In vivo and in vitro evaluation of the estrogenic properties of the 17β-(butylamino)-1,3,5(10)-estratrien-3-ol(buame) related to 17β-estradiol

Background: buame [17β-(butylamino)-1,3,5(10)-estratrien-3-ol] possesses anticoagulant and antiplatelet activities that are potentially antithrombotic. since its estrogenicity is unknown,it was evaluated by established methods. methods: buame (10,100,500,and 1,000 μg/kg),17β-estradiol (e2) (100 μg/kg),or propylene glycol (10 ml/kg) were subcutaneously (sc) administered for three days to immature wistar female rats (21 days old). the relative uterotrophic effect to e2 was 78 (e2 = 100) with a relative uterotrophic potency of 1.48 (e 2 = 100). adult ovariectomized wistar rats received an sc injection at 8:00 h (reversed cycle) of: 7.5 μg of e2 (≈ 30 μg/kg),buame (≈ 750,1,500,3,000 μg/kg),or corn oil (≈ 1.2 ml/kg). after 24 h,progesterone (4-5 mg/kg) was administered. sexual receptivity was assessed 5 to 7 h later,and the lordosis quotient (lq; number lordosis/number mounts x 100) was evaluated. results: buame induced lordosis (lqmax 85 ± 9; ed50 952 ± 19 μg/kg) and e2 lqmax 56 ± 8; ed50 10 ± 2 μg/kg; the relative lq-potency was 0.51 (e2 = 100). buame competed with [3h]e2 for the estrogen receptor (buame rba= 0.15 and ki = 5.9 × 10-7 m; e2 rba= 100;ki = 6.6 × 10-9 m). buame increased mcf-7 cells proliferation,from 10-11 to10-9 m,its proliferative effectwas 1.73-1.79 (e2 = 3.0-3.9); its relative proliferative effect to e2 was 33-40%(e2 = 100%) and relative potency 10.4-10.7 (e2 = 100). tamoxifen and fulvestrant (ici 182,780) inhibited buame's proliferation indicating mediation through estrogen receptors in this response. conclusion: buame is therefore an estrogen partial agonist with a weak estrogenic activity. copyright © 2012 by institute of pharmacology polish academy of sciences.