Neurosteroid biosynthesis in vertebrate brains

Kazuyoshi Tsutsui, Kazuyoshi Ukena, Minoru Takase, Chie Kohchi, Robert W. Lea

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113 Citations (Scopus)

Abstract

In mammals, neurosteroids are now known to be synthesized de novo in the brain as well as other areas of the nervous system through mechanisms at least partly independent of the peripheral steroidogenic glands. However, limited information is available on neurosteroids in non-mammalian vertebrates. We therefore have attempted to demonstrate neurosteroid biosynthesis in the brain of birds and amphibians. These vertebrate brains possessed the steroidogenic enzymes, cytochrome P450 side-chain cleavage enzyme (P450scc) and 3β-hydroxysteroid dehydrogenase/Δ54-isomerase (3β-HSD), and produced pregnenolone, pregnenolone sulfate ester and progesterone from cholesterol. Significant seasonal changes in neurosteroids in the brain were observed in seasonally breeding vertebrates. In addition, we attempted to identify the cell type involved in neurosteroidogenesis in mammalian and non-mammalian vertebrates in order to understand the physiological role of neurosteroids. Glial cells are generally accepted to be the primary site for neurosteroid formation, but the concept of neurosteroidogenesis in brain neurons has up to now been uncertain. We recently demonstrated neuronal neurosteroidogenesis in the brain and indicated that the Purkinje cell, a typical cerebellar neuron, actively synthesizes several neurosteroids de novo from cholesterol in both mammals and non-mammals. This paper summarizes the advances made in our understanding of neurosteroid biosynthesis, including neuronal neurosteroidogenesis, in a variety of vertebrate types. Copyright (C) 1999 Elsevier Science Ireland Ltd.

Original languageEnglish
Pages (from-to)121-129
Number of pages9
JournalComparative Biochemistry and Physiology - C Pharmacology Toxicology and Endocrinology
Volume124
Issue number2
DOIs
Publication statusPublished - 1999 Oct
Externally publishedYes

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Keywords

  • 3β-Hydroxysteroid dehydrogenase/Δ-Δ-isomerase
  • Brain
  • Cytochrome P450 side-chain cleavage enzyme
  • Neurosteroids
  • Pregnenolone
  • Pregnenolone sulfate
  • Progesterone
  • Purkinje neurons
  • Seasonal breeder
  • Vertebrates

ASJC Scopus subject areas

  • Pharmacology
  • Immunology

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