# CONTROL OF GNRH GENE EXPRESSION

> **NIH NIH K04** · UNIVERSITY OF COLORADO DENVER · 1994 · $40,551

## Abstract

Gonadotropin releasing hormone (GnRH) is a decapeptide expressed in
hypothalamic neurons where it plays a penultimate role in the control of
the hypothalamic-pituitary-gonadal axis and reproduction.  In addition,
a cDNA coding for GnRH was initially isolated from a placental library
and the protein has been demonstrated in the placenta of many species
where it may play a role in early hCG production and maintenance of early
pregnancy.  Although much is known about the secretory dynamics and post-
translational regulation of GnRH, little information is available
concerning the mechanisms which control its tissue specific expression
and how steroid hormones may regulate its production.  The clearly
defined ontogeny of GnRH secretion across sexual maturation suggests a
complex control of developmental as well as tissue specific expression.
With the use of two recently derived neuronal cell lines that express
GnRH as well as placental cell lines, we have a unique opportunity to
address the mechanisms by which tissue specificity, developmental
expression, and steroid hormone regulation of GnRH promoter activity
occurs.  The specific aims of this five year proposal are to:

1. To analyze the specific cis-acting DNA sequences and the trans-acting
nuclear protein-DNA interactions that mediate tissue specific and
developmental expression of GnRH; and

2. To characterize the cis-acting DNA sequence elements and the protein-
DNA or protein-protein interactions that confer steroid hormone
regulation to the GnRH promoter.

The cis-acting DNA promoter sequences and trans-acting nuclear factors
which direct developmental and tissue specific regulation and control by
steroid hormones will be characterized by gene transfer studies, DNase
I protection, gel retardation assays, methylation interference assays,
site directed mutagenesis, and in vitro cell free transcription studies.
The results of these studies will impact on our understanding of sexual
maturation and hypogonadism, as well as the basic mechanisms which
control tissue specific, developmental, and hormonal regulation of
neuroendocrine genes.

## Key facts

- **NIH application ID:** 2194566
- **Project number:** 5K04HD001026-02
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **SAM.gov UEI:** MW8JHK6ZYEX8
- **Principal Investigator:** Margaret E Wierman
- **Activity code:** K04 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $40,551
- **Award type:** 5
- **Project period:** 1993-07-01 → 1995-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2194566

## Citation

> US National Institutes of Health, RePORTER application 2194566, CONTROL OF GNRH GENE EXPRESSION (5K04HD001026-02). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2194566. Licensed CC0.

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