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This version published online on March 10, 2005
Endocrinology, doi:10.1210/en.2004-1630
A more recent version of this article appeared on June 1, 2005
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Submitted on December 17, 2004
Accepted on February 28, 2005

The role of androgens in Sertoli cell proliferation and functional maturation: studies in mice with total (ARKO) or Sertoli cell-selective (SCARKO) ablation of the androgen receptor

Karen AL Tan, Karel De Gendt, Nina Atanassova, Marion Walker, Richard M Sharpe, Philippa TK Saunders, Evi Denolet, and Guido Verhoeven*

MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Chancellors Building, University of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, Scotland, UK; Laboratory for Experimental Medicine & Endocrinology, Department of Developmental Biology, Catholic University of Leuven, Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium; Institute of Experimental Morphology & Anthropology, Bulgarian Academy of Science, Acad. G Bonchev Street, block 25, 1113 Sofia, Bulgaria

* To whom correspondence should be addressed. E-mail: Guido.Verhoeven{at}med.kuleuven.ac.be.

The role of androgens in the proliferation and maturation of Sertoli cells (SC) and in the development of their capacity to support spermatogenesis remains poorly understood. We evaluated these functions in complete androgen receptor (AR) knockout (ARKO) and SC-selective AR knockout (SCARKO) mice. Compared with controls, ARKO mice exhibited a progressive reduction in SC number/testis while SCARKOs showed minor changes, suggesting that androgen effects on SC number are not mediated via direct action on SC. Immunoexpression of AMH, p27kip1, GATA-1 and SGP-2, which changes according to SC maturational status, occurred normally in ARKOs and SCARKOs. Functional capacity of SC to support spermatogonia was similar in SCARKOs and controls, whereas ARKOs showed reduced capacity with age. SC capacity to support total germ cells revealed major deficits in ARKO and SCARKO adults, particularly with respect to post-meiotic germ cells. Using quantitative RT-PCR, the expression of SC markers was compared in d 50 testes. In ARKOs, expression of Pem, FABP, PDGF-A and transferrin were all significantly reduced, whereas FSH receptor and AMH were increased. In SCARKOs, there were modest reductions in expression of cystatin-TE and claudin-11 whereas expression of Pem, FABP and PDGF-A was markedly reduced, highlighting these as potentially androgen-regulated SC genes that merit further study. In conclusion, androgen action is not required for maturation-dependent changes in immunoexpression of the SC markers AMH, p27kip1, GATA-1 and SGP-2, but is essential for expression of other SC genes, the attainment of normal SC number and the support of meiotic and post-meiotic germ cell development.
Key words: testis • Pem • AMH • p27kip1 • GATA-1 • SGP-2 • ABP • FABP • PDGF-A • transferrin • cystatin-TE • claudin-11 • FSH receptor




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