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
TLDR
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.Abstract:
Defects in the conversion of androstenedione to testosterone in the fetal testes by the enzyme 17β–hydroxysteroid dehydrogenase (17β–HSD) give rise to genetic males with female external genitalia. We have used expression cloning to isolate cDNAs encoding a microsomal 17β–HSD type 3 isozyme that shares 23% sequence identity with other 1 7β–HSD enzymes, uses NADPH as a cofactor, and is expressed predominantly in the testes. The 17βHSD3 gene on chromosome 9q22 contains 11 exons. Four substitution and two splice junction mutations were identified in the 17βHSD3 genes of five unrelated male pseudohermaphrodites. The substitution mutations severely compromised the activity of the 17β–HSD type 3 isozyme.read more
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Species used for drug testing reveal different inhibition susceptibility for 17beta-hydroxysteroid dehydrogenase type 1.
Gabriele Möller,Bettina Husen,Dorota Kowalik,Leena Hirvelä,Dariusz Plewczynski,Leszek Rychlewski,Josef Messinger,Hubert Thole,Jerzy Adamski +8 more
TL;DR: It is shown that experiments with good candidate compounds would out-select them in the rodent model during preclinical optimization steps, therefore, potentially active human-relevant drugs would no longer be further developed.
Journal ArticleDOI
Caenorhabditis elegans LET-767 is able to metabolize androgens and estrogens and likely shares common ancestor with human types 3 and 12 17β-hydroxysteroid dehydrogenases
Serge Desnoyers,Pierre-Gilles Blanchard,Jean-François St-Laurent,Steve N. Gagnon,David L. Baillie,Van Luu-The +5 more
TL;DR: Using LET-767 transiently transfected into human embryonic kidney-293 cells, it is found that the enzyme catalyzes the transformation of both 4-androstenedione into testosterone and estrone into estradiol, similar to that of mouse 17beta-HSD12 but different from human and primate enzymes that catalyze the transformation.
Journal ArticleDOI
Characterization and modulation of sex steroid metabolizing activity in normal human keratinocytes in primary culture and HaCaT cells
TL;DR: It was found that interleukin-4 (IL-4) induced the expression of 3beta-HSD in HaCaT cells, thus allowing the cells to produce a different set of sex steroids from adrenal C19 precursors, suggesting that inflammatory cytokines might play a role in the differentiation of keratinocytes.
Journal ArticleDOI
Roles for the backdoor pathway of androgen metabolism in prostate cancer response to castration and drug treatment.
TL;DR: The goal of this review is to describe the evolution of adrenal androgen blockade, how new androgen measurement methods have furthered understanding of androgens metabolism, and how further understanding of the backdoor pathway of androgen metabolism may lead to interventions that extend survival even more.
Journal ArticleDOI
Expression and localization of estrogenic type 12 17β-hydroxysteroid dehydrogenase in the cynomolgus monkey
TL;DR: The results strongly suggest that the Macaca fascicularis 17β-HSD12 is an essential partner of aromatase in the biosynthesis of estradiol (E2), which is in contrast with the hypothesis suggesting that 4-androstenedione is converted to testosterone followed by the aromatization of testosterone.
References
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Book
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TL;DR: Molecular Cloning has served as the foundation of technical expertise in labs worldwide for 30 years as mentioned in this paper and has been so popular, or so influential, that no other manual has been more widely used and influential.
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Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes.
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Cloning, structure, and expression of the mitochondrial cytochrome P-450 sterol 26-hydroxylase, a bile acid biosynthetic enzyme.
TL;DR: The structure of the sterol 26-hydroxylase cDNA reveals it to be a mitochondrial cytochrome P-450, and blotting experiments revealed that the mRNA for this enzyme is expressed in many tissues and that it is encoded by a low copy number gene in the rabbit genome.
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Cloning, structure and expression of the mitochondrial cytochrome P-450 sterol 26-hydroxylase
TL;DR: In this article, the authors used protein sequencing and molecular cloning techniques to isolate and characterize a cDNA encoding the rabbit mitochondrial sterol 26-hydroxylase, which catalyzes the first step in the oxidation of the side chain of sterol intermediates in the biosynthesis of bile acids.