SwePub
Sök i LIBRIS databas

  Utökad sökning

L773:0022 3565
 

Sökning: L773:0022 3565 > Role of pituitary h...

  • Henriquez-Hernandez, L. A. (författare)

Role of pituitary hormones on 17 alpha-ethinylestradiol-induced cholestasis in rat

  • Artikel/kapitelEngelska2007

Förlag, utgivningsår, omfång ...

  • 2006-11-15
  • American Society for Pharmacology & Experimental Therapeutics (ASPET),2007
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:kth-16332
  • https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-16332URI
  • https://doi.org/10.1124/jpet.106.113209DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:13919220URI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • QC 20100525
  • Estrogens cause intrahepatic cholestasis in susceptible women during pregnancy, after administration of oral contraceptives, or during postmenopausal hormone replacement therapy. 17 alpha-Ethinylestradiol ( EE) is a synthetic estrogen widely used to cause experimental cholestasis in rodents with the aim of examining molecular mechanisms involved in this disease. EE actions on the liver are thought to be mediated by estrogen receptor alpha ( ER alpha) and pituitary hormones. We tested this hypothesis by analyzing metabolic changes induced by EE in livers from hypophysectomized ( HYPOX) and hypothyroid rats. Microarray studies revealed that the number of genes regulated by EE was increased almost 4-fold in HYPOX rat livers compared with intact males. Little overlap was apparent between the effects of EE in intact and HYPOX rats, demonstrating that pituitary hormones play a critical role in the hepatic effects of EE. Consistently, hypophysectomy protects the liver against induction by EE of serum bilirubin and alkaline phosphatase, two markers of cholestasis and hepatotoxicity and modulates the effects of EE on several genes involved in bile acid homeostasis ( e. g., FXR, SHP, BSEP, and Cyp8b1). Finally, we demonstrate a novel mechanism of action of EE through binding and negative regulation of glucocorticoid receptor-mediated transcription. In summary, pituitary- and ER alpha- independent mechanisms contribute to development of EE-induced changes in liver transcriptome. Such mechanisms may be relevant when this model of EE-induced cholestasis is evaluated. The observation that the pharmacological effects of estrogen in liver differ in the absence or presence of the pituitary could be clinically relevant, because different drugs that block actions of pituitary hormones are now available.

Ämnesord och genrebeteckningar

  • small heterodimer partner
  • growth-hormone
  • gene-expression
  • in-vivo
  • cholesterol 7-alpha-hydroxylase
  • estrogen-receptor
  • bile-acids
  • sterol 12-alpha-hydroxylase
  • microarray data
  • target genes

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Flores-Morales, A.Karolinska Institutet (författare)
  • Santana-Farre, R. (författare)
  • Axelson, M. (författare)
  • Nilsson, PeterKTH,Proteomik(Swepub:kth)u1ws88sk (författare)
  • Norstedt, G.Karolinska Institutet (författare)
  • Fernandez-Perez, L. (författare)
  • Karolinska InstitutetProteomik (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Journal of Pharmacology and Experimental Therapeutics: American Society for Pharmacology & Experimental Therapeutics (ASPET)320:2, s. 695-7050022-35651521-0103

Internetlänk

Hitta via bibliotek

Till lärosätets databas

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy