pregnenolone

出典: meddic

プレグネノロン

  • (副腎皮質ホルモン前駆体;神経ステロイド)レグネノロン


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出典(authority):フリー百科事典『ウィキペディア(Wikipedia)』「2014/04/14 15:09:07」(JST)

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英文文献

  • Pregnane X receptor agonists enhance intestinal epithelial wound healing and repair of the intestinal barrier following the induction of experimental colitis.
  • Terc J1, Hansen A1, Alston L1, Hirota SA2.Author information 1Departments of Physiology & Pharmacology, University of Calgary, 3330 Hospital Dr. NW, Health Sciences Room 1802, Calgary, Alberta T2N4N1, Canada; Microbiology, Immunology & Infectious Diseases, University of Calgary, 3330 Hospital Dr. NW, Health Sciences Room 1802, Calgary, Alberta T2N4N1, Canada.2Departments of Physiology & Pharmacology, University of Calgary, 3330 Hospital Dr. NW, Health Sciences Room 1802, Calgary, Alberta T2N4N1, Canada; Microbiology, Immunology & Infectious Diseases, University of Calgary, 3330 Hospital Dr. NW, Health Sciences Room 1802, Calgary, Alberta T2N4N1, Canada. Electronic address: simon.hirota@ucalgary.ca.AbstractThe intestinal epithelial barrier plays a key role in the maintenance of homeostasis within the gastrointestinal tract. Barrier dysfunction leading to increased epithelial permeability is associated with a number of gastrointestinal disorders including the inflammatory bowel diseases (IBD) - Crohn's disease and ulcerative colitis. It is thought that the increased permeability in patients with IBD may be driven by alterations in the epithelial wound healing response. To this end considerable study has been undertaken to identify signaling pathways that may accelerate intestinal epithelial wound healing and normalize the barrier dysfunction observed in IBD. In the current study we examined the role of the pregnane X receptor (PXR) in modulating the intestinal epithelial wound healing response. Mutations and reduced mucosal expression of the PXR are associated with IBD, and others have reported that PXR agonists can dampen intestinal inflammation. Furthermore, stimulation of the PXR has been associated with increased cell migration and proliferation, two of the key processes involved in wound healing. We hypothesized that PXR agonists would enhance intestinal epithelial repair. Stimulation of Caco-2 intestinal epithelial cells with rifaximin, rifampicin and SR12813, all potent agonists of the PXR, significantly increased wound closure. This effect was driven by p38 MAP kinase-dependent cell migration, and occurred in the absence of cell proliferation. Treating mice with a rodent specific PXR agonist, pregnenolone 16α-carbonitrile (PCN), attenuated the intestinal barrier dysfunction observed in the dextran sulphate sodium (DSS) model of experimental colitis, an effect that occurred independent of the known anti-inflammatory effects of PCN. Taken together our data indicate that the activation of the PXR can enhance intestinal epithelial repair and suggest that targeting the PXR may help to normalize intestinal barrier dysfunction observed in patients with IBD. Furthermore, our data provide additional insight into the potential mechanisms through which rifaximin elicits its clinical efficacy in the treatment of IBD.
  • European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.Eur J Pharm Sci.2014 May 13;55:12-9. doi: 10.1016/j.ejps.2014.01.007. Epub 2014 Jan 29.
  • The intestinal epithelial barrier plays a key role in the maintenance of homeostasis within the gastrointestinal tract. Barrier dysfunction leading to increased epithelial permeability is associated with a number of gastrointestinal disorders including the inflammatory bowel diseases (IBD) - Crohn's
  • PMID 24486481
  • Ligand-based virtual screening to predict inhibitors against metastatic lymph node 64.
  • Chitrala KN1, Yeguvapalli S.Author information 1Department of Zoology, Sri Venkateswara University , Tirupati, Andhra Pradesh , India.AbstractAbstract Conversion of cholesterol to pregnenolone is the rate-limiting step in steroidogenesis, which is mediated by StAR protein. The mammalian genome contains 15 START domain proteins (StARD1-StARD15) of which C-terminal cytosolic START domain of metastatic lymph node 64 (MLN64 or StARD3), is known to mobilize cholesterol and proposed to participate in steroidogenesis. Being a key in steroidogenesis, it is of interest to identify new inhibitors that are able to bind MLN64 protein. In the present study, we used ligand-based virtual screening approach to identify ligands from the ZINC database with D(-)-Tartaric Acid (TAR) serving as a template.
  • Journal of receptor and signal transduction research.J Recept Signal Transduct Res.2014 Apr;34(2):92-6. doi: 10.3109/10799893.2013.862269. Epub 2013 Dec 9.
  • Abstract Conversion of cholesterol to pregnenolone is the rate-limiting step in steroidogenesis, which is mediated by StAR protein. The mammalian genome contains 15 START domain proteins (StARD1-StARD15) of which C-terminal cytosolic START domain of metastatic lymph node 64 (MLN64 or StARD3), is kno
  • PMID 24320143
  • Identification and stress-induced expression of three 3β-hydroxysteroid dehydrogenases from Erysimum crepidifolium Rchb. and their putative role in cardenolide biosynthesis.
  • Munkert J1, Ernst M1, Müller-Uri F1, Kreis W2.Author information 1Pharmaceutical Biology, Department Biology, Friedrich-Alexander University Erlangen-Nürnberg, Staudtstr. 5, 91058 Erlangen, Germany.2Pharmaceutical Biology, Department Biology, Friedrich-Alexander University Erlangen-Nürnberg, Staudtstr. 5, 91058 Erlangen, Germany; ECROPS Erlangen Center of Plant Science, Germany. Electronic address: wolfgang.kreis@fau.de.Abstract3β-Hydroxysteroid dehydrogenases (3βHSD) are supposed to be involved in cardenolide biosynthesis in plants. Erysimum crepidifolium Rchb., a member of the Brassicaceae accumulating cardenolides, is a close relative to Arabidopsis thaliana. Full length cDNAs encoding for three individual 3βHSDs (EcHSD1, EcHSD2, EcHSD3) were isolated from E. crepidifolium leaves. EcHSD1 and EcHSD2 encode proteins assembled from 257 amino acids whereas EcHSD3 encodes a protein assembled from 260 amino acids. All three proteins qualify as members of the short-chain dehydrogenases/reductases family of proteins (SDRs). EcHSD1 and EcHSD2 shared a high amino acid sequence identity of about 86% and 91% with putative 3βHSDs of A. thaliana (AT2G47140 and AT2G47130). EcHSD3 showed high homology to the A. thaliana SDRs AT2G47150 (74%) and AT2G47120 (81%). All three EcHSD genes were expressed in Escherichia coli and the recombinant enzymes were characterized biochemically. All three recombinant EcHSDs catalyzed the dehydrogenation of pregnenolone and the 3-reduction of 5α/β-pregnane-3,20-dione when NAD and NADH were used as cosubstrates, respectively. After exposure to different stress conditions, no increased transcription was seen for EcHSD1 whereas EcHSD2 was expressed four times higher under osmotic stress than under control conditions. EcHSD3 expression was 10 times and 6 times higher after osmotic stress and MeJA treatment, respectively, than in controls.
  • Phytochemistry.Phytochemistry.2014 Apr;100:26-33. doi: 10.1016/j.phytochem.2014.01.006. Epub 2014 Feb 7.
  • 3β-Hydroxysteroid dehydrogenases (3βHSD) are supposed to be involved in cardenolide biosynthesis in plants. Erysimum crepidifolium Rchb., a member of the Brassicaceae accumulating cardenolides, is a close relative to Arabidopsis thaliana. Full length cDNAs encoding for three individual 3βHSDs (Ec
  • PMID 24512841

