ESTROGENIC EFFECTS OF THE SYNTHETIC AMINOESTROGEN 5-HYDROXY-1-PENTYLAMINO)-1,3,5(10)-ESTRATRIEN-3-OL (PENTOLAME)

In this study, we investigated the effects of pentolame, a 17 beta-ami noestrogen derivative, upon coagulation, serum LH, pituitary progestin receptors, uterine weight, and endometrium morphological changes in t he castrated female rat. Groups of animals were subcutaneously (s.c.) injected with either estradiol (E-2) (0.1 up to 1000 mu g/animal), pen tolame (1 up to 1000 mu g/animal), or the vehicle alone daily for 5 co nsecutive days starting 2 weeks following ovariectomy. Administration of pentolame (10 to 1000 mu g/animal) increased significantly (p < 0.0 5) the blood clotting time when compared with that obtained in the gro up of control animals (EC50 582 mu g). Pentolame (500 and 1000 mu g/ra t for 5 days) caused a significant inhibition (p < 0.01) of serum LH l evels (IC50 860 mu g), which remained suppressed until Day 5 post last injection. In addition, treatment with pentolame was able to restore in the castrated female rat the presence of specific estrogen-dependen t progestin binding sites at the anterior pituitary level. The affinit y constants and the number of binding sites of pentolame-induced proge stin receptors were similar to those obtained with estradiol at equipo tent doses (860 mu g vs. 1 mu g/animal, respectively). Administration of the 17 beta-aminoestrogen derivative resulted in a significant incr ease in uterine weight (EC50 420 mu g) and endometrial characteristics were indistinguishable from those observed in the group of rats treat ed with E-2. (C) 1998 by Elsevier Science Inc.