Sex differences in impacts of epilepsy on GnRH neuron firing activity. Mean ± S.E.M. for mean firing rate of GnRH neurons from saline-injected controls (white bars) and KA-injected female mice recorded on diestrus and on estrus (A) and male mice (B). KA-injected females are divided into KA-long (red bars) and KA-regular (blue bars) groups based on estrous cycle length (long = ≥7 days, regular = 4–6 days). Cells are classified based on anatomic location of somata in medial septum (MS), preoptic area (POA), and anterior hypothalamic area (AHA). Adapted from Li et al. (2018).

Biosynthetic pathways of neurosteroid synthesis in the brain and nervous system. Enzymatic pathways for the production of three prototype neurosteroids allopregnanolone (now called brexanolone), allotetrahydrodeoxycorticosterone (THDOC), and androstanediol are illustrated from cholesterol and intermediate steroid precursors. Cholesterol is converted to pregnenolone by P450scc in the inner mitochondrial membrane. Pregnenolone is the precursor for progesterone and other neurosteroids. Progesterone, deoxycorticosterone, and testosterone undergo two sequential A-ring reduction steps catalyzed by 5α-reductase and 3α-HSOR to form the 5α, 3α-reduced neurosteroids. The conversion of progesterone, deoxycorticosterone, or testosterone into neurosteroids occurs in several regions within the brain. The 5α-reductase, 3α-HSOR, and other enzymes are present in the brain. 3β-HSD, 3β-hydroxysteroid dehydrogenase; 3α-HSOR, 3α-hydroxysteroid oxidoreductase; 17β-HSD, 17β-hydroxysteroid dehydrogenase; P450c21, cytochrome P450 21-hydroxylase; P450scc, cholesterol side-chain cleavage enzyme. Adapted from Reddy (2013).