title: Leukemia inhibitory factor and ciliary neurotropic factor promote the survival of Sertoli cells and gonocytes in coculture system.
abstract: Leukemia inhibitory factor (LIF) and ciliary neurotropic factor (CNTF) were found to be pleiotropic modulators of Sertoli cell and gonocyte development (both isolated from the neonatal rat testis) in a coculture system, whereas IL-6, another member of this cytokine family, had no effect on these cells. LIF and CNTF significantly enhanced the survival of the Sertoli cells in a dose- and time-dependent manner. The effect of LIF on the Sertoli cells was significant at a concentration of 1 ng/ml after 3 or 6 days of culture, whereas CNTF had a significant effect at 10 ng/ml. Neither LIF nor CNTF had an effect on Sertoli cell proliferation. The survival of proliferating gonocytes (isolated from 3-day-old rats testes) was also significantly higher in cultures to which LIF (7.5 ng/ml) or CNTF (10 ng/ml) was added. No effect of these cytokines was found on the mitotic activity of proliferating gonocytes. However, LIF (7.5 ng/ml) stimulated the proliferation of quiescent gonocytes (isolated from day 1 testes) after 3 days of culture. Combinations of LIF (or CNTF) with fibroblast growth factor 2 (10 ng/ml) and steel factor (50 ng/ml) did not further improve the long term culture of the gonocytes. LIf- and CNTF-like proteins of the expected molecular masses (32,000 and 22,000 daltons, respectively, under reducing conditions) were found by Western blotting in testicular extracts of 3-day-old rats. Taken together, these results indicate that LIF or CNTF may play a role at the start of the spermatogenesis. The characterization of receptors for LIF or CNTF on the gonocytes and/or neonatal Sertoli cells will aid in a better understanding of the physiological role of these cytokines in the reproductive system.
authors.affiliation: Department of Veterinary Anatomy and Cell Biology, Veterinary School, Utrecht University, The Netherlands.
authors.forename: M P
authors.initials: MP
authors.lastname: De Miguel
authors.forename: M
authors.initials: M
authors.lastname: De Boer-Brouwer
authors.forename: R
authors.initials: R
authors.lastname: Paniagua
authors.forename: R
authors.initials: R
authors.lastname: van den Hurk
authors.forename: D G
authors.initials: DG
authors.lastname: De Rooij
authors.forename: F M
authors.initials: FM
authors.lastname: Van Dissel-Emiliani
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002455:Cell Division; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D020934:Ciliary Neurotrophic Factor; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006131:Growth Inhibitors / Q000032:analysis / Q000494:pharmacology*; D015850:Interleukin-6; D007700:Kinetics; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000032:analysis / Q000494:pharmacology*; D008297:Male; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012708:Sertoli Cells / Q000502:physiology*; D013094:Spermatozoa / Q000502:physiology*; D019089:Stem Cell Factor / Q000494:pharmacology; D013737:Testis / Q000737:chemistry / Q000166:cytology
chemical_list: D020934:Ciliary Neurotrophic Factor; D006131:Growth Inhibitors; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D009419:Nerve Tissue Proteins; D019089:Stem Cell Factor; D016222:Fibroblast Growth Factor 2