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Hair Loss Study Abstract: Effects of antiandrogen TZP-4238 on the prostatic androgen receptor and prostatic androgen in rat
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Title
[Effects of antiandrogen TZP-4238 on the prostatic androgen receptor and prostatic
androgen in rat]
Author
Honma S; Suzuki K; Takezawa Y; Minato K; Fukabori Y; Yamanaka H
Address
Pharmacokinetics Research Department, Teikoku Hormone Mfg. Co., LTD., Kawasaki, Japan.
Source
Nippon Naibunpi Gakkai Zasshi, 70: 8, 1994 Oct 20, 925-40
Abstract
TZP-4238, a new steroidal antiandrogen, is an orally active drug in rats and dogs. The
effects of TZP-4238 on the androgen receptor and androgen content were examined in
comparison with other antiandrogens in rats. The prostate DHT levels decreased markedly
within 4-8 hr after a single oral administration of TZP-4238 8mg/kg. The prostatic
testosterone concentrations fell below the detection limit (5pg/g of tissue) at 4-12 hr
after the initiation of treatment. The plasma testosterone level also fell to 60% of the
control level after 4-8 hr and then returned to the normal range. Eight percent of DHT
present in normal prostatic tissue was located in the nuclear fraction. TZP-4238 reduced
the concentration of DHT in nuclei to 50% of the normal level. The concentration of the
plasma drug which induced a 50% decrease in the prostatic DHT, the IC50, was about
10ng/ml, while the IC50 value for plasma testosterone was 30-50ng/ml. After oral
administration of 15-OH TZP-4238, the main metabolite, the level of plasma testosterone
was significantly elevated above the control level. The androgen receptor level was
markedly reduced at 24 hr following castration and returned to the normal range within 5
hr of a single injection of testosterone. TZP-4238 reduced the nuclear androgen receptor
level to 60% at 24 hr after a single oral dose and then, the receptor content returned to
its original level. Both 15-OH TZP-4238 and cyproterone acetate also reduced the androgen
receptor and DHT contents to 50%. A series of in vivo studies demonstrated that TZP-4238
inhibited the uptake of testosterone and the decrease of DHT and testosterone, and
decreased the nuclear androgen receptor in the rat prostate.
Language of Publication
Japanese
Unique Identifier
95094945
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