Sensitivity and specificity of bioassay of estrogenicity on mammary gland and uterus of female mice.
Young intact (18 days of age) and adult ovariectomized (OV-X, ovariectomized between 21 to 24 days of age) C3H/Di mice were used to measure the estrogenicity on the basis of the growth response of mammary epithelial structures and weight of the uterus. The percentage area of the mammary fat pad occupied by mammary epithelial structures was progressively increased by 17beta estradiol from dose 0.001 microg.d(-1). The maximum effective dose of estradiol was 0.01 microg.d(-1) and the dose 10 microg.d(-1) of estradiol decreased mammary size to control levels (inverted-U-shaped dose-response curve). Progesterone alone progressively stimulated mammary growth in young intact females from dose 125 microg.d(-1), in adult OV-X animals from dose 1000 microg.d(-1). Both in young intact and adult OV-X animals, uterine weight progressively increased during estradiol treatment. Progesterone alone had no effect on uterine weight in young intact animals; in adult OV-X animals, uterine weight was increased starting from dose 250 microg.d(-1). Progesterone acted synergistically with estradiol to produce higher mammary growth than that in females treated with estradiol alone. The effects of a combination of estradiol plus progesterone in the mammary gland were mimicked by norethindrone acetate and inhibited by cortisol in both young intact and adult OV-X animals. Testosterone inhibited estradiol plus progesterone stimulated growth of mammary gland only in OV-X animals, but stimulated uterine weights in both young intact and adult OV-X animals. Spleen weight and size of mammary lymph nodes were not affected by estradiol, progesterone, norethindrone acetate or testosterone, but were decreased by cortisol. Cortisol also decreased the percent area of the mammary fat pad occupied by mammary epithelial structures, but had no effect on weight of the uterus. These results show that bioassay of estrogenicity in females is not specific. Mammary and uterine growth is stimulated not only by estrogens but also by progesterone and testosterone, respectively.
Skarda
J
J
Institute of Animal Physiology and Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic. skarda@iapg.cas.cy
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D012739:Gonadal Steroid Hormones / Q000494:pharmacology; D006854:Hydrocortisone / Q000494:pharmacology; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000254:growth & development*; D051379:Mice; D008809:Mice, Inbred C3H; D009640:Norethindrone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077563:Norethindrone Acetate; D009929:Organ Size / Q000187:drug effects*; D010052:Ovariectomy; D011374:Progesterone / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013739:Testosterone / Q000494:pharmacology; D014599:Uterus / Q000033:anatomy & histology*
D012739:Gonadal Steroid Hormones; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D000077563:Norethindrone Acetate; D009640:Norethindrone; D006854:Hydrocortisone