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

Abstract

BackgroundBuame [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. MethodsBuame (10, 100, 500, and 1,000μg/kg), 17β-estradiol (E2) (100μg/kg), or propylene glycol (10ml/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 (E2=100). Adult ovariectomized Wistar rats received an sc injection at 8:00h (reversed cycle) of: 7.5μg of E2 (≈30μg/kg), buame (≈750, 1,500, 3,000μg/kg), or corn oil (≈1.2ml/kg). After 24h, progesterone (4–5mg/kg) was administered. Sexual receptivity was assessed 5 to 7h later, and the lordosis quotient (LQ; number lordosis/number mounts×100) was evaluated. ResultsBuame induced lordosis (LQmax 85±9; ED50 952±19μg/kg) and E2 LQmax 56±8; ED50 10±2μg/kg; the relative LQpotency was 0.51 (E2=100). Buame competed with [3H]E2 for the estrogen receptor (Buame RBA=0.15 and Ki=5.9×10−7M; E2 RBA=100; Ki=6.6×10−9M). Buame increased MCF-7 cells proliferation, from 10−11 to 10−9M, its proliferative effect was 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. ConclusionBuame is therefore an estrogen partial agonist with a weak estrogenic activity.