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Extra‐pituitary function of GnRH‐I and GnRH‐II in human reproduction
Author(s) -
Leung Peter C.K.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a352-d
Subject(s) - endocrinology , medicine , gnrhr , gonadotropin releasing hormone , plasminogen activator , trophoblast , biology , autocrine signalling , luteal phase , endometrium , stromal cell , luteinizing hormone , receptor , hormone , placenta , pregnancy , fetus , genetics
Recent studies have indicated that both the classical form of mammalian GnRH (GnRH‐I) and its novel isoform (GnRH‐II) are potent autocrine regulators in several non‐pituitary tissues, including the ovary, endometrium and placenta. In human granulosa‐luteal cells, we have demonstrated the expression of GnRH‐I and GnRH‐II, as well as GnRH receptor (GnRH‐R). GnRH‐II, like GnRH‐I, directly inhibits progesterone production in human granulosa‐luteal cells. In normal ovarian surface epithelium (OSE) and in 80% of human ovarian epithelial tumors, GnRHR is expressed. A direct anti‐proliferative effect has been observed following treatment with GnRH‐I or GnRH‐II in different ovarian cancer cell lines, presumably via a common GnRHR (the type I GnRH‐R). In human endometrial stromal cells and in the first‐trimester trophoblast, GnRH‐I and GnRH‐II are expressed. These peptides differentially regulate the balance between the urokinase‐type plasminogen activator (uPA) and plasminogen activator inhibitor (PAI‐1) levels in the human decidua. GnRH‐I and GnRH‐II are potent regulators of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) that are important for the overall proteolytic activity of trophoblasts during human implantation. Together, these findings strongly support a multi‐faceted role of the GnRH/GnRH‐R system in the control of reproduction. [This research was supported by the Canadian Institutes of Health Research].