Different signaling pathways elicited by bFGF and IL1b regulate CREB phosphorylation in Sertoli cells

GALARDO MN; RIERA MF; REGUEIRA M; PELLIZZARI EH; CIGORRAGA SB; MERONI SB

JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION

EDITRICE KURTIS S R L

Año: 2013 vol. 36 p. 331 - 338

0391-4097

BACKGROUND AND AIM: bFGF and IL1b 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 IL1b 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 IL1b 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 IL1b 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 IL1b to stimulate Ldh A expression and LDH activity. Concerning transferrin, PD98059 and U0126 were able to inhibit the ability of bFGF to stimulate its secretion. On the contrary, SB203580 was unable to block IL1b 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 IL1b through p42/p44-MAPK and p38-MAPK pathways and that this transcription factor may be partially responsible for the regulation of Sertoli cell function.