Glucocorticoids and the plasma membrane.
Glucocorticoids affect the composition and function of the plasma membrane in a variety of cell types. Cultured rat hepatoma (HTC) cells in tissue culture provide an excellent model system for analysis of such effects. In these cells, dexamethasone rapidly and dramatically inhibits the influx of amino acids sharing the A or alanine-preferring transport system. Inhibition is half-maximal within 2 h, and maximal after 6 h incubation with the hormone. The inhibition is rapidly reversed by insulin, and more slowly by removing the steroid. Microtubules and microfilaments are not apparently involved in this hormonal effect, but continuous protein synthesis is required for the glucocorticoid inhibition of transport. Dexamethasone also decreases the number of microvilli on the surface of HTC cells, increases their adhesiveness to a substratum, and dramatically decreases the production of plasminogen activator, but it does not affect the growth rate or plating efficiency of the cells. Variant cell lines stably resistant to dexamethasone inhibition of plasminogen activator production have been isolated using an agar-fibrin overlay technique to detect protease production by individual colonies of HTC cells. The hormonal resistance to inhibition of protease production is associated witha  maintenance of inducibility of other glucocorticoid-regulated functions and therefore is not apparently secondary to abnormal or absent glucocorticoid receptor, but due to a lesion in a later step in hormone action specific for plasminogen activator. Combined genetic and biochemical analysis of such dexamethasone-resistant variants should facilitate study of the hormonal regulation of specific membrane phenotypes and of the role of proteases in this regulation.
D000409:Alanine / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D000621:Aminoisobutyric Acids / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D007700:Kinetics; D008114:Liver Neoplasms, Experimental / Q000378:metabolism; D009154:Mutation; D010641:Phenotype; D051381:Rats
D000596:Amino Acids; D000621:Aminoisobutyric Acids; D005938:Glucocorticoids; D003609:Dactinomycin; D003907:Dexamethasone; D000409:Alanine