Edinburgh Napier University

  GABAA receptor (GABAAR) function may be inhibitory or excitatory in the brain depending on the chloride electrochemical gradient over the neuronal membrane. This gradient is tightly regulated by cation-chloride transporter (CCC) expression.
Premature birth (PTB) occurs in 5-18% of pregnancies, however the mechanism behind PTB remains unknown. The progesterone metabolite, allopregnanolone (APα) inhibits uterine contractions and GABAAR sensitivity to APα is increased by presence of the π subunit. GABAAR π subunit expression and the presence of APα may therefore be contributing factors in premature birth.
The hormones that regulate pregnancy have also been shown to regulate endometrial cancer. Analysis of GABAARs and CCCs expression patterns in endometrial cancer samples may indicate changes during pregnancy, contributing to premature birth.
This study aimed to provide the first complete quantitative analysis of GABAAR and CCC gene expression in the uterus, and endometrial cancer and to develop an appropriate in vitro model to investigate the effects of APα on uterine cell function to further understand the functional role of GABAARs and CCCs in the uterus.
Gene expression was analysed in healthy human uterus, endometrial cancer and APα treated COLO684 cells using qRT-PCR. COLO684 cells were used as an in vitro uterine model and treated with physiologically-relevant concentrations of APα. Protein expression was assessed by immunoblotting.
GABAAR subunits and CCCs changed in expression when comparing healthy uterus to endometrial cancer data. The data from APα treated COLO684 cells indicated that the GABAAR π subunit was not expressed but other GABAAR subunits were. These results support the hypothesis that GABAARs and CCCs are present and possibly functional in the uterus, and that GABAAR π subunit expression may be influenced by APα which subsequently may indicate a role in preterm birth.