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Keywords:

  • androgen-metabolizing enzymes;
  • aromatase;
  • 3α-hydroxysteroid dehydrogenase;
  • neurosteroid;
  • 5α-reductase

Abstract

The present review describes concisely the topography and function of the three androgen-metabolizing enzymes, namely aromatase, 5α-reductase and 3α-hydroxysteroid dehydrogenase, in the central nervous system (CNS). Aromatase, estrogen synthetase, is the key enzyme for converting androgens to estrogens. Aromatase is indispensable for the sexual differentiation of the brain and the enzyme activity and expression of aromatase are high during the critical period of neural development, which extends from the late embryonal to the early neonatal period in rodents. Aromatase is expressed in neurons within specific hypothalamic and limbic regions. The locations of aromatase-immunoreactive neurons are divided into three groups according to the period of enzyme expression. Steroid 5α-reductase converts a number of steroids with a C3 ketone group and a C4–C5 double bond (Δ4; androgens, progestins and glucocorticoids) to their 5α-reduced metabolites. Two isoforms of 5α-reductase are found and type 1 is predominant in neural tissues. The enzyme activity of 5α-reductase is found widely in the CNS and is high in white matter regions. The enzyme expression of 5α-reductase peaks during the late embryonic period. 3α-Hydroxysteroid dehydrogenase is the oxidoreductase that interconverts 3-ketosteroids to 3α-hydroxysteroids. Four isozymes have been found in humans and only one type has been found in rats. The enzyme converts 5α-reduced steroids (e.g. 5α-dihydroprogesterone) to tetrahydrosteroids (e.g. 3α,5α-tetrahydroprogesterone). The latter steroid is a potent stimulator of the GABAA receptor. The activity of 3α-hydroxysteroid dehydrogenase is high during the first 1–2 postnatal weeks, decreases with development and this enzyme is highly expressed in astrocytes.