Mieda M, Ohta Y, Saito T, Takahashi H, Shimazawa E, Miyasaka K
Pharmacological Research Department, Teikoku Hormone Mfg. Co., Ltd., Kawasaki, Japan.
Endocr J. 1994 Aug;41(4):445-52. doi: 10.1507/endocrj.41.445.
TZP-4238 is a new potent, orally active steroidal antiandrogen. Antiandrogenic activity and endocrinological profile of TZP-4238 were investigated in rats, except that progestational activity was determined in rabbits. TZP-4238 suppressed the testosterone propionate-induced increases in the weights of the ventral prostate, seminal vesicle and levator ani in castrated immature male rats. TZP-4238 also decreased the weights of the ventral prostate, seminal vesicle and levator ani in intact adult male rats, but did not affect the weight of the testis or the serum concentrations of luteinizing hormone and testosterone. TZP-4238 did not have such an inhibitory effect on the weight of the adrenal gland as seen in other steroidal antiandrogens. It exhibited potent progestational activity. Although TZP-4238 did not exert androgenic or estrogenic activity, it had weak antiestrogenic activity. These results suggest that TZP-4238 exerts an antiandrogenic effect on the prostate without any compensatory change in the serum concentration of luteinizing hormone or testosterone in rats, and it is a useful drug for the treatment of androgen-dependent diseases such as prostatic hypertrophy and prostatic cancer.
TZP - 4238是一种新型强效、口服活性甾体类抗雄激素药物。除了在兔子身上测定其孕激素活性外，还在大鼠身上研究了TZP - 4238的抗雄激素活性和内分泌特征。TZP - 4238抑制了丙酸睾酮诱导的去势未成熟雄性大鼠前列腺腹侧、精囊和提肛肌重量的增加。TZP - 4238还降低了成年完整雄性大鼠前列腺腹侧、精囊和提肛肌的重量，但不影响睾丸重量或黄体生成素和睾酮的血清浓度。TZP - 4238对肾上腺重量没有其他甾体类抗雄激素药物所具有的那种抑制作用。它表现出强效的孕激素活性。虽然TZP - 4238没有雄激素或雌激素活性，但具有微弱的抗雌激素活性。这些结果表明，TZP - 4238对大鼠前列腺发挥抗雄激素作用，而不会引起黄体生成素或睾酮血清浓度的任何代偿性变化，它是治疗前列腺肥大和前列腺癌等雄激素依赖性疾病的有用药物。
