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This version published online on June 19, 2008
Endocrinology, doi:10.1210/en.2007-1661
A more recent version of this article appeared on October 1, 2008
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Submitted on November 30, 2007
Accepted on June 9, 2008

Catecholamine uptake, storage, and regulated release by ovarian granulosa cells

Monika Greiner, Alfonso Paredes, Verónica Rey-Ares, Sabine Saller, Artur Mayerhofer, and Hernán E. Lara*

Laboratory of Neurobiochemistry, Department of Biochemistry and Molecular Biology, Faculty of Chemistry and Pharmaceutical Sciences, Universidad de Chile, Santiago 1, Chile; and Institute for Cell Biology, Ludwig-Maximilians University, Munich, Germany

* To whom correspondence should be addressed. E-mail: hlara{at}ciq.uchile.cl.

Catecholamines present in the mammalian ovary are involved in many normal aspects of ovarian functions, including initial follicle growth, steroidogenesis and pathological states such as polycystic ovary syndrome (PCOS). Sympathetic nerve fibers are the largest source of norepinephrine (NE), but not the only one. Surgical denervation of the rat ovary, reduces, but does not eliminate, the ovarian content of NE. The aim of this work is to explore which intraovarian cells may participate in the ovarian NE homeostasis and the mechanisms involved. It was found that denervated rat ovaries can take up NE and cocaine considerably, decreased its uptake, suggesting involvement of catecholamine transporters. Granulosa cells of rat ovarian follicles present dopamine transporter (DAT) and NE transporter (NET). Their functionality was confirmed in isolated rat granulosa cells while cocaine blocked the uptake of NE. Furthermore, the presence of the vesicular monoamine transporter 2 (VMAT2), together with the exocytotic protein (SNAP25) in granulosa cells, implies catecholamine storage and regulated release. Regulated calcium-dependent release of NE was shown after depolarization by potassium, implying all neuron-like cellular machinery in granulosa cells. These results in rats may be of relevance for the human ovary, as DAT, NET, VMAT2 and SNAP25 protein and mRNA are found in human ovarian follicles and/or isolated granulosa cells. Thus, ovarian non-neuronal granulosa cells, after taking up catecholamines, can serve as an intraovarian catecholamine-storing compartment, releasing them in a regulated way. This suggests a more complex involvement of catecholamines in ovarian functions as is currently being recognized.


Key words: ovary • granulosa cells • norepinephrine release • norepinephrine and dopamine transporter







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