Here we summarize recent data from our laboratory pertaining to the effects of fluctuations in the brain concentrations of the progesterone (PROG) metabolite allopregnanolone (3α,5α-TH PROG) on the expression and function of γ-aminobutyric acid type A (GABA A ) receptors. The effects of long-term exposure to progesterone and of its sudden withdrawal on the activity of GABA A receptors and on the abundance of receptor subunit mRNAs were examined in cultured rat cerebellar granule cells and cortical neurons. The effects of a persistent reduction in the brain concentration of 3α,5α-TH PROG on GABA A receptor function and gene expression were examined in vivo in rats subjected to long-term administration of oral contraceptives. Our results demonstrate that long-lasting changes in the exposure of GABA A receptors to this PROG metabolite induce marked effects on receptor structure and function. These effects of 3α,5α-TH PROG appear to be mediated through modulation of GABA A receptor signaling mechanisms that control the expression of specific receptor subunit genes. Furthermore, the specific outcomes of such signaling appear to differ among neurons derived from different regions of the brain. Neuroactive steroids such as 3α,5α-TH PROG might thus exert differential actions on GABA A receptor plasticity in distinct neuronal cell populations, likely accounting for some of the physiological effects induced by these compounds.
Brain Research Reviews – Elsevier
Published: Nov 1, 2001
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