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.
Journal Title: Pharmacological Reports - Year 2012, Vol 64, Issue 4
Abstract
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 (E(2)) (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 E(2) was 78 (E(2) = 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 E(2) (≈ 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 E(2) LQmax 56 ± 8; ED50 10 ± 2 μg/kg; the relative LQ-potency was 0.51 (E(2) = 100). Buame competed with [(3)H]E(2) for the estrogen receptor (Buame RBA= 0.15 and Ki = 5.9 x 10(-7) M; E(2) RBA= 100;Ki = 6.6 x 10(-9) M). Buame increased MCF-7 cells proliferation, from 10(-11) to 10(-)9 M, its proliferative effectwas 1.73-1.79 (E(2) = 3.0-3.9); its relative proliferative effect to E(2) was 33-40% (E(2) = 100%) and relative potency 10.4-10.7 (E(2) = 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.
Authors and Affiliations
Cristina Lemini, Martha Medina, María Avila, Pablo Cruz-Lemini, Enrique Canchola, René Santillan, Ana Lemus
Keywords
Related Articles
- EP ID EP145840
- DOI -
- Views 92
- Downloads 0
Effect of exposure to fluoride and acetaminophen on oxidative/nitrosative status of liver and kidney in male and female rats.
Background: This study was undertaken to investigate, the effect of 6 weeks treatment with acetaminophen (AAP) and fluoride (F), administered either separately or together, on nitric oxide generation, lipid and protein p...
Monocyte suppressing action of fenofibrate.
Since atherosclerosis has been proven to be an inflammatory disease, itis obvious that the proper treatment for dyslipidemia should not only correct lipid parameters but alsoinhibit inflammation. Monocytes and monocyte-d...
Comparative evaluation of different doses of PPAR-γ agonist alone and in combination with sulfasalazine in experimentally induced inflammatory bowel disease in rats.
Inflammatory bowel disease (IBD) is an idiopathic, chronic inflammatory condition, which affects the gastrointestinal tract and has no curative treatment. The present study aimed to investigate the effect of different do...
Extralipid effects of micronized fenofibrate in dyslipidemic patients.
The aim of this study was to evaluate the levels of lipid and extralipid parameters in patients with atherogenic dyslipidemia. We investigated the lipid-lowering therapeutic efficacy of fenofibrate and its extralipid inf...
Role of phosphoinositide 3-kinase in ischemic postconditioning-induced attenuation of cerebral ischemia-evoked behavioral deficits in mice.
The present study has been designed to pharmacologically investigate the role of phosphoinositide 3-kinase in ischemic postconditioning-induced reversal of global cerebral ischemia and reperfusion-induced behavioral dysf...