和文文献

  • Effect of Polyphenols on Production of Steroid Hormones from Human Adrenocortical NCI-H295R Cells
  • Hasegawa Eri,Nakagawa Saori,Sato Momoe [他]
  • Biological & pharmaceutical bulletin 36(2), 228-237, 2013-02-00
  • NAID 40019558450
  • A condensed phenylpropanoid glucoside and pregnane saponins from the roots of Hemidesmus indicus
  • Zhao Zhimin,Matsunami Katsuyoshi,Otsuka Hideaki [他]
  • Journal of natural medicines 67(1), 137-142, 2013-00-00
  • NAID 40019527742
  • Effect of Polyphenols on Production of Steroid Hormones from Human Adrenocortical NCI-H295R Cells
  • Hasegawa Eri,Nakagawa Saori,Sato Momoe,Tachikawa Eiichi,Yamato Susumu
  • Biological and Pharmaceutical Bulletin 36(2), 228-237, 2013
  • … Here we cultured forskolin-stimulated NCI-H295R, a human adrenocortical carcinoma cell line, in the presence of a polyphenol and employed GC-MS to simultaneously determine the levels of nine steroid hormones (pregnenolone, progesterone, deoxycorticosterone, aldosterone, 17α-hydroxyprogesterone, dehydroepiandrosterone, androstenedione, testosterone, and estradiol) in cell culture supernatant. …
  • NAID 130003361368

