Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In cultured fetal human adrenocortical cells, metabolism of the carcinogen benzo[a]pyrene was found to be unresponsive to the xenobiotic inducers 3-methylcholanthrene, benz[a]anthracene and 2,3,7,8-tetrachlorodibenzo-p-dioxin. However, exposure of cultures to the hormone adrenocorticotropin (ACTH) for 48 hours stimulated benzo[a]pyrene metabolism 3-fold. The major metabolite was the 7,8-diol. Other compounds which stimulate the production of adrenocortical cell cyclic AMP (forskolin and cholera toxin) as well as monobutyryl cyclic AMP also increased benzo[a]pyrene metabolism. Human adrenocortical cells thus provide an unusual example of hormonal regulation of the metabolism of a carcinogen.
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PMID:Hormonal regulation of benzo[a]pyrene metabolism in human adrenocortical cell cultures. 299 46

The effects of adrenocorticotropic hormone (ACTH) administration to guinea pigs on the activities of adrenal microsomal monooxygenases were studied. ACTH treatment decreased the rates of adrenal benzphetamine (BZ) demethylation and benzo[a]pyrene (BP) hydroxylation but had no effect on the same reactions in hepatic microsomes. Adrenal microsomal steroid hydroxylation reactions were unaffected (21-hydroxylation) or stimulated (17 alpha-hydroxylation) by ACTH. Although ACTH treatment decreased adrenal BP hydroxylase activity, the relative quantity of the various BP metabolites, as determined by HPLC, did not change. Adrenal microsomal cytochrome P-450 concentrations were decreased by ACTH but proportionately less than the decreases in adrenal xenobiotic metabolism. The maximal type I spectral changes produced by xenobiotics in adrenal microsomes were decreased in size by ACTH treatment, but steroid-induced difference spectra were unaffected. The results indicate that ACTH selectively decreases the rates of adrenal xenobiotic metabolism, perhaps by producing a selective decline in the concentration(s) of those cytochromes P-450 involved in the metabolism of foreign compounds.
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PMID:Differential effects of adrenocorticotropic hormone on adrenal microsomal xenobiotic and steroid metabolism in guinea pigs. 612 29

1. Hormonal factors participate in the regulation of xenobiotic metabolising enzymes in liver. Hepatic xenobiotic oxidation capacity is decreased in adrenalectomised rats, which directly implicates adrenal hormones in the control of cytochrome P450 (CYP) expression. In addition, recent studies in cultured hepatocytes have demonstrated that low concentrations of glucocorticoid upregulate the male-specific CYP2C11, which is a major enzyme that catalyses xenobiotic and steroid hydroxylations in rat liver. The present study evaluated whether glucocorticoid or mineralocorticoid may be the adrenal factor that contributes to the in vivo expression of CYP2C11 in liver. 2. Adrenalectomy of male rats selectively decreased CYP2C11-dependent 2alpha-/16alpha-hydroxylation of testosterone and other steroid substrates to 60-70% of control, whereas activities mediated by other constitutive CYPs were unaffected. The decrease in CYP2C11 activity was due to impaired protein expression in liver after adrenalectomy. Administration of dexamethasone (DEX; 0.2 mg/kg i.p. daily for 6 days) restored CYP2C11 activity and protein, whereas the mineralocorticoid deoxycorticosterone (DOC) and adrenocorticotropic hormone (ACTH) were ineffective. 3. These findings establish that glucocorticoids have a partial role in the maintenance of CYP2C11 expression and associated microsomal oxidation in liver and provide a physiological correlate for similar observations made in vitro in hepatocyte culture.
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PMID:Glucocorticoid-dependent maintenance of CYP2C11-dependent oxidation in male rat liver in vivo. 1077 43