# REGULATION OF ESTROGEN-RESPONSIVE GENES

> **NIH NIH R29** · WEST VIRGINIA UNIVERSITY · 1994 · $104,494

## Abstract

The long range objective of this research is to understand the mechanisms
by which steroid hormones direct the transcription of genes.  This proposal
is designed to examine the molecular basis for the biological effects of
estrogen during avian reproduction.  The yolk protein genes are all
responsive to estrogen; however, the kinetics of induction vary.  Following
the administration of estrogen, very low density apolipoprotein II (apo-II)
RNA appears within 2-3 hours while there is a lag of about 20 hours before
vitellogenin I (VTG-I) RNA can be measured.  The basis for these
differences is completely unknown.  The proposed experiments are designed
to examine the role of estrogen response elements, the requirement for
additional transcriptional factors, and to determine whether such
differences reflect primary and/or secondary effects of estrogen.  To
accomplish this goal, information about the regulatory regions of several
genes is required.  The VTG-II gene has been characterized in terms of
regulatory components and gene structure.  Sequence analysis and
footprinting data are available for the apo-II gene, but functional
analysis remains to be accomplished.  The specific aims of this proposal
are to 1) Identify sequences of the apo-II locus that direct transcription
of the gene in functional assays, 2) Isolate and characterize genomic
clones coding for the VTG-I gene, 3) Identify sequences of the VTG-I locus
that direct transcription of the gene in functional assays, and 4)
Determine the basis for the slow response to estrogen of the VTG-I gene
compared to the rapid response of the apo-II gene.  These studies will rely
predominately on functional analysis of the DNA sequences by transfection
into the estrogen responsive human hepatoma cell line, HepG2.  A novel
approach will be used in which two different reporter genes will be
cotransfected to allow analysis in the same cells.

Steroid hormones are crucial in reproduction and development, as well as in
health and disease.  Basic information concerning the mechanisms of steroid
regulation should provide a foundation for  understanding the growth of
hormone dependent tumors, and may lead to improved drug therapy for
estrogen dependent breast tumors.

## Key facts

- **NIH application ID:** 2199897
- **Project number:** 5R29HD026339-05
- **Recipient organization:** WEST VIRGINIA UNIVERSITY
- **SAM.gov UEI:** M7PNRH24BBM8
- **Principal Investigator:** MARILYN I EVANS
- **Activity code:** R29 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $104,494
- **Award type:** 5
- **Project period:** 1989-12-01 → 1994-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2199897

## Citation

> US National Institutes of Health, RePORTER application 2199897, REGULATION OF ESTROGEN-RESPONSIVE GENES (5R29HD026339-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2199897. Licensed CC0.

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