Regulation of Uterine γ-Aminobutyric AcidA Receptor Subunit Expression throughout Pregnancy1

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 expressio...