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Institut National de la Santé et de la Recherche Médicale U676, Hôpital Robert-Debré, 48 Boulevard Sérurier, F-75019 Paris, France
Department of Physiology and Pharmacology L334, Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Portland, Oregon 97201-3098, USA
Institut de Physiologie et Biologie Cellulaires, Centre National de la Recherche Scientifique-Unité Mixte de Recherche, 6187 Pôle Biologie Santé, 40 Avenue du Recteur Pineau, 86022 Poitiers, France
Mental Retardation Research Center, University of California, Neurosciences Research Building, 655 Charles Young Drive South, Los Angeles, California 90095-7088, USA
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Institut National de la Santé et de la Recherche Médicale U676, Hôpital Robert-Debré, 48 Boulevard Sérurier, F-75019 Paris, France
Department of Physiology and Pharmacology L334, Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Portland, Oregon 97201-3098, USA
Institut de Physiologie et Biologie Cellulaires, Centre National de la Recherche Scientifique-Unité Mixte de Recherche, 6187 Pôle Biologie Santé, 40 Avenue du Recteur Pineau, 86022 Poitiers, France
Mental Retardation Research Center, University of California, Neurosciences Research Building, 655 Charles Young Drive South, Los Angeles, California 90095-7088, USA
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Institut National de la Santé et de la Recherche Médicale U676, Hôpital Robert-Debré, 48 Boulevard Sérurier, F-75019 Paris, France
Department of Physiology and Pharmacology L334, Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Portland, Oregon 97201-3098, USA
Institut de Physiologie et Biologie Cellulaires, Centre National de la Recherche Scientifique-Unité Mixte de Recherche, 6187 Pôle Biologie Santé, 40 Avenue du Recteur Pineau, 86022 Poitiers, France
Mental Retardation Research Center, University of California, Neurosciences Research Building, 655 Charles Young Drive South, Los Angeles, California 90095-7088, USA
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Institut National de la Santé et de la Recherche Médicale U676, Hôpital Robert-Debré, 48 Boulevard Sérurier, F-75019 Paris, France
Department of Physiology and Pharmacology L334, Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Portland, Oregon 97201-3098, USA
Institut de Physiologie et Biologie Cellulaires, Centre National de la Recherche Scientifique-Unité Mixte de Recherche, 6187 Pôle Biologie Santé, 40 Avenue du Recteur Pineau, 86022 Poitiers, France
Mental Retardation Research Center, University of California, Neurosciences Research Building, 655 Charles Young Drive South, Los Angeles, California 90095-7088, USA
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Institut National de la Santé et de la Recherche Médicale U676, Hôpital Robert-Debré, 48 Boulevard Sérurier, F-75019 Paris, France
Department of Physiology and Pharmacology L334, Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Portland, Oregon 97201-3098, USA
Institut de Physiologie et Biologie Cellulaires, Centre National de la Recherche Scientifique-Unité Mixte de Recherche, 6187 Pôle Biologie Santé, 40 Avenue du Recteur Pineau, 86022 Poitiers, France
Mental Retardation Research Center, University of California, Neurosciences Research Building, 655 Charles Young Drive South, Los Angeles, California 90095-7088, USA
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Institut National de la Santé et de la Recherche Médicale U676, Hôpital Robert-Debré, 48 Boulevard Sérurier, F-75019 Paris, France
Department of Physiology and Pharmacology L334, Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Portland, Oregon 97201-3098, USA
Institut de Physiologie et Biologie Cellulaires, Centre National de la Recherche Scientifique-Unité Mixte de Recherche, 6187 Pôle Biologie Santé, 40 Avenue du Recteur Pineau, 86022 Poitiers, France
Mental Retardation Research Center, University of California, Neurosciences Research Building, 655 Charles Young Drive South, Los Angeles, California 90095-7088, USA
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The neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide have long been considered as putative regulators of testicular functions. In vitro evidence suggests that VIP could play an important role in testosterone biosynthesis. However, the endogenous role of VIP on testicular functions remained to be demonstrated. In C57BL/6 mice exhibiting a complete disruption of the VIP gene, we first observed here that serum testosterone levels were lower than those of WT littermates. At the age of 4 months, this phenotype was accompanied with a reduction of expression of StAR and 3-β-hydroxysteroid dehydrogenase (3β-HSD) in the testis. In addition, serum levels of FSH but not LH were reduced in young knock-out (KO) males. Testicular anatomy also revealed a higher percentage of degenerated seminiferous tubules in the 4-month-old VIP KO animals when compared with WT. In 15-month-old animals, control males showed typical testicular aging, including a severe degeneration of seminiferous tubules, a dramatic decrease in serum levels of testosterone, and a reduction in StAR and 3β-HSD gene expression. In age-matching VIP KO males, the levels of serum testosterone and steroidogenic enzymes were still very low. Interestingly, in contrast to that observed in young mice, testicular degeneration at 15 months was significantly less severe in VIP KO than WT mice. All together, these results suggest that 1) VIP is an important factor for regulating testosterone biosynthesis and FSH secretion and 2) VIP may influence testicular aging.
