Participation of phosphatidyl inositol-3 kinase/protein kinase B (PI3K/PKB) and extracellular signal regulated kinase 1 and 2 (ERK1/2) pathways in interleukin1ƒÒ stimulation of lactate production in Sertoli cells

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

REPRODUCTION

Published for the Society for Reproduction and Fertility by BioScientifica

Año: 2006

1470-1626

IL1b belongs to the set of intratesticular regulators that provide the fine-tuning of cellular processes implicated in the maintenance of spermatogenesis. The aim of the present study was to analyze the signalling pathways that may participate in IL1b regulation of Sertoli cell function. Twenty-day-old rat Sertoli cell cultures were used. Stimulation of the cultures with IL1b showed increments in phosphorylated PKB, P70S6K and ERK1/2 levels. A PI3K inhibitor ¾wortmannin (W)¾ , a mTOR inhibitor ¾rapamycin (R)¾  and a MEK inhibitor ¾ PD98059 (PD)¾ were utilized to evaluate the participation of PI3K/PKB, P70S6K and ERK1/2 pathways in the regulation by IL1b of lactate production. PD and W, but not R, decreased IL1b-stimulated lactate production. The participation of these pathways in the regulation by IL1b of glucose uptake and LDH A mRNA levels was also analysed. It was observed that W decreased IL1b-stimulated glucose uptake and that PD and R did not modify it. On the other hand, PD decreased the stimulation of LDH A mRNA levels by IL1b whereas W and R did not modify it. In summary, results presented herein demonstrate that IL1b stimulates PI3K/PKB-, P70S6K- and ERK1/2-dependent pathways in rat Sertoli cells. Moreover, these results show that while IL1b utilizes the PI3K/PKB pathway to regulate glucose transport, it utilizes the ERK1/2 pathway to regulate LDH A mRNA levels. This study reveals that IL1b utilizes different signal transduction pathways to modify biochemical steps that are important to regulate lactate production in rat Sertoli cells.