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Hum. Reprod. Advance Access published online on December 11, 2007
Human Reproduction, doi:10.1093/humrep/dem343
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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

Activin receptor subunits in normal and dysfunctional adult human testis

V. Dias1, S. Meachem2, E. Rajpert-De Meyts3, R. McLachlan2, U. Manuelpillai1,4 and K.L. Loveland1,5,6

1 Monash Institute of Medical Research, 27-31 Wright Street Clayton, Victoria 3168, Australia 2 Prince Henry’s Institute, Clayton, Victoria, Australia 3 Department of Growth and Reproduction, University of Copenhagen (Rigshospitalet), Copenhagen, Denmark 4 Department of Obstetrics and Gynecology, Monash University, Clayton, Victoria, Australia 5 The Australian Research Council Centre of Excellence in Biotechnology and Development, Australia

6 Correspondence address. Tel: +6-13-9594-7418; Fax: +6-13-9594-7111; E-mail: kate.loveland{at}med.monash.edu.au

BACKGROUND: The cellular sites of activin action and its regulation in the normal and dysfunctional adult human testis are unknown.

METHODS: Activin type I (ALK2 and ALK4) and type II (ActRIIA and ActRIIB) receptors were detected using immunohistochemistry on Bouins fixed sections of normal, carcinoma in situ (CIS), seminoma, non-seminoma and gonadotropin-deprived human testis. ActRIIA mRNA was localized by in situ hybridization.

RESULTS: ALK2, ALK4 and ActRIIB proteins were observed in Sertoli cells, spermatogonia and some spermatocytes within normal and gonadotropin-suppressed adult human testis; all three receptor subunits were also detected in CIS, seminoma and non-seminoma cells. ActRIIA immunoreactivity was faint to absent in the normal testis and in CIS and non-seminoma cells, whereas some seminoma cells displayed a strong signal. Also in contrast to the normal testis, a majority of spermatogonia and Sertoli cells in gonadotropin-deprived samples exhibited a strong ActRIIA immunohistochemical and in situ hybridization signal.

CONCLUSIONS: Spermatogonia and Sertoli cells appear as the primary targets of activin action in the adult human testis. Changes in testicular function associated with altered hormone levels may enhance ActRIIA mRNA and protein synthesis, thus modifying signalling by activin or other TGFβ ligands within specific cells of the seminiferous epithelium.

Key words: activin receptor/human testis/spermatogonia/seminoma/gonadotropins

Submitted on May 11, 2007; resubmitted on August 31, 2007; accepted on October 1, 2007.


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V. L Dias, E. Rajpert-De Meyts, R. McLachlan, and K. L. Loveland
Analysis of activin/TGFB-signaling modulators within the normal and dysfunctional adult human testis reveals evidence of altered signaling capacity in a subset of seminomas
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