Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0338671 (Steroids)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review examines the relationship between renal transplantation and two important metabolic consequences: hyperlipidemia and glucose intolerance. Before cyclosporine, hypertriglyceridemia and hypercholesterolemia were common abnormalities that worsened in the cyclosporine era. In addition to obesity, steroid use, and reduced renal function, cyclosporine plays an independent role in elevating cholesterol levels, with particular reference to the modulation of the low-density lipoprotein receptor. Management includes maintaining low levels of steroid, manipulation of cyclosporine appropriately, diets low in fat and cholesterol, and an exercise program. Pharmacologic management in general revolves around the HMG-COA reductase drugs, which can be used safely if liver function tests and muscle enzymes are monitored. The unmasking of clinically important glucose intolerance occurs in 5 to 10% of patients in the cyclosporine era, not different from the earlier experience. Steroids and cyclosporine independently can worsen glucose tolerance to unmask a genetic predisposition to Type II diabetes in some and to even create glucose intolerance in otherwise normal individuals. Management is based on dietary and immunosuppressive drug dosing manipulations and the judicious use of oral hypoglycemic agents. Half of these recipients may ultimately need insulin. In summary, hyperlipidemia and glucose intolerance remain important metabolic consequences of renal transplantation that affect long-term patient survival unless recognized and treated.
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PMID:Hyperlipidemia and glucose intolerance in the post-renal transplant patient. 819 94

4alpha-(2-Propenyl)-5alpha-cholest-24-en-3alpha-ol (3) was shown recently in a Chinese hamster ovary (CHO) cell-based low-density lipoprotein receptor/luciferase (LDLR/Luc) assay to be a potent transcriptional activator of the LDL receptor promoter in the presence of 25-hydroxycholesterol. Because of the involvement of 12alpha-hydroxylation in the metabolism of cholesterol, we are interested in investigating the effect of introducing a 12alpha-hydroxyl group to 3 on the transcriptional activity of the LDL receptor promoter. Thus 4alpha-(2-propenyl)-5alpha-cholest-24-en-3alpha,12a lpha-diol (14), a 12alpha-hydroxyl analog of 3, was synthesized from deoxycholic acid via the formation of 12alpha-[[(tertbutyl)dimethylsilyl]oxy]-4alpha-( 2-propenyl)-5alpha-cholest-24-en-3-one (11). Test results show that 14 is inactive at concentrations of up to 20 microg/ml, compared to 3 with an EC30 value of 2.6 microM, in the CHO cell-based LDLR/Luc assay. Apparently introduction of a 12alpha-hydroxyl group abolishes the capability of 3alpha-sterol 14 to activate the transcription of the LDL receptor promoter. However, in the [1-14C-acetate]cholesterol biosynthesis inhibition assay in CHO cells, 14 at 10 microg/ml (23 microM) is shown to inhibit the cholesterol biosynthesis by 51% relative to the control cells. Our previous studies indicated that 3 showed a 38% inhibition, but 4alpha-(2-propenyl)-5alpha-cholestan-3alpha-ol (1) exhibited no inhibition in the same assay at 10 microg/ml. In summary the results indicate that, in addition to the 24,25-unsaturation, the 12alpha-hydroxyl group in 14 has also conferred an inhibitory effect on cholesterol biosynthesis in CHO cells; however, the inhibition of cholesterol biosynthesis by 14 does not lead to the transcriptional activation of the LDL receptor promoter.
Steroids 1999 Oct
PMID:Synthesis and in vitro biological activity of 4alpha-(2-propenyl)-5alpha-cholest-24-en-3alpha,12 alpha-diol, a 12alpha-hydroxyl analog of 4alpha-(2-propenyl)-5alpha-cholest-24-en-3alpha-ol: the latter is a potent activator of the low-density lipoprotein receptor promoter. 1049 32