G Protein-Coupled Estrogen Receptor–Protein Kinase A–ERK–CREB Signaling Pathway is Involved in the Regulation of Mouse Gubernaculum Testis Cells by Diethylstilbestrol

• Published in: Archives of environmental contamination and toxicology 2014-07, Vol.67 (1), p.97-103
• Main Authors: Zhang, Xuan, Li, Jian-hong, Duan, Shou-xing, Lin, Qing-Jun, Ke, Song, Ma, Lian, Huang, Tian-hua, Jiang, Xue-wu
• Format: Article
• Language: English
• Subjects: Animals; Binding sites; Biological and medical sciences; cAMP-dependent protein kinase; Cell growth; cell proliferation; Cells; Chemical and industrial products toxicology. Toxic occupational diseases; Contamination; Cyclic AMP-Dependent Protein Kinases - metabolism; Cytoplasm; diethylstilbestrol; Diethylstilbestrol - toxicity; Earth and Environmental Science; Ecotoxicology; Environment; Environmental Chemistry; Environmental factors; Environmental Health; Estrogens; Estrogens, Non-Steroidal - toxicity; Hormonal effects; Kinases; Localization; Male; MAP Kinase Signaling System - physiology; Medical sciences; Membranes; Mice; Monitoring/Environmental Analysis; Morphology; Pediatrics; Pollution; Polyclonal antibodies; Proteins; Receptors, G-Protein-Coupled - metabolism; Reproductive system; Rodents; signal transduction; Signal Transduction - drug effects; Soil Science & Conservation; Studies; Testes; Testis - drug effects; Testis - metabolism; Toxicology; Various organic compounds
• ISSN: 0090-4341; 1432-0703
• DOI: 10.1007/s00244-013-9976-3

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.