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. 2014 Jun 17;8:174. doi: 10.3389/fncel.2014.00174

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Copyright © 2014 Poisbeau, Keller, Aouad, Kamoun, Groyer and Schumacher.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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(A) Simplified diagram summarizing the key steps of neurosteroidogenesis from cholesterol precursors to 3α-reduced neurosteroids (3α-androstanediol, 3α-THDOC, 3α-THP). These end-chain metabolites are potent positive allosteric modulators of GABA_ARs after binding to specific binding sites. Abbreviations: DOC, deoxycorticosterone; DHDOC, 5α-dihydrodeoxycorticosterone; THDOC, 3α,5α-tetrahydrodeoxycorticosterone; DHP, 5alpha-dihydroprogesterone; THP, 3α,5α-tetrahydroprogesterone (= AP); 5α-R, 5α-reductase; 5α-HSOR, 3α-hydroxysteroid oxydoreductase; P450scc, P450 side-chain cleavage enzyme. (B) Top graphs summarize the global changes in blood estradiol (blue) and progesterone (red) during different phases of the reproductive cycle in female rats. Patch clamp traces below are representative of inhibitory postsynaptic currents mediated by GABA_ARs in the spinal cord of female Sprague-Dawley rats during estrus and proestrus (i.e., when progesterone levels are low and high, respectively). Adapted from Keller (2002).