# ESTROGEN CONTROL OF UTERINE CELL PROLIFERATION

> **NIH NIH R01** · UNIVERSITY OF CINCINNATI · 1993 · $155,100

## Abstract

Estradiol administration initiates rapid and dramatic growth responses in
the uterus. This growth requires the coordinated control and sequential
increase in expression of many genes. Although it has been shown that
estradiol increases very early proto-oncogene expression in the
ovariectomized rat uterus, the relationship of these inductions to uterine
mitogenic responses in specific uterine tissues has not been determined.
We propose that estrogens elicit their effects in causing uterine cell
proliferation through the increased expression of proto-oncogenes. To
elucidate the role of oncogene expression in steroid-induced uterine
responses, the following specific aims are proposed to examine the kinetics
of induction, the tissue location, and hormonal control of uterine
proto-oncogene expression. (1) Uterine mRNA's encoding c-jun, jun B, jun
D, c-fos, c-ski and c-myc will be quantitated at short intervals after
estradiol treatment of ovariectomized mature rats. With the kinetics of the
inductions established, the hormone specificity and dose responses of the
inductions will be determined. (2) In situ hybridization and
immunohistochemistry will be used to identify the specific uterine cell
types expressing each proto-oncogene. (3) To determine whether altered
proto-oncogene expression is a primary response to estradiol, the
sensitivity of increases in mRNA levels of cycloheximide and actinomycin
D will be determined. (4) The mechanisms by which estradiol increase proto-
oncogene expression will be examined by determining the effects of the
hormone on rates of transcription and on levels of mRNA translational
activity. (5) Treatments with short acting estrogens which initiate only
early uterine responses will be used to examine the functions of
proto-oncogene expression in early components of the response to estradiol.
Treatment with progesterone which redirects the tissue location of uterine
responses estradiol will be used to examine the tissue specificity of
proto-oncogene expression. The information gained from these proposed
studies will enable us to examine the biochemical function of oncogene
products in the uterine response to estradiol. Improved understanding of
these mechanisms will enhance our capability of controlling normal uterine
physiology and cancer cell proliferation.

## Key facts

- **NIH application ID:** 2198701
- **Project number:** 5R01HD022918-06
- **Recipient organization:** UNIVERSITY OF CINCINNATI
- **SAM.gov UEI:** DZ4YCZ3QSPR5
- **Principal Investigator:** Sohaib A. Khan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $155,100
- **Award type:** 5
- **Project period:** 1987-04-01 → 1994-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2198701

## Citation

> US National Institutes of Health, RePORTER application 2198701, ESTROGEN CONTROL OF UTERINE CELL PROLIFERATION (5R01HD022918-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2198701. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*