FK143, a novel nonsteroidal inhibitor of steroid 5 alpha-reductase: (2) In vivo effects on rat and dog prostates.
FK143 is a nonsteroidal new inhibitor of steroid 5 alpha-reductase, an enzyme which converts testosterone into 5 alpha-dihydrotestosterone (DHT). We studied in vivo effects of FK143 on rat and dog prostates. FK143 was orally administered to mature male rats for 14 days. At doses above 1 mg/kg, FK143 significantly reduced the wet weights of the ventral prostate and seminal vesicle, but showed no effects on those of the epididymis, testis, and adrenal. Growth of ventral prostate and seminal vesicle was induced by the subcutaneous injection of testosterone propionate (TP) in the castrated young rats and was reduced by FK143 administration at doses above 3.2 mg/kg, while growth induced by 5 alpha-dihydrotestosterone propionate (DHTP) was not affected. FK143 had no binding affinity for the rat androgen receptor. FK143 showed neither estrogenic and antiestrogenic effects on the rat uterus nor androgenic effect on the rat prostate. Concentration of testosterone and DHT in the rat and dog prostates were measured by GC-MS, and administration of 10 mg/kg of FK143 significantly reduced the intraprostatic concentration of DHT. These results indicate that FK143 reduced the prostate growth by inhibiting 5 alpha-reductase activities in the prostates.
Hirosumi
J
J
Exploratory Research Laboratories, Fujisawa Pharmaceutical Co. Ltd, Tsukuba, Japan.
Nakayama
O
O
Chida
N
N
Inami
M
M
Fagan
T
T
Sawada
K
K
Shigematsu
S
S
Kojo
H
H
Notsu
Y
Y
Okuhara
M
M
D058891:5-alpha Reductase Inhibitors; D000284:Administration, Oral; D000367:Age Factors; D000728:Androgens / Q000032:analysis; D000818:Animals; D003600:Cytosol; D013196:Dihydrotestosterone / Q000032:analysis; D004285:Dogs; D005260:Female; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D009919:Orchiectomy; D009929:Organ Size / Q000187:drug effects; D010654:Phenylbutyrates / Q000494:pharmacology*; D011467:Prostate / Q000737:chemistry / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D011944:Receptors, Androgen / Q000032:analysis; D012669:Seminal Vesicles / Q000187:drug effects; D012737:Sex Factors; D013739:Testosterone / Q000032:analysis; D014599:Uterus / Q000187:drug effects
C093354:4-(3-(3-(bis(4-isobutylphenyl)methylamino)benzoyl)-1H-indol-1-yl)butyric acid; D058891:5-alpha Reductase Inhibitors; D000728:Androgens; D007211:Indoles; D010654:Phenylbutyrates; D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D013739:Testosterone