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The Journal of Neuroscience, June 21, 2006, 26(25):6749-6760; doi:10.1523/JNEUROSCI.4469-05.2006

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Cellular/Molecular
Vasotocin and Mesotocin Stimulate the Biosynthesis of Neurosteroids in the Frog Brain

Jean-Luc Do-Rego,¹ Sujata Acharjee,² Jae Young Seong,³ Ludovic Galas,¹ David Alexandre,¹ Patrice Bizet,¹ Arlette Burlet,⁴ Hyuk Bang Kwon,² Van Luu-The,⁵ Georges Pelletier,⁵ and Hubert Vaudry¹

¹Institut National de la Santé et de la Recherche Médicale, Unité 413, Laboratory of Cellular and Molecular Neuroendocrinology, European Institute for Peptide Research, University of Rouen, 76821 Mont-Saint-Aignan, France, ²Hormone Research Center, Chonnam National University, Gwangju 500-757, Korea, ³Graduate School of Medicine, Korea University College of Medicine, Seoul 136-705, Korea, ⁴Department of Cellular Biology, University of Nancy, 54000 Nancy, France, and ⁵Laboratory of Molecular Endocrinology and Oncology, Laval University Hospital Center, Québec, Québec, Canada G1V 4G2

Correspondence should be addressed to Dr. Hubert Vaudry, European Institute for Peptide Research, Laboratory of Cellular and Molecular Neuroendocrinology, Institut National de la Santé et de la Recherche Médicale Unité 413, UA Centre National de la Recherche Scientifique, University of Rouen, 76821 Mont-Saint-Aignan, France. Email: hubert.vaudry{at}univ-rouen.fr

The neurohypophysial nonapeptides vasopressin (VP) and oxytocin (OT) modulate a broad range of cognitive and social activities. Notably, in amphibians, vasotocin (VT), the ortholog of mammalian VP, plays a crucial role in the control of sexual behaviors. Because several neurosteroids also regulate reproduction-related behaviors, we investigated the possible effect of VT and the OT ortholog mesotocin (MT) in the control of neurosteroid production. Double immunohistochemical labeling of frog brain sections revealed the presence of VT/MT-positive fibers in close proximity of neurons expressing the steroidogenic enzymes 3-hydroxysteroid dehydrogenase/⁵-⁴ isomerase (3-HSD) and cytochrome P450 17-hydroxylase/c17, 20-lyase (P450_C17). High concentrations of VT and MT receptor mRNAs were observed in diencephalic nuclei containing the 3-HSD and P450_C17 neuronal populations. Exposure of frog hypothalamic explants to graded concentrations of VT or MT produced a dose-dependent increase in the formation of progesterone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, and dehydroepiandrosterone. The stimulatory effect of VT and MT on neurosteroid biosynthesis was mimicked by VP and OT, as well as by a selective V1b receptor agonist, whereas V2 and OT receptor agonists had no effect. VT-induced neurosteroid production was completely suppressed by selective V1a receptor antagonists and was not affected by V2 and OT receptor antagonists. Concurrently, the effect of MT on neurosteroidogenesis was markedly attenuated by selective OT and V1a receptor antagonists but not by a V2 antagonist. The present study provides the first evidence for a regulatory effect of VT and MT on neurosteroid biosynthesis. These data suggest that neurosteroids may mediate some of the behavioral actions of VT and MT.

Key words: neurosteroid biosynthesis; vasotocin; mesotocin; 3-hydroxysteroid dehydrogenase/⁵-⁴ isomerase; cytochrome P450 17-hydroxylase/c17, 20-lyase; hypothalamus

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Received Oct. 19, 2005; revised April 25, 2006; accepted April 25, 2006.

Correspondence should be addressed to Dr. Hubert Vaudry, European Institute for Peptide Research, Laboratory of Cellular and Molecular Neuroendocrinology, Institut National de la Santé et de la Recherche Médicale Unité 413, UA Centre National de la Recherche Scientifique, University of Rouen, 76821 Mont-Saint-Aignan, France. Email: hubert.vaudry{at}univ-rouen.fr

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