# MATURATIONAL ROLES OF GNRH PULSE FREQUENCY

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 1994 · $143,730

## Abstract

The overall goal of this project is to examine the regulation and roles of
pulsatile GnRH secretion in human beings: a) throughout sexual maturation,
and b) in the maintenance of normal cyclical ovulation.  All of the
proposed studies are directed toward the unifying hypothesis that the
ability to secrete GnRH at a "fast" approximately circhoral, or "faster"
frequency throughout the day develops during puberty, and that the ability
to change the frequency and amplitude of pulsatile GnRH secretion is
critical for cyclical ovarian follicular maturation and ovulation.  This
hypothesis will be approached in several ways.  Specifically we plan 1)
detailed evaluation of the sleep-entrained patterns of GnRH and sex steroid
(T and E2) secretion in normal and hypogonadal children; 2) examination of
the acute effects of sex steroids, either via stimulation by pulsatile
GnRH, intravenous infusion, or transcutaneous absorption, on the sleep-
entrained patterns of GnRH secretion in pubertal boys and men; 3)
examination of the role of endogenous opioids, via opioid receptor blockade
in the sex steroid regulation of GnRH secretion in pubertal boys and normal
men; 4) examination of the role of E2 in regulating GnRH pulse frequency
throughout the transition from luteal to follicular stages of the menstrual
cycle; 5) examination of the hypothesis that polycystic ovarian disease
(PCO) results from fast frequency GnRH secretion, and evaluation of the
effects of E2 and P in slowing GnRH secretion and inducing ovulation; and
6) examination of the role of excess hypothalamic opioid activity in the
slow frequency GnRH secretion in hypothalamic amenorrhea, and evaluation of
naltrexone in inducing ovulation.  The principal approaches to these
objectives will include: a) indirect assessment of GnRH secretion via
detailed assessment of the secretory patterns of immunoreactive LH; b)
assessment of the acute effects of sex steroid infusion on the sleep-
entrained increase in gonadotropin secretion in pubertal boys; c) opioid
receptor blockade via nalaxone or naltrexone to investigate the role(s) of
endogenous opioids in gonadotropin regulation; d) administration of
physiological amounts of E2 and P to normal women and women with PCO to
test the hypothesis that PCO syndrome is the result of excess hypothalamic
pulsatile secretion of GnRH, and e) evaluation of the effects of
dexamethasone on LH secretion in patients who have hypothalamic amenorrhea
but who are unresponsive to opioid blockade.  Normal adult men and women,
and adults and children with suspected or proven hypothalamic/pituitary
dysfunction will participate in detailed protocols performed in the
Clinical Research Center.  Well established radioimmunoassays will be used
for serial hormone determinations, and objective computer analyses will be
used for determination of pulsatile secretory patterns.  These studies
should provide a more thorough understanding of the physiology of human
reproduction and should lead to ...

## Key facts

- **NIH application ID:** 2197257
- **Project number:** 5R01HD016000-13
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **SAM.gov UEI:** GNJ7BBP73WE9
- **Principal Investigator:** ROBERT P KELCH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $143,730
- **Award type:** 5
- **Project period:** 1982-03-01 → 1996-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2197257

## Citation

> US National Institutes of Health, RePORTER application 2197257, MATURATIONAL ROLES OF GNRH PULSE FREQUENCY (5R01HD016000-13). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2197257. Licensed CC0.

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