title: Role of phospholipase D in regulation of testicular Leydig cell hyperplasia in Sprague-Dawley rats treated with di(2-ethylhexyl) phthalate.
abstract: This study was conducted to determine the functional role of phospholipase D (PLD) involved in testicular Leydig cell damage caused by di (2-ethylhexyl) phthalate (DEHP) in Sprague-Dawley rats. DEHP (500 mg/kg/day) was administered orally to prepubertal rats for 1, 7, 14, 21 or 28 days. After 7 days of exposure, DEHP produced morphological changes in the testis, including alterations in seminiferous tubule diameters and loss of spermatogenic cells. Immunohistochemistry (IHC) analyses revealed that DEHP increased Leydig cell number in the testes as well as significantly increased the expression of PLD1/2 in Leydig cells after 7 days of exposure. Furthermore, the protein levels of phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2) increased in a similar manner to the PLD1/2 expression patterns. DEHP significantly reduced the expression of sperm-associated antigen 4 (Spag4) and lactate dehydrogenase A (LDHA) mRNA. In contrast, there was a significant increase in the expression of steroidogenic acute regulatory (StAR) mRNA against DEHP in a time-dependent manner, but serum testosterone concentration was decreased. These findings demonstrate that DEHP induces PLD expression in the testicular Leydig cells; this plays a key role in hyperplasia of Leydig cells and steroidogenic pathway via pERK1/2 activation.
authors.affiliation: Laboratory of Molecular Toxicology, College of Pharmacy, Pusan National University, San 30, Jangjeon-dong, Geumjeung-gu, Busan 609-735, South Korea.
authors.forename: Young Jun
authors.initials: YJ
authors.lastname: Lee
authors.forename: Mee Young
authors.initials: MY
authors.lastname: Ahn
authors.forename: Hyung Sik
authors.initials: HS
authors.lastname: Kim
authors.forename: Seung Jun
authors.initials: SJ
authors.lastname: Kwack
authors.forename: Kul Lea
authors.initials: KL
authors.lastname: Park
authors.forename: Sik
authors.initials: S
authors.lastname: Yoon
authors.forename: Dosik
authors.initials: D
authors.lastname: Min
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004051:Diethylhexyl Phthalate / Q000008:administration & dosage / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects; D006965:Hyperplasia; D007985:Leydig Cells / Q000187:drug effects* / Q000473:pathology; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010739:Phospholipase D / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010968:Plasticizers / Q000008:administration & dosage / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013737:Testis / Q000187:drug effects* / Q000473:pathology; D013997:Time Factors
chemical_list: D010968:Plasticizers; D004051:Diethylhexyl Phthalate; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D010739:Phospholipase D