Search results for "estrogen"

Chiral Inversion of 1-Hydroxyethylpyrene Enantiomers Mediated by Enantioselective Sulfotransferases

1998

The benzylic alcohol 1-hydroxyethylpyrene (1-HEP) is activated to a mutagen by sulfotransferases. The sulfuric acid ester formed is difficult to detect, as it is rapidly hydrolysed back to the alcohol. Incubation of the individual enantiomers of 1-HEP with human hydroxysteroid sulfotransferase (hHST) or estrogen sulfotransferase (hEST), expressed in bacteria, led to the formation of the other enantiomer. The rates of sulfation were determined from the initial rates of chiral inversion of the alcohol, knowing that hydrolysis follows an SN1 mechanism and therefore produces racemic alcohol. hEST showed high enantioselectivity for S-1-HEP, whereas hHST strongly preferred the R-enantiomer. The r…

The risk for cardiovascular disease in women: from estrogens to selective estrogen receptor modulators.

2006

Cardiovascular disease, a generic denomination including coronary heart disease (CHD), stroke, and venous thromboembolic disease (VTED), has shown sensitivity to estrogens. The relative protection of women as compared with men has nourished a debate about a possible protective role for estrogens, but the prejudicial effects detected in clinical trials has created confusion on the risk/benefit ratio induced by hormone administration. The hypothesis that agonists distinct to estrogens might improve the effects associated with estrogens is at the base of the increasing interest on the role of selective estrogen receptor modulators (SERMs). There is a lack of definitive clearcut clinical data o…

Enhanced steatosis by nuclear receptor ligands: a study in cultured human hepatocytes and hepatoma cells with a characterized nuclear receptor expres…

2010

Steatosis is the first step in the development of non-alcoholic fatty liver disease (NAFLD). However, the mechanisms involved in its pathogenesis are not fully understood. Many nuclear receptors (NRs) involved in energy homeostasis and biotransformation constitute a network connecting fatty acids, cholesterol and xenobiotic metabolisms; therefore, multiple NRs and their ligands may play a prominent role in liver fat metabolism and accumulation. In this study we have attempted to gain insight into the relevance of the NR superfamily in NAFLD by investigating the steatogenic potential of 76 different NR ligands in fatty acid overloaded human hepatocytes and hepatoma cells. Moreover, we have d…

Raloxifene increases proliferation of human endothelial cells in association with increased gene expression of cyclins A and B1.

2006

Objective To examine the proliferative effect of of raloxifene on human umbilical-vein endothelial cells (HUVECs), and to investigate whether there is an associated increased expression of some key regulators of the cell cycle. Design Cell culture for different incubation times. Setting University research laboratory. Patient(s) Sources of HUVECs. Intervention(s) Measurement of cell proliferation, of protein levels of cyclin A, cyclin B1, cyclin D1, cyclin-dependent protein kinase (CDK) 2, CDK4, and p27 Kip1 , and of messenger RNA expression of cyclin A, cyclin B1, and p27 Kip1 . Main Outcome Measure(s) Cell proliferation was measured by the 3-(4.5-dimethylthiazol-2-yl)-2,5-diphenyltetrazol…

Selective estrogen receptor modulators and risk for coronary heart disease.

2007

Coronary heart disease (CHD) is the leading cause of death in women in most countries. Atherosclerosis is the main biological process determining CHD. Clinical data support the notion that CHD is sensitive to estrogens, but debate exists concerning the effects of the hormone on atherosclerosis and its complications. Selective estrogen receptor modulators (SERMs) are compounds capable of binding the estrogen receptor to induce a functional profile distinct from estrogens. The possibility that SERMs may shift the estrogenic balance on cardiovascular risk towards a more beneficial profile has generated interest in recent years. There is considerable information on the effects of SERMs on disti…

Therapeutic dosages of raloxifene do not modify myeloperoxidase and F2alpha-isoprostane levels in postmenopausal women.

2005

We investigated the effect of a therapeutic dose of raloxifene on the plasma levels of myeloperoxidase and F2alpha-isoprostanes, two markers of oxidative stress recently described as reliable indicators of coronary heart disease. Contrary to changes described in the literature for estrogens (E), raloxifene did not modify the levels of either myeloproxidase or F2alpha-isoprostanes after 3 or 6 months of treatment.

Are the serum levels of sCD40L modified by raloxifene in postmenopausal women?

2008

Raloxifene increases the capacity of serum to promote prostacyclin release in human endothelial cells: implication of COX-1 and COX-2.

2004

OBJECTIVE Prostacyclin is a potent vasodilator synthesized by two isoforms of cyclooxygenase in endothelium. The aim of this study was to investigate the effect of serum from postmenopausal women treated with raloxifene on prostacyclin production by human umbilical vein endothelial cells and on cyclooxygenases-1 and -2. DESIGN Serum was collected from 21 women receiving 60 mg/day of raloxifene, at baseline and at 3 and 6 months. Human umbilical vein endothelial cells were exposed to serum for 24 hours, and prostacyclin production was evaluated in supernatants. Selective inhibitors of cyclooxygenases-1 and -2 (SC-560 and NS-398) were used to investigate the relative contribution of each enzy…

The adverse effects of estrogen and selective estrogen receptor modulators on hemostasis and thrombosis.

2012

Agonists of the estrogen receptor include estrogens and selective estrogen receptor modulators (SERMs). Both types of compounds increase the risk for thrombosis in the arterial and the venous tree. The magnitude of the effect is influenced by potency, which depends on the type of compound and the dose. The particulars of the process change in each territory. Atherosclerosis, which creates local inflammatory conditions, may favor thrombogenesis in arteries. A direct effect of estrogen agonists is also well endorsed at both arteries, as suggested from data with high-estrogenic contraceptives, and veins. Dose reduction has been proved to be an effective strategy, but there is debate on whether…

Circulating miR-21, miR-146a and Fas ligand respond to postmenopausal estrogen-based hormone replacement therapy--a study with monozygotic twin pairs.

2014

Biological aging is associated with physiological deteriorations and its’ remodeling, which are partly due to changes in the hormonal profile. MicroRNAs are known to post-transcriptionally regulate various cellular processes associated with cell senescence; differentiation, replication and apoptosis. Measured from the serum, microRNAs have the potential to serve as noninvasive markers for diagnostics/prognostics and therapeutic targets. We analysed the association of estrogen-based hormone replacement therapy (HRT) with selected microRNAs and inflammation markers from the serum, leukocytes and muscle tissue biopsy samples obtained from 54-62 year-old postmenopausal monozygotic twins (n=11 p…