Differential expression of androgen and estrogen receptors in PCB (Aroclor 1254)-exposed rat ventral prostate: Impact of alpha-tocopherol K. Selvakumar, L. Sheerin Banu, G. Krishnamoorthy, P. Venkataraman, P. Elumalai, J. Arunakaran n Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai-600 113, India article info Article history: Received 2 May 2009 Accepted 22 October 2009 Keywords: Polychlorinated biphenyls (Aroclor 1254) a-Tocopherol Androgen receptor Estrogen receptor-a and b Ventral prostate abstract Polychlorinated biphenyls (PCBs) are environmental toxicants, which affect male fertility by altering the androgen and estrogen levels. PCB-induced toxic manifestations are associated with the production of reactive oxygen species. Vitamin E (a-tocopherol) is a major lipophilic chain breaking antioxidant, which protects polyunsaturated fatty acids in tissues against peroxidation, a property that could be beneficial in the male reproductive biology. The purpose of this study was to determine the impact of a-tocopherol on PCB (Aroclor 1254)-induced changes in androgen receptor (AR) and estrogen receptors (ERs) expression in Wistar rat ventral prostate. Rats were divided into 3 groups of 6 animals each. Group I rats were administered corn oil (vehicle) intraperitoneally (i.p.); Group II rats were treated with 2 mg kg À1 day À1 of PCB (i.p.); Group III rats were treated with 2 mg kg À1 day À1 of PCB (i.p.) along with simultaneous oral supplementation of 50 mg kg À1 day À1 of a-tocopherol. Serum testosterone and estradiol titers were assayed. Prostatic acid phosphatase activity (PAcP), citric acid concentration, generation of hydrogen peroxide (H 2 O 2 ) and lipid peroxides (LPO) were estimated. mRNA and protein expression of AR, ER-a and ER-b in ventral prostate were quantified. Serum testosterone, estradiol, PAcP, citric acid levels, AR and ER-a expressions were significantly decreased while H 2 O 2 generation, LPO, ER-b were increased in PCB-exposed animals. Simultaneous supplementation of a-tocopherol in PCB-exposed rats resulted in significant restoration of all the parameters to the control. The results suggest that a-tocopherol has definite protective effect against PCB-induced toxicity in ventral prostatic dysfunction. & 2009 Elsevier GmbH. All rights reserved. Introduction Polychlorinated biphenyls (PCBs), a variety of environmentally persistent contaminants, are able to bioaccumulate in the aquatic food chain and pose a threat to the health and reproductive success of people and wildlife that depend on locally caught fish as a source of dietary protein. Exposure to polychlorinated biphenyls and 1,1-bis (4-chlorophenyl)-2,2-dichloroethylene (DDE) has been linked to higher rates of cancer, reproductive problems, and endocrine disorders. PCB-exposure induced a decline in sperm production, chromatin DNA damage and decreased motility (Rozati et al., 2000; Risbridger et al., 2007). PCBs decreased the levels of serum luteinizing hormone, follicle stimulating hormone, thyroid hormone, testosterone and estra- diol levels in adult male rats (Murugesan et al., 2005a, b). PCB- induced toxic manifestations are associated with the production of reactive oxygen species. Excessive oxygen free radical genera- tion induced lipid peroxidation, oxidative stress and excessive damage of cellular macromolecules such as proteins, lipids and nucleic acids have been shown to be major contributors to the toxicity of contaminants (Schildermann et al., 2000; Tharappel et al., 2002). PCBs inhibit testosterone biosynthesis by inhibiting steroidogenic enzyme activities and antioxidant enzymes level in cultured rat Leydig cells (Murugesan et al., 2008). PCBs induced oxidative stress and interrupted the ventral prostatic utility through the disruption of hypothalamo–hypophyseal testicular axis (Sridhar et al., 2004; Venkataraman et al., 2004a). The prostate is an essential male accessory sex gland that provides about 20% of the total volume of seminal plasma. Any changes in the secretions from the prostate will certainly be reflected in reproductive disorders. Prostatic acid phosphatase and citric acid are the functional markers of the prostate gland (Costello and Franklin, 2000). Citrate and acid phosphatase synthesis in the prostate are directly synchronized by androgen and estrogen. These hormones result in optimal functions of the prostate, which are required to regulate the synthesis of spermatozoa. Vitamin E is the generic descriptor for two families of compounds namely the tocopherols and tocotrienols, which are fat soluble vitamins with antioxidant properties (McLaughlin and Weihrauch, 1979). a-Tocopherol exerts its effect by scavenging the free radicals directly and thereby stabilizing membranes containing Contents lists available at ScienceDirect journal homepage: www.elsevier.de/etp Experimental and Toxicologic Pathology 0940-2993/$ - see front matter & 2009 Elsevier GmbH. All rights reserved. doi:10.1016/j.etp.2009.10.003 n Corresponding author. Tel.: + 91 44 24547043; fax: + 91 44 24540709. E-mail address: j_arunakaran@hotmail.com (J. Arunakaran). Experimental and Toxicologic Pathology 63 (2011) 105–112