Differential responses of rat hepatic microsomal carboxylesterase isozymes to glucocorticoids and pregnenolone 16 alpha-carbonitrile. 1993

M Hosokawa, and K Hattori, and T Satoh
Laboratory of Biochemical Pharmacology and Biotoxicology, Faculty of Pharmaceutical Sciences, Chiba University, Japan.

Differences in the responses to glucocorticoids and pregnenolone 16 alpha-carbonitrile (PCN) of three isozymes of hepatic microsomal carboxylesterase, namely RL1, RL2 and RH1, in male rats were studied. The administration of dexamethasone dose-dependently increased isocarboxazid hydrolase activity, whereas p-nitrophenyl acetate-hydrolyzing activity was decreased dose-dependently. Betamethasone, methylprednisolone and PCN also markedly increased isocarboxazid hydrolase activity. A radial immunodiffusion assay indicated that carboxylesterase reactive with antibodies was induced by these steroids. Carboxylesterase isozyme RL2 was strongly induced by dexamethasone, methylprednisolone and PCN. In contrast, RL1 and RH1 were decreased by dexamethasone, but not by the other steroids. Estradiol benzoate had a synergic effect on the PCN-induced increase of isocarboxazid hydrolase, but the actions of the glucocorticoids were not affected. It is concluded that hepatic microsomal carboxylesterase isozymes in rats differ considerably from each other in their response to various steroids. These data are also indicative of the importance of glucocorticoids in hepatic xenobiotic metabolism.

UI MeSH Term Description Entries
D007527 Isoenzymes Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics. Alloenzyme,Allozyme,Isoenzyme,Isozyme,Isozymes,Alloenzymes,Allozymes
D008297 Male Males
D008775 Methylprednisolone A PREDNISOLONE derivative with similar anti-inflammatory action. 6-Methylprednisolone,Medrol,Metipred,Urbason,6 Methylprednisolone
D008862 Microsomes, Liver Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough. Liver Microsomes,Liver Microsome,Microsome, Liver
D011285 Pregnenolone Carbonitrile A catatoxic steroid and microsomal enzyme inducer having significant effects on the induction of cytochrome P450. It has also demonstrated the potential for protective capability against acetaminophen-induced liver damage. PCN,Pregnenolone 16 alpha-Carbonitrile,Pregnenolone Carbonitrile, (3 beta)-Isomer,Pregnenolone Carbonitrile, (3 beta,16 beta)-Isomer,16 alpha-Carbonitrile, Pregnenolone,Carbonitrile, Pregnenolone,Pregnenolone 16 alpha Carbonitrile
D002265 Carboxylic Ester Hydrolases Enzymes which catalyze the hydrolysis of carboxylic acid esters with the formation of an alcohol and a carboxylic acid anion. Carboxylesterases,Ester Hydrolases, Carboxylic,Hydrolases, Carboxylic Ester
D003907 Dexamethasone An anti-inflammatory 9-fluoro-glucocorticoid. Hexadecadrol,Decaject,Decaject-L.A.,Decameth,Decaspray,Dexasone,Dexpak,Hexadrol,Maxidex,Methylfluorprednisolone,Millicorten,Oradexon,Decaject L.A.
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004789 Enzyme Activation Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D006728 Hormones Chemical substances having a specific regulatory effect on the activity of a certain organ or organs. The term was originally applied to substances secreted by various ENDOCRINE GLANDS and transported in the bloodstream to the target organs. It is sometimes extended to include those substances that are not produced by the endocrine glands but that have similar effects. Hormone,Hormone Receptor Agonists,Agonists, Hormone Receptor,Receptor Agonists, Hormone

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