# NEUROENDOCRINE REGULATION OF IN VIVO LHRH RELEASE

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 1993 · $116,571

## Abstract

The central nervous system regulates gonadotropin secretion and
maintains reproductive cycles through intermittent release of
luteinizing hormone-releasing hormone (LHRH).  The decapeptide is
synthesized in neuronal perikarya, released from neurovascular
terminals into the hypophysical portal vessels and conveyed to
the anterior pituitary to regulate LH secretion.  The amplitude
and frequency of these neuroendocrine events are influenced, in
turn, by feedback actions of two circulating ovarian steroids,
estrogen (E2) and progesterone (P).  The objective of the
proposed studies is to gain an intergrated understanding of
regulatory mechanisms which govern three critical functions of
LHRH neurons - LHRH synthesis, LHRH release, and LHRH actions.
Three approaches have been developed towards this end:  in vivo
radiolabeling will be used to estimate rates of LHRH
biosynthesis, pituitary microdialysis will be utilized to measure
in vivo LHRH release patterns, and an in vivo isolated pituitary
paradigm will be employed to analyze physiological actions of
LHRH.  Using these methods, we will study the physiological
role(s) of LHRH neurons in the generation of the preovulatory LH
surge and in homeostatic suppression of LH secretion at other
times during the ovulatory cycle.  One major hypothesis to be
tested holds that high levels of circulating ovarian steroids
directly or indirectly accelerate LHRH biosynthesis, leading to
increase the amplitude of LHRH secretion and initiation of the LH
surge.  Possible noradrenergic and opioid peptidergic mediation
of these effects will receive particular attention.  LHRH
biosynthesis and release will be measured during the ovulatory
cycle, and the effects of E2, P, and noradrenergic or opiatergic
agonists and antagonists will be assessed.  Release profiles of
norepinephrine throughout entire ovulatory cycles will also be
characterized by microdialysis procedures.  A second hypothesis
holds that negative feedback actions of steroids are exerted, in
part, by deceleration of a hypothalamic ultradian pulse
generator.  Release patterns of LHRH will be monitored in
individual animals over several days following ovariectomy, with
or without steroid treatments.  Physiological significance of
observed changes in LHRH pulse amplitude or frequency will then
be assessed by mimicking these profiles in hypophysectomized rats
bearing pituitary during "permissive" LHRH stimulation.  These
studies should provide substantial amount of new information
regarding the role of LHRH neurons in the maintenance of normal
ovulatory cyclicity.  Such knowledge may help to enhance
prospects of devising contraceptive strategies based upon
perturbations of hypothalamic/hypophysical function, and aid in
treatment of reproductive disorders, such as hypothalamic
amenorrhea.

## Key facts

- **NIH application ID:** 2198065
- **Project number:** 5R01HD020677-08
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **SAM.gov UEI:** EXZVPWZBLUE8
- **Principal Investigator:** Jon E Levine
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $116,571
- **Award type:** 5
- **Project period:** 1985-07-01 → 1995-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2198065

## Citation

> US National Institutes of Health, RePORTER application 2198065, NEUROENDOCRINE REGULATION OF IN VIVO LHRH RELEASE (5R01HD020677-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2198065. Licensed CC0.

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