Absence of nuclear receptors for oxysterols liver X receptor induces ovarian hyperstimulation syndrome in mice

Endocrinology. 2009 Jul;150(7):3369-75. doi: 10.1210/en.2008-1519. Epub 2009 Mar 26.

Abstract

Ovarian hyperstimulation syndrome is a frequent complication occurring during in vitro fertilization cycles. It is characterized by a massive ovarian enlargement associated with an accumulation of extra vascular fluid. Here we show that liver X receptor (LXR)-alpha and LXR-beta deficient mice present many clinical and biological signs of ovarian hyperstimulation syndrome: ovarian enlargement, hemorrhagic corpora lutea, increased ovarian vascular permeability, and elevated estradiol. Ovulation stimulation resulted in excessive ovarian response to exogenous gonadotropins because follicle number and estradiol production were higher in transgenic mice. LXR deficiency also leads to perturbations in general inflammatory status, associated with ovarian il-6 deregulation. Upon treatment with the synthetic LXR agonist T09101317, serum estradiol and expression of star and cyp11a1 genes were markedly increased in wild-type mice, showing that LXRs are key regulators of ovarian steroidogenesis. These results suggest that LXRs control the ovulation by regulating endocrine and vascular processes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chorionic Gonadotropin / pharmacology
  • DNA-Binding Proteins / deficiency*
  • DNA-Binding Proteins / physiology*
  • Estradiol / biosynthesis
  • Female
  • Hydrocarbons, Fluorinated / pharmacology
  • Inflammation / physiopathology
  • Liver X Receptors
  • Mice
  • Mice, Knockout
  • Orphan Nuclear Receptors
  • Ovarian Hyperstimulation Syndrome / etiology*
  • Ovarian Hyperstimulation Syndrome / pathology
  • Ovulation
  • Ovulation Induction
  • Receptors, Cytoplasmic and Nuclear / deficiency*
  • Receptors, Cytoplasmic and Nuclear / physiology*
  • Sulfonamides / pharmacology

Substances

  • Chorionic Gonadotropin
  • DNA-Binding Proteins
  • Hydrocarbons, Fluorinated
  • Liver X Receptors
  • Nr1h3 protein, mouse
  • Orphan Nuclear Receptors
  • Receptors, Cytoplasmic and Nuclear
  • Sulfonamides
  • T0901317
  • Estradiol