# CONTROL AND INTEGRATION OF GNRH NEURAL PATHWAYS

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 1994 · $240,361

## Abstract

Scattered GnRH neurons in the primate hypothalamus perform different
functions and engage in selective interactions.  To establish which
interactions are relevant to neuroendocrine regulation, (1) We will
identify neuroendocrine GnRH neurons in the primate, and determine the
afferent inputs involved in their control.  We will identify
neuroendocrine GnRH neurons in pre-ovulatory female primates by
retrograde labeling from the median eminence (ME) and immunocytochemical
(ICC) staining for GnRH with.  DAB.  We will use ICC staining with
colloidal gold (red) to identify their specific afferents, e.g. dopamine
(DA), norepinephrine (NE), and serotonin (5-HT), the peptide
beta-endorphin (b-E), gamma-aminobutyric acid (GABA), and the excitatory
amino acids (EAAs) glutamate and aspartate.  Synapses will be
characterized at the electron microscopic (EM) level and quantified. (2)
We will determine which afferents mediate estrogen (E2) and progesterone
(P4) feedback on neuroendocrine GnRH neurons.  Since GnRH neurons lack E2
receptors, inhibitory feedback is thought to occur through afferent DA,
b-E, or GABA neurons, which concentrate E2 and in some cases P4.  We will
use ICC staining with heavy metal-intensified DAB (black) to reveal
neuronal nuclei containing E2 receptors in pre-ovulatory female primates,
and identify neuroendocrine GnRH neurons with standard DAB (brown).  We
will perform ICC staining for DA, b-E, or GABA neurons with colloidal
gold to identify which afferents mediate E2 feedback.  Types and numbers
of synapses will be evaluated by EM and quantified.  Using the same
protocol, we will perform ICC staining for P4 receptors and determine
which afferents mediate P4 feedback.  We will repeat these studies in
early follicular and mid-luteal phase animals to examine feedback sites
and effects of changing steroid levels.
     Puberty in primates involves reactivation of the dormant prepubertal
GnRH pulse generator.  While this implies that a competent GnRH neuronal
system is present in juveniles, neuroanatomical changes which ma\,
enhance pulsatile GnRH secretion have yet to be assessed. (3) We will
determine if GnRH neuronal connections or afferent synapses are altered
during the peripubertal period.  We will perform double EM ICC staining
for GnRH. neurons (with DAB) and their afferents (with colloidal gold) in
prepubertal and adult male monkeys.  We will quantify and compare the
types, characteristics, and numbers of GnRH neuronal interactions and
afferent synapses.  Using serial plasma LH measurements (by RIA), we will
identify peripubertal (nocturnal LH surge) animals, perform ICC staining,
and evaluate participation of the neural changes observed.  In subsequent
studies, we will examine prepubertal and peripubertal female monkeys and
quantify their GnRH neurointeractions.  We will compare the data to that
previously obtained in adult, cycling females, and correlate the observed
changes with associated peripubertal events.  Together, these s...

## Key facts

- **NIH application ID:** 2196756
- **Project number:** 5R01HD010907-16
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **SAM.gov UEI:** KMH5K9V7S518
- **Principal Investigator:** PAUL C GOLDSMITH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $240,361
- **Award type:** 5
- **Project period:** 1977-04-01 → 1996-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2196756

## Citation

> US National Institutes of Health, RePORTER application 2196756, CONTROL AND INTEGRATION OF GNRH NEURAL PATHWAYS (5R01HD010907-16). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2196756. Licensed CC0.

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