Role of GnRH-GnRH receptor signaling at the maternal-fetal interface.
OBJECTIVE
To investigate the expression and function of GnRH and GnRH receptor (GnRHR) subtypes at the maternal-fetal interface.


METHODS
In vitro experiments using freshly isolated human trophoblast cells, decidual stromal cells (DSCs), and immortalized cell lines.


METHODS
University teaching hospital.


METHODS
Placenta-fetal membranes from term deliveries.


METHODS
Human trophoblast and DSCs were isolated, purified, and cultured.


METHODS
Expression of GnRH-I, GnRH-II, and GnRHR-I mRNA and protein in human trophoblast cell lines and tissues were evaluated by reverse-transcription polymerase chain reaction and Western blot. The effect of GnRH-I and -II on the production of select cytokines (hCG, interleukin [IL] 8, IL-6, matrix metalloproteinase 3, monocyte chemoattractant protein 1, vascular endothelial growth factor, soluble Fms-like tyrosine kinase 1, urokinase-type plasminogen activator, and plasminogen activator inhibitor 1) were measured by ELISA and normalized for protein content.


RESULTS
GnRH-I, GnRH-II, and GnRHR-I mRNA and protein were identified in trophoblasts and decidua. GnRH-I and -II stimulated hCG production by trophoblast and trophoblast-derived cell lines in a dose-dependent fashion (e.g., 2.8-fold, from 2.5 ± 0.5 to 7.0 ± 0.4 ng/mg protein per 24 h, for 1,000 nmol/L GnRH-I and 2.4-fold, from 2.5 ± 0.5 to 6.1 ± 0.6 ng/mg protein per 24 h, for 1,000 nmol/L GnRH-II) without affecting the production of other cytokines.


CONCLUSIONS
Trophoblasts and decidua express GnRH-I, GnRH-II, and GnRHR-I mRNA and protein. GnRH-I and -II selectively stimulate hCG production by trophoblast cells without altering the production of select cytokines by trophoblasts or decidua. The role of GnRH-GnRHR signaling at the maternal-fetal interface therefore appears to be limited to the regulation of trophoblast hCG production.
Lee
Hee Joong
HJ
Department of Obstetrics and Gynecology, Catholic University of Korea, Seoul, South Korea.
Snegovskikh
Victoria V
VV
Park
Joong Shin
JS
Foyouzi
Nastaran
N
Han
Ku Taek
KT
Hodgson
Eric J
EJ
Guller
Seth
S
Norwitz
Errol R
ER
D000818:Animals; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D006063:Chorionic Gonadotropin / Q000235:genetics / Q000378:metabolism; D005321:Extraembryonic Membranes / Q000378:metabolism / Q000502:physiology; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D033261:Maternal-Fetal Relations / Q000502:physiology*; D051379:Mice; D010920:Placenta / Q000378:metabolism / Q000502:physiology; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D011966:Receptors, LHRH / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D014327:Trophoblasts / Q000378:metabolism / Q000502:physiology
D006063:Chorionic Gonadotropin; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone