Dexamethasone suppresses neurosteroid biosynthesis via downregulation of steroidogenic enzyme gene expression in human glioma GI-1 cells

Fuyuko Koibuchi, Natsumi Ritoh, Ryohei Aoyagi, Megumi Tago, Hiroomi Tamura

Research output: Contribution to journalArticle

Abstract

Emerging evidence indicates that stress hormone glucocorticoids (GC) are an important modulator of brain development and function. To investigate whether GCs modulate neurosteroid biosynthesis in neural cells, we studied the effects of GCs on steroidogenic gene expression in human glioma GI-1 cells. The GC dexamethasone (Dex) reduced steroidogenic acute regulatory protein (StAR), CYP11A1 and 3β-hydroxysteroid dehydrogenase gene expression in a dose- and GC receptor-dependent manner. In addition to its effects on steroidogenic gene expression, Dex also reduced de novo synthesis of progesterone (PROG). Furthermore, Dex inhibited all-trans retinoic acid (ATRA) and vitamin D 3-induced steroidogenic gene expression and PROG production. This suggests that GC regulates steroidogenic gene expression in neural cells via cross-talk with the two fat-soluble vitamins, A and D. The relationship between the effects of GCs on neurosteroid biosynthesis and on cognitive behaviors and hippocampal neural activity is also discussed herein.

Original languageEnglish
Pages (from-to)1241-1247
Number of pages7
JournalBiological and Pharmaceutical Bulletin
Volume37
Issue number7
DOIs
Publication statusPublished - 2014

Fingerprint

Glioma
Dexamethasone
Neurotransmitter Agents
Down-Regulation
Gene Expression
Glucocorticoids
Enzymes
Progesterone
3-Hydroxysteroid Dehydrogenases
Cholesterol Side-Chain Cleavage Enzyme
Cholecalciferol
Glucocorticoid Receptors
Tretinoin
Vitamin A
Vitamin D
Fats
Hormones
Brain

Keywords

  • CYP11A1
  • Dexamethasone
  • Glia
  • Neurosteroid
  • Progesterone
  • Steroidogenic acute regulatory protein (StAR)

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Pharmacology
  • Medicine(all)

Cite this

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title = "Dexamethasone suppresses neurosteroid biosynthesis via downregulation of steroidogenic enzyme gene expression in human glioma GI-1 cells",
abstract = "Emerging evidence indicates that stress hormone glucocorticoids (GC) are an important modulator of brain development and function. To investigate whether GCs modulate neurosteroid biosynthesis in neural cells, we studied the effects of GCs on steroidogenic gene expression in human glioma GI-1 cells. The GC dexamethasone (Dex) reduced steroidogenic acute regulatory protein (StAR), CYP11A1 and 3β-hydroxysteroid dehydrogenase gene expression in a dose- and GC receptor-dependent manner. In addition to its effects on steroidogenic gene expression, Dex also reduced de novo synthesis of progesterone (PROG). Furthermore, Dex inhibited all-trans retinoic acid (ATRA) and vitamin D 3-induced steroidogenic gene expression and PROG production. This suggests that GC regulates steroidogenic gene expression in neural cells via cross-talk with the two fat-soluble vitamins, A and D. The relationship between the effects of GCs on neurosteroid biosynthesis and on cognitive behaviors and hippocampal neural activity is also discussed herein.",
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author = "Fuyuko Koibuchi and Natsumi Ritoh and Ryohei Aoyagi and Megumi Tago and Hiroomi Tamura",
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AU - Ritoh, Natsumi

AU - Aoyagi, Ryohei

AU - Tago, Megumi

AU - Tamura, Hiroomi

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