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  • Title: Anti-androgen TSAA-291. II. Manifestation of the anti-androgenic action of a steroid ester TSAA-330 (16 beta-ethyl-17 beta-hydroxy-4-oestren-3-one caproate) and elucidation of its long-lasting mechanism using a simple steroid determination technique.
    Author: Masuoka M, Shikata M, Fuziwara R, Nakayama R.
    Journal: Acta Endocrinol Suppl (Copenh); 1979; 229():24-35. PubMed ID: 294105.
    Abstract:
    Using a simple steroid determination technique, in situ steroid absorption from a subcutaneously injected sesame oil solution in rats was pursued following the time-course changes in the steroid concentration. Based on the knowledge thus obtained, the anti-androgenic effect of a steroidal compound, TSAA-330, could be manifested in the subcutaneous route. (1) Anti-androgenic steroid TSAA-291 and its esters in the subcutaneously injected sesame oil solution were selectively absorbed into the general circulation at different rates according to their chemical nature and structures, while the oil itself remained at the injected site for a considerably long period. At the injected site where subcutaneous doses of steroids molar equivalent to 50 mg of TSAA-291 were administered in 5 ml/rat of sesame oil, TSAA-291 decreased to the level of 10% of the initial concentration on the 4th day. TSAA-328 decreased slowly to the 50% and 20% levels on the 7th and 21st day, respectively. TSAA-335 decreased more slowly to the 50% level on the 14th day. TSAA-330 decreased most slowly only to the 70% level on the 49th day. (2) A single subcutaneous administration of 200 mg of TSAA-330 suppressed the weight increase of the accessory sex organs caused by a single subcutaneous injection of testosterone caproate (10 mg) in the immature orchiectomized rat. The suppressive effect was obvious from 2 weeks after the administration, and seemed to last for more than two weeks. The levator ani weight was not affected by the administration of TSAA-330. (3) Dose-dependent inhibitions of the accessory sex organs were obtained three weeks after a single subcutaneous administration of 50 to 400 mg of TSAA-330 in the adult male rat. (4) Daily oral administrations of 50 mg of TSAA-291 or TSAA-330 to the adult male rat for 8 days resulted in depression of the accessory sex organs to almost the same extent obtained with either agent. One week after the last administration, however, the weight of the accessory sex organs of the TSAA-291-administered animals recovered to almost the comparable level with the control, whereas a significant after-effect of the inhibition was still evident in the TSAA-330-administered animals.
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