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Action of hypothalamic nEuropeptides on anteriorpituitary folliculostellate cell function in acute pituitary slices


Research objectives and content The anterior pituitary gland has been referred to as the ' master' gland in that it secretes hormones in response to the input of l hypothalamic clocks which in turn control the physiology of a wide variety of organs. Dr. Mollard's group recently has shown l that the pituitary is partitioned into distinct assemblies of endocrine cells that pace synchronously their cytosolic calcium transients, key elements of the stimulus-secretion coupling. The working hypothesis is now that other cells (e.g. the network of: gap junctional coupled folliculostellate cells) might pace collective rhythms within the anterior gland despite the apparent wide' range of distances between the active endocrine cell domains. I propose to use the acute slice preparation applied to bothnormal and generated knock-out mice in combination with 3D real-time confocal calcium imaging and
immunofluorescent stainings to investigate whether the stimulation of FS cells with PACAP, a hypothalamic neuropeptide, would trigger waves in cytosolic calcium that would spread, not only into the FS cell network, but also to distinct endocrine cell domains. Extensive analysis of this putative mode of cell-to-cell communication would be of particular interest, insofar that long-distance I synchrony may be an important determinant for shaping the patterns of hormone release.
Training content (objective, benefit and expected impact)
The work will be carried out at the INSERM unit 469 (Director: Dr. C. Barberis, Supervisor of the applicant: Dr. P. Mollard) | which is a department of the CNRS-INSERM Centre of Pharmacology-Endocrinology (Director: J. Bockaert), a leading I research center in the field in Europe. I should benefit from the suggested proposal in a number of ways. It will allow train) | in different experimental techniques (acute slice preparation, real-time confocal microscopy) that are complementary to ones currently used. The expected results should also help advance our understanding of the mechanisms of cell-to-c I communications operating during the control of hormone release from the anterior pituitary gland. This project will area I strengthen the progress of research in the field of endocrinology and will in particular reinforce the position of Europe science in the international competition.
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