title: G protein-coupled estrogen receptor-protein kinase A-ERK-CREB signaling pathway is involved in the regulation of mouse gubernaculum testis cells by diethylstilbestrol.
abstract: The etiology of testicular dysgenesis syndrome is multifactorial and involves environmental factors, such as environmental estrogens. Several studies have shown that hormonal effects on the gubernaculum may affect testicular descent. Diethylstilbestrol (DES) is a nonsteroidal synthetic estrogen that disrupts the morphology and proliferation of gubernacular cells, but the underlying mechanisms remain elusive. In this study, we aimed to determine whether DES may regulate the function of gubernaculum testis cells by way of nongenomic effects mediated by G protein-coupled estrogen receptor (GPER). We used cultured mouse gubernacular testis cells to demonstrate that GPER is expressed in gubernaculum testis cells. Erk1/2 inhibitor PD98059, PKA inhibitor H89, and Src inhibitor PP2 relieved DES-induced inhibition of gubernaculum testis cell proliferation, but ER inhibitor ICI 182780 had no effects on DES-induced inhibition of gubernaculum testis cell proliferation. In addition, we found that DES induced the activation of CREB downstream of PKA, Src, and ERK1/2 in these cells. These data suggest that the effects of DES on mouse gubernaculum testis cells are mediated at least partially by GPER-protein kinase A-ERK-CREB signaling pathway.
authors.affiliation: Department of Pediatric Surgery, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Jian-hong
authors.initials: JH
authors.lastname: Li
authors.forename: Shou-xing
authors.initials: SX
authors.lastname: Duan
authors.forename: Qing-Jun
authors.initials: QJ
authors.lastname: Lin
authors.forename: Song
authors.initials: S
authors.lastname: Ke
authors.forename: Lian
authors.initials: L
authors.lastname: Ma
authors.forename: Tian-hua
authors.initials: TH
authors.lastname: Huang
authors.forename: Xue-wu
authors.initials: XW
authors.lastname: Jiang
mesh_terms: D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004054:Diethylstilbestrol / Q000633:toxicity*; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D051379:Mice; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013737:Testis / Q000187:drug effects* / Q000378:metabolism
chemical_list: D004968:Estrogens, Non-Steroidal; D043562:Receptors, G-Protein-Coupled; D004054:Diethylstilbestrol; D017868:Cyclic AMP-Dependent Protein Kinases