# LHRH PHYSIOLOGY IN MAN:  IN VIVO AND IN VITRO APPROACHES

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 1994 · $102,705

## Abstract

The broad goal of this competing renewal application is to examine the          
physiology and pathophysiology of the reproductive system in the human male     
by combining the in vivo clinical models of normal men, GnRH deficient men      
undergoing longterm GnrH replacement, and men with reproductive disorders       
with the latest in vitro techniques such as monoclonal antibody technology,     
radioreceptor assays, and molecular biology.                                    
                                                                                
Monoclonal antibodies quite specific for the measurement of the free alpha      
subunit (FAS) of the gonadotropins will be used to define the physiologic       
regulation of FAS secretion and excretion.  Since this surrogate marker of      
endogenous GnRH secretion can be monitored via its urinary excretion, its       
role as a non-invasive marker of the neuroendocrine integrity of GnRH           
secretion across normal sexual development and disorders of sexual              
maturation in males merits definition.                                          
                                                                                
Using newly developed radioreceptor assays (RRAs) for measurement of LH and     
FSH, the ratio between these receptor-based determinations and the dimer-       
specific sandwich assays for the gonadotropins is usually near unity (i.e.      
the RRA/RIA ration = 1) in normal men.  However, in discrete subsets of men     
with hypogonadism in the face of elevated gonadotropins by RIAs, we have        
now been identified 2 separate types of abnormalities, high and low RRA/RIA     
ratios.                                                                         
                                                                                
Using PCR amplification, a family with low RRA/RIA ratios have been             
documented to have a point mutation in the LH beta gene.  Using                 
immunoprecipitation, the subjects with elevated RRA/RIA have been               
discovered to have circulating gonadotropin receptor binding competitors.       
The realization that hypergonadotropic hypogonadism is not always               
indicative of primary gonadal pathology may well have important therapeutic     
implications.  the scope and import of both of these groups of                  
abnormalities will be defined further.                                          
                                                                                
Finally, methodologic stumbling blocks still remain to the accurate             
measurement of inhibin in the circulation of the human.  Using a newly-         
designed, beta/alpha sandwich assay and techniques to block inhibin binding     
to proteins, specific measurements of inhibin will now be possible and the      
physiology of dimeric inhibin as well as that of its alpha subunit can now      
be ...

## Key facts

- **NIH application ID:** 2197238
- **Project number:** 5R01HD015788-12
- **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:** $102,705
- **Award type:** 5
- **Project period:** 1981-07-01 → 1995-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2197238

## Citation

> US National Institutes of Health, RePORTER application 2197238, LHRH PHYSIOLOGY IN MAN:  IN VIVO AND IN VITRO APPROACHES (5R01HD015788-12). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2197238. Licensed CC0.

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