Mouse bioassay to assess oestrogenic and anti-oestrogenic compounds: hydroxytamoxifen, diethylstilbestrol and genistein.
Young intact and adult gonadectomized C3H male and female mice were utilized as bioassay models to detect endocrine disruption chemicals. Animals treated with oestradiol (E) or progesterone (Prog) or E plus Prog were used to assess steroid hormone agonist and antagonist activities of 4-OH-tamoxifen (TAM), diethylstilbestrol (DES) and genistein (GEN) by bioassay. The stimulation or inhibition of mammary growth by TAM depended on sex, the state of animal (intact or gonadectomized), hormonal treatment (Prog, E, E plus Prog) and dose of TAM. TAM stimulated mammary growth in untreated ovariectomized (OV-X) females and in Prog-treated intact males and OV-X females. In intact males, mammary growth was increased by TAM at dose 0.1-1 microg day(-1) and decreased at dose 10 microg day(-1). Mammary growth was inhibited by TAM in Prog-treated intact females and in E or E plus Prog-treated intact and gonadectomized males and females. Uterine weights were increased by TAM in both untreated and treated (E, Prog, E plus Prog) intact and OV-X females; however, seminal vesicle weights were decreased by TAM in both untreated and treated (E, Prog, E plus Prog) intact males. DES alone affected mammary growth (an inverted-U-shaped dose-response curve) both in male and female mice. DES increased uterine weights; however, seminal vesicle weights were decreased. GEN increased mammary and uterine growth in OV-X females, GEN plus Prog stimulated mammary growth in intact males. The results obtained in these studies show clearly that only a bioassay consisting of several endpoints reflective to the mechanism of oestrogen and anti-oestrogen action has the ability to evaluate activities of a molecule.
Institute of Animal Physiology and Genetics, Academy of Sciences of the Czech Republic, Vídenská 1083, 142 20 Prague 4 - Krc, Czech Republic.
E
E
Köhlerová
J
J
Skarda
D000818:Animals; D004054:Diethylstilbestrol / Q000494:pharmacology; D004958:Estradiol / Q000819:agonists / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D019833:Genistein / Q000494:pharmacology; D008297:Male; D008321:Mammary Glands, Animal / Q000187:drug effects*; D051379:Mice; D008809:Mice, Inbred C3H; D023421:Models, Animal; D011374:Progesterone / Q000494:pharmacology; D012669:Seminal Vesicles / Q000187:drug effects; D013154:Spleen / Q000187:drug effects; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology; D014599:Uterus / Q000187:drug effects*
D004965:Estrogen Antagonists; D004967:Estrogens; D013629:Tamoxifen; C016601:afimoxifene; D011374:Progesterone; D004958:Estradiol; D004054:Diethylstilbestrol; D019833:Genistein