Interleukin 1 alpha stimulates lactate dehydrogenase a expression and lactate production in cultured porcine Sertoli cells

By using cultured porcine Sertoli cells as a model, the action of interleuk in 1 alpha (IL-1 alpha) on lactate production and the site of this action w ere studied. IL-1 alpha stimulated Sertoli cell lactate production in a tim e- and dose-dependent manner (with a half-maximal effect [ED50] of 6 pM). T wo major sites involved in IL-1 alpha action were identified. First, IL-1 a lpha was shown to increase the uptake of glucose substrate in a time- and d ose-dependent manner. The maximal effect, with an ED50 of 10 pM, was observ ed after 24 h of treatment. Second, IL-1 alpha increased the activity of th e lactate dehydrogenase (LDH) A4 isoform, which is involved in the conversi on of pyruvate into lactate. This increase in LDH A4 activity was detected at 12 h and was maximal, with an ED50 of 9 pM, after 24-h treatment with IL -1 alpha. The increase was related to an increase in LDH A4 expression, sin ce IL-1 alpha stimulated LDH A mRNA (size: 1.5 kilobases, evidenced through Northern blotting analysis) in a dose- and time-dependent manner. Assuming that IL-1 alpha might be produced in the seminiferous tubules by both Sert oli and germ cells, which utilize lactate for their energy metabolism, we s uggest that these results together show 1) that the cytokine may represent a signal in the metabolic cooperation existing between Sertoli cells and ge rm cells, and 2) that a redistribution of LDH isoforms in favor of LDH A4 u nder IL-1 alpha control is a key mechanism(s) in such cooperation used by g erm cells to enhance lactate production in Sertoli cells.