# PHYSIOLOGICAL REGULATION OF GONADOTROPIN GENE EXPRESSION

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 1994 · $165,679

## Abstract

The aim of this proposal is to elucidate the roles of the pattern of the
gonadotropin-releasing hormone (GnRH) pulse signal and the ambient
ovarian hormonal milieu, in regulating expression of the 3 gonadotropin
subunit genes in female rats.  We also plan to explore a possible
mechanism of steroidal regulation of subunit gene transcription, namely
regulation of the duration of transcription.

Reproduction in mammals is controlled by the pituitary hormones,
luteinizing hormone (LH) and follicle-stimulating hormone (FSH).  LH and
FSH consist of a common alpha subunit and specific beta subunits, which
in turn are coded by 3 genes in the gonadotrope cell.  Only a single
hypothalamic GnRH is known to regulate subunit gene expression and
hormone secretion, though differential regulation of LH and FSH synthesis
and secretion is known to occur in normal physiology.  Thus differential
synthesis and secretion appear to be regulated by different patterns
(amplitude and frequency) of GnRH pulsatile secretion, together with the
direct feedback effects of gonadal steroids and peptides on the pituitary
gonadotrope cell.  We propose to validate a GnRH deficient female rat
model; assess effects of different patterns of exogenous GnRH pulses on
subunit mRNA expression; establish if other neuropeptides are required
to rapidly increase LH beta mRNA; and determine if responses are
modulated by estradiol (E2), progesterone (P), inhibin, and follistatin;
investigate the physiologic mechanisms regulating gene expression during
the rat estrous cycle.  The second goal is to test our hypothesis that
the duration of increased subunit gene transcription in response to
pulsatile Gn RH signals is regulated by gonadal steroid hormones.  We
have preliminary evidence that in response to Gn RH pulses, transcription
occurs for a shorter duration in the presence of steroids and we will
evaluate the roles of gonadal steroids in this respect.  If proven to be
true, this would be a novel mechanism of steroid regulation of
gonadotropin synthesis and secretion.

The critical importance of pulsatile GnRH stimulus to initiate subunit
gene transcription and to maintain hormonal secretion is well documented.
The pattern of GnRH pulses is known to change during ovulatory cycles and
abnormalities of the mechanisms regulating GnRH frequency and amplitude
appear to be an important part of syndromes causing anovulation in women.
GnRH pulses are slow in hypothalamic amenorrhea (HA) and
hyperprolactinemia and occur at fast frequency in polycystic ovarian
disease (PCO).  Our prior data in rats showed that slow frequency GnRH
stimuli favor FSH beta mRNA expression and FSH secretion (as seen in HA
and hyperprolactinemia), and fast frequency GnRH pulses favor alpha and
LH beta mRNA expression and LH secretion (as occurs in PCO).  This
provides strong support to our contention that the proposed studies of
the mechanisms of GnRH action in regulating gene expression in rats will
allow insight into normal ...

## Key facts

- **NIH application ID:** 2196818
- **Project number:** 5R01HD011489-17
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **SAM.gov UEI:** JJG6HU8PA4S5
- **Principal Investigator:** John C Marshall
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $165,679
- **Award type:** 5
- **Project period:** 1991-01-01 → 1998-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2196818

## Citation

> US National Institutes of Health, RePORTER application 2196818, PHYSIOLOGICAL REGULATION OF GONADOTROPIN GENE EXPRESSION (5R01HD011489-17). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2196818. Licensed CC0.

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