title: Different signal transduction pathways elicited by basic fibroblast growth factor and interleukin 1β regulate CREB phosphorylation in Sertoli cells.
abstract: OBJECTIVE
  Basic fibroblast growth factor (bFGF) and interleukin 1β (IL1β) belong to the set of intratesticular regulators that provide for the fine-tuning of processes implicated in the maintenance of spermatogenesis. The aim of this study was to investigate if bFGF and IL1β activate CREB, what signaling pathways may be participating and the possible relationship between CREB activation and the regulation of Sertoli cell function.
  
  
  METHODS
  Twenty-day-old rat Sertoli cell cultures were used.
  
  
  RESULTS
  Cultures stimulated with bFGF and IL1β produced a time-dependent increment in phosphorylated CREB levels that reached maximal values in 5- and 15-minute incubations respectively. MEK inhibitors--PD98059 and U0126--blocked the effect of bFGF on phosphorylated CREB while a p38-MAPK inhibitor--SB203580--blocked the effect of IL1β on phosphorylated CREB. A possible correlation between CREB regulation and two Sertoli cell-differentiated functions, Ldh A and transferrin expression, was explored. PD98059 blocked the ability of bFGF to stimulate Ldh A expression and SB203580 blocked the ability of IL1β to stimulate Ldh A expression and LDH activity. Concerning transferrin, PD98059 and U0126 were able to inhibit the ability of bFGF to stimulate its secre tion. On the contrary, SB203580 was unable to block IL1β induced increase in transferrin secretion suggesting that the p38-MAPK pathway does not participate in the mechanism of action of the cytokine to regulate transferrin.
  
  
  CONCLUSIONS
  The results presented herein suggest that CREB is stimulated in response to bFGF and IL1β through p42/p44-MAPK and p38-MAPK pathways and that this transcription factor may be partially responsible for the regulation of Sertoli cell function.
authors.affiliation: Centro de Investigaciones Endocrinológicas, CEDIE-CONICET, Hospital de Niños Ricardo Gutiérrez, Gallo 1330, C1425EDF Buenos Aires, Argentina.
authors.forename: M N
authors.initials: MN
authors.lastname: Galardo
authors.forename: M F
authors.initials: MF
authors.lastname: Riera
authors.forename: M
authors.initials: M
authors.lastname: Regueira
authors.forename: E H
authors.initials: EH
authors.lastname: Pellizzari
authors.forename: S B
authors.initials: SB
authors.lastname: Cigorraga
authors.forename: S B
authors.initials: SB
authors.lastname: Meroni
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism*; D007700:Kinetics; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000378:metabolism; D012708:Sertoli Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: C508137:Creb1 protein, rat; D017362:Cyclic AMP Response Element-Binding Protein; D053583:Interleukin-1beta; D047428:Protein Kinase Inhibitors; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D048051:p38 Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases