Decreased cholesterol uptake and increased liver X receptor-mediated cholesterol efflux pathways during prostaglandin F2 alpha-induced and spontaneous luteolysis in sheep

Nickie L. Seto, Randy L. Bogan

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

In nonprimate species, it has been well established that prostaglandin F2 alpha (PGF2alpha) initiates luteolysis. Changes in intracellular cholesterol concentrations caused by modulation of cholesterol uptake and efflux may mediate PGF2alphainduced luteolysis. These changes in cholesterol efflux and uptake are controlled, in part, by the liver x receptors (LXR) alpha (NR1H3) and beta (NR1H2), nuclear receptors that increase expression of genes necessary for cholesterol efflux or limiting cholesterol uptake. Therefore, we hypothesized that PGF2alpha reduces expression of cholesterol uptake and increases expression of cholesterol efflux genes, mediated in part by enhanced LXR activity. To test this hypothesis, an induced luteolysis model was used whereby ewes were treated during their midluteal phase with saline or PGF2alpha and corpora lutea (CL) collected 12, 24, or 48 h later for determination of mRNA and protein concentrations by quantitative real-time PCR and Western blot analysis, respectively. As a complementary approach, CL undergoing spontaneous luteolysis were compared to midluteal phase CL. The lipoprotein receptors responsible for cholesterol uptake were significantly decreased in both luteolysis models. Expression of the LXR target gene ATP binding cassette subfamily A1 (ABCA1), an important mediator of cholesterol efflux, was significantly increased in both experimental models. Chromatin immunoprecipitation confirmed that PGF2alpha treatment resulted in enhanced NR1H3 and NR1H2 binding to the ABCA1 promoter. Qualitative changes in lipid droplet distribution were also observed following PGF2alpha treatment. These data support the hypothesis that reduced cholesterol uptake and increased efflux mediate luteolysis in sheep, which is partially controlled by PGF2alpha stimulation of LXR activity.

Original languageEnglish (US)
Article number128
JournalBiology of reproduction
Volume92
Issue number5
DOIs
StatePublished - May 1 2015

Keywords

  • Cholesterol
  • Corpus luteum
  • Liver x receptor
  • Luteolysis
  • Ovine
  • Prostaglandin F2 alpha

ASJC Scopus subject areas

  • Reproductive Medicine
  • Cell Biology

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