# ESTROGEN CONTROL OF UTERINE GROWTH AND CELL DIVISION

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 1994 · $201,274

## Abstract

Our goal is to elucidate the mechanisms by which estrogens
regulate uterine growth.  These are important to understand: (1) the
physiological actions of estrogens during the menstrual cycle; (2) the
pharmacological actions of the hormone such as replacement therapy during
menopause; and (3) the basis for pathological effects such as
reproductive dysfunction and endometrial cancer.  To produce its effects,
the hormone binds to a receptor that interacts with specific nucleotide
sequences termed estrogen responsive elements or EREs.  These
interactions at ERE sites activate target genes.  We will study two
genes, the nuclear protooncogene c-_fos and the epidermal growth factor
(EGF) receptor, that are regulated by estrogens and likely to be involved
in uterine growth.  The structure of the ERE(s) for growth related genes
such as fos and the EGF receptor is unknown.  The essence of this project
is to precisely determine how estrogens regulate these genes in the
physiological setting, and then to determine the ERE(s) and other
regulatory sequences that mediate the in vivo uterine responses.
Specific aims are: to define the EREs that activate the selected target
genes; to determine the structure-activity relationships for induction of
the c-fos and the EGF receptor genes; to determine the mechanisms that
limit as well as increase target gene expression in response to
estrogens; to determine how other drugs and hormones interact with
estrogens to activate target genes and vice versa; to determine if
neonatal estrogen exposure, which causes reproductive tract
abnormalities, also produces aberrant expression of these target genes;
and to determine how selective manipulation of these target genes affects
uterine growth.  To determine ERE sequences, we will construct hybrid
genes containing candidate EREs sequences linked to reporter genes.
These hybrid genes win be transfected into cultured cells to determine
which sequences confer estrogen responsiveness on reporter genes.  This
proposal describes parallel sets of studies that: (1) investigate the in
vivo regulation of key uterine genes and (2) investigate the regulation
of transfected reporter gene constructs that contain regulatory sequences
from the same uterine genes.  This combined approach will define and
characterize the regulatory elements involved more precisely than would
be possible from in vivo studies alone, and will assess the physiological
significance of the regulatory mechanisms observed more accurately than
would be possible from transfection studies alone.

## Key facts

- **NIH application ID:** 2196615
- **Project number:** 5R01HD008615-20
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **SAM.gov UEI:** ZUFBNVZ587D4
- **Principal Investigator:** GEORGE M. STANCEL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $201,274
- **Award type:** 5
- **Project period:** 1977-09-30 → 1996-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2196615

## Citation

> US National Institutes of Health, RePORTER application 2196615, ESTROGEN CONTROL OF UTERINE GROWTH AND CELL DIVISION (5R01HD008615-20). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2196615. Licensed CC0.

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