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Hum. Reprod. Advance Access originally published online on July 26, 2007
Human Reproduction 2007 22(10):2594-2605; doi:10.1093/humrep/dem243
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© The Author 2007. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Human sperm express a functional androgen receptor: effects on PI3K/AKT pathway

Saveria Aquila1,2, Emilia Middea1,2, Stefania Catalano1, Stefania Marsico1,2, Marilena Lanzino1,2, Ivan Casaburi1, Ines Barone1,2, Rosalinda Bruno1, Silvia Zupo1,2 and Sebastiano Andò1,2,3

1 Department of Pharmaco-Biology, Faculty of Pharmacy, University of Calabria, 87036 Arcavacata di Rende, Cosenza, Italy 2 Centro Sanitario, University of Calabria, 87036 Arcavacata di Rende, Cosenza, Italy 3 Department of Cellular Biology, Faculty of Biological Sciences, University of Calabria, 87036 Arcavacata di Rende, Cosenza, Italy

3 Correspondence address. Tel: +39 984 496201; Fax: +39 984 496203, E-mail: sebastiano.ando{at}unical.it, aquisav{at}libero.it

BACKGROUND: Results from mice lacking the androgen receptor (AR) showed that it is critical for the proper development and function of the testes. The aim of this study was to investigate whether a functional AR is present in human sperm.

METHODS: The expression of AR and its effects on sperm were evaluated by RT-PCR, Western Blot, Immunocytochemistry, PI3Kinase and DNA laddering assays.

RESULTS: We showed in human sperm that AR is located at the head region. Dihydrotestosterone (DHT), in a dose-dependent manner, leads to the rapid phosphorylation of the AR on tyrosine, serine and threonine residues and this effect was reduced by the AR antagonist hydroxyflutamide (OH-Flut). The effects of AR were evaluated on the phosphoinositide-3 kinase/protein kinase B (PI3K/AKT) pathway. Specifically, 0.1 and 1 nM DHT stimulated PI3K activity, whereas 10 nM DHT decreased PI3K activity and levels of p-AKT S473 and p-AKT T308, p-BCL2, and enhanced phosphatase and tensin homologue (PTEN) phosphorylation. In addition, 10 nM DHT was able to induce the cleavage of caspases 8, 9 and 3 and cause DNA laddering, and these effects were reversed either by casodex or OHFlut. By using wortmannin, a specific PI3K inhibitor, the cleavage of caspase 3 was reproduced, confirming that in sperm the PI3K/AKT pathway is involved in caspase activation.

CONCLUSIONS: Human sperm express a functional AR that have the ability to modulate the PI3K/AKT pathway, on the basis of androgen concentration.

Key words: androgen receptor/androgens/human sperm/male reproduction/PI3K/AKT

Submitted on March 5, 2007; resubmitted on May 25, 2007; accepted on June 28, 2007.


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