Document Detail

p19Ink4d and p18Ink4c cyclin-dependent kinase inhibitors in the male reproductive axis.
MedLine Citation:
PMID:  17342741     Owner:  NLM     Status:  MEDLINE    
The loss of the cyclin-dependent kinase inhibitors (CKIs) p18(Ink4c) and p19(Ink4d) leads to male reproductive defects (Franklin et al., 1998. Genes Dev 12: 2899-2911; Zindy et al., 2000. Mol Cell Biol 20: 372-378; Zindy et al., 2001. Mol Cell Biol 21: 3244-3255). In order to assess whether these inhibitors directly or indirectly affect male germ cell differentiation, we examined the expression of p18(Ink4c) and p19(Ink4d) in spermatogenic and supporting cells in the testis and in pituitary gonadotropes. Both p18(Ink4c) and p19(Ink4d) are most abundant in the testis after 18 days of age and are expressed in purified populations of spermatogenic and testicular somatic cells. Different p18(Ink4c) mRNAs are expressed in isolated spermatogenic and Leydig cells. Spermatogenic cells also express a novel p19(Ink4d) transcript that is distinct from the smaller transcript expressed in Sertoli cells, Leydig cells and in other tissues. Immunohistochemistry detected significant levels of p19(Ink4d) in preleptotene spermatocytes, pachytene spermatocytes, condensing spermatids, and Sertoli cells. Immunoprecipitation-Western analysis detected both CKI proteins in isolated pachytene spermatocytes and round spermatids. CDK4/6-CKI complexes were detected in germ cells by co-immunoprecipitation, although the composition differed by cell type. p19(Ink4d) was also identified in FSH+ gonadotrophs, suggesting that this CKI may be independently required in the pituitary. Possible cell autonomous and paracrine mechanisms for the spermatogenic defects in mice lacking p18(Ink4c) or p19(Ink4d) are supported by expression of these CKIs in spermatogenic cells and in somatic cells of the testis and pituitary.
Gregory M Buchold; Patricia L Magyar; Ramamani Arumugam; Mary M Lee; Deborah A O'Brien
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular reproduction and development     Volume:  74     ISSN:  1040-452X     ISO Abbreviation:  Mol. Reprod. Dev.     Publication Date:  2007 Aug 
Date Detail:
Created Date:  2007-05-22     Completed Date:  2007-08-28     Revised Date:  2014-09-24    
Medline Journal Info:
Nlm Unique ID:  8903333     Medline TA:  Mol Reprod Dev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  997-1007     Citation Subset:  IM    
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MeSH Terms
Cyclin-Dependent Kinase 4 / metabolism
Cyclin-Dependent Kinase 6 / metabolism
Cyclin-Dependent Kinase Inhibitor p18 / genetics,  metabolism*
Cyclin-Dependent Kinase Inhibitor p19 / genetics,  metabolism*
Gonadotrophs / cytology,  metabolism*
Mice, Knockout
Pituitary Gland, Anterior / cytology,  metabolism
Reproduction / physiology*
Testis / cytology,  metabolism*
Grant Support
Reg. No./Substance:
0/Cdkn2c protein, mouse; 0/Cdkn2d protein, mouse; 0/Cyclin-Dependent Kinase Inhibitor p18; 0/Cyclin-Dependent Kinase Inhibitor p19; 0/Ribonucleoproteins; 0/messenger ribonucleoprotein; EC Kinase 4; EC Kinase 6

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