caa a22 4500 445853808 CHVBK 20180317145422.0 cr unu---uuuuu 170323e20110801xx s 000 0 eng 10.1007/s00204-010-0618-5 doi (NATIONALLICENCE)springer-10.1007/s00204-010-0618-5 Role of phospholipase D in regulation of testicular Leydig cell hyperplasia in Sprague-Dawley rats treated with di(2-ethylhexyl) phthalate [Elektronische Daten] [Young Lee, Mee Ahn, Hyung Kim, Seung Kwack, Kul Park, Sik Yoon, Dosik Min] 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 (500mg/kg/day) was administered orally to prepubertal rats for 1, 7, 14, 21 or 28days. After 7days 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 7days 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. Springer-Verlag, 2010 DEHP nationallicence Phospholipase D nationallicence Leydig cells nationallicence Hyperplasia nationallicence Steroidogenesis nationallicence Lee Young Laboratory of Molecular Toxicology, College of Pharmacy, Pusan National University, San 30, Jangjeon-dong, Geumjeung-gu, 609-735, Busan, South Korea aut Ahn Mee Laboratory of Molecular Toxicology, College of Pharmacy, Pusan National University, San 30, Jangjeon-dong, Geumjeung-gu, 609-735, Busan, South Korea aut Kim Hyung Laboratory of Molecular Toxicology, College of Pharmacy, Pusan National University, San 30, Jangjeon-dong, Geumjeung-gu, 609-735, Busan, South Korea aut Kwack Seung National Institute of Food and Drug Safety Evaluation, Korea Food and Drug Administration, 5 Nokbun-dong, Eunpyung-ku, 122-704, Seoul, South Korea aut Park Kul National Institute of Food and Drug Safety Evaluation, Korea Food and Drug Administration, 5 Nokbun-dong, Eunpyung-ku, 122-704, Seoul, South Korea aut Yoon Sik Department of Anatomy, School of Medicine, Pusan National University, Mulgeum-Eup, Beomeo-Ri, 626-870, Yangsan, South Korea aut Min Dosik Department of Molecular Biology, College of Natural Science, Pusan National University, San 30, Jangjeon-dong, Geumjeung-gu, 609-735, Busan, South Korea aut Archives of Toxicology Springer-Verlag 85/8(2011-08-01), 975-985 0340-5761 85:8<975 2011 85 204 https://doi.org/10.1007/s00204-010-0618-5 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00204-010-0618-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Lee Young Laboratory of Molecular Toxicology, College of Pharmacy, Pusan National University, San 30, Jangjeon-dong, Geumjeung-gu, 609-735, Busan, South Korea aut NATIONALLICENCE 700 1- Ahn Mee Laboratory of Molecular Toxicology, College of Pharmacy, Pusan National University, San 30, Jangjeon-dong, Geumjeung-gu, 609-735, Busan, South Korea aut NATIONALLICENCE 700 1- Kim Hyung Laboratory of Molecular Toxicology, College of Pharmacy, Pusan National University, San 30, Jangjeon-dong, Geumjeung-gu, 609-735, Busan, South Korea aut NATIONALLICENCE 700 1- Kwack Seung National Institute of Food and Drug Safety Evaluation, Korea Food and Drug Administration, 5 Nokbun-dong, Eunpyung-ku, 122-704, Seoul, South Korea aut NATIONALLICENCE 700 1- Park Kul National Institute of Food and Drug Safety Evaluation, Korea Food and Drug Administration, 5 Nokbun-dong, Eunpyung-ku, 122-704, Seoul, South Korea aut NATIONALLICENCE 700 1- Yoon Sik Department of Anatomy, School of Medicine, Pusan National University, Mulgeum-Eup, Beomeo-Ri, 626-870, Yangsan, South Korea aut NATIONALLICENCE 700 1- Min Dosik Department of Molecular Biology, College of Natural Science, Pusan National University, San 30, Jangjeon-dong, Geumjeung-gu, 609-735, Busan, South Korea aut NATIONALLICENCE 773 0- Archives of Toxicology Springer-Verlag 85/8(2011-08-01), 975-985 0340-5761 85:8<975 2011 85 204 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer