Document Detail


Insufficient androgen and FSH signaling may be responsible for the azoospermia of the infantile primate testes despite exposure to an adult-like hormonal milieu.
MedLine Citation:
PMID:  22669085     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: In humans, as well as in other higher primates, the infantile testis is exposed to an adult-like hormonal milieu, but spermatogenesis is not initiated at this stage of primate development. In the present study, we examined the molecular basis of this intriguing infertile state of the primate testis.
METHODS: The integrity of androgen receptor (AR) and FSH receptor (FSHR) signaling pathways in primary cultures of Sertoli cells (Scs) harvested from azoospermic infant and spermatogenic pubertal monkey testes were investigated under identical in vitro hormonal conditions. In order to synchronously harvest Scs from early pubertal testis, the activation of testicular puberty was timed experimentally by prematurely initiating gonadotrophin secretion in juvenile animals with an intermittent infusion of gonadotrophin-releasing hormone.
RESULTS: While qRT-PCR demonstrated that AR and FSHR mRNA expression in Scs from infant and pubertal testes were comparable, androgen-binding and FSH-mediated cAMP production by infant Scs was extremely low. Compromised AR and FSHR signaling in infant Scs was further supported by the finding that testosterone (T) and FSH failed to augment the expression of the T responsive gene, claudin 11, and the FSH responsive genes, inhibin-βB, stem cell factor (SCF) and glial cell line-derived neurotrophic factor (GDNF) in Scs harvested at this stage of development.
CONCLUSION: These results indicate that compromised AR and FSHR signaling pathways in Scs underlie the inability of the infant primate testis to respond to an endogenous hormonal milieu that later in development, at the time puberty, stimulates the initiation of spermatogenesis. This finding may have relevance to some forms of idiopathic infertility in men.
Authors:
Subeer S Majumdar; Kanchan Sarda; Indrashis Bhattacharya; Tony M Plant
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-06-04
Journal Detail:
Title:  Human reproduction (Oxford, England)     Volume:  27     ISSN:  1460-2350     ISO Abbreviation:  Hum. Reprod.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-07-18     Completed Date:  2012-12-06     Revised Date:  2013-08-14    
Medline Journal Info:
Nlm Unique ID:  8701199     Medline TA:  Hum Reprod     Country:  England    
Other Details:
Languages:  eng     Pagination:  2515-25     Citation Subset:  IM    
Affiliation:
Division of Cellular Endocrinology, National Institute of Immunology, New Delhi 110067, India. planttm@mwri.magee.edu
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MeSH Terms
Descriptor/Qualifier:
Androgens / metabolism*
Animals
Azoospermia / metabolism*
Follicle Stimulating Hormone / metabolism*
Ligands
Macaca mulatta
Male
RNA, Messenger / metabolism
Receptors, Androgen / metabolism
Receptors, FSH / metabolism
Sertoli Cells / metabolism
Spermatogenesis
Testis / growth & development*,  metabolism
Testosterone / metabolism
Time Factors
Grant Support
ID/Acronym/Agency:
HD08610/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Androgens; 0/Ligands; 0/RNA, Messenger; 0/Receptors, Androgen; 0/Receptors, FSH; 58-22-0/Testosterone; 9002-68-0/Follicle Stimulating Hormone
Comments/Corrections

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