# NEUROENDOCRINE-GONADAL FUNCTION IN PUBERTY

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 1994 · $141,312

## Abstract

The broad goal of this revised application remains to dissect the
individual contributions of the neuroendocrine, adrenal, and gonadal
components to sexual maturation in the human. Utilizing the model of
central precocious puberty (CPP), GnRHa-induced suppression of gonadal
steroids, and a longitudinal study design, we will continue to address
these broad goals in the next 4 years. However, significant revisions have
been incorporated in accord with the Study Section's recommendations. In
the final four years of the longitudinal studies in the CPP population, we
will bring new tools to bear on pubertal physiology and pathophysiology,
including the regulation of FSH secretion, developmental aspects of PCOS,
and the underlying mechanisms of autonomous gonadal function in patients
with gonadotropin-independent precocity (GIP).  SA #1, to determine the
relative contributions of gonadal vs. adrenal sex steroids to growth and
skeletal maturation in childhood and to use this information to develop
robust predictive models of the impact of sex steroid suppression on long-
term growth, final height, and bone maturation with broad applicability to
a variety of growth disorders, addresses the completion of the ongoing
longitudinal studies in CPP with particularly attention to making the
valuable data gleaned over 13 years of study a rich resource for
investigators and clinicians through the development of predictive models
for growth during gonadal suppression. SA #2, to define the association
between the development of a polycystic ovarian morphology, insulin
resistance, hyperandrogenic disorders, and mature ovulatory function
during pubertal maturation will look at the development of PCOS from a
developmental spectrum and is driven in large by a mandate to better
understand the high prevalence of polycystic ovaries which we have defined
in our population. SA #3, To characterize the biologic controls of FSH
secretion during sexual maturation by correlating the neuroendocrine
pattern of FSH secretion and its biologic activity with the developmental
profile of inhibin, inhibin subunits, and follistatin secretion, will
advantage of the unique opportunities afforded by the CPP model to chart
pubertal physiology with novel tools that will shed light on the
developmental regulation of FSH in the human, including an FSH bioassay
utilizing the recombinant human FSH receptor, as well as new immunoassays
specific for follistatin and inhibin dimers and subunits of varying MW.
SA#4, To define the clinical, genetic, biochemical, pathological, and
molecular spectrum of defects in children with GIP will combine state of
the art molecular techniques with clinical investigations to further
understand the signalling pathways of the gonadotropin receptors and the
phenotypes that their constitutive activation can yield.

## Key facts

- **NIH application ID:** 2197584
- **Project number:** 2R01HD018169-11A2
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **SAM.gov UEI:** FLJ7DQKLL226
- **Principal Investigator:** William Francis Crowley
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $141,312
- **Award type:** 2
- **Project period:** 1983-07-01 → 1998-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2197584

## Citation

> US National Institutes of Health, RePORTER application 2197584, NEUROENDOCRINE-GONADAL FUNCTION IN PUBERTY (2R01HD018169-11A2). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2197584. Licensed CC0.

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