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Endocrinology Vol. 138, No. 5 1964-1971
Copyright © 1997 by The Endocrine Society


Articles

Tumor Necrosis Factor-{alpha}-Stimulated Lactate Production Is Linked to Lactate Dehydrogenase A Expression and Activity Increase in Porcine Cultured Sertoli Cells1

Diane Nehar, Claire Mauduit, Fayçal Boussouar and Mohamed Benahmed

INSERM U-407, Communications Cellulaires en Biologie de la Reproduction, Centre Hospitalier Lyon-Sud, Pierre-Benite, France

Address all correspondence and requests for reprints to: Dr. M. Benahmed, INSERM U-407, Communications Cellulaires en Biologie de la Reproduction, Bât 3 B, Centre Hospitalier Lyon-Sud, 69 495 Pierre-Benite, France.

By using, as a model, cultured testicular immature Sertoli cells, the action of tumor necrosis factor-{alpha} (TNF{alpha}) and the site of action of the cytokine on lactate production were studied. TNF{alpha} stimulated in a time- and dose-dependent manner (with an ED50 of 0.1 nM) Sertoli cell lactate production. Two major sites involved in TNF{alpha} action were identified. Firstly, TNF{alpha} was shown to increase the uptake of glucose substrate in a time- and dose-dependent manner. The maximal effect was observed after 24 h of treatment, with an ED50 of 0.1 nM. Secondly, TNF{alpha} increased the activity of lactate dehydrogenase (LDH) A isoform, which is involved in the conversion of pyruvate into lactate. This increase in LDH-A activity was detected at 12 h and was maximal after 24 h of treatment with TNF{alpha}. The stimulatory effect of the cytokine on the LDH-A isoform was observed with an ED50 of 0.05 nM. Such an increase in LDH-A activity was related to an increase in LDH-A expression, because TNF{alpha} stimulated LDH-A messenger RNA (size, 1.5 kilobases, determined by Northern blotting analysis). Together, assuming that in the seminiferous tubules, TNF{alpha} is produced by spermatids that use lactate for their energetic metabolism, we suggest that the cytokine may potentially represent a signal used by germ cells to enhance lactate production in Sertoli cells through, at least, a redistribution of LDH isoforms in favor of LDH-A.




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