関連リンク

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植物由来のプレグネノロン(Pregnenolone) PREG:プログネノロンは副腎と脳内で作られ、全身すみずみにまで働きかける神経ホルモンの一つです。 中枢神経の働きの向上、神経疲労を回復し、気分を改善します。ストレスの防止したり ...

関連画像

Cannabinoids, Cannabis CancerPregnenoloneRemembering to take multivitamins and of your pregnenolone substrate goes to Pregnenolone 50 mg - 60 CapuslesPregnenolone


★リンクテーブル★
リンク元副腎皮質ホルモン」「プレグネノロン
拡張検索pregnenolone carbonitrile」「17α-hydroxypregnenolone」「17-OH pregnenolone

副腎皮質ホルモン」

  [★]

adrenocortical hormone
副腎皮質ステロイド adrenocorticoids
副腎皮質刺激ホルモン放出ホルモン副腎皮質刺激ホルモン
ステロイド
副腎副腎皮質ステロイドコルチコステロイドステロイドホルモンコルチコイド副腎皮質ホルモン剤

種類(主要なもののみ)

球状層から分泌される。アルドステロン
索状層から分泌される。コルチゾール
網状層から分泌される。アンドロステンジオン
コレステロール
cholesterol
       
 ↓CYP11A1        
プレグネノロン
pregnenolone
--→
CYP17
17α-hydroxylase
17α-ヒドロキシプレグネノロン
17α-hydroxypregnenolone
--→
CYP17
17α-hydroxylase
デヒドロエピアンドロステロン
dehydroepiandrosterone
DHEA
 ↓3β-HSD 3β-hydroxysteroid dehydrogenase    ↓3β-HSD    ↓3β-HSD
プロゲステロン
progesterone
--→
CYP17
17α-hydroxylase
17α-ヒドロキシプロゲステロン
17α-hydroxyprogesterone
--→
CYP17
17α-hydroxylase
アンドロステンジオン
androstenedione
Δ4androstene-3,17-dion
 ↓CYP21 21-hydroxylase    ↓CYP21 21-hydroxylase    
デオキシコルチコステロン
deoxycorticosterone
  11-デオキシコルチゾール
11-deoxycortisol
   
 ↓CYP11B2 11β-hydroxylase    ↓CYP11B1 11β-hydroxylase    
コルチコステロン
corticosterone
  コルチゾール
cortisol
   
 ↓CYP11B2 18-hydroxylase        
18-ヒドロキシコルチコステロン
18-hydroxycorticosterone
       
 ↓CYP11B2 18-hydroxydehydrogenase        
アルドステロン
aldosterone
       
         
球状増
zona glomerulosa
  索状層
zona fasciculata
  網状層
zona reticularis

臨床関連

21-hydroxylaseが正常に機能しないことにより生じる (L.320)

薬理学

副腎皮質から分泌されるホルモン (SP.895)

名称 血漿濃度
(ng/ml)
1日分泌量
(mg/day)
糖質コルチコイド コルチゾール 40~180 15~20
コルチコステロン 2~6 2~5
鉱質コルチコイド アルドステロン 0.05~0.20 0.05~0.15
11-DOC 0.05~0.30 0.10~0.20
副腎アンドロジェン DHEA 2~8 7~15
DHEA-S 1~4  
アンドロステンジオン 1~2 2~3



プレグネノロン」

  [★]

pregnenolone
5-pregnen-3β-ol-20-one
コレステロール副腎皮質ホルモン



pregnenolone carbonitrile」

  [★]

プレグネノロンカルボニトリル

17α-hydroxypregnenolone」

  [★] 17α-ヒドロキシプレグネノロン

17-OH pregnenolone」

  [★] 17-OHプレグネノロン



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