Steroid Signaling Establishes a Female Metabolic State and Regulates SREBP to Control Oocyte Lipid Accumulation

Curr Biol. 2015 Apr 20;25(8):993-1004. doi: 10.1016/j.cub.2015.02.019. Epub 2015 Mar 19.


Disruptions in energy homeostasis severely affect reproduction in many organisms and are linked to several reproductive disorders in humans. As a result, understanding the mechanisms that control nutrient accumulation in the oocyte will provide valuable insights into the links between metabolic disease and reproductive dysfunction. We show that the steroid hormone ecdysone functions in Drosophila to control lipid metabolism and support oocyte production. First, local EcR-mediated signaling induces a stage-specific accumulation of lipids in stage-10 oocytes. EcR induces lipid accumulation by promoting the activation of the lipogenic transcription factor SREBP and by controlling the expression of the low-density lipoprotein (LDL) receptor homolog, LpR2. Second, global signaling via the ecdysone receptor, EcR, establishes a female metabolic state and promotes whole-body triglyceride and glycogen storage at high levels. EcR acts in the CNS to mediate these effects, in part by promoting higher levels of feeding in females. Thus, ecdysone functions at two levels to support reproduction: first by inducing lipid accumulation in the late stages of oocyte development and second by providing a signal that coordinates lipid metabolism in the germline with whole-animal lipid homeostasis. Ecdysone regulation allows females to assess the demands of oogenesis and alter their behavior and metabolic state to support the biosynthetic requirements of oocyte production.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drosophila / metabolism
  • Drosophila Proteins / metabolism
  • Ecdysone / pharmacology*
  • Feeding Behavior / drug effects
  • Female
  • Glycogen / metabolism
  • Lipid Metabolism / drug effects*
  • Oocytes / drug effects*
  • Oocytes / metabolism
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Receptors, Steroid / metabolism
  • Signal Transduction / drug effects*
  • Steroids / pharmacology*
  • Sterol Regulatory Element Binding Proteins / metabolism
  • Triglycerides / metabolism


  • Drosophila Proteins
  • Lpr2 protein, Drosophila
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Steroid
  • Steroids
  • Sterol Regulatory Element Binding Proteins
  • Triglycerides
  • ecdysone receptor
  • Ecdysone
  • Glycogen

Associated data

  • GEO/GSE65567