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.
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TL;DR: The inability of phytoestrogens to acutely inhibit steroidogenic enzymes in humanGL cells suggests that they are either rapidly metabolized to relatively inactive compounds or that the high enzyme activity in human GL cells masks any inhibitory effects of the compounds at the concentration tested.
Abstract: Background Studies using purified enzyme preparations, placental microsomes or cell lines have shown that certain phytoestrogens can inhibit the enzymes that convert androgens to estrogens, namely aromatase and 17beta-hydroxysteroid dehydrogenase (HSD) type 1 and type 5. The study aim was to investigate the effects of selected phytoestrogens on aromatase and 17beta-HSD type 1 activity in primary cultures of human granulosa-luteal (GL) cells. Methods and results GL cells, cultured for 48 h in medium containing 5% fetal calf serum and for a further 24 h in serum-free medium with or without hFSH or hCG, were exposed to steroid substrates during the last 1-4 h of the experiment. The production of progesterone in the presence of pregnenolone or estradiol synthesis from androstenedione, estrone or testosterone showed dose- and time-dependent increases. Whilst hCG priming had no effect on progesterone production, FSH priming induced mean 68 and 56% increases in the production of estradiol from androstenedione (A-dione) and estrone respectively, but had no significant effect on the metabolism of testosterone to estradiol. None of the phytoestrogens investigated had any acute effects on enzyme activity. In contrast, when GL cells were exposed to the compounds for 24 h prior to exposure to steroid substrates for 4 h, 10 micro mol/l apigenin and zearalenone significantly inhibited aromatase activity, whilst biochanin A and quercetin had no effect. None of the phytoestrogens inhibited FSH-induced 17beta-HSD type 1 activity, and only quercetin significantly inhibited progesterone production. Conclusions The inability of phytoestrogens to acutely inhibit steroidogenic enzymes in human GL cells (as has been shown in cell-free models) suggests that they are either rapidly metabolized to relatively inactive compounds or that the high enzyme activity in human GL cells masks any inhibitory effects of the compounds at the concentration tested.
67 citations
Patent•
16 Dec 2005TL;DR: In this article, the authors provided compounds of formula I that are useful as potent and selective inhibitors of 11-beta hydroxysteroid dehydrogenase 1 (HBDE) and a pharmaceutical composition which comprises a compound of Formula I, or a pharmaceutical salt thereof, and a pharmaceutically acceptable carrier, diluent, or excipient.
Abstract: The present invention provides compounds of formula I that are useful as potent and selective inhibitors of 11-beta hydroxysteroid dehydrogenase 1. The present invention further provides a pharmaceutical composition which comprises a compound of Formula I, or a pharmaceutical salt thereof, and a pharmaceutically acceptable carrier, diluent, or excipient. In addition, the present invention compositions containing these compounds for the treatment of metabolic syndrome, diabetes, hyperglycemia, obesity, hypertension, hyperlipidemia, other symptoms associated with hyperglycemia, and related disorders. Formula I wherein G1 is methylene or ethylene; L is-(C1-C4)alkylene-, -S-, -CH(OH)-, or -O-; R0 is Formula II or Formula III and the other substituents are as defined in the claims.
67 citations
TL;DR: The usual mechanism for testosterone formation in affected individuals at puberty appears to be conversion of androstenedione to testosterone in extraglandular tissues by one or more of the unaffected 17β-hydroxysteroid dehydrogenase isoenzymes.
Abstract: Five known isoenzymes catalyze the 17β-hydroxysteroid dehydrogenase reaction that controls the interconversion of estrone and estradiol and of testosterone and androstenedione. Mutations in the 17β-hydroxysteroid dehydrogenase 3 gene impair the formation of testosterone in the fetal testis and give rise to genetic males with normal male Wolffian duct structures but female external genitalia. Such individuals are usually raised as females but virilize at the time of puberty as the result of a rise in serum testosterone. The 14 mutations characterized to date in 17 affected families include 10 missense mutations, 3 splice junction abnormalities, and 1 frame shift mutation. Three of the mutations have occurred in more than 1 family. The usual mechanism for testosterone formation in affected individuals at puberty appears to be conversion of androstenedione to testosterone in extraglandular tissues by one or more of the unaffected 17β-hydroxysteroid dehydrogenase isoenzymes.
66 citations
TL;DR: A dose-response relationship in the inhibitory effect of this compound further confirmed the validity of the model for testing the drug candidates in vivo for evaluating putative inhibitors for the human enzyme in vivo.
66 citations
TL;DR: It is concluded that in 3 alpha-HSD, the time dependence of the change in Trp 86 fluorescence is due to cofactor anchoring, and thus,trp 86 is a distal reporter of this event, and the loop movement that accompanies cofactor binding is spectrally silent.
Abstract: Fluorescence stopped-flow studies were conducted with recombinant rat liver 3α-HSD, an aldo-keto reductase (AKR) that plays critical roles in steroid hormone inactivation, to characterize the bindi...
66 citations