# MOLECULAR BIOLOGY OF HORMONES THAT REGULATE REPRODUCTION

> **NIH NIH K04** · NORTHWESTERN UNIVERSITY · 1994 · $63,472

## Abstract

The goal of this project is to examine the expression and regulation of
genes encoding brain and gonadal hormones that are involved in controlling
mammalian reproduction.  Four polypeptide hormones that modulate the
synthesis and secretion of the pituitary gonadotropins have been described.
These are the hypothalamic peptide gonadotropin-releasing hormone (GnRH),
the related gonadal hormones inhibin and activin, and the recently
described ovarian hormone follistatin.  Inhibin, activin, and follistatin
regulate the secretion of follicle-stimulating hormone (FSH) and GnRH
regulates the secretion of FSH and lutienizing hormone (LH) from the
pituitary.  Because FSH and LH play a crucial role in modulating the
gametogenic and steroidogenic functions of the gonads, these regulatory
hormones are likely to be important for homeostasis in the reproductive
system.  We have isolated cDNA clones from the rat for all of these peptide
hormones:  GnRH, follistatin, and the alpha- and beta-chains of
inhibin/activin.  We have used these cDNAs to examine expression of the
corresponding mRNAs in reproductive tissues using in situ hybridization
histochemistry, and have begun to explore the regulation of these genes
during the rat estrous cycle and during pregnancy.  We now propose to
extend these studies in two directions.  Firstly, we plan to explore the
molecular mechanisms by which these genes are regulated.  We will complete
in vivo experiments to examine changes in GnRH, inhibin, and activin mRNA
levels during the estrous cycle and in response to specific hormones.  We
will develop in vitro assays, including ovarian organ cultures and primary
rat granulosa cell cultures, to directly examine the effects of steroid and
polypeptide hormones on inhibin gene expression.  The granulosa cells will
also be utilized for transfection studies in which inhibin and activin gene
regulatory elements will be characterized.  Secondly, we plan to examine
the biological significance of expression of these genes in several novel
tissues.  The inhibin/activin beta-chain mRNA has been found in diverse
tissues including the brain, pituitary, hematopoietic system, and the
placenta.  This is particularly intriguing in light of its similarity to
the transforming growth factor-beta family of growth and differentiation
regulators.  We will investigate when in development the inhibin/activin
beta-chain gene is expressed in these tissues, and determine whether the
gene is regulated in a manner similar to that observed in the gonads.  We
will also examine extra-gonadal expression of the rat follistatin gene,
pursuing our recent observation that this gene is highly expressed in
decidual tissue early in pregnancy.  To aid in these studies, we will
generate immunological reagents specific for the activin and follistatin
proteins.  We expect these experiments to enhance our understanding of the
roles these hormones play in regulating normal reproduction, and to provide
a framework for examining ...

## Key facts

- **NIH application ID:** 2194392
- **Project number:** 5K04HD000920-04
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **SAM.gov UEI:** EXZVPWZBLUE8
- **Principal Investigator:** KELLY E MAYO
- **Activity code:** K04 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $63,472
- **Award type:** 5
- **Project period:** 1991-02-01 → 1996-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2194392

## Citation

> US National Institutes of Health, RePORTER application 2194392, MOLECULAR BIOLOGY OF HORMONES THAT REGULATE REPRODUCTION (5K04HD000920-04). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2194392. Licensed CC0.

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