# REPRODUCTIVE PHYSIOLOGY OF GONADOTROPIN SYNTHESIS

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 1994 · $246,410

## Abstract

Lutropin (LH) and follitropin (FSH) are the pituitary gonadotropins which       
regulate sex-steroid hormone secretion and biosynthesis, and gametogenesis.     
In addition, LH and FSH are glycoprotein hormones that are synthesized and      
secreted by gonadotrope in the anterior pituitary gland, and are essential      
for normal sexual development and reproduction.  Each hormone is composed       
of two different subunits, alpha and beta, which are encoded by separate        
genes located on different chromosomes.  The long-term objective of this        
work is to understand how various hormones, including the newly described       
gonadal peptides, regulate the biosynthesis of LH and FSH at the pre-           
translational level.  The key goal of this proposal is to characterize          
further hormonal regulation of expression of FSH subunit genes in the           
gonadotrope.  The Specific Aims are:  (1) to determine the effects of           
inhibins, activins, and follistatins, and their interactions, on the            
biosynthesis of LH and FSH at the pre-translational level in cultured rat       
pituitary cells in the absence of GnRH; (2) to explore the effects of these     
gonadal peptidase in the presence of constant or pulsatile GnRH in static       
or perifused rat pituitary cells; (3) to elucidate molecular mechanisms by      
which steady-state FSH-beta mRNA levels are altered; (4) to identify            
critical cis-DNA elements, and subsequently related trans-acting factors,       
within the regulatory regions of the rat FSH-beta gene that mediate hormone     
responses, using reporter gene constructs and gene transfer in a transient      
expression assay; and (5) to establish permanent gonadotrope cell lines         
utilizing transgenic mouse models to induce specific  gonadotrope tumors        
and retrovirus-mediated oncogene transduction of primary rat pituitary          
cultures, with subsequent selection of cell lines with hormone-regulated        
differentiated function.  The pre-translational studies will involved           
determinations of steady-state levels of subunit mRNAs, transcriptional         
rates, and stability of subunit mRNAs.  It is expected that such studies        
will allow a deeper understanding into the regulation of gonadotropin           
production at one of the major steps in the biosynthetic pathway, that is,      
the positive and negative effects of various hypothalamic and gonadal           
factors on gonadotropin subunit synthesis at the genomic level.

## Key facts

- **NIH application ID:** 2197907
- **Project number:** 5R01HD019938-11
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **SAM.gov UEI:** QN6MS4VN7BD1
- **Principal Investigator:** WILLIAM W. CHIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $246,410
- **Award type:** 5
- **Project period:** 1990-08-01 → 1996-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2197907

## Citation

> US National Institutes of Health, RePORTER application 2197907, REPRODUCTIVE PHYSIOLOGY OF GONADOTROPIN SYNTHESIS (5R01HD019938-11). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2197907. Licensed CC0.

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