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 D3-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.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Keio University.
authors.forename: Fuyuko
authors.initials: F
authors.lastname: Koibuchi
authors.forename: Natsumi
authors.initials: N
authors.lastname: Ritoh
authors.forename: Ryohei
authors.initials: R
authors.lastname: Aoyagi
authors.forename: Megumi
authors.initials: M
authors.lastname: Funakoshi-Tago
authors.forename: Hiroomi
authors.initials: H
authors.lastname: Tamura
mesh_terms: D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics*; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D009097:Multienzyme Complexes / Q000235:genetics*; D009457:Neuroglia / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D010750:Phosphoproteins / Q000235:genetics*; D011374:Progesterone / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D011375:Progesterone Reductase / Q000235:genetics*; D011965:Receptors, Glucocorticoid / Q000235:genetics; D013251:Steroid Isomerases / Q000235:genetics*; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: C021425:3 beta-hydroxysteroid oxidoreductase-delta(5) 3-ketosteroid isomerase; D005938:Glucocorticoids; D009097:Multienzyme Complexes; D018377:Neurotransmitter Agents; D010750:Phosphoproteins; D011965:Receptors, Glucocorticoid; D000098682:Steroidogenic Acute Regulatory Protein; D011374:Progesterone; D003907:Dexamethasone; D011375:Progesterone Reductase; D002786:Cholesterol Side-Chain Cleavage Enzyme; D013251:Steroid Isomerases