副腎性アンドロゲン投与下におけるラット副性器に対する種々抗前立腺剤の効果

Abstract

DHEA-S(硫酸デヒドロエピアンドロステロン)及びA (アンドロステンジオン)で治療されなかった非去勢ラットにおいて検討した全ての抗アンドロゲンは副性器重量を用量依存性に減少させた.LHRH(黄体化ホルモン放出ホルモン)作用薬DHEA-S, 及びAで治療したラットにおいて全ての抗アンドロゲン(3.3 mg/日)は無傷ラットで同じ効果を示したが, 非ステロイド抗アンドロゲン及びT2p-4238 (17α-acetoxy-6-chloro-2-oxapregna-4, 6-diene-3, 20-dione)は他に

It is well known that some adrenal androgens are converted into testosterone and dihydrotestosterone which are more powerful androgens than the adrenal androgens. However, most of the experiments to investigate the antiprostatic agents have been done on rats which secrete only a marginal amount of adrenal androgen. A study was performed to investigate the effects of antiprostatic agents on the action of the adrenals in rats. Non-sterodidal antiandrogens flutamide and 1-chloro-2-hydroxy-2-methyl-N-(3, 4, 5-trichlorophenyl)propanamide (AA560), steroidal anti-androgens, chlormadinone acetate (CMA) and 17 alpha-acetoxy-6-chloro-2-oxapregna-4, 6-diene-3, 20-dione (TZP-4238) and 5 alpha-reductase inhibitor, sodium (-)-4[2-[2, 3-dimethyl-4-[1-(4-isobutylphenyl)ethoxy]benzolamino ] phenoxy]butyrate (ONO-3805) and N-(2-methyl-2-propyl)-3-oxo-4-aza-5 alpha-androst-l-ene-17 beta-carboxamide (MK-906) were tested in rats treated with dehydroepiandrosterone sulfate (DHEA-S) and androstenendione (A). In the noncastrated rats not treated with DHEA-S and A, all of these agents decreased the accessory organ weights in a dose dependent manner. In the rats treated with LHRH agonist and DHEA-S and A, all agents (3.3 mg/day) showed similar effects in intact rats. However nonsteroidal antiandrogens and TZP-4238 were stronger than the others. It was not clear whether this effect was mediated through the suppression of adrenal androgen action or the inhibition of physiological increase in testosterone caused by an LHRH agonist. The effects of Flu, ONO-3805, CMA and TZP-4238 on the accessory sex organs were investigated in castrated rats receiving DHEA-S and A.(ABSTRACT TRUNCATED AT 250 WORDS)