-
Views
-
Cite
Cite
Eriko Fujii, Synthia H. Mellon, Regulation of Uterine γ-Aminobutyric AcidA Receptor Subunit Expression throughout Pregnancy, Endocrinology, Volume 142, Issue 5, 1 May 2001, Pages 1770–1777, https://doi.org/10.1210/endo.142.5.8153
Close - Share Icon Share
Abstract
Uterine contractions at parturition depend upon a variety of factors, including γ-aminobutyric acid (GABA)-ergic stimulation. A new subunit of the GABAA receptor, π, has recently been identified as being particularly abundant in the rat uterus. Reduced derivatives of progesterone, such as the 3α,5α-reduced derivative termed allopregnanolone, modulate GABAA receptor activity and neuronal inhibition by modulating the frequency and duration of GABAA channel opening. This modulation depends on the specific subunit composition of the GABAA receptor. In particular, assembly of recombinant π and δ GABAA receptor subunits into a functional GABAA receptor have been reported to reduce sensitivity to allopregnanolone. As allopregnanolone works through the GABAA receptor to reduce uterine contraction, we hypothesized that incorporation of theπ -subunit into this receptor in the uterus might change the sensitivity of the GABAA receptor to allopregnanolone and modulate parturition. We therefore determined the expression of GABAA receptor subunit messenger RNAs (mRNAs) in rat uteri from various gestational ages and determined the physiological properties of the receptors. GABAA π-subunit mRNA abundance was constant throughout gestation, but decreased at the onset of labor. Other GABAA subunits fluctuated differently during pregnancy: GABAA α1-subunit mRNA expression increased, whereas α2- and δ-subunit mRNA expression decreased during pregnancy, and β3-subunit mRNA only appeared on postpartum day 1. We determined how allopregnanolone affected the binding of muscimol, a ligand for the GABAA receptor, to rat uterine GABAA receptors throughout pregnancy. Allopregnanolone caused the greatest increase in muscimol binding to uterine GABAA receptors at 19.5 days gestation and the least increase during labor, a time when π andα 1 receptor subunit mRNA concentrations were low, and δ and α2 receptor subunit mRNA concentrations were high. Thus, the subunit composition of the GABAA receptor differs in rat uteri throughout gestation. These changes may also affect the sensitivity of the GABAA receptor to allopregnanolone and thus contribute to the regulation of parturition.
