This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Taylor, M. F. Articles by Morris, I. D. Search for Related Content PubMed PubMed Citation Articles by Taylor, M. F. Articles by Morris, I. D.

Leydig Cell Apoptosis after the Administration of Ethane Dimethanesulfonate to the Adult Male Rat Is a Fas-Mediated Process¹

University of Manchester School of Biological Sciences, Manchester, United Kingdom M13 9PT; and the Department of Cell Biology and Histology, Faculty of Veterinary Medicine, Utrecht University (M.d.B.-B., K.J.T.), Utrecht 3508, The Netherlands

Address all correspondence and requests for reprints to: Dr. Ian Morris, Division of Pharmacology, Physiology, and Toxicology, G.38 Stopford Building, University of Manchester School of Biological Sciences, Oxford Road, Manchester, United Kingdom M13 9PT. E-mail: ian.morris{at}man.ac.uk

Leydig cells undergo apoptosis in response to the cytotoxin ethane dimethanesulfonate (EDS), with numbers declining at 12–18 h and maximal apoptosis at 24 h postinjection. The Bcl-2 family members, Bcl-2, Bcl-xl, and Bax, appear not to be involved in this process. To further investigate this phenomena, a single dose of EDS was administered to adult rats to induce the killing of Leydig cells. The interstitial cells were examined up to 3 days after EDS administration by Western blot analysis for the Bcl-2 family members (Bak and Bcl-w). Western blotting showed that Bak expression in the interstitial cell preparations was unchanged after EDS, and immunohistochemistry showed that it was not up-regulated in Leydig cells in response to EDS. Bcl-w expression in the Leydig cells and interstitial cell preparations was unchanged until 48 h when it became undetectable, suggesting that Leydig cell-associated Bcl-w is not involved in initiating apoptosis. We also investigated the role of the Fas system in Leydig cell apoptosis. Both Fas receptor and Fas ligand protein levels increased after EDS, peaking at 12–18 h and declining thereafter. Fas receptor and ligand were shown by immunohistochemistry to be present in Leydig cells, and after EDS all Leydig cells became strongly positive for both proteins. The intensity of staining increased in the early stages of apoptosis and decreased as the nuclear morphology became more fragmented. These data suggest that Bcl-2 family members are not involved in Leydig cell apoptosis after EDS administration. However, up-regulation of the Fas system does occur, implicating activation of Fas receptor in the induction of Leydig cell apoptosis.

This article has been cited by other articles:

				G. Shetty, S. H. Shao, and C. C. Y. Weng p53-Dependent Apoptosis in the Inhibition of Spermatogonial Differentiation in Juvenile Spermatogonial Depletion (Utp14bjsd) Mice Endocrinology, June 1, 2008; 149(6): 2773 - 2781. [Abstract] [Full Text] [PDF]

				V. L. Williams, A. DeGuzman, H. Dang, M. Kawaminami, T. W. C. Ho, D. G. Carter, and A. M. Walker Common and specific effects of the two major forms of prolactin in the rat testis Am J Physiol Endocrinol Metab, December 1, 2007; 293(6): E1795 - E1803. [Abstract] [Full Text] [PDF]

				V. A. Biron, M. M. Iglesias, M. F. Troncoso, M. Besio-Moreno, Z. J. Patrignani, O. P. Pignataro, and C. Wolfenstein-Todel Galectin-1: biphasic growth regulation of Leydig tumor cells Glycobiology, September 1, 2006; 16(9): 810 - 821. [Abstract] [Full Text] [PDF]

				V. G. Martinez, E. H. Pellizzari, E. S. Diaz, S. B. Cigorraga, L. Lustig, B. Denduchis, C. Wolfenstein-Todel, and M. M. Iglesias Galectin-1, a cell adhesion modulator, induces apoptosis of rat Leydig cells in vitro Glycobiology, February 1, 2004; 14(2): 127 - 137. [Abstract] [Full Text] [PDF]

				A. Guais, B. Solhonne, N. Melaine, G. Guellaen, and F. Bulle Goliath, a Ring-H2 Mitochondrial Protein, Regulated by Luteinizing Hormone/Human Chorionic Gonadotropin in Rat Leydig Cells Biol Reprod, January 1, 2004; 70(1): 204 - 213. [Abstract] [Full Text] [PDF]

				W. Yan, M. Samson, B. Jégou, and J. Toppari Bcl-w Forms Complexes with Bax and Bak, and Elevated Ratios of Bax/Bcl-w and Bak/Bcl-w Correspond to Spermatogonial and Spermatocyte Apoptosis in the Testis Mol. Endocrinol., May 1, 2000; 14(5): 682 - 699. [Abstract] [Full Text]

				J.-M. Kim, L. Luo, and B. R. Zirkin Caspase-3 Activation Is Required for Leydig Cell Apoptosis Induced by Ethane Dimethanesulfonate Endocrinology, May 1, 2000; 141(5): 1846 - 1853. [Abstract] [Full Text] [PDF]