scispace - formally typeset
Search or ask a question
Topic

Hydroxysteroid dehydrogenase

About: Hydroxysteroid dehydrogenase is a research topic. Over the lifetime, 1087 publications have been published within this topic receiving 28468 citations. The topic is also known as: hydroxysteroid dehydrogenase.


Papers
More filters
Journal ArticleDOI
TL;DR: In this article, a review of 17β-hydroxysteroid dehydrogenase type 1 inhibitors is presented, which are divided into two separate groups according to their chemical structures.
Abstract: Carcinogenesis of hormone-related cancers involves hormone-stimulated cell proliferation, which increases the number of cell divisions and the opportunity for random genetic errors. In target tissues, steroid hormones are interconverted between their potent, high affinity forms for their respective receptors and their inactive, low affinity forms. One group of enzymes responsible for these interconversions are the hydroxysteroid dehydrogenases, which regulate ligand access to steroid receptors and thus act at a pre-receptor level. As part of this group, the 17β-hydroxysteroid dehydrogenases catalyze either oxidation of hydroxyl groups or reduction of keto groups at steroid position C17. The thoroughly characterized 17β-hydroxysteroid dehydrogenase type 1 activates the less active estrone to estradiol, a potent ligand for estrogen receptors. This isoform is expressed in gonads, where it affects circulating levels of estradiol, and in peripheral tissue, where it regulates ligand occupancy of estrogen receptors. Inhibitors of 17β-hydroxysteroid dehydrogenase type 1 are thus highly interesting potential therapeutic agents for the control of estrogen-dependent diseases such as endometriosis, as well as breast and ovarian cancers. Here, we present the review on the recent development of inhibitors of 17β-hydroxysteroid dehydrogenase type 1 published and patented since the previous review of 17β-hydroxysteroid dehydrogenase inhibitors of Poirier (Curr. Med. Chem., 2003, 10, 453). These inhibitors are divided into two separate groups according to their chemical structures: steroidal and non-steroidal 17β- hydroxysteroid dehydrogenase type 1 inhibitors. Their estrogenic/ proliferative activities and selectivities over other 17β-hydroxysteroid dehydrogenases that are involved in local regulation of estrogen action (types 2, 7 and 12) are also presented.

85 citations

Journal ArticleDOI
TL;DR: It is hypothesized that the differential expression of the two 17HSD enzymes, with opposite activities in same cell types, could modulate intracellular E2 concentrations during the end of the luteal phase of the menstrual cycle.
Abstract: According to the current hypothesis, 17β-hydroxysteroid dehydrogenases (17HSDs) regulate the extent of estrogen influence in the endometrium by converting estradiol (E2) locally into a biologically less active sex steroid, estrone (E1), and vice versa. Recently, we have shown that both 17HSD type 1 and type 2 are expressed in the human endometrium, and in the present work, using in situ hybridization, we show that 17HSD type 2 is localized in the glandular epithelial cells as previously shown for the type 1 enzyme, but in contrast to type 1, the expression of type 2 is highest at the end of the cycle. Hence, we hypothesize that the differential expression of the two 17HSD enzymes, with opposite activities in same cell types, could modulate intracellular E2 concentrations during the end of the luteal phase of the menstrual cycle. We further analyzed the expression of 17HSD type 1 and type 2 mRNAs in term human placenta. Expression of 17HSD type 1 mRNA was detected in the syncytiotrophoblasts, and signals f...

84 citations

Journal ArticleDOI
TL;DR: It is clear that major efforts should now be turned towards intracrinology in order to understand better the physiological mechanisms controlling local steroid formation in peripheral target tissues and thus to develop novel therapeutic approaches that take into account the high proportion of steroids that are made locally.
Abstract: Summary In addition to the classical steroidogenic tissues, namely the ovaries, testes, adrenals and placenta, a large series of human peripheral tissues possess all the enzymatic systems required for the formation of active androgens and oestrogens from a relatively large supply of precursor steroids provided by the adrenals. This chapter describes the structure, function, tissue-specific expression and regulation of the 3β-HSD and 17β-HSD gene families as well as some information about the aromatase gene. While, so far, most therapeutic approaches have been aimed and limited at controlling steroid formation by the classical steroidogenic tissues, it is clear that major efforts should now be turned towards intracrinology in order to understand better the physiological mechanisms controlling local steroid formation in peripheral target tissues and thus be in a position to develop novel therapeutic approaches that take into account the high proportion of steroids that are made locally and are responsible for the growth and function of normal as well as cancerous tissue.

83 citations

Journal ArticleDOI
TL;DR: The 7α-hydroxy-DHEA produced by the cytochrome CYP7B1 in tissues may exert anti-glucocorticoid effects through interference with the 11β-HSD1-mediated cortisone reduction.

83 citations

Journal ArticleDOI
TL;DR: The current findings boost to 16 the number of mutations in the HSD17B3 gene that impair testosterone synthesis and cause male pseudohermaphroditism, and add 1 apparently silent polymorphism to this tally.
Abstract: Isozymes of 17β-hydroxysteroid dehydrogenase (17βHSD) regulate levels of bioactive androgens and estrogens in a variety of tissues. For example, the 17βHSD type 3 isozyme catalyzes the conversion of the inactive C19-steroid androstenedione to the biologically active androgen, testosterone, in the testis. Testosterone is essential for the correct development of male internal and external genitalia; hence, deleterious mutations in the HSD17B3 gene give rise to a rare form of male pseudohermaphroditism termed 17βHSD deficiency. Here, 2 additional missense mutations in the HSD17B3 gene in subjects with 17βHSD deficiency are described. One mutation (A56T) impairs enzyme function by affecting NADPH cofactor binding. A second mutation (N130S) led to complete loss of enzyme activity. Also, a single base pair polymorphism in exon 11 of the HSD17B3 gene is described. The polymorphic A allele encodes a protein with a serine rather than a glycine at position 289 (GGT → AGT). The frequency of the G allele (Gly) was 0....

81 citations


Network Information
Related Topics (5)
Hormone
38.3K papers, 1.2M citations
83% related
Estrogen
40.7K papers, 1.7M citations
83% related
Estrogen receptor
34.2K papers, 1.4M citations
80% related
Secretion
24.8K papers, 1.2M citations
78% related
Receptor
159.3K papers, 8.2M citations
78% related
Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202319
202217
20218
202016
201916
20186