title: Recombinant long-glucocorticoid-induced leucine zipper (L-GILZ) protein restores the control of proliferation in gilz KO spermatogonia.
abstract: No genes are yet directly implicated in etiology of male infertility. Identification of genes critical at various stages of spermatogenesis is pivotal for the timely diagnostic and treatment of infertility. We previously found that L-GILZ deficiency in a mouse KO model leads to hyperactivation of Ras signaling and increased proliferation in spermatogonia, resulting in male sterility. The possibility to establish culture cell system that maintains spermatogonial cells in vitro allowed us to delivery a recombinant protein TAT-L-GILZ able to restore normal proliferation rate in gilz KO spermatogonia. We also found that N-terminal part of L-GILZ protein is responsible for Ras/L-GILZ protein-to-protein interaction, important for the control of proliferation rate of spermatogonia. Therefore, treatments increasing L-GILZ expression, such as delivering small molecules or peptides that mimic L-GILZ functions, are approaches with great potential of applicability for new therapeutic strategies based on gene/protein delivery to the affected testes.
authors.affiliation: Department of Medicine, Section of Pharmacology, University of Perugia, Piazza Gambuli, 1, S. Andrea delle Fratte, 06132 Perugia, Italy; Department of Biomedical Sciences, University of Sassari, Via Muroni 23, Sassari, Italy; Laboratory of Gender Medicine, National Institute of Biostructures and Biosystems and Department of Neurological Sciences, University of Sassari, Via Muroni, 23, 07100, Sassari, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Venanzi
authors.affiliation: Department of Medicine, Section of Pharmacology, University of Perugia, Piazza Gambuli, 1, S. Andrea delle Fratte, 06132 Perugia, Italy.
authors.forename: Moises
authors.initials: M
authors.lastname: Di Sante
authors.affiliation: Department of Medicine, Section of Pharmacology, University of Perugia, Piazza Gambuli, 1, S. Andrea delle Fratte, 06132 Perugia, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Bruscoli
authors.affiliation: Department of Medicine, Section of Pharmacology, University of Perugia, Piazza Gambuli, 1, S. Andrea delle Fratte, 06132 Perugia, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Biagioli
authors.affiliation: Department of Medicine, Section of Pharmacology, University of Perugia, Piazza Gambuli, 1, S. Andrea delle Fratte, 06132 Perugia, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Sorcini
authors.affiliation: Department of Medicine, Section of Pharmacology, University of Perugia, Piazza Gambuli, 1, S. Andrea delle Fratte, 06132 Perugia, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Cimino
authors.affiliation: Department of Medicine, Section of Pharmacology, University of Perugia, Piazza Gambuli, 1, S. Andrea delle Fratte, 06132 Perugia, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Frammartino
authors.affiliation: Department of Medicine, Section of Pharmacology, University of Perugia, Piazza Gambuli, 1, S. Andrea delle Fratte, 06132 Perugia, Italy.
authors.forename: Oxana
authors.initials: O
authors.lastname: Bereshchenko
authors.affiliation: Department of Biomedical Sciences, University of Sassari, Via Muroni 23, Sassari, Italy; Laboratory of Gender Medicine, National Institute of Biostructures and Biosystems and Department of Neurological Sciences, University of Sassari, Via Muroni, 23, 07100, Sassari, Italy.
authors.forename: Flavia
authors.initials: F
authors.lastname: Franconi
authors.affiliation: Department of Medicine, Section of Pharmacology, University of Perugia, Piazza Gambuli, 1, S. Andrea delle Fratte, 06132 Perugia, Italy. Electronic address: carlo.riccardi@unipg.it.
authors.forename: Carlo
authors.initials: C
authors.lastname: Riccardi
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D005938:Glucocorticoids / Q000378:metabolism / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D011994:Recombinant Proteins / Q000378:metabolism; D013093:Spermatogonia / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000172:deficiency* / Q000378:metabolism*
chemical_list: D005938:Glucocorticoids; D011994:Recombinant Proteins; C404226:TSC22D3 protein, human; D014157:Transcription Factors
keywords: Bromodeoxyuridine (PubChem CID: 6035); Cell proliferation; Glucocorticoid-induced leucine zipper; Ras signaling; Spermatogenesis; TAT peptide: (PubChem CID: 16197759)