HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Benbrahim-Tallaa, L. Articles by Benahmed, M. Search for Related Content PubMed PubMed Citation Articles by Benbrahim-Tallaa, L. Articles by Benahmed, M. Agricola Articles by Benbrahim-Tallaa, L. Articles by Benahmed, M.

Glutathione S-Transferase Alpha Expressed in Porcine Sertoli Cells Is under the Control of Follicle-Stimulating Hormone and Testosterone¹

^a Unité 407, Institut National de la Santé et de la Recherche Médicale (INSERM), Communication Cellulaire en Biologie de la Reproduction, Faculté de Médecine Lyon-Sud, 69921 Oullins Cedex, France ^b Laboratoire de Génétique Cellulaire, Institut National de la Recherche Agronomique (INRA), Chemin de Borde-Rouge, F-31326 Castanet Tolosan, France

Glutathione S-transferases (GSTs) are a family of detoxification isoenzymes present in different tissues including the testis and that conjugate many toxic substrates to glutathione. Among these substrates are carcinogens, mutagens and products of oxidative processes. In the present report we show that GST is expressed in somatic testicular Leydig cells and Sertoli cells. GST expression in Sertoli cells is under the hormonal control of FSH, testosterone, and estradiol. In Leydig cells, immunoreactive GST was present at the neonatal, pubertal, and adult periods. In Sertoli cells, GST was predominant in pubertal and adult testes (but not in neonatal testes), suggesting that its expression is controlled by gonadotropins. The regulatory action and the mechanisms of action of FSH and testosterone on GST mRNA and protein levels were studied by using a model of primary cultures of porcine testicular Sertoli cells. FSH increased GST mRNA levels in a dose-dependent manner (ED₅₀ = 18.5 nm/ml) with a maximal effect observed after 48 h of exposure (a 3-fold increase; P < 0.001). In addition, FSH increased GST protein, which was detected as a doublet of 28 kDa. Treatment with testosterone enhanced GST mRNA levels in a dose-dependent (ED₅₀ = 1.4 ng/ml) and time-dependent manner with a maximal effect delayed at 8 h of exposure (a 2-fold increase; P < 0.001). Similarly, Sertoli cell treatment with testosterone metabolites, dihydrotestosterone (DHT) and estradiol, led to an increase in GST mRNA levels. Because stimulatory effects of FSH and androgens were also observed on GST protein, we therefore had to determine whether the different hormones were affecting GST gene transcriptional activity, or GST mRNA stability, or both. FSH and 8-Br-cAMP (but not testosterone) increased the stability of GST mRNA. The effects of FSH and testosterone on GST protein were additive, confirming that both hormones act through distinct mechanisms on the expression of the enzyme. Taken together, the present observations indicate that Sertoli cell GST is targeted by FSH, testosterone, and its metabolites, and they reinforce the concept that Sertoli cells exert a protective role and are under endocrine control to ward against toxic agents in the context of Sertoli-germ cell interactions during spermatogenesis.

First decision: 29 August 2001.

¹ This work was supported by Institut National de la Santé et de la Recherche Médicale (INSERM), University Claude Bernard Lyon I, and Association pour la Recherche contre le Cancer (contract ARC 9678).

² Correspondence: Mohamed Benahmed, INSERM U407, Faculté de Médecine Lyon-Sud, 165 Chemin du grand revoyet, BP12, F-69621 Oullins Cedex, France. FAX: 33 4 78 86 31 16; benahmed{at}lsgrisn1.univ-lyon1.fr

This article has been cited by other articles:

				L. Benbrahim-Tallaa, B. Siddeek, A. Bozec, V. Tronchon, A. Florin, C. Friry, E. Tabone, C. Mauduit, and M. Benahmed Alterations of Sertoli cell activity in the long-term testicular germ cell death process induced by fetal androgen disruption J. Endocrinol., January 1, 2008; 196(1): 21 - 31. [Abstract] [Full Text] [PDF]

				J. M. Naciff, K. A. Hess, G. J. Overmann, S. M. Torontali, G. J. Carr, J. P. Tiesman, L. M. Foertsch, B. D. Richardson, J. E. Martinez, and G. P. Daston Gene Expression Changes Induced in the Testis by Transplacental Exposure to High and Low Doses of 17{alpha}-Ethynyl Estradiol, Genistein, or Bisphenol A Toxicol. Sci., August 1, 2005; 86(2): 396 - 416. [Abstract] [Full Text] [PDF]

				Q. Zhou, J. E. Shima, R. Nie, P. J. Friel, and M. D. Griswold Androgen-Regulated Transcripts in the Neonatal Mouse Testis as Determined Through Microarray Analysis Biol Reprod, April 1, 2005; 72(4): 1010 - 1019. [Abstract] [Full Text] [PDF]

				X. Gueripel, M. Benahmed, and A. Gougeon Sequential Gonadotropin Treatment of Immature Mice Leads to Amplification of Transforming Growth Factor {beta} Action, Via Upregulation of Receptor-Type 1, Smad 2 and 4, and Downregulation of Smad 6 Biol Reprod, March 1, 2004; 70(3): 640 - 648. [Abstract] [Full Text] [PDF]