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A Mechanism of Estrogen Action on Gene Expression at the Level of Translation¹

Department of Microbiology, University of Colorado Medical Center, Denver, Colorado 80220

One of the earliest events following the administration of estradiol to ovariectomized rats is an increase in transfer RNA (tRNA) methyltransferase activity of the uterus. Ovariectomy diminishes by about one-half the capacity of extracts of uteri to introduce methyl groups in vitro into heterologous tRNA. Administration of estradiol to ovariectomized animals restores the tRNA methyltransferase capacity to normal. Alterations in the population of uterine serine tRNA were also observed following ovariectomy. These findings represent reversible qualitative changes produced by a hormone in the target tissue.

Whether the tRNA's are involved in regulating hormone-induced protein synthesis was investigated by studying the estrogen-induced ovalbumin synthesis in immature chick oviducts. tRNA's from oviducts of estrogen-stimulated chicks or from oviducts of laying hens produced an enhanced stimulation of ovalbumin synthesis in vitro compared with tRNA's from oviducts of immature chicks that were withdrawn from estrogen stimulation (these chicks do not synthesize ovalbumin). Some of these hormone-induced alterations may be of importance in understanding the molecular mechanisms of estrogen action on gene expression.

During these studies, we have observed a novel effect of the administration of the carcinogen, ethionine, in the immature chicks. Ethionine induces ovalbumin and conalbumin synthesis in immature chick oviducts that were withdrawn from estrogen for 3 to 4 weeks following primary estrogen stimulation.

¹ Presented at the Conference, "Regulation of Gene Expression in Development and Neoplasia," June 2 to 5, 1976, Santa Ynez, Calif. Supported by grants from the Energy Research and Development Administration [E (11-1)-2066] and the National Cancer Institute (NO1-CM-12186).

² Presenter.