title: Involvement of epidermal growth factor receptors and mitogen-activated protein kinase in progestin-induction of sperm hypermotility in Atlantic croaker through membrane progestin receptor-alpha.
abstract: The intracellular pathways mediating rapid, nongenomic progestin stimulation of sperm motility remain unclear. The role of epidermal growth factor receptors (Egfr and ErbB2) and mitogen-activated protein kinase (Mapk) in membrane progestin receptor-alpha (mPRα)-mediated progestin stimulation of sperm hypermotility was examined in a teleost, Atlantic croaker. Inhibition of upstream regulators of Egfr, intracellular tyrosine kinase (Src) with PP2, and matrix metalloproteinase (MMP) with Ilomastat, abolished progestin-initiated sperm hypermotility by 17,20β,21-trihydroxy-4-pregnen-3-one (20β-S; 20 nM) and a specific mPRα agonist, Org OD 02-0 (20 nM). Pretreatment of croaker sperm with EGFR inhibitors, AG1478 (5 μM) and RG13022 (50 μM), the ErbB2 inhibitor, AG879 (5 nM), or the MEK1/2 inhibitor, U0126 (500 nM) blocked progestin stimulation of sperm motility. Levels of phosphorylated extracellular-related kinase 1 and 2 (P-Erk1/2) were increased after 20β-S treatment. These results demonstrate that progestin-mediated hypermotility via mPRα in croaker sperm involves activation of the Egfr, ErbB2 and Mapk pathways.
authors.affiliation: The University of Texas Marine Science Institute, 750 Channel View Drive, Port Aransas, TX 78373, United States.
authors.forename: Wenxian
authors.initials: W
authors.lastname: Tan
authors.affiliation: The University of Texas Marine Science Institute, 750 Channel View Drive, Port Aransas, TX 78373, United States. Electronic address: peter.thomas@utexas.edu.
authors.forename: Peter
authors.initials: P
authors.lastname: Thomas
mesh_terms: D000818:Animals; D003350:Cortodoxone / Q000031:analogs & derivatives / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism*; D029941:Fish Proteins / Q000378:metabolism; D006877:Hydroxamic Acids; D007211:Indoles / Q000494:pharmacology; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010473:Perciformes / Q000378:metabolism / Q000502:physiology*; D011372:Progestins / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013081:Sperm Motility / Q000187:drug effects*
chemical_list: D003350:Cortodoxone; D066246:ErbB Receptors; D029941:Fish Proteins; D006877:Hydroxamic Acids; D007211:Indoles; D020928:Mitogen-Activated Protein Kinases; D011372:Progestins; D011743:Pyrimidines; D018719:Erb-b2 Receptor Tyrosine Kinases; C412373:AG 1879; C051954:17,20,21-trihydroxy-4-pregnen-3-one; C119203:ilomastat
keywords: Atlantic croaker; EGFR; Epidermal growth factor receptor; ErbB2; Membrane progestin receptor alpha; Progestin; Sperm motility