title: Di-(2-ethylhexyl) phthalate inhibits testosterone level through disturbed hypothalamic-pituitary-testis axis and ERK-mediated 5α-Reductase 2.
abstract: Di-(2-ethylhexyl) phthalate (DEHP) has reproductive toxicity and can affect male reproductive development. In order to clarify adverse effects of DEHP on testicular physiology and testosterone production, Sprague-Dawley (SD) rats were dosed daily with DEHP by gavage for 30days; TM3 cells (mouse Leydig cell line) were treated with DEHP for 24h after pretreatment with vitamin C or U0126. Results indicated that the hypothalamic-pituitary-testis (HPT) axis was disturbed and serum testosterone, LH and FSH levels were decreased following DEHP exposure. Histomorphological changes of rat testes were also observed, such as deformed seminiferous tubules, aggregated chromatin, multiple vacuoles, swollen mitochondria, apoptotic germ cells and Sertoli cells, as well as increased Leydig cell numbers. Moreover, DEHP caused oxidative stress in vivo and in vitro and then induced the ERK pathway, which was required to mediate 5α-Reductase 2 and scavenger receptor class B-1 (SRB1) levels. However, levels of steroidogenic acute regulatory protein (StAR), 3β-hydroxysteroid dehydrogenase (3β-HSD), 17β-hydroxysteroid dehydrogenase (17β-HSD), P450 17α-hydroxylase/17.20 lyase (P450c17), and P450 side-chain cleavage enzyme (P450scc) were not significantly altered after DEHP exposure. Taken together, DEHP-disturbed HPT axis and induced 5α-Reductase 2 contribute to the reduction of serum testosterone level. The activated ERK pathway is required to modulate expressions of 5α-Reductase 2 and SRB1.
authors.affiliation: School of Nursing, Chongqing Medical and Pharmaceutical College, Chongqing 400020, PR China.
authors.forename: Mei
authors.initials: M
authors.lastname: Ha
authors.affiliation: Key Lab of Birth Defects and Reproductive Health of National Health and Family Planning Commission, Chongqing Population and Family Planning Science and Technology Research Institute, Chongqing 400020, PR China.
authors.forename: Xie
authors.initials: X
authors.lastname: Guan
authors.affiliation: Key Lab of Birth Defects and Reproductive Health of National Health and Family Planning Commission, Chongqing Population and Family Planning Science and Technology Research Institute, Chongqing 400020, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Wei
authors.affiliation: Chongqing General Hospital, Chongqing 400020, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: Key Lab of Birth Defects and Reproductive Health of National Health and Family Planning Commission, Chongqing Population and Family Planning Science and Technology Research Institute, Chongqing 400020, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.affiliation: Key Lab of Birth Defects and Reproductive Health of National Health and Family Planning Commission, Chongqing Population and Family Planning Science and Technology Research Institute, Chongqing 400020, PR China. Electronic address: cj_514@163.com.
authors.forename: Changjiang
authors.initials: C
authors.lastname: Liu
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D004785:Environmental Pollutants / Q000633:toxicity*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051122:Scavenger Receptors, Class B / Q000235:genetics* / Q000378:metabolism; D013737:Testis / Q000187:drug effects; D013739:Testosterone / Q000097:blood*
chemical_list: D004785:Environmental Pollutants; D008565:Membrane Proteins; C495125:Scarb1 protein, rat; D051122:Scavenger Receptors, Class B; D013739:Testosterone; D004051:Diethylhexyl Phthalate; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C548474:Srd5a2 protein, rat
keywords: 5α-Reductase 2; DEHP; ERK; Hypothalamic–pituitary–testis axis; Testosterone