Steroid hormone regulations of uterine peroxidase activity.
Uterine peroxidase enzyme activity has been studied as a marker for estrogen action in the uterus to help clarify the mechanism of estrogen action and its modulation by antiestrogens and progestins. Estrogen-induced increases in peroxidase were found to closely parallel increases in uterine weight and DNA content in the castrate rat. In the cycling female rat, uterine peroxidase levels were highest during proestrus and estrus and the lower levels of metestrous and diestrous uteri could be raised to estrous levels by administration of estrogen. However, the estrous levels were not further increased by estrogen treatment. The antiestrogen, CI628, while a very weak inducer of uterine peroxidase, is an effective antagonist of the estrogen induction of the enzyme. The prolonged duration of this CI628-effected inhibition corresponds to the prolonged depletion of cytoplasmic estrogen receptor seen with CI628 treatment. Progesterone, R5020 and norethindrone were also found to be effective antagonists of estrogen-induced uterine peroxidase. Medrogestone and clogestrone, less potent progestins in the rat, were also less effective antagonists of peroxidase induction. Since progesterone was found to inhibit peroxidase induction due to both estrone and diethylstilbestrol, as well as estradiol, it is considered unlikely that this antagonism relates to progestin-induced increases in uterine 17 beta-hydroxysteroid dehydrogenase. Rather, it is proposed that progestins, acting through progestin  receptor, may have a more direct role, possibly acting at the level of the genome to repress the expression of estrogen-induced products.
D000818:Animals; D004247:DNA / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D004971:Estrus; D005260:Female; D007700:Kinetics; D010544:Peroxidases / Q000378:metabolism*; D011247:Pregnancy; D045167:Progesterone Congeners / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D014599:Uterus / Q000187:drug effects / Q000201:enzymology*
D004967:Estrogens; D045167:Progesterone Congeners; D004958:Estradiol; D004247:DNA; D010544:Peroxidases