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Activin A and Follicle-Stimulating Hormone Control Tight Junctions in Avian Granulosa Cells by Regulating Occludin Expression¹

Department of Medical Biochemistry, Division of Molecular Genetics, Max F. Perutz Laboratories, Medical Universityand Biocenter of Vienna, A-1030 Vienna, Austria

Within the avian ovarian follicle, the oocyte is surrounded by a monolayer of granulosa cells, which exhibit pronounced epithelial properties. Here we demonstrate the presence of the major tight junction protein occludin in granulosa cells. As shown by immunohistochemistry, occludin localizes to the oocyte-facing granulosa cell surface. Occludin and thus tight junctions are dynamically regulated in a developmental stage-specific manner. Small white follicles, which have not yet started yellow yolk incorporation, show pronounced occludin expression in vitro and in vivo. By contrast, yellow yolk-incorporating small yellow follicles exhibit much lower levels of occludin, and hierarchical, preovulatory follicles are virtually devoid of this essential tight junction component. Using a primary granulosa cell culture system, we demonstrate that concerted action of two well-established ovarian growth regulators, follicle-stimulating hormone and activin A, leads to strong induction of occludin expression in vitro. We suggest that the stage-dependent decrease in the granulosa cell growth factor responsiveness triggers the disruption of tight junctions, enabling rapid and high capacity transport of macromolecules into the oocyte through a paracellular pathway. Such a high-capacity transport for yolk components may represent a crucial prerequisite for rapid oocyte growth once follicles have entered the follicular hierarchy.

¹ Supported by the Austrian Science Foundation (FWF), grant SFB-604 to K.K. M.K.S. and B.S. contributed equally to this work.

² Correspondence: Karl Kuchler, Department of Medical Biochemistry, Division of Molecular Genetics, Max F. Perutz Laboratories, Medical University and Biocenter of Vienna, Dr. Bohr-Gasse 9/2, A-1030, Vienna, Austria. FAX: 43 1 4277 9618; karl.kuchler{at}univie.ac.at

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