroid which is an irreversible inhibitor of Δ5-3-ketosteroid isomerase was tested for its possible antiandrogenicity in the hamster flank organ test. The organs of female animals topically treated with 4 μg of testosterone propionate (TP) for 4 weeks enlarged in size and showed pigmentation resembling adult males. When compound II was applied concomitantly with TP, androgenic stimulation was completely blocked and the flank organs remained small like those of female animals. These results suggest that compound II may be a useful anti-androgen when applied topically. It may well act mainly by inhibition of the formation of 5α-reduced metabolites of testosterone, as judged by its effect on rat prostatic 5α-reductase. Thus, incubation of a rat prostatic homogenate with [4-14C]testosterone produced 5α-dihydrotestosterone and 5α- androstane-3α,17β-diol as the main products. However, when compound II was included in the incubation mixture, the production of these 5α-reduced metabolites was markedly inhibited.
UR - http://www.scopus.com/inward/record.url?scp=0017799141&partnerID=8YFLogxK
U2 - 10.1530/acta.0.0870668
DO - 10.1530/acta.0.0870668
M3 - Article
C2 - 580152
AN - SCOPUS:0017799141
SN - 0001-5598
VL - 87
SP - 668
EP - 672
JO - Acta Endocrinologica
JF - Acta Endocrinologica
IS - 3
ER -