Cell surface modulation of gene expression in brain cells by down regulation of glucocorticoid receptors

Journal Article · Sun Feb 01 04:00:00 EST 1981 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.78.2.1288· OSTI ID:6412196

McGinnis, J F; de Vellis, J

The concentration of glycerol-3-phosphate dehydrogenase (GPDH; sn-glycerol-3-phosphate:NAD/sup +/ 2-oxidoreductase, EC 1.1.1.8) had previously been determined to be regulated by glucocorticoids in rat brain cells in vivo and in cell culture. We now demonstrate that concanavalin A (Con A) can inhibit the induction of GPDH in a dose-dependent manner in C6 rat glioma cells and in primary cultures of rat brain oligodendrocytes. The inhibition specifically prevents the appearance of new molecules of GPDH, although Con A does not significantly inhibit protein synthesis in these cells, nor does it affect the activity of another solube enzyme, lactate dehydrogenase. The ability to block enzyme induction is not limited to Con A, because other lectins also inhibit induction. The molecular mechanism by which Con A inhibits GPDH induction appears to be by the down regulation of the cytoplasmic glucocorticoid receptors, because exposure to Con A results in the loss of more than 90% of the receptor activity. Con A does not inhibit the receptor assay and no direct interaction between the receptor and Con A could be demonstrated. This down regulation is not tumor cell specific and appears to be a general phenomenon, because it occurs in normal oligodendrocytes and even in normal astrocytes (a cell type in which the gene for GPDH is not expressed). The down regulation of glucocorticoid receptors in normal brain cells suggests two important corollaries. First, it demonstrates the existence of a rate-limiting step controlling the glucocorticoid-dependent gene expression in brain cells and possibly represents a regulatory site common to all glucocorticoid target cells. Second, it suggests that the response to glucocorticoids of oligodendrocytes and astrocytes can be regulated in vivo by cell surface contact with endogenous lectins, neighboring cells, or both.

• Research Organization: Univ. of California, Los Angeles
• OSTI ID: 6412196
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 78:2; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550200* -- Biochemistry
59 BASIC BIOLOGICAL SCIENCES
ADRENAL HORMONES
AGGLUTININS
ANIMAL CELLS
ANIMALS
ANTIBODIES
BIOLOGICAL EFFECTS
BIOSYNTHESIS
BODY
BRAIN
CELL CONSTITUENTS
CELL CULTURES
CELL MEMBRANES
CENTRAL NERVOUS SYSTEM
CONCANAVALIN
CORTICOSTEROIDS
DATA
DOSE-RESPONSE RELATIONSHIPS
ENZYMES
EXPERIMENTAL DATA
GENES
GLUCOCORTICOIDS
HEMAGGLUTININS
HEMIACETAL DEHYDROGENASES
HORMONES
HYDROXY COMPOUNDS
INFORMATION
INHIBITION
KETONES
LACTATE DEHYDROGENASE
MAMMALS
MEMBRANES
NERVOUS SYSTEM
NUMERICAL DATA
ORGANIC COMPOUNDS
ORGANS
OXIDOREDUCTASES
PREGNANES
PROTEINS
RATS
RECEPTORS
RODENTS
STEROID HORMONES
STEROIDS
SURFACES
SYNTHESIS
TUMOR CELLS
VERTEBRATES