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Synthesis, Enzyme Localization, and Regulation of Neurosteroids
Published in Sheryl S. Smith, Neurosteroid Effects in the Central Nervous System, 2003
801, 1992. Bureau, M.H. and Olsen, R.W., GABAA receptor subtypes: ligand binding heterogeneity demonstrated by photoaffinity labeling and autoradiography, J. Neurochem., 61, 1479, 1993.Nguyen, Q. et al., Modulation of GABAA receptor binding in human brain by neuroactive steroids: species and brain regional differences, Synapse, 19, 77, 1995.McCabe, R.T. et al., Osmotic shock: a method to eliminate endogenous γ-aminobutyric acid and account for the influence on benzodiazepine binding affinity in autoradiographic studies, J. Pharmacol. Exp. Ther., 245, 342, 1988.Srinivasan, S. et al., Biphasic modulation of GABAA receptor binding by steroids suggests functional correlates, Neurochem. Res., 24, 1363, 1999.Prince, R.J. and Simmonds, M.A., Differential antagonism by epipregnanolone of alphaxalone and pregnanolone potentiation of [3H]flunitrazepam binding suggests more than one class of binding site for steroids at GABAA receptors, Neuropharma-
24 hour patterning in gene expression of pineal neurosteroid biosynthesis in young chickens (Gallus gallus domesticus L.)
Published in Chronobiology International, 2021
Magdalena Chustecka, Natalia Blügental, Pawel Marek Majewski, Iwona Adamska
Neurosteroid biosynthesis is strongly conserved in all vertebrates, following similar pathways to those in the steroidogenic organs (Tsutsui 2019). Biosynthesis begins with translocation of cholesterol across the mitochondrial membrane by a complex transport mechanism involving several proteins. These include the steroidogenic acute regulatory protein (STAR, synonym STARD1), the translocator protein (TSPO, synonyms PBR, MBR), the adenine nucleotide transporter protein (ANT), and voltage-dependent anion channel protein (VDAC) (Morohaku et al. 2014; Papadopoulos et al. 2018; Selvaraj and Stocco 2015). Pregnenolone (PREG) is then formed by cleavage of the cholesterol side-chain by cytochrome P450scc (E.C 1.14.15.6) encoded by Cyp11a1. PREG is further metabolized in two ways. The first is by hydroxylation to 7α-OH PREG or 7β-hydroxypregnenolone (7β-OH PREG) catalyzed by cytochrome P4507α (E.C 1.14.14.29) encoded by Cyp7b1 (Spg5a). The second is dehydrogenation and isomerization to progesterone (PRO) by 3β-hydroxysteroid dehydrogenase (3β-HSD, E.C 1.1.1.145) encoded by Hsd3b2 (Sdr11e2). PRO can be reduced in two-steps catalyzed by 5α-reductase (E.C 1.3.99.5) encoded by Srd5a1 and 3α-hydroxysteroid dehydrogenase (3α-HSD, E.C 1.3.99.6) encoded by Akr1d1 (Srd5b1) to ALLO. PRO can also be converted to epipregnanolone (EPI) in two steps catalyzed by 3β-HSD and 5β-reductase (E.C 1.3.1.94) encoded by Srd5a3 (Srd5a2l) gene (Figure 1) (Do Rego et al. 2009).