Journal of Biological Chemistry
Volume 286, Issue 50, 16 December 2011, Pages 43193-43203
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Signal Transduction
Regulation of Oocyte and Cumulus Cell Interactions by Intermedin/Adrenomedullin 2*

https://doi.org/10.1074/jbc.M111.297358Get rights and content
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Ovarian folliculogenesis has been studied as a model of hormonal regulation of development and differentiation, cell death, and cell-cell communication. In addition to gonadotropins from the pituitary and follicular paracrine factors, oocyte secreted factors have been shown to play critical roles in the regulation of follicular cell functions. Except for the well characterized BMP family proteins, including GDF9 and BMP15, oocytes are known to secrete oocyte secreted factors that are important for the regulation of cumulus cell survival and the maintenance of tertiary structure of cumulus cell-enclosed oocyte complexes (COCs). Based on genomic screening and studies of COCs cultured in vitro, we showed that intermedin (IMD)/adrenomedullin 2 (ADM2) is a novel oocyte-derived ligand important for the regulation of cell interactions in COCs that functions, in part, by suppressing cumulus cell apoptosis. Consistently, we showed that suppression of IMD/ADM2 signaling in growing rat ovaries in vivo leads to oocyte atresia and aberrant cell cycle progression in follicular cells. Together, our studies indicated that mammalian oocytes deploy a G protein-coupled receptor ligand to coordinate normal interactions of oocytes and cumulus cells and provided a better understanding of how the tertiary structure of a COC is maintained as follicles undergo exponential growth during the late stages of folliculogenesis.

Apoptosis
Bioinformatics
Cell Compartmentation
Cyclic AMP (cAMP)
G Protein-coupled Receptors (GPCR)
Ovary
Peptide Hormones
Adrenomedullin
CGRP

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*

This work was supported, in whole or in part, by National Institutes of Health Grant DK70652 (to S. Y. T. H.). This work was also supported by Avon Foundation Research Award 02-2009-054 (to S. Y. T. H.), New Century Health Care Promotion Foundation, Taiwan, Grant NCHCPF-94001 (to C. L. C.), and Chang Gung Memorial Hospital Grant CMRPG34002 (to C. L. C.).

The on-line version of this article (available at http://www.jbc.org) contains supplemental Table 1 and Figs. 1 and 2.