Molecular Mechanisms Involved in Sertoli Cell

26 27 Sertoli cells provide the physical support and the necessary environment to germ 28 cell development. Among the products secreted by Sertoli cells, lactate —the preferred 29 energy substrate for spermatocytes and spermatids— is present. Considering the essential 30 role of lactate on germ cell metabolism, it is supposed that Sertoli cells must ensure its 31 production even in adverse conditions as those that would result from a decrease in glucose 32 levels in the extracellular milieu. The aim of the present study was to investigate: a) a 33 possible effect of glucose deprivation on glucose uptake and on the expression of glucose 34 transporters in rat Sertoli cells and b) the participation of different signal transduction 35 pathways in the above-mentioned regulation. Results obtained show that decreasing 36 glucose levels in Sertoli cell culture medium provokes: i) an increase in glucose uptake 37 accompanied by only a slight decrease in lactate production, ii) an increase in GLUT1 and 38 a decrease in GLUT3 expression and iii) an activation of AMPK-, PI3K/PKBand 39 p38MAPK-dependent pathways. Additionally, by using specific inhibitors of these 40 pathways, a possible participation of AMPKand p38MAPK-dependent pathways in the 41 regulation of glucose uptake and GLUT1 expression is shown. These results suggest that 42 Sertoli cells adapt to conditions of glucose deprivation in order to ensure an adequate 43 lactate concentration in the microenvironment where germ cell development occurs. 44 45 46 47