Participation of phosphatidyl inositol 3-kinase/protein kinase B and ERK1/2 pathways in interleukin-1β stimulation of lactate production in Sertoli cells

Abstract

Interleukin-1b (IL1b) belongs to a 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 signaling pathways that may participate in IL1b regulation of Sertoli cell function. Sertoli cell cultures from 20-day-old rat were used. Stimulation of the cultures with IL1b showed increments in phosphorylated protein kinase B (PKB), P70S6K, and ERK1/2 levels. A phosphatidyl inositol 3-kinase (PI3K) inhibitor (wortmannin (W)), a mammalian target of rapamycin inhibitor (rapamycin (R)), and a MEK inhibitor (PD98059 (PD)) were utilized to evaluate the participation of PI3K/PKB, P70S6K, and ERK1/2 pathways in the regulation of lactate production by IL1b. PD and W, but not R, decreased IL1b-stimulated lactate production. The participation of these pathways in the regulation of glucose uptake and lactate dehydrogenase (LDH) A mRNA levels by IL1b was also analyzed. It was observed that W decreased IL1b-stimulated glucose uptake, whereas 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 the biochemical steps that are important to regulate lactate production in rat Sertoli cells.

Molecular mechanisms involved in Sertoli cell adaptation to glucose deprivation

“…This conclusion arose from the observations made on the lack of effect of wortmannin, an inhibitor of PI3K, on glucose uptake. The latter results are somehow surprising considering that the PI3K/PKB pathway is widely used to regulate glucose uptake in response to several hormonal stimuli in Sertoli cells (27,35,36). On the other hand, results presented herein are in agreement with the observations made in muscle cells under conditions of hypoxia, where stimulation of glucose uptake independent of PI3K and involving an AMPK-dependent pathway has been observed (12,21,29,38).…”

“…In addition, we have previously demonstrated that in Sertoli cells the PI3K/PKB signaling pathway participates in several responses to hormones, particularly in the regulation of glucose uptake into the cell (27,35,36).…”

The Immunophysiology of Male Reproduction

“…423 Regulation of Sertoli cell function by exogenous IL1 has been found to involve multiple pathway intermediates, including MAPK14, MAPK8 and MAPK3/MAPK1, PIK3/AKT, PTGS2/PGE 2 and NOS2/NO, although the more predictable participation of MYD88 and NFκB still awaits investigation. 417,[424][425][426][427]…”

IL1α and IL4 signalling in human ovarian surface epithelial cells

“…IL1a-induced 3b-HSD2 mRNA levels were also found to be a result of activation of the PI3K signalling pathway. Although the PI3K pathway is not the most common target of IL1R1 transactivation, recent studies in rat Sertoli cells suggest involvement of this pathway in IL1 signalling cascades (Riera et al 2007). In addition, the PI3K pathway appeared to be a component in the effects of IL4 on 3b-HSD1 and 3b-HSD2 mRNA.…”