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Cell Type-Specific Localization of c-Myc Protein in the Mouse Uterus: Modulation by Steroid Hormones and Analysis of the Periimplantation Period^*

YVETTE M. HUET-HUDSON, GLEN K. ANDREWS and SUDHANSU K. DEY

Departments of Physiology and Obstetrics and Gynecology Kansas City, Kansas 66103
Biochemistry and Molecular Biology, Ralph L. Smith Research Center, University of Kansas Medical Center Kansas City, Kansas 66103

Address all correspondence and requests for reprints to: Dr. S. K. Dey, Departments of Obstetrics and Gynecology and Physiology, Ralph L. Smith Research Center, University of Kansas Medical Center, Kansas City, Kansas 66103.

Abstract

Estrogen has been shown to induce a rapid transient increase in c-myc mRNA in the rat uterus. However, no studies of the cell specificity of c-myc expression in the uterus have been reported, and nothing is known about the expression of c-myc in response to other steroids or during normal uterine preparation for implantation. To this end, the cell type-specific localization of c-myc protein was determined in the ovariectomized mouse uterus after progesterone (P₄) and/or 17β-estradiol (E₂) injection as well as during the periimplantation period. After E₂ injection, a rapid accumulation of c-myc protein was detected exclusively in the uterine luminal and glandular epithelial nuclei in the ovariectomized mouse. Essentially all of these cells contained immunoreactive c-myc by 12 h postinjection. In contrast, after P₄ injection, rapid accumulation of c-myc was noted exclusively in some of the stromal cell nuclei. Pretreatment of the ovariectomized mouse for 4 days with P₄ (P₄ priming) followed by E₂ injection resulted in an increase in the number of c-myc-positive stromal cells, but few, if any, c-myc-positive cells were detected in the luminal and glandular epithelia. These uterine cell type-specific localizations of c-myc protein, induced by E₂ or P₄ injection, were followed within 18-24 h by DNA synthesis ([³H]thymidine incorporation) restricted to the epithelia or stroma, respectively. c-Myc was detected in the nuclei of luminal and glandular epithelia during proestrus and on days 1 and 2 of pregnancy, a period when the uterus is under the influence of estrogen. c-Myc-positive cells were detected in the stroma on day 3, and by day 4 a large number of stromal cell nuclei were c-myc positive. These changes are coincident with increasing P₄ levels during early pregnancy. At the implantation chamber on day 5, many cells in the primary decidual zone as well as some of the deeper stromal cells were c-myc protein positive, whereas on day 6, c-myc protein was detected only in the secondary decidual zone. During this period of uterine preparation for embryo implantation and subsequent decidualization, there was a positive correlation between c-myc protein localized in specific populations of uterine cells and subsequent DNA synthesis in those cell types. Thus, both E₂ and P₄ induce cell type-specific accumulation of c-myc protein in the uterus of the ovariectomized mouse, with E₂ induction of c-myc being restricted to epithelia, and P₄ induction restricted to stroma. However, P₄ priming can modify this E₂ effect, blocking c-myc accumulation in the epithelia and enhancing c-myc levels in the stroma. These hormonally induced cell type-specific patterns of c-myc protein accumulation in the uterus are also reflected in the intact animal during the periimplantation period and are positively correlated with cell division.

Footnotes

^* A portion of this work was presented in a preliminary form at the symposium on Development of Preimplantation Embryos and Their Environment (Satellite Symposium of the 8th International Congress of Endocrinology), Kyoto, Japan, 1988, and at the UCLA Symposium on Molecular and Cellular Biology (Early Embryo Development and Paracrine Relationships), Taos, NM, 1989. This work was supported in part by NIH Grant HD-12304.

Supported by fellowships from the NSF and the Ford Foundation.

Received April 3, 1989.

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