Search results for "Steroid Hydroxylases"
showing 10 items of 17 documents
EBI2 Is Highly Expressed in Multiple Sclerosis Lesions and Promotes Early CNS Migration of Encephalitogenic CD4 T Cells
2017
Arrival of encephalitogenic T cells at inflammatory foci represents a critical step in development of experimental autoimmune encephalomyelitis (EAE), the animal model for multiple sclerosis. EBI2 and its ligand, 7{alpha},25-OHC, direct immune cell localization in secondary lymphoid organs. CH25H and CYP7B1 hydroxylate cholesterol to 7{alpha},25-OHC. During EAE, we found increased expression of CH25H by microglia and CYP7B1 by CNS-infiltrating immune cells elevating the ligand concentration in the CNS. Two critical pro-inflammatory cytokines, interleukin-23 (IL-23) and interleukin-1 beta (IL-1{beta}), maintained expression of EBI2 in differentiating Th17 cells. In line with this, EBI2 enhan…
Pituitary-adrenal responses to corticotropin-releasing factor in late onset 21-hydroxylase deficiency
1990
Intravenous corticotropin-releasing factor (CRF) and adrenocorticotropin hormone (ACTH) were administered in patients with adult onset 21-hydroxylase deficiency to compare their diagnostic capability as well as to investigate hypothalamic-pituitary-adrenal function in this disorder. Responses of 17-hydroxyprogesterone, which were markedly elevated compared with controls, were identical with CRF and ACTH. However, intravenous ACTH resulted in higher androstenedione levels in comparison to CRF. Adrenocorticotropin hormone also resulted in decreased cortisol responses, confirming a defect in steroidogenesis, a finding that was not evident with CRF. Plasma ACTH responses to CRF were similar in …
The endocrine pattern of late onset adrenal hyperplasia (21-hydroxylase deficiency)
1984
We describe 5 adult women with severe hirsutism due to late onset 21-hydroxylase deficiency. Diagnosis was performed on the finding of high serum 17-hydroxyprogesterone (17OHP) levels with a marked hyperresponse to an ACTH test. The endocrine study showed in most patients a gonadotropin behavior similar to that observed in classical polycystic ovary (PCO) syndrome. Prolactin levels were slightly increased in basal conditions and presented an exaggerated response to TRH stimulation.
Prevalence of late-onset 11 β-hydroxylase-deficiency in hirsute patients
1988
Serum levels of 11-deoxycortisol were determined in 182 hirsute women. Three patients presented high basal 11-deoxycortisol levels and an exaggerated response of this steroid to ACTH stimulation. A fourth patient had normal basal 11-deoxycortisol but was hyperresponsive to ACTH stimulation. Therefore diagnosis of late-onset 11 beta-hydroxylase deficiency was made in 4 out of 182 hirsute women with a prevalence of 2.2% in the group studied. In these patients, clinical findings and other hormonal patterns were not different from those of other women suffering from hirsutism.
Re-expression of C/EBP alpha induces CYP2B6, CYP2C9 and CYP2D6 genes in HepG2 cells.
1998
Cytochrome P450 (CYP) activity is very low or even absent in human hepatomas, a phenomenon that is accompanied by low levels of some liver transcription factors, notably C/EBP alpha. To investigate a possible link between this transcription factor and hepatic CYP expression, we have stably transfected HepG2 cells with a C/EBP alpha vector containing a Zn-inducible metallothionein promoter. Expression of functional C/EBP alpha up to liver levels concomitantly increased the mRNAs of several members of the CYP2 family (2B6, 2C9 and 2D6), suggesting that this transcription factor may play a relevant role in controlling the hepatic expression of CYP enzymes.
Hepatic metabolism of diclofenac: role of human CYP in the minor oxidative pathways.
