cortodoxone and ilomastat

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.

Topics: Animals; Cortodoxone; ErbB Receptors; Fish Proteins; Hydroxamic Acids; Indoles; Male; Mitogen-Activated Protein Kinases; Perciformes; Progestins; Pyrimidines; Receptor, ErbB-2; Signal Transduction; Sperm Motility