Document Detail

Insights into male germ cell apoptosis due to depletion of gonadotropins caused by GnRH antagonists.
MedLine Citation:
PMID:  17268770     Owner:  NLM     Status:  MEDLINE    
The role of pituitary gonadotropins in the regulation of spermatogenesis has been unequivocally demonstrated, although, the precise mechanism of this regulation is not clearly understood. Previous studies have shown that specific immunoneutralization of LH/testosterone caused apoptotic cell death of meiotic and post-meiotic germ cells while that of FSH resulted in similar death of meiotic cells. In the present study, the death process of germ cells has been characterized by depleting both FSH and testosterone by administering two different potent GnRH antagonists, Cetrorelix and Acyline to both rats and mice. Pro-survival factors like Bcl-2 and Bcl-x/l were unaltered in germ cells due to GnRH antagonist treatment, although a significant increase in several pro-apoptotic markers including Fas and Bax were evident at both protein and RNA levels. This culminated in cytochrome C release from mitochondria and eventually increase in the activity of caspase-8 and caspase-3. These data suggest that both extrinsic and intrinsic apoptotic death pathways are operative in the germ cells death following decrease in FSH and testosterone levels. Multiple injections of GnRH antagonist resulted in complete disappearance of germ cells except the spermatogonial cells and discontinuation of the treatment resulted in full recovery of spermatogenesis. In conclusion our present data suggest that the principal role of FSH and testosterone is to maintain spermatogenic homeostasis by inhibiting death signals for the germ cells.
Tej K Pareek; Ayesha R Joshi; Amartya Sanyal; Rajan R Dighe
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Apoptosis : an international journal on programmed cell death     Volume:  12     ISSN:  1360-8185     ISO Abbreviation:  Apoptosis     Publication Date:  2007 Jun 
Date Detail:
Created Date:  2007-05-04     Completed Date:  2007-08-22     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  9712129     Medline TA:  Apoptosis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1085-100     Citation Subset:  IM    
Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, Karnataka 560 012, India.
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MeSH Terms
Apoptosis / drug effects*
Biological Markers / metabolism
Caspases / metabolism
Cytochromes c / secretion
Cytoplasm / drug effects,  metabolism
Death Domain Receptor Signaling Adaptor Proteins / genetics,  metabolism
Follicle Stimulating Hormone / blood,  deficiency*
Gonadotropin-Releasing Hormone / analogs & derivatives*,  antagonists & inhibitors*,  pharmacology
Organ Size / drug effects
Protein Structure, Quaternary
Rats, Wistar
Spermatozoa / cytology*
Testis / enzymology,  growth & development
Testosterone / blood,  deficiency*
bcl-2-Associated X Protein / chemistry
Reg. No./Substance:
0/Biological Markers; 0/Death Domain Receptor Signaling Adaptor Proteins; 0/bcl-2-Associated X Protein; 33515-09-2/Gonadotropin-Releasing Hormone; 58-22-0/Testosterone; 9002-68-0/Follicle Stimulating Hormone; 9007-43-6/Cytochromes c; EC 3.4.22.-/Caspases; OON1HFZ4BA/cetrorelix

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