Steroid Hormone Regulation 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 17β-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.
KeywordsEstrous Cycle Uterine Weight Progestin Receptor Steroid Hormone Regulation Effective Antagonist
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- 1).Jensen, E. V., Numata, M., Brecher, P.I., and DeSombre, E.R. (1971). In “The Biochemistry of Steroid Hormone Action, ” R. M. S. Smellie, ed. Academic Press, London. pp 133–159.Google Scholar
- 3).O’Malley, B. W., and Means, A.R. (1974). Science 183: 610–620Google Scholar
- 4).Yamamoto, K.R., and Alberts, B.M. (1976). Annu. Rev. Biochem. 45: 721–746.Google Scholar
- 5).Gorski, J., and Gannon, F. (1976). Annu. Rev. Physiol. 38: 425–450.Google Scholar
- 6).Liao, S. (1975). Int. Rev. Cytol. 41: 87–172.Google Scholar
- 7).McKnight, G. S., Pennequin, P., and Schimke, R. T. (1975). J. Biol. Chem. 250: 8105–8110.Google Scholar
- 9).Tsai, S. Y., Tsai, M. J., Schwartz, R., Kalimi, M., Clark, J. H., and O’Malley, B. W. (1975). Proc. Natl. Acad. Sci. U.S. 72: 4228–4232.Google Scholar
- 11).Lyttle, C. R., and DeSombre, E. R. (1977). Proc. Natl. Acad. Sci. U. S. 74: 3162–3166.Google Scholar
- 13).Lucas, F. V., Neufeld, H. A., Utterback, J. G., Martin, A. P., and Stotz, E. (1955). J. Biol. Chem. 214: 775–780.Google Scholar
- 23).Katzenellenbogen, B. S. (1978). In “Progress in Cancer Research and Therapy, Vol 10, Hormones, Receptors and Breast Cancer, ” W. L. McGuire, ed. Raven Press, N.Y. pp 135–157.Google Scholar
- 24).DeSombre, E.R., and Lyttle, C.R. (1978). In “Progress in Cancer Research and Therapy, Vol 10, Hormones, Receptors and Breast Cancer, ” W. L. McGuire, ed. Raven Press, N.Y. pp 181–197.Google Scholar
- 26).Lerner, L. J. (1964). Rec. Prog. Hormone Res. 20: 435490.Google Scholar
- 27).Brenner, R.M. (1969). In “The Mammalian Oviduct, ” E. S. E. Hafez and R.J. Blandau, eds. Univ. Chicago Press, Chicago, pp 203–229.Google Scholar
- 29).Raynaud, J. P. (1977). In “Progesterone Receptors in Normal and Neoplastic Tissues, ” W. L. McGuire, J. P. Raynaud and E.E. Saulieu, eds. Raven Press, N. Y. pp 9–21.Google Scholar
- 31).Tseng, L., and Gurpide, E. (1975). Endocrinology 97: 825833.Google Scholar
- 32).Tseng, L., and Gurpide, E. (1973). Endocrinology 93: 245248.Google Scholar
- 33).Leung, B. S., and Sasaki, G. H. (1973). Biochem. Biophys. Res. Commun 55: 1180–1185.Google Scholar
- 37).Bhakoo, H. S., and Katzenellenbogen, B. S. (1977). Mol. Cell. Endocrinol. 8: 121–134.Google Scholar
- 38).Clark, J. H., Hsueh, A.J.W., and Peck, E. J., Jr. (1977). Ann. N. Y. Acad. Sci. 286: 161–176.Google Scholar
- 39).Jensen, E. V., Numata, M., Smith, S., Suzuki, T., Brecher, P. I., and DeSombre, E. R. (1969). Dev. Biology Suppl. 3: 151–171.Google Scholar