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Marie Wetzel

Bio: Marie Wetzel is an academic researcher from Saarland University. The author has contributed to research in topics: Hydroxysteroid dehydrogenase & Estrogen. The author has an hindex of 8, co-authored 9 publications receiving 370 citations.

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Journal ArticleDOI
TL;DR: An overview of functional and structural aspects for the different 17β-HSDs is given and the selective inhibition of the concerned enzymes might provide an effective treatment and a good alternative to the existing endocrine therapies.

183 citations

Journal ArticleDOI
TL;DR: Inhibition of 17β-HSD1 inhibitors from the hydroxyphenylnaphthol class by introduction of different heteroaromatic rings as well as substituted phenyl groups showed a good membrane permeation and metabolic stability and was orally available in the rat.
Abstract: Inhibition of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) is a novel and attractive approach to reduce the local levels of the active estrogen 17β-estradiol in patients with estrogen-depende...

51 citations

Journal ArticleDOI
TL;DR: Inhibition of 17β-HSD2 may provide a new and promising approach to prevent the onset of osteoporosis, keeping a certain level in estrogens and androgens in bone cells of ageing people.

43 citations

Journal ArticleDOI
TL;DR: Compound 19 turned out to be the most potent and selective inhibitor of 17 β-HSD2 in cell-free assays and had a very good cellular activity in MDA-MB-231 cells, expressing naturally 17β- HSD2.
Abstract: Estrogen deficiency in postmenopausal women or elderly men is often associated with the skeletal disease osteoporosis. The supplementation of estradiol (E2) in osteoporotic patients is known to prevent bone fracture but cannot be administered because of adverse effect. As 17β-hydroxysteroid dehydrogenase type 2 (17β-HSD2) oxidizes E2 to its inactive form estrone (E1) and has been found in osteoblastic cells, it is an attractive target for the treatment of osteoporosis. Twenty-one novel, naphthalene-derived compounds have been synthesized and evaluated for their 17β-HSD2 inhibition and their selectivity toward 17β-HSD1 and the estrogen receptors (ERs) α and β. Compound 19 turned out to be the most potent and selective inhibitor of 17β-HSD2 in cell-free assays and had a very good cellular activity in MDA-MB-231 cells, expressing naturally 17β-HSD2. It also showed marked inhibition of the E1-formation by the rat and mouse orthologous enzymes and strong inhibition of monkey 17β-HSD2. It is thus an appropriate...

43 citations

Journal ArticleDOI
TL;DR: Highly selective compounds (11, 12, 14, 21 and 22) have been identified, the most promising one (12) showing an IC(50) value in the low nanomolar range (101 nM) and a selectivity factor of 13 toward 17β-HSD1 and an interesting candidate for further biological evaluation.

25 citations


Cited by
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Journal ArticleDOI
TL;DR: In this article, an overview of steroid hormone biosynthesis and metabolism by the liver and peripheral tissues is presented, specifically highlighting the pathways linking and differentiating the serum and urine steroid metabolomes.

187 citations

Journal ArticleDOI
TL;DR: The association of variants in HSD17B13 with specific features of NAFLD histology is demonstrated and the enzyme is identified as a lipid droplet–associated RDH; the data suggest that HSD 17B13 plays a role inNAFLD through its enzymatic activity.

184 citations

Journal ArticleDOI
TL;DR: The present review is an update on some of the steroidal leads obtained during past 25 years, various steroid based enzyme inhibitors, antiestrogens, cytotoxic conjugates and steroidal cytot toxic molecules of natural as well as synthetic origin have been highlighted.

163 citations

Journal ArticleDOI
TL;DR: The aim of this study was to determine the function of 17β-hydroxysteroid dehydrogenase-13 (17β-HSD13), one of the authors' newly identified LD-associated proteins in human subjects with normal liver histology and simple steatosis, in NAFLD development.
Abstract: Nonalcoholic fatty liver disease (NAFLD) is characterized by a massive accumulation of lipid droplets (LDs). The aim of this study was to determine the function of 17β-hydroxysteroid dehydrogenase-13 (17β-HSD13), one of our newly identified LD-associated proteins in human subjects with normal liver histology and simple steatosis, in NAFLD development. LDs were isolated from 21 human liver biopsies, including 9 cases with normal liver histology (group 1) and 12 cases with simple steatosis (group 2). A complete set of LD-associated proteins from three liver samples of group 1 or group 2 were determined by 2D LC-MS/MS. By comparing the LD-associated protein profiles between subjects with or without NAFLD, 54 up-regulated and 35 down-regulated LD-associated proteins were found in NAFLD patients. Among them, 17β-HSD13 represents a previously unidentified LD-associated protein with a significant up-regulation in NAFLD. Because the 17β-HSD family plays an important role in lipid metabolism, 17β-HSD13 was selected for validating the proteomic findings and exploring its role in the pathogenesis of NAFLD. Increased hepatic 17β-HSD13 and its LD surface location were confirmed in db/db (diabetic) and high-fat diet-fed mice. Adenovirus-mediated hepatic overexpression of human 17β-HSD13 induced a fatty liver phenotype in C57BL/6 mice, with a significant increase in mature sterol regulatory element-binding protein 1 and fatty acid synthase levels. The present study reports an extensive set of human liver LD proteins and an array of proteins differentially expressed in human NAFLD. We also identified 17β-HSD13 as a pathogenic protein in the development of NAFLD.

147 citations

Journal ArticleDOI
TL;DR: Endometrial or endometriotic tissue E2 concentrations are actively regulated by local estrogen metabolism in the tissue, and the inhibition of local E2 synthesis is a valid, novel approach to reduce local E1-dependent growth of endometiotic tissue.
Abstract: Context: Aberrant estrogen synthesis and metabolism have been suggested to increase local estradiol (E2) concentration in endometriosis and thus to promote the growth of the lesions. However, tissue estrogen concentrations within the endometrium and different types of endometriosis lesions have not been described. Objective: The aim of the study was to evaluate local E2 and estrone (E1) concentrations in the endometrium and different types of endometriosis lesions, and to correlate them with the expression of estrogen-metabolizing enzymes. Patients: Patients with endometriosis (n = 60) and healthy controls (n = 16) participated in the study. Main Outcome Measures: We measured serum and tissue concentrations of E2 and E1 as well as mRNA expression of the estrogen-metabolizing enzymes. Results: Endometrial or endometriotic intratissue E2 concentrations did not reflect the corresponding serum levels. In the proliferative phase, endometrial E2 concentration was five to eight times higher than in the serum, wh...

145 citations