Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q7LGC8 (HSD)
 3,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The occurrence of osteoporosis is closely related to serum estradiol level. CYP19 is the most important biosynthesis enzyme and CYP1A2, CYP3A4, and 17 beta-HSD are important metabolism enzymes. Any changes in these enzymes activity affects estradiol biosynthesis or metabolism, and changes the estradiol serum level. By reviewing the recent literature, it was found that the genetic variations of CYP19, CYP1A2, CYP3A4, and 17 beta-HSD are important factors affecting the estradiol serum level, and may be closely related to the development of osteoporosis.
 ...
PMID:Contribution of genetic variations in estradiol biosynthesis and metabolism enzymes to osteoporosis. 1136 Jun 62

Altered cytochrome P450-catalyzed metabolism of 17beta-estradiol (E2) and estrone (E1) in the liver and (or) extrahepatic tissues may affect estrogen-sensitive tumorigenesis. We examined the effects of oral treatments of (i) indole-3-carbinol (13C) at 250 or 500 mg/kg or beta-naphthoflavone (beta-NF) at 40 mg/kg of body weight (bw)/day from 51 to 54 days of age (acute regimen), and (ii) 13C at 250 mg/kg or beta-NF at 20 mg/kg bw given 3x/week from 10 to 22 weeks of age (chronic regimen) in female Sprague-Dawley rats. We determined the effects of these treatments on the P450 content and P450 (CYP)-specific activities in the liver, P450-dependent metabolism of E2 and E1 by the liver and mammary gland, and interconversion of E1 and E2 catalyzed by 17beta-hydroxysteroid dehydrogenase (17beta-HSD) in these tissues and malignant mammary tumors. 13C at the two levels of acute regimen elicited similar responses. Acute and chronic treatments with 13C, but not beta-NF, increased P450 content approximately 2-fold. 13C, and to a lesser extent beta-NF, increased CYP1A1 and CYP1A2 probe activities in liver up to 117- and 27- fold, respectively, and after acute regimens, that of CYP3A by approximately 1.8-fold. 13C also increased activity of CYP2B up to 100-fold. Overall hepatic metabolism of E2 and E1, which was approximately 2-fold greater at 55 than 155 days of age, was increased (approximately 2.8-fold) by 13C with 2-, 4-, 16alpha-, 6alpha-, 6beta-, and 15alpha-hydroxy (OH) comprising > or = 54, 3, 2, approximately 2, approximately 5, 7, and 2%, respectively, of E1 and E2 metabolites. Acute regimens of beta-NF increased 2- and 15alpha-OH-E2 (62 and 5% of total) from E2 and 2-, 4-, and 6alpha-OH-E1 + 6beta-OH-E1 (32, 13, and 4% of total) from E1. Mammary gland metabolized E2 to E1 and small amounts of 15alpha-, 4-, 16alpha-, 6beta-, and 6alpha-OH-E2. After the acute IC3 regimen, E2 was also converted to 2-OH-E2. 17Beta-HSD-catalyzed oxidation of E2 was favored in the liver and reduction of E1 was favored in mammary gland and tumor (= 1% of hepatic activity). An increased (approximately 2-fold) ratio of reductive to oxidative activities in malignant mammary tumors by chronic 13C regimen may stimulate tumor growth. This is the first report showing that after chronic oral regimens, the 13C-, but not beta-NF-, induced changes in CYP complement led to elevated E2 and E1 metabolism. The persistent effects of increased putative carcinogenic and estrogenic 4- and 16alpha-OH as well as 6alpha- and 6beta-OH-E2 and 6beta-OH-E1 might counteract those of the less estrogenic 2-OH metabolites, thus accounting for the lack of suppression of mammary tumorigenesis by 13C in our previous study.
 ...
PMID:Oxidations of 17beta-estradiol and estrone and their interconversions catalyzed by liver, mammary gland and mammary tumor after acute and chronic treatment of rats with indole-3-carbinol or beta-naphthoflavone. 1143 May 90

