“…Naturally occurring neurosteroids are synthesized from cholesterol in both peripheral organs and in the central nervous system (CNS), primarily by glial cells, and can be classified as positive (enhancing) or negative (blocking) allosteric modulators of the GABA A receptor (for review, Baulieu, 1998;Compagnone and Mellon, 2000;Belelli and Lambert, 2005). Synthetic steroids, including anesthetics such as alphaxalone and ganaxolone (for review, Belelli and Lambert, 2005) and the anabolic androgenic steroids (AAS) (for review, Clark et al, 2004;2006) also act as allosteric modulators of the GABA A receptor. Reproductive biologists have demonstrated an indisputable role for nuclear hormone receptor-mediated steroid signaling in governing reproductive processes (for review, Course and Korach, 1998) and neuroendocrinologists have firmly established that allosteric modulation γ-aminobutyric acid type A (GABA A ) receptors has a critical role in mediating aggression, stress and anxiety; behaviors that are known to vary with hormonal state (for review, Finn et al, 2004;Henderson and Jorge, 2004;Smith, 2004).…”