Hirosumi J, Nakayama O, Chida N, Inami M, Fagan T, Sawada K, Shigematsu S, Kojo H, Notsu Y, Okuhara M
Exploratory Research Laboratories, Fujisawa Pharmaceutical Co. Ltd, Tsukuba, Japan.
J Steroid Biochem Mol Biol. 1995 Apr;52(4):365-73. doi: 10.1016/0960-0760(94)00188-r.
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.
FK143是一种非甾体类新型类固醇5α-还原酶抑制剂，该酶可将睾酮转化为5α-双氢睾酮（DHT）。我们研究了FK143对大鼠和犬前列腺的体内作用。将FK143口服给予成年雄性大鼠，持续14天。在剂量高于1mg/kg时，FK143显著降低了腹侧前列腺和精囊的湿重，但对附睾、睾丸和肾上腺的湿重没有影响。在去势幼鼠中，皮下注射丙酸睾酮（TP）可诱导腹侧前列腺和精囊生长，而给予剂量高于3.2mg/kg的FK143可使其生长受到抑制，而丙酸5α-双氢睾酮（DHTP）诱导的生长则不受影响。FK143对大鼠雄激素受体没有结合亲和力。FK143对大鼠子宫既无雌激素作用也无抗雌激素作用，对大鼠前列腺也无雄激素作用。通过气相色谱-质谱联用（GC-MS）法测定大鼠和犬前列腺中睾酮和DHT的浓度，给予10mg/kg的FK143可显著降低前列腺内DHT的浓度。这些结果表明，FK143通过抑制前列腺中的5α-还原酶活性来减少前列腺生长。
