title: Description and analysis of differential sensitivity to glucocorticoids in Fao cells.
abstract: This study shows that the derived hepatoma cell line Fao displays different sensitivities for glucocorticoid induction of tyrosine aminotransferase (TAT), alanine aminotransferase (AAT) and gamma-glutamyltransferase (GGT). This was seen in the different behaviors of nine steroids with respect to these three effects: (1) in the presence of full agonists (dexamethasone or deacylcortivazol), half-maximal induction of GGT occurred at approx 5- to 6-fold higher agonist concentrations than those required for half-maximal induction of AAT and TAT; (2) in the presence of full antagonists (RU 486, R5020, or progesterone) the GGT response induced by an equal agonist concentration was inhibited at concentrations approx 4- to 5-fold lower than those required for an equivalent inhibition of TAT response; (3) in the presence of cortexolone, deoxycorticosterone, 11 beta-hydroxyprogesterone and dexamethasone-3'-oxetanone, there was a partial agonistic effect (30-50%) on TAT and AAT responses, whereas there was a mainly antagonistic effect (very weak agonistic effect: 0-10%) on GGT response; (4) regardless of the steroid or its full or partial agonist activity, a given TAT induction level (50%, for example) always corresponded to the same AAT and GGT induction levels (50 and 10% respectively). We provide evidence showing that the three above-mentioned biological responses are mediated via the same type of glucocorticoid receptor binding site. Consequently, this differential behavior probably originates from a phenomenon occurring after the common steps (activation, translocation) that follow the formation of the steroid-receptor complex. This leads us to propose a model in which this phenomenon is assumed to originate from a difference in the affinities of the activated receptor for the nuclear acceptor sites of the TAT and GGT genes.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 58, Montpellier, France.
authors.forename: D
authors.initials: D
authors.lastname: Gagne
authors.forename: M
authors.initials: M
authors.lastname: Labhilili
authors.forename: M
authors.initials: M
authors.lastname: Pons
mesh_terms: D000410:Alanine Transaminase / Q000096:biosynthesis; D000818:Animals; D002460:Cell Line; D003350:Cortodoxone / Q000494:pharmacology; D003900:Desoxycorticosterone / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004790:Enzyme Induction; D004963:Estrenes / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D006908:Hydroxyprogesterones / Q000494:pharmacology; D008114:Liver Neoplasms, Experimental / Q000201:enzymology*; D015735:Mifepristone; D011281:Pregnatrienes / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology; D011397:Promegestone / Q000494:pharmacology; D014444:Tyrosine Transaminase / Q000096:biosynthesis; D005723:gamma-Glutamyltransferase / Q000096:biosynthesis
chemical_list: D004963:Estrenes; D005938:Glucocorticoids; D006908:Hydroxyprogesterones; D011281:Pregnatrienes; C030228:11-hydroxyprogesterone; D015735:Mifepristone; C029415:deacylcortivazol; D003900:Desoxycorticosterone; D011374:Progesterone; D003907:Dexamethasone; D011397:Promegestone; D005723:gamma-Glutamyltransferase; D000410:Alanine Transaminase; D014444:Tyrosine Transaminase; D003350:Cortodoxone