title: Nociceptin and meiosis during spermatogenesis in postnatal testes.
abstract: Phosphorylated Rec8, a key component of cohesin, mediates the association and disassociation, "dynamics," of chromosomes occurring in synaptonemal complex formation, crossover recombination, and sister chromatid cohesion during meiosis in germ cells. Yet, the extrinsic factors triggering meiotic chromosome dynamics remained unclear. In postnatal testes, follicle-stimulating hormone (FSH) acts directly on somatic Sertoli cells to activate gene expression via an intracellular signaling pathway composed of cAMP, cAMP-dependent protein kinase (PKA), and cAMP-response element-binding protein (CREB), and promotes germ cell development and spermatogenesis indirectly. Yet, the paracrine factors mediating the FSH effects to germ cells remained elusive. We have shown that nociceptin, known as a neuropeptide, is upregulated by FSH signaling through cAMP/PKA/CREB pathway in Sertoli cells of postnatal murine testes. Chromatin immunoprecipitation from Sertoli cells demonstrated that CREB phosphorylated at Ser133 associates with prepronociceptin gene encoding nociceptin. Analyses with Sertoli cells and testes revealed that both prepronociceptin mRNA and the nociceptin peptide are induced after FSH signaling is activated. In addition, the nociceptin peptide is induced in testes after 9 days post partum following FSH surge. Thus, our findings may identify nociceptin as a novel paracrine mediator of the FSH effects in the regulation of spermatogenesis; however, very little has known about the functional role of nociceptin in spermatogenesis. We have shown that nociceptin induces Rec8 phosphorylation, triggering chromosome dynamics, during meiosis in spermatocytes of postnatal murine testes. The nociceptin receptor Oprl-1 is exclusively expressed in the plasma membrane of testicular germ cells, mostly spermatocytes. Treatment of testes with nociceptin resulted in a rapid phosphorylation of Rec8. Injection of nociceptin into mice stimulated Rec8 phosphorylation and meiotic chromosome dynamics in testes, whereas injection of nocistatin, a specific inhibitor for nociceptin, abolished them. Therefore, our findings suggest that nociceptin is a novel extrinsic factor that plays a crucial role in the progress of meiosis during spermatogenesis.
authors: Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, Kumamoto City, Kumamoto, Japan. Electronic address: etoko@gpo.kumamoto-u.ac.jp.
authors: Ko
authors: K
authors: Eto
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D006801:Humans; D008297:Male; D008540:Meiosis; D018847:Opioid Peptides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D012708:Sertoli Cells / Q000166:cytology / Q000378:metabolism; D013091:Spermatogenesis; D013737:Testis / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D000097629:Nociceptin
chemical_list: D018797:Cell Cycle Proteins; D018847:Opioid Peptides; D000097629:Nociceptin; C507675:REC8 protein, human; C111148:nocistatin
keywords: Chromosome dynamics; Cohesin; FSH signaling; Meiosis; Nociceptin signaling; Postnatal testes; Rec8 phosphorylation; Sertoli cells; Spermatocytes; Spermatogenesis