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Effects of progesterone or neuroactive steroid?

Nature volume 395, page 652 (1998)Cite this article

Abstract

Smithet al.1 reported some interesting results about the effects of progesterone treatment and withdrawal on the gene encoding the GABAAreceptor α4 subunit, a constituent of receptors for the neurotransmitter GABA (γ-aminobutyric acid). However, we disagree with their conclusion that the effects of progesterone withdrawal are mediated by reduced levels in the brain of the GABAAreceptor active neurosteroid 3α-OH-5α-pregnan-20-one (3α,5α-THP, or allopregnanalone). The ability of indomethacin to reverse the effects of progesterone was interpreted as evidence that the effects of progesterone were mediated by 3α,5α-THP. Smith et al.1 did not provide direct evidence that levels of 3α,5α-THP were reduced by indomethacin (which reversed the effects of progesterone), or that progesterone levels were not altered by indomethacin. In some cases, indomethacin can increase progesterone levels directly2, which may explain why indomethacin can reverse the effects of progesterone withdrawal.

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Figure 1: Indomethacin increases stress-induced 3α,5α-THP levels in rat cerebral cortex.

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Authors and Affiliations

  1. Departments of Pharmacology, and Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, 27599-7178, North Carolina, USA

    A. Leslie Morrow

  2. Departments of Psychiatry and, University of North Carolina School of Medicine, Chapel Hill, 27599-7178, North Carolina, USA

    Margaret J. VanDoren & Leslie L. Devaud

Authors
  1. A. Leslie Morrow
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  2. Margaret J. VanDoren
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  3. Leslie L. Devaud
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Morrow, A., VanDoren, M. & Devaud, L. Effects of progesterone or neuroactive steroid?. Nature 395, 652 (1998). https://doi.org/10.1038/27106

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