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Submitted on May 26, 2006
Accepted on August 25, 2006
Department of Obstetrics and Gynecology, Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada, V6H 3V, Department of Pathology, Vancouver General Hospital and UBC, Vancouver, BC, Canada V5Z 1M9
* To whom correspondence should be addressed. E-mail: peleung{at}interchange.ubc.ca.
Context: Gonadotropin releasing hormone (GnRH) and its receptor have been detected, at the mRNA level, in different ovarian cell types, implicating an autocrine role of the GnRH system in the human ovary. However, the expression, at the protein level, of GnRH and its receptor in specific cell types during follicular development has not been documented in humans.
Objective: We evaluated the immunohistochemical expression of GnRH-I (the classical form of mammalian GnRH), GnRH-II (the novel isoform) and the type-I GnRH receptor (GnRHR) that is known to bind both forms of GnRH, in ovaries of pre-menopausal women.
Main Outcome Measures: Immunohistochemistry, immunofluorescence, immunoblot assay and real-time RT-PCR were performed.
Results: GnRH-I, GnRH-II and GnRHR were not immunostained in the follicles from the primordial to the early antral stage. In preovulatory follicles, both forms of GnRH and their common receptor were localized predominantly to the granulosa cell layer, whereas the theca interna layer was weakly positive. In the corpus luteum, significant levels of GnRH-I, GnRH-II as well as GnRHR were observed in granulosa luteal cells, but not in theca luteal cells. Both GnRH isoforms and the type-I GnRHR were localized also to the ovarian surface epithelium (OSE) from which over 85% of ovarian cancer are thought to be derived.
Conclusion: The expression of GnRH-I, GnRH-II and GnRHR protein in the human ovary is temporally and spatially specific, and further support the physiological role of an autocrine regulatory system involving GnRH-I, GnRH-II and GnRHR in follicular development and corpus luteal function.
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