1999
The aim of this study was to re-examine the human hepatic metabolism of diclofenac, with special focus on the generation of minor hydroxylated metabolites implicated in the idiosyncratic hepatotoxicity of the drug. Different experimental approaches were used: human hepatocytes, human microsomes, and engineered cells expressing single human CYP (cytochromes P450). Human hepatocytes formed 3'-hydroxy-, 4'-hydroxy-, 5-hydroxy- 4',5-dihydroxy-, and N,5-dihydroxydiclofenac, as well as several lactams. Formation of 4'- and 5-hydroxydiclofenac by human liver microsomes followed a Michaelis-Menten kinetics (Km 9 +/- 1 microM; Vmax 432 +/- 15 pmol/min/mg and Km 43 +/- 5 microM; and Vmax 15.4 +/- 0.6…
Xenobiotic metabolizing enzyme activities and viability are well preserved in EDTA-isolated rat liver parenchymal cells after cryopreservation
1995
Rat liver parenchymal cells (PC) were isolated by EDTA perfusion and were purified by a subsequent Percoll centrifugation. The isolated PC had a viability of 95%, as judged by trypan blue exclusion. Freshly isolated PC were cryopreserved with an optimized protocol in a computer-controlled freezer. After thawing, the PC still retained a viability of 89%. The activities of representative xenobiotic metabolizing enzymes were compared between freshly isolated and cryopreserved PC after thawing. The cytochrome P450 content and the cytochrome P450 2C11 isoenzyme activity, determined by hydroxylation of testosterone in intact cells, were not affected by the cryopreservation. The following phase II…
Androgen hydroxylation catalysed by a cell line (SD1) that stably expresses rat hepatic cytochrome P-450 PB-4 (IIB1).
1989
Androgen hydroxylation catalysed by Chinese hamster fibroblast SD1 cells, which stably express cytochrome P-450 form PB-4, the rat P450IIB1 gene product, was assessed and compared to that catalysed by purified cytochrome P-450 PB-4 isolated from rat liver. SD1 cell homogenates catalysed the NADPH-dependent hydroxylation of androstenedione and testosterone with a regioselectivity very similar to that purified by P-450 PB-4 (16 beta-hydroxylation/16 alpha-hydroxylation = 6.0-6.8 for androstenedione; 16 beta/16 alpha = 0.9 for testosterone). Homogenates prepared from the parental cell line V79, which does not express detectable levels of P-450 PB-4 or any other cytochrome P-450, exhibited no a…
Steady-state levels of retinal 24S-hydroxycholesterol are maintained by glial cells intervention after elevation of intraocular pressure in the rat
2012
Purpose: Our previous studies suggested that CYP46A1 and 24S-hydroxycholesterol. (24SOH) may be associated with glaucoma. Loss of CYP46A1-expressing retinal. ganglion cells is involved in the activation of glia, and therefore possibly in the. disbalance of cholesterol. In this context, the purpose of our present work was to. emphasize the glial and longitudinal CYP46A1 expression after an interventional. glaucoma-related stress triggered by elevated intraocular pressure (IOP). Methods: Sprague–Dawley rats were submitted to laser photocoagulation of the. trabecular meshwork, limbus and episcleral veins in one eye to induce elevated IOP. Rats were euthanized at days 3, 14, 30 and 60 (n = 10 p…
NR1H4 rs35724 G>C variant modulates liver damage in nonalcoholic fatty liver disease
2021
Background and Aims: Farnesoid X receptor (FXR) plays a key role in bile acid and lipid homeostasis. Experimental evidence suggests that it can modulate liver damage related to nonalcoholic fatty liver disease (NAFLD). We examined the impact of the NR1H4 rs35724 G>C, encoding for FXR, on liver damage in a large cohort of patients at risk of steatohepatitis. Methods: We considered 2,660 consecutive individuals at risk of steatohepatitis with liver histology. The rs35724 G>C polymorphisms were genotyped by TaqMan assays. Gene expression was evaluated by RNASeq in a subset of patients (n = 124). Results: The NR1H4 rs35724 CC genotype, after adjusting for clinic-metabolic and genetic conf…