# ONTOGENY OF GONADOTROPIN SECRETION

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 1994 · $153,753

## Abstract

The long term goal of this research program is to elucidate the
neuroendocrine mechanisms that underlie the timing of the onset of puberty
in the rhesus monkey, a representative higher primate.  In man and monkey,
the prepubertal hiatus in gonadotropin secretion, which is responsible for
the protracted delay from birth until puberty in this species, is
occasioned by an interruption of pulsatile hypothalamic GnRH release.  The
restraint on the GnRH pulse generator during prepubertal development is
largely imposed by mechanisms of extra-gonadal origin.  Since a comparable
control system does not appear to operate in non-primate species, studies
of puberty in the monkey have particular relevance to the understanding of
this fundamental event in human development.  The Specific Aims of this
proposal are to:  1) further examine the hypothesis that puberty is
triggered by activation of the NMDA receptor; 2) begin to examine the view
that the onset of puberty is governed by either a growth tracking device
(somatometer) or a time keeping device (clock) in the central nervous
system; 3) determine whether thyroid hormone is necessary for manifestation
of the restraint imposed upon the hypothalamic GnRH pulse generator during
prepubertal development.  Using the rhesus monkey as an experimental
paradigm, physiological and pharmacological approaches will be brought to
bear upon the question of the neurobiological basis of the prepubertal
hiatus in pulsatile GnRH release from the primate hypothalamus.  The notion
that activation of the NMDA receptor is involved in triggering puberty will
be examined directly by measuring release rates of Glu and Asp in
hypothalamus using push-pull perfusion, and by determining whether NMDA
receptor antagonists interrupt the onset of puberty.  The technique of
cross-perfusion, using extracorporal circuits and centrifugal pumps
permanently coated with bioactive heparin, will be used to test whether
circulating signals relay information on body growth to the somatometer,
and thereby determine the time of puberty.  The notion of a pubertal clock,
on the other hand, will be examined by rearing male monkeys from birth in
an artificial photoperiod cycle consisting of 16 weeks of long days and 16
weeks of short days.  This is expected to entrain the circannual cycle to
an abbreviated calendar year, and therefore to induce precocious puberty if
a pubertal clock monitors time by tracking circannual cycles.  When chronic
access to the hypothalamus and venous circulation is required, remote
withdrawal-infusion devices will be employed that do not demand either
restraint or tranquilization of the experimental primate.

## Key facts

- **NIH application ID:** 2196991
- **Project number:** 5R01HD013254-12
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **SAM.gov UEI:** MKAGLD59JRL1
- **Principal Investigator:** TONY M PLANT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $153,753
- **Award type:** 5
- **Project period:** 1980-04-01 → 1997-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2196991

## Citation

> US National Institutes of Health, RePORTER application 2196991, ONTOGENY OF GONADOTROPIN SECRETION (5R01HD013254-12). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2196991. Licensed CC0.

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