Immunolocalization of gonadotropin-releasing hormone (GnRH)-I, GnRH-II, and type I GnRH receptor during follicular development in the human ovary.
BACKGROUND
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 premenopausal women.


METHODS
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 from which over 85% of ovarian cancers are thought to be derived.


CONCLUSIONS
The expression of GnRH-I, GnRH-II, and GnRHR protein in the human ovary is temporally and spatially specific and further supports the physiological role of an autocrine regulatory system involving GnRH-I, GnRH-II, and GnRHR in follicular development and corpus luteal function.
Choi
Jung-Hye
JH
Department of Obstetrics and Gynecology, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada V6H 3V5.
Gilks
C Blake
CB
Auersperg
Nelly
N
Leung
Peter C K
PC
D000328:Adult; D018929:Cell Culture Techniques; D002460:Cell Line; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008875:Middle Aged; D006080:Ovarian Follicle / Q000254:growth & development* / Q000378:metabolism*; D010053:Ovary / Q000254:growth & development* / Q000378:metabolism*; D017697:Premenopause / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism*; D011966:Receptors, LHRH / Q000378:metabolism*; D014018:Tissue Distribution
C484844:GNRHR protein, human; D011498:Protein Precursors; D011966:Receptors, LHRH; C050866:progonadoliberin I; D007987:Gonadotropin-Releasing Hormone; C047717:LHRH, His(5)-Trp(7)-Tyr(8)-