title: Alteration of testicular steroidogenesis and histopathology of reproductive system in male rats treated with triclosan.
abstract: Triclosan (TCS), a chlorophenol, is widely used as a preservative in different types of commercial preparations. The reports on TCS-mediated endocrine disruption are controversial and the present study aimed to elucidate the probable mode of action of TCS as an antiandrogenic compound using a robust study design. Male albino rats, Rattus norvegicus, were treated with three doses of triclosan for a period of 60 days followed by the analysis of various biochemical parameters. RT-PCR analysis demonstrated a significant decrease in mRNA levels for testicular steroidogenic acute regulatory (StAR) protein, cytochrome P450(SCC), cytochrome P450(C17), 3beta-hydroxysteroid dehydrogenase (3beta-HSD), 17beta-hydroxysteroid dehydrogenase (17beta-HSD) and androgen receptor (AR) in TCS treated rats (p<0.05). TCS also induced a perturbed translation of testicular StAR, and AR proteins as shown by Western blot analysis in treated groups of rats. A reduced level of StAR was further indicated by immunohistochemistry in testicular Leydig cells. Further, there was a significant decrease (p<0.05) in the level of serum lutenizing hormone (LH), follicle stimulating hormone (FSH), cholesterol, pregnenolone, and testosterone. In vitro assays demonstrated more than 30% decrease in testicular 3beta-HSD and 17beta-HSD enzyme activities in treated group of animals. Extensive histopathological malformations were observed in the testis and sex accessory tissues of the treated rats. Overall this study showed that TCS decreased the synthesis of androgens followed by reduced sperm production in treated male rats which could be mediated by a decreased synthesis of LH and FSH thus involving hypothalamo-pituitary-gonadal axis.
authors.affiliation: Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India.
authors.forename: Vikas
authors.initials: V
authors.lastname: Kumar
authors.forename: Ajanta
authors.initials: A
authors.lastname: Chakraborty
authors.forename: Mool Raj
authors.initials: MR
authors.lastname: Kural
authors.forename: Partha
authors.initials: P
authors.lastname: Roy
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000726:Androgen Antagonists / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000633:toxicity*; D005640:Follicle Stimulating Hormone / Q000097:blood; D005786:Gene Expression Regulation / Q000187:drug effects; D012739:Gonadal Steroid Hormones / Q000097:blood*; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010750:Phosphoproteins / Q000378:metabolism; D011284:Pregnenolone / Q000097:blood; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011944:Receptors, Androgen / Q000378:metabolism; D013091:Spermatogenesis / Q000187:drug effects*; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism; D013737:Testis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013739:Testosterone / Q000097:blood; D014260:Triclosan / Q000633:toxicity*; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D000726:Androgen Antagonists; D052244:Endocrine Disruptors; D012739:Gonadal Steroid Hormones; D010750:Phosphoproteins; D012333:RNA, Messenger; D011944:Receptors, Androgen; D000098682:Steroidogenic Acute Regulatory Protein; D013739:Testosterone; D014260:Triclosan; D011284:Pregnenolone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D002784:Cholesterol; D015067:17-Hydroxysteroid Dehydrogenases; D015096:3-Hydroxysteroid Dehydrogenases; D013254:Steroid 17-alpha-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme