Document Detail

Glial cell line-derived neurotrophic factor is constitutively produced by human testicular peritubular cells and may contribute to the spermatogonial stem cell niche in man.
MedLine Citation:
PMID:  20601681     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Testicular peritubular cells form an ill-characterized cellular compartment of the human testis, which forms a border with Sertoli cells and spermatogonial stem cells (SSCs). A recently developed culture method has identified parts of the secretory repertoire of human testicular peritubular cells (HTPCs), which includes nerve growth factor. Whether peritubular cells produce glial cell line-derived neurotrophic factor (GDNF) and may thus contribute to the stem cell niche is not known.
METHODS: We studied GDNF production in isolated peritubular cells from men with normal spermatogenesis (HTPCs) and impaired spermatogenesis and testicular fibrosis (HTPC-Fs). Human testicular biopsies and peritubular cells in culture were evaluated using immunohistochemistry, laser microdissection (LMD), RT-PCR and measurement of GDNF and cAMP by enzyme-linked immunosorbent assay. We also tested whether GDNF production is regulated by tumour necrosis factor-alpha (TNF-alpha) or tryptase, the products of mast cells or macrophages.
RESULTS: Peritubular wall cells are in close proximity to cells expressing the GDNF family co-receptor-alpha1. GDNF mRNA was detected in LMD samples of the peritubular and tubular but not interstitial compartments. HTPCs and HTPC-Fs lack FSH- and LH-receptors but express receptors for TNF-alpha and tryptase. Importantly, peritubular cells express GDNF and constitutively released GDNF into the medium in comparably high amounts. TNF-alpha and tryptase had no effect on the secretion of GDNF by HTPCs or HTPC-Fs.
CONCLUSIONS: Peritubular cells in testes of normal and sub-/infertile men produce GDNF and are likely constitutive contributors of the SSC niche in the human testis.
K Spinnler; F M Köhn; U Schwarzer; A Mayerhofer
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-07-03
Journal Detail:
Title:  Human reproduction (Oxford, England)     Volume:  25     ISSN:  1460-2350     ISO Abbreviation:  Hum. Reprod.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-18     Completed Date:  2010-12-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8701199     Medline TA:  Hum Reprod     Country:  England    
Other Details:
Languages:  eng     Pagination:  2181-7     Citation Subset:  IM    
Institute for Cell Biology, Anatomy and Center for Integrated Protein Science Munich (CIPSM), Ludwig Maximilian University, Biedersteiner Strasse 29, D-80802 Munich, Germany.
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MeSH Terms
Biological Specimen Banks
Cells, Cultured
Cyclic AMP / metabolism
Gene Expression
Glial Cell Line-Derived Neurotrophic Factor / genetics,  physiology*,  secretion
Glial Cell Line-Derived Neurotrophic Factor Receptors / genetics,  metabolism
Infertility, Male / metabolism
Oligospermia / metabolism
Organ Specificity
RNA, Messenger / metabolism
Seminiferous Tubules / metabolism,  pathology
Spermatogonia / metabolism*
Stem Cell Niche / metabolism*
Testis / cytology,  metabolism*,  pathology,  secretion
Tryptases / metabolism
Tumor Necrosis Factor-alpha / metabolism
Reg. No./Substance:
0/GDNF protein, human; 0/GFRA1 protein, human; 0/Glial Cell Line-Derived Neurotrophic Factor; 0/Glial Cell Line-Derived Neurotrophic Factor Receptors; 0/RNA, Messenger; 0/Tumor Necrosis Factor-alpha; 60-92-4/Cyclic AMP; EC

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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