title: Epidermal growth factor regulates glucose metabolism through lactate dehydrogenase A messenger ribonucleic acid expression in cultured porcine Sertoli cells.
abstract: 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 (ED(50) = 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-beta-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.
authors.affiliation: 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.
authors.forename: F
authors.initials: F
authors.lastname: Boussouar
authors.forename: M
authors.initials: M
authors.lastname: Benahmed
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000502:physiology*; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D005947:Glucose / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis*; D012708:Sertoli Cells / Q000378:metabolism*; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D007375:Interleukin-1; D007527:Isoenzymes; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D004815:Epidermal Growth Factor; D005640:Follicle Stimulating Hormone; D007770:L-Lactate Dehydrogenase; D011493:Protein Kinase C; D005947:Glucose