In the present study, the effects on expression of cytochrome P450 (CYP1A1, CYP1A2, CYP3A4 and CYP3A5), carboxylesterase (CES1 and CES2) and sulfotransferase (CHST1, CHST3, CHST4, CST, SULT2A1 and TPST2) mRNA in primary cultures of cryopreserved human hepatocytes were evaluated after exposure to NO-1886 (diethyl 4-[(4-bromo-2-cyanophenyl) carbamoyl] benzylphosphonate) for 48 hr at 2, 10, and 50 microM. Analysis was performed by RT-PCR in the presence of TaqMan probe. CYP1A1 and CYP1A2 mRNA levels after exposure to 50 microM omeprazole (positive control for CYP1As) were increased by 162 (p<0.001) and 37 times (p<0.001), respectively, compared with untreated controls. However, these mRNA levels were increased by 2 times or less after exposure to NO-1886. CYP3A4 and CYP3A5 mRNA levels after exposure to 50 microM rifampicin (positive control for CYP3As) were significantly increased by 5.8 (p<0.01) and 2.0 times (p<0.01), respectively, compared with untreated controls. The CYP3A4 mRNA level after exposure to 10 microM NO-1886 was increased by 1.3 times (p<0.05). Further, the CYP3A4 mRNA level after exposure to 50 microM NO-1886 was significantly increased by 3.6 times (p<0.001). However, the CYP3A5 mRNA level after exposure to 50 microM NO-1886 was not significantly increased. CES1 and CES2 mRNA levels after exposure to 50 microM NO-1886 were significantly increased by 1.4 (p<0.05) and 2.6 times (p<0.01), respectively, compared with untreated controls. CHST1, CST and SULT2A1 mRNA levels after exposure to 50 microM NO-1886 were significantly increased by 3.8 (p<0.001), 1.8 (p<0.01) and 4.4 times (p<0.01), respectively. CHST3, CHST4 and TPST2 mRNA levels after exposure to 50 microM NO-1886 were not significantly increased. This in vitro technique using primary cultured human hepatocytes is expected to be very useful for the preclinical evaluation of the induction of drug-metabolizing enzymes in humans.
 ...
PMID:Effects of NO-1886 (Ibrolipim), a lipoprotein lipase-promoting agent, on gene induction of cytochrome P450s, carboxylesterases, and sulfotransferases in primary cultures of human hepatocytes. 1568 96

Riluzole is the only FDA approved drug for the treatment of amyotrophic lateral sclerosis. Riluzole is assumed to be mainly metabolized by the liver cytochrome CYP1A2 and by the extra-hepatic cytochrome CYP1A1. CYP1A2 and CYP1A1 genetic polymorphisms are known, but their relationship to riluzole metabolism in ALS patients has not been investigated. The aim of this study was to determine whether the polymorphisms of the CYP1A2 and the CYP1A1 genes in ALS patients are associated with riluzole metabolic profiles. Thirty-two patients with a diagnosis of probable or definite ALS and who were on riluzole, participated in the study. Trough and peak plasma riluzole levels were measured using analytical chromatography-mass spectrometry methods. Association of the genotypes of the SNPs spanning the CYP1A1 and CYP1A2 genes (including one SNP in the intergenic region) with mean riluzole peak and trough levels was studied using ANOVA and Tukey's HSD. The mean peak riluzole level was 202+/-111 ng/ml and mean trough level 54.3+/-37.5 ng/ml. Our data do not support any association of the four CYP1A1 and CYP1A2 polymorphisms with the riluzole metabolic profile. In conclusion, genetic variations in CYP1A1 and CYP1A2 genes do not seem to influence riluzole levels. Further work is needed to better understand the genetic regulation of CYP1A enzymes and their role in riluzole metabolism.
 ...
PMID:Riluzole metabolism and CYP1A1/2 polymorphisms in patients with ALS. 1785 22