Masuoka M, Masaki T, Yamazaki I, Hori T, Nakayama R
Acta Endocrinol Suppl (Copenh). 1979;229:36-52. doi: 10.1530/acta.0.092s036.
For the purpose of obtaining hormonal spectra of anti-androgen TSAA-291 and its derivatives, a variety of endocrine characteristics were studied. (1) Androgenic and anabolic activity : Subcutaneous administration of anti-androgen TSAA-291 and its acetate, TSAA-328, to the immature orchiectomized rat resulted in significant weight increase of the levator ani but in only a nominal response of seminal vesicles and prostates even at a large daily dose of 9.6 mg. The resultant anabolic/androgenic ratio was estimated to be extremely high. (2) Oestrogenic activity : Uterine weight in response to these anti-androgens were sluggishly dose-dependent, and the maximal plateau response remained considerably lower than that induced by oestradiol-17 beta. The oestrogenic activity of these anti-androgens was estimated to be 1/200 000 or less as that of oestradiol-17 beta. A single subcutaneous dose of 100 mg of TSAA-291 or its caproate, TSAA-330, did not induce the vaginal cornification in the adult ovariectomized rat. (3) Anti-oestrogenic activity : Antagonistic effect of these anti-androgenic compounds on the uterine weight response to oestradiol-17 beta was found in the immature ovariectomized rat. A single subcutaneous dose of 100 mg of TSAA-291 or TSAA-330 also induced the antagonism against the cornification caused by daily treatments with 1 microgram oestrone in the adult ovariectomized rat. (4) Progestational activity : These anti-androgenic compounds proved to be less active than progesterone in the McPhail's test. (5) Anti-inflammatory activity : Daily subcutaneous dose of 20 mg of TSAA-291 for 6 days did not significantly depress the weight of granuloma developed around the cotton-pellet implanted in the young male rat. TSAA-291 did not affect the anti-inflammatory action of 1/6 mg of prednisolone phosphate. Combination of both agents seemed to be effective in enhancing the anti-androgenic action of TSAA-291, whereas prednisolone phosphate alone rather increased the weight of the accessory sex organs. (6) Liver glycogen deposition activity : Daily intramuscular doses up to 38.4 mg of TSAA-291 for 5 days did not increase the liver glycogen level in the adrenalectomized rat.
为获取抗雄激素TSAA - 291及其衍生物的激素谱，研究了多种内分泌特征。(1)雄激素和同化活性：对未成熟去势大鼠皮下注射抗雄激素TSAA - 291及其醋酸酯TSAA - 328，即使每日大剂量达9.6 mg，提肛肌重量显著增加，但精囊和前列腺仅有轻微反应。由此估计同化/雄激素比率极高。(2)雌激素活性：这些抗雄激素对子宫重量的影响呈缓慢的剂量依赖性，最大平台反应仍显著低于17β - 雌二醇诱导的反应。这些抗雄激素的雌激素活性估计仅为17β - 雌二醇的1/200000或更低。对成年去卵巢大鼠皮下单次注射100 mg的TSAA - 291或其己酸酯TSAA - 330，未诱导阴道角化。(3)抗雌激素活性：在未成熟去卵巢大鼠中发现这些抗雄激素化合物对子宫重量对17β - 雌二醇反应有拮抗作用。对成年去卵巢大鼠皮下单次注射100 mg的TSAA - 291或TSAA - 330，也可拮抗每日用1 μg雌酮处理引起的角化。(4)孕激素活性：在麦克费尔试验中，这些抗雄激素化合物的活性低于孕酮。(5)抗炎活性：对幼年雄性大鼠皮下每日注射20 mg的TSAA - 291，连续6天，对植入棉球周围形成的肉芽肿重量无显著抑制作用。TSAA - 291不影响1/6 mg磷酸泼尼松龙的抗炎作用。两种药物联合似乎可有效增强TSAA - 291的抗雄激素作用，而单独使用磷酸泼尼松龙反而增加附属生殖器官的重量。(6)肝糖原沉积活性：对肾上腺切除大鼠每日肌肉注射高达38.4 mg的TSAA - 291，连续5天，未增加肝糖原水平。
