Anti-androgen TSAA-291. III. Hormonal spectra of anti-androgen TSAA-291 (16 beta-ethyl-17 beta-hydroxy-4-oestren-3-one) and its derivatives.
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.
D000726:Androgen Antagonists / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002369:Castration; D003534:Cyproterone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004717:Endometrium / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D004970:Estrone / Q000494:pharmacology; D005260:Female; D007279:Injections, Subcutaneous; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D009277:Nandrolone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D011374:Progesterone / Q000494:pharmacology; D011467:Prostate / Q000187:drug effects; D051381:Rats; D012669:Seminal Vesicles / Q000187:drug effects; D014599:Uterus / Q000187:drug effects; D014621:Vagina / Q000187:drug effects; D014626:Vaginal Smears
D000726:Androgen Antagonists; D008112:Liver Glycogen; D004970:Estrone; D011374:Progesterone; D004958:Estradiol; D009277:Nandrolone; D003534:Cyproterone