Journal ArticleDOI
Differential estrogen substrate specificities for transiently expressed human placental 17 beta-hydroxysteroid dehydrogenase and an endogenous enzyme expressed in cultured COS-m6 cells
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TLDR
The metabolism of estrogens catalyzed by human placental 17 beta-hydroxysteroid dehydrogenase transiently expressed in COS-m6 cells was studied, and the properties of the enzyme were compared with those of an endogenous hydroxysteroid dehydration enzyme expressed in the cells, suggesting that different 17HSD enzymes exist, with differential estrogen substrate specificities in cultured cells.Abstract:
The metabolism of estrogens catalyzed by human placental 17 beta-hydroxysteroid dehydrogenase (17HSD) transiently expressed in COS-m6 cells was studied, and the properties of the enzyme were compared with those of an endogenous hydroxysteroid dehydrogenase (HSD) expressed in the cells In cultured cells, the endogenous HSD had almost exclusively oxidative activity, converting estradiol to estrone (oxidative and reductive activity, 084 +/- 0164 and 0034 +/- 001 nmol/mg proteinh, respectively) This was, nevertheless, opposed to the activity of the transiently expressed human placental 17HSD, as a high reductive activity (086 +/- 030 nmol/mg proteinh) appeared in the cells after transfection, whereas oxidative activity was not significantly induced In the different transfections, the reductive activity was induced 13- to 34-fold, and the oxidative activity in the 17HSD-transfected cells was 65-162% of that in the mock-transfected cells Thus, in cultured cells, these two enzymes preferentially cataread more
Citations
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Journal ArticleDOI
Male pseudohermaphroditism caused by mutations of testicular 17β-hydroxysteroid dehydrogenase 3
Wayne M. Geissler,Daphne L. Davis,Ling Wu,Karen D. Bradshaw,S. Patel,Berenice B. Mendonca,Keith O. Elliston,Jean D. Wilson,David W. Russell,Stefan Andersson +9 more
TL;DR: Four substitution and two splice junction mutations were identified in the 17βHSD3 genes of five unrelated male pseudohermaphrodites that severely compromised the activity of the 17 β–HSD type 3 isozyme.
Journal ArticleDOI
Molecular Endocrinology of Hydroxysteroid Dehydrogenases
TL;DR: This work states that the 3β-HSD/KSI cDNAs and 3α- HSD deficiencies are likely to be driven by the same underlying mechanism, namely phosphorylation of H2O by the H3O2 “spatially aggregating” substance.
Journal ArticleDOI
The structure of a complex of human 17β-hydroxysteroid dehydrogenase with estradiol and NADP+ identifies two principal targets for the design of inhibitors
TL;DR: From the structure of the complex of the enzyme with the substrate and cofactor of the oxidation reaction, the orientation of the substrates for the reduction reaction can be deduced with confidence.
Journal ArticleDOI
Estrogen-specific 17 beta-hydroxysteroid oxidoreductase type 1 (E.C. 1.1.1.62) as a possible target for the action of phytoestrogens.
TL;DR: Several plant estrogens, especially coumestrol and genistein, were found to reduce the conversion of 17β-HSOR Type 1 catalyzed by estrogenspecific 17 β-hydroxysteroid oxidoreductase Type 1 in vitro, and they may thus replace endogenous estrogens.
Journal ArticleDOI
Expression Cloning of a Novel Estrogenic Mouse 17β-Hydroxysteroid Dehydrogenase/ 17-Ketosteroid Reductase (m17HSD7), Previously Described as a Prolactin Receptor-Associated Protein (PRAP) in Rat
TL;DR: The results indicate that 17HSD7 is an enzyme of E2 biosynthesis, which is predominantly expressed in the corpus luteum of the pregnant animal, and it is suggested that rPRAP is rat 17 HSD type 7.
References
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Journal ArticleDOI
Induction of human endometrial estradiol dehydrogenase by progestins.
Linda Tseng,Erlio Gurpide +1 more
TL;DR: In vitro and in vivo results point to progesterone as the agent responsible for the 10-fold increase in endometrial estradiol dehydrogenase activity observed during the luteal phase in menstruating women.
Journal ArticleDOI
Distribution of 17 beta-hydroxysteroid dehydrogenase gene expression and activity in rat and human tissues.
Céline Martel,Eric Rhéaume,Masakazu Takahashi,Claude Trudel,Jacques Couet,Van Luu-The,J. Simard,Fernand Labrie +7 more
TL;DR: The widespread distribution of 17β-HSD in rat and human tissues clearly indicates the importance of this enzyme in peripheral sex steroid formation or intracrinology.
Journal ArticleDOI
THE RELATIONSHIP BETWEEN 17β-HYDROXYSTEROID DEHYDROGENASE ACTIVITY AND OESTROGEN CONCENTRATIONS IN HUMAN BREAST TUMOURS AND IN NORMAL BREAST TISSUE
TL;DR: The activity of 17β‐hydroxysteroid dehydrogenase was measured in human breast tumours and in normal breast tissue from premenopausal, perimenopausal and postmenopausal women and the physiological status of the women in the study did not relate to the activity of the enzyme.
Journal ArticleDOI
Progestin Effect on Cell Proliferation and 17β-Hydroxysteroid Dehydrogenase Activity in Normal Human Breast Cells in Culture*
Anne Gompel,C. Malet,Poli Mara Spritzer,Jean-Pierre Lalardrie,Frédérique Kuttenn,Pierre Mauvais-Jarvis +5 more
TL;DR: E2 stimulated proliferation of human breast epithelial cells in culture, whereas the progestin R5020 inhibited cell multiplication and favored differentiation, and the antiprogesterone RU486 had a biphasic effect acting both as progest in agonist and partial antagonist.
Journal ArticleDOI
Structure of two in tandem human 17β-hydroxysteroid dehydrogenase genes
Van Luu-The,Claude Labrie,Jacques Simard,Yves Lachance,Hui-Fen Zhao,Jacques Couet,Gilles Leblanc,Fernand Labrie +7 more
TL;DR: The complete exon and intron sequences of the two genes as well as their 5′ and 3′-flanking regions are determined and provide the basis for a better understanding of the molecular mechanisms involved in 17β-HSD deficiency and peripheral sex steroid metabolism.