Catecholamine uptake, storage, and regulated release by ovarian granulosa cells.
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. 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 was 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 and NE transporter. 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, together with the exocytotic protein (synaptosome-associated protein of 25 kDa) 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 because dopamine transporter, NE transporter, vesicular monoamine transporter 2, and synaptosome-associated protein of 25-kDa protein and mRNA are found in human ovarian follicles and/or isolated granulosa cells. Thus, ovarian nonneuronal 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.
Department of Biochemistry and Molecular Biology, Faculty of Chemistry and Pharmaceutical Sciences, Universidad de Chile, P.O. Box 233, Santiago-1, Chile.
Monika
M
Greiner
Alfonso
A
Paredes
Verónica
V
Rey-Ares
Sabine
S
Saller
Artur
A
Mayerhofer
Hernán E
HE
Lara
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism*; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013562:Sympathectomy; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism*; D050825:Synaptosomal-Associated Protein 25 / Q000235:genetics / Q000378:metabolism; D050493:Vesicular Monoamine Transport Proteins / Q000235:genetics / Q000378:metabolism
D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D050484:Norepinephrine Plasma Membrane Transport Proteins; D012333:RNA, Messenger; C493454:Slc18a2 protein, rat; C493226:Slc6a2 protein, rat; C494210:Snap25 protein, rat; D050825:Synaptosomal-Associated Protein 25; D050493:Vesicular Monoamine Transport Proteins; D003042:Cocaine; D002118:Calcium; D009638:Norepinephrine