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Biology of Reproduction 61, 1139-1145 (1999)
©Copyright 1999 Society for the Study of Reproduction, Inc.


Articles

Epidermal Growth Factor Regulates Glucose Metabolism Through Lactate Dehydrogenase A Messenger Ribonucleic Acid Expression in Cultured Porcine Sertoli Cells1

Fayçal Boussouara, and Mohamed Benahmed2,a

a Unité 407 de l'Institut National de la Santé et de la Recherche Médicale (INSERM U407), Faculté de Médecine Lyon-Sud, BP12, F-69921 Oullins Cedex, France

In a previous work, we reported that lactate dehydrogenase A4 (LDH A4) activity is a key step in the stimulatory effect of epidermal growth factor (EGF) on lactate production in cultured Sertoli cells. Here, we further investigated the regulatory mechanisms involved in EGF action on LDH A mRNA expression. Steady-state levels of LDH A mRNA analyzed by Northern blot hybridization were induced to 2.9-fold in response to a 36-h incubation with EGF (ED50 = 4 ng/ml, 0.63 x 10-9 M). Whether EGF-induced increases of LDH A mRNA levels are the result of increased transcription and/or altered mRNA stability was investigated. The decay curves for the 1.5-kilobase LDH A mRNA transcript in Sertoli cells were not different in the absence or presence of EGF, suggesting that EGF did not affect LDH A mRNA stability. Inhibitors of protein synthesis (cycloheximide) and RNA synthesis (actinomycin D, and 5,6-dichloro-1-ß-ribofuranosyl benzimidazole) completely abrogated the EGF-induced LDH A mRNA expression, indicating that EGF increased LDH A mRNA levels through a transcriptional mechanism, which probably involves protein synthesis. Finally, the partial inhibitory effect of a protein kinase C (PKC) inhibitor, bisindolylmaleimide, on EGF-stimulated LDH A mRNA supports a partial involvement of PKC in the action of the growth factor. Since EGF is produced in Sertoli and in germ cells, its action is probably exerted in a context of a local control. As EGF also regulates other parameters involved in glucose metabolism, its effect on LDH A might be viewed in a general context related to the control of energy metabolism by the growth factor in the testicular cells.

1 This work was supported by Institut National de la Santé et de la Recherche Médicale and by a fellowship to F.B. from the Ministère de l'Enseignement Supérieur et de la Recherche Scientifique (MESRS, Algérie) and the Centre National des Oeuvres Universitaires et Sociales (CNOUS, France).

2 Correspondence. FAX: 33 4 78 86 31 16; benahmed{at}lsgrisn1.univ-lyon1.fr




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F. Boussouar, C. Mauduit, E. Tabone, L. Pellerin, P. J. Magistretti, and M. Benahmed
Developmental and Hormonal Regulation of the Monocarboxylate Transporter 2 (MCT2) Expression in the Mouse Germ Cells
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J. Biol. Chem.Home page
S. Short, D. Tian, M. L. Short, and R. A. Jungmann
Structural Determinants for Post-transcriptional Stabilization of Lactate Dehydrogenase A mRNA by the Protein Kinase C Signal Pathway
J. Biol. Chem., April 21, 2000; 275(17): 12963 - 12969.
[Abstract] [Full Text] [PDF]




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