title: 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: 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 effect was 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.
  
  
  CONCLUSIONS
  Buame is therefore an estrogen partial agonist with a weak estrogenic activity.
authors.affiliation: Departament of Pharmacology, National Autonomous University of Mexico, Mexico City, Mexico. clemini@servidor.unam.mx
authors.forename: Cristina
authors.initials: C
authors.lastname: Lemini
authors.forename: Martha
authors.initials: M
authors.lastname: Medina
authors.forename: María E
authors.initials: ME
authors.lastname: Avila
authors.forename: Pablo
authors.initials: P
authors.lastname: Cruz-Lemini
authors.forename: Enrique
authors.initials: E
authors.lastname: Canchola
authors.forename: René
authors.initials: R
authors.lastname: Santillan
authors.forename: Ana E
authors.initials: AE
authors.lastname: Lemus
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003314:Corn Oil / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology*; D045166:Estradiol Congeners / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D008141:Lordosis / Q000188:drug therapy / Q000378:metabolism; D061986:MCF-7 Cells; D011374:Progesterone / Q000008:administration & dosage; D019946:Propylene Glycol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011960:Receptors, Estrogen / Q000378:metabolism; D012726:Sexual Behavior, Animal / Q000187:drug effects; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: D045166:Estradiol Congeners; D004967:Estrogens; D011960:Receptors, Estrogen; D013629:Tamoxifen; C083897:buame; D000077267:Fulvestrant; D011374:Progesterone; D004958:Estradiol; D019946:Propylene Glycol; D003314:Corn Oil