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Arachidonic acid is involved in the regulation of hCG induced steroidogenesis in rat Leydig cells
Authors:A K Didolkar  K Sundaram
Affiliation:1. Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, Yamagata, Japan;2. Department of Immunology, Faculty of Medicine, Yamagata University, Yamagata, Japan;3. Department of Pathological Diagnostics, Faculty of Medicine, Yamagata University, Yamagata, Japan;4. Physical Chemistry for Life Science Laboratory, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan;5. AMED-CREST, Japan Agency for Medical Research and Development, Chiyoda-ku, Tokyo, Japan;6. Miyata Diabetes and Metabolism Clinic, Fukushima-ku, Osaka, Japan;1. INIBIOLP (UNLP-CONICET CCT La Plata), Facultad de Ciencias Médicas, Calles 60 y 120, La Plata, Argentina;2. CINIBA (UNLP-CONICET CCT La Plata), Facultad de Ciencias MéG dicas, Calles 60 y 120, La Plata, Argentina;1. Department of Pharmacology and Pharmacy and State Key Laboratory of Pharmaceutical Biotechnology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China;2. Department of Anaesthesiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China;3. Theme of Cancer Biology and Experimental Therapeutics, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China;4. Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China;5. School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
Abstract:Phospholipase C (PLC), an enzyme involved in the hydrolysis of membrane phospholipid- phosphatidylinositol-bisphosphate to inositol triphosphate and diacylglycerol, and Phorbol 12, myristate 13, acetate (PMA), a tumor promoting agent, could significantly stimulate testosterone (T) secretion from Leydig cells. Arachidonic acid (AA) stimulated T secretion by about 2 fold. The steroidogenic effect of PLC and AA was biphasic. At low concentrations both PLC and AA (100 mU and 12.5 microM, respectively) augmented hCG induced T secretion, while at higher concentrations (PLC: 500 mU and AA: 200 microM) they inhibited steroid production. AA also had a biphasic effect on hCG induced cyclic AMP secretion. 5, 8, 11, 14 Eicosatetraynoic acid (ETYA), a general inhibitor of AA metabolism, and Nordihydroguaiaretic acid (NDGA), an inhibitor of the lipoxygenase pathway of AA metabolism, inhibited hCG induced T secretion while indomethacin, an inhibitor of cyclo-oxygenase pathway, had no effect on hCG induced T secretion. We conclude from these data that AA plays a role in the regulation of hCG induced steroidogenic responses in rat Leydig cells and that the metabolite(s) of AA that are involved are not cyclooxygenase products.
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