Estrogenic effects of 17 beta-aminoestrogens assessed in uteri of rats and mice.
Administration of exogenous estrogens has been associated with an increase of thromboembolic events. The 17 beta-aminoestrogens produce anticoagulant effects contrasting with the procoagulant effects of the natural occurring estradiol in rodents. This work compares the estrogenic effects induced by 17 beta-aminoestrogens prolame, butolame, pentolame, and estradiol in vivo models. Dose-response curves were performed using immature CD1 mice and Wistar rats. The animals were injected with estradiol or 17 beta-aminoestrogens (0.01 to 1000 microg/kg), or vehicle. The uterine wet and dry weights were determined. The 17 beta-aminoestrogens increased uterine weight in a dose-dependent manner. The uterotrophic effect produced by estradiol induced lower ED50 (6.5 and 4 microg/kg) and higher E(max) values (+523-350%) in mice as compared with those from the rat, indicating more susceptibility of the mice model. The 17 beta-aminoestrogens are partial estrogenic agonists with a relative uterotrophic effect of estradiol (100%) from 9-86%. Only the ED50 values of 17 beta-aminoestrogens in CD1 mice showed a direct correlation to the length of the amine group substitution in C-17 since their efficacy and potency were in the order: prolame>butolame>pentolame.
Lemini
Cristina
C
Departamento de Farmacología, Edificio D, 1er Piso, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad Universitaria CP 04510, México, D.F., C.P. 04510, Apartado Postal 70-297, Mexico City, Mexico. clemini@servidor.unam.mx
Franco
Yanira
Y
Avila
Ma Estela
ME
Jaimez
Ruth
R
D000605:Amino Alcohols / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology; D045166:Estradiol Congeners / Q000008:administration & dosage / Q000494:pharmacology*; D004963:Estrenes / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014599:Uterus / Q000033:anatomy & histology / Q000187:drug effects*
D000605:Amino Alcohols; D045166:Estradiol Congeners; D004963:Estrenes; C083219:butolame; C083220:pentolame; D004958:Estradiol; C047867:prolame