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Brain-Endocrine Interactions: A Microvascular Route in the Mediobasal Hypothalamus

Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 862 (P.C., O.L.), Neurocentre Magendie, and Université de Bordeaux (P.C., M.G., O.L.), F-33077 Bordeaux, France; Centre National de la Recherche Scientifique (M.G.), Unite Mixte de Recherche 5227, F-33077 Bordeaux, France; EA2972 (P.L.), Université de Bordeaux, F-33405 Talence, France; INSERM Unité 837 (A.L., V.P.), F-59045 Lille, France; Université de Lille 2 (A.L., V.P.), F-59045 Lille, France; and Department of Neurobiology and Physiology (J.E.L.), Northwestern University, Evanston, IL 60208

Address all correspondence and requests for reprints to: Philippe Ciofi, Institut National de la Santé et de la Recherche Médicale Unité 862, Neurocentre Magendie, 146 rue Léo Saignat, F-33077 Bordeaux Cedex, France. E-mail: philippe.ciofi{at}inserm.fr.

Blood-borne hormones acting in the mediobasal hypothalamus, like those controlling food intake, require relatively direct access to target chemosensory neurons of the arcuate nucleus (ARC). An anatomical substrate for this is a permeable microvasculature with fenestrated endothelial cells in the ARC, a system that has awaited comprehensive documentation. Here, the immunofluorescent detection of endothelial fenestral diaphragms in the rat ARC allowed us to quantitate permeable microvessels throughout its rostrocaudal extent. We have determined that permeable microvessels are part of the subependymal plexus irrigating exclusively the ventromedial (vm) ARC from the subadjacent neuroendocrine median eminence. Unexpectedly, permeable microvessels were concentrated proximal to the pituitary stalk. This marked topography strongly supports the functional importance of retrograde blood flow from the pituitary to the vmARC, therefore making a functional relationship between peripheral long-loop, pituitary short-loop, and neuroendocrine ultra-short loop feedback, altogether converging for integration in the vmARC (formerly known as the hypophysiotrophic area), thereby so pivotal as a multicompetent brain endocrinostat.