Strain differences in the induction of mono-oxygenase activity in mouse skin by topical clobetasol propionate: evidence of a role for the hr locus.
The effect of the topical application of clobetasol propionate on cutaneous ethoxycoumarin O'dealkylation (EOD) has been studied in various strains of mice. Clobetasol propionate markedly increased cutaneous EOD activity in adult hairless mice only. Similar treatment of adult haired C57BL/6J mice, or adult haired DBA/2J mice had no significant effect on cutaneous EOD activity. In contrast 3 methylcholanthrene induced cutaneous EOD activity in both hairless and C57 strains to a far greater extent than in the DBA strain. EOD activity in hairless mice non-responsive to polycyclic hydrocarbons, derived by selective breeding of hairless and DBA strains was induced by clobetasol propionate to a similar extent to that observed in responsive hairless strains. Hepatic EOD activity was not induced by clobetasol propionate in any of the strains tested. Strain differences in the induction of EOD by clobetasol propionate were not related to differences in either the concentration of cytosolic glucocorticoid receptor in the skin, the dissociation constant of the cytosolic receptor, or differences in percutaneous absorption. Polycyclic hydrocarbons did not compete with triaminolone acetonide for binding to the cytosolic glucocorticoid receptor. Strain differences in the induction of EOD activity by clobetasol propionate appear therefore not to be related to strain differences in either the Ah receptor of the glucocorticoid receptor, but to be regulated by the hr locus.
D015660:7-Alkoxycoumarin O-Dealkylase; D000287:Administration, Topical; D000818:Animals; D001623:Betamethasone / Q000031:analogs & derivatives*; D002990:Clobetasol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004790:Enzyme Induction; D006197:Hair; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010105:Oxygenases / Q000096:biosynthesis*; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug / Q000032:analysis; D011965:Receptors, Glucocorticoid / Q000032:analysis; D012867:Skin / Q000187:drug effects / Q000201:enzymology*; D013045:Species Specificity
D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug; D011965:Receptors, Glucocorticoid; D001623:Betamethasone; D002990:Clobetasol; D010105:Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase