# IDENTIFYING AND CHARACTERIZING BRAIN GNRH RECEPTORS

> **NIH NIH R01** · UNIVERSITY OF KENTUCKY · 1994 · $167,444

## Abstract

The overall goal of the proposed studies is to characterize further the
intracerebral sites of action of gonadotropin releasing hormone (GnRH) and
to identify the neurotransmitters which regulate the GnRH neuronal system
in the rat. Specifically, we propose to:

1. Identify with immunohistochemistry and "in situ" hybridization the
cells in brain which express the GnRH receptor. We recently generated a
panel of specific antibodies against synthetic peptide sequences that are
part of the intra- and extracellular domains of the pituitary GnRH
receptor protein and we have developed cRNA probes to determine the sites
of synthesis of the GnRH receptor in the brain. We propose now to
determine: a. the location of the GnRH-receptor producing neurons; b. the
identity of the neurotransmitters in the GnRH-receptor synthesizing
neurons and whether the relative amounts of GnRH-receptor mRNA change in
response to estradiol.

2. Identify the GnRH-mediated effects on hippocampal neurons. During the
prior funding period we identified and characterized the structure/binding
relationships of the brain GnRH receptors and showed that GnRH causes a
transient induction of c-fos in certain hippocampal neurons. We propose
now to determine whether GnRH causes the release of neuroactive messengers
from the hippocampus and whether this effect is modulated by gonadal
steroids.

3. Identify the second messenger systems which transmit the GnRH signal to
the inside of the hippocampal target neurons. We will focus on the role of
Ca++-influx and redistribution as well as on inositol phosphate hydrolysis
since both messenger systems are activated by GnRH in the anterior
pituitary gonadotropes.

4. Identify the norepinephrine neurons which mediate estradiol positive
feedback actions. We propose: a. to determine precisely which
noradrenergic cell groups project to the GnRH perikarya and to the GnRH
axon terminals in the median eminence; b. to determine if these
noradrenergic neurons contain steroid hormone receptors; c. to determine
whether the gonadal steroids cause a change in the mRNA encoding for
tyrosine hydroxylase.

The proposed combination of morphological, physiological and molecular
biological approaches will provide detailed information on the nature of
the effects of GnRH in the hippocampus and will reveal some of the
mechanisms by which the GnRH neuronal system is regulated. Together, the
results will be important for our basic understanding of how the brain
participates in the regulation of hormonal homeostasis and may provide
clues for treatment of disorders caused by a central failure to maintain
an adequate GnRH release.

## Key facts

- **NIH application ID:** 2199285
- **Project number:** 5R01HD024697-05
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **SAM.gov UEI:** H1HYA8Z1NTM5
- **Principal Investigator:** LOTHAR H JENNES
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $167,444
- **Award type:** 5
- **Project period:** 1989-09-01 → 1997-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2199285

## Citation

> US National Institutes of Health, RePORTER application 2199285, IDENTIFYING AND CHARACTERIZING BRAIN GNRH RECEPTORS (5R01HD024697-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2199285. Licensed CC0.

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