Sensitivity
and Specificity of Bioassay of Estrogenicity on
Mammary Gland and Uterus of Female Mice
J.
ŠKARDA
Institute of Animal Physiology and Genetics,
Academy of Sciences of the Czech Republic,
Prague, Czech Republic
Received October 3, 2001
Accepted January 9, 2002
Summary
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 17ß estradiol from dose 0.001 µg.d-1. The
maximum effective dose of estradiol was 0.01 µg.d-1
and the dose 10 µg.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 µg.d-1, in adult
OV-X animals from dose 1000 µg.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 µg.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.
.
Key
words
Bioassay
· Estrogenicity · Mammary gland · Uterus ·
Female micey
Reprint
requests
Josef Škarda, Institute of Animal Physiology and
Genetics, Academy of Sciences of the Czech
Republic, Přátelství 560, 104 00 Prague 10-Uhříněves,
Czech Republic. E-mail:skarda@iapg.cas.cz
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