Anorectic estrogen mimics leptin's effect on the rewiring of melanocortin cells and Stat3 signaling in obese animals

Nat Med. 2007 Jan;13(1):89-94. doi: 10.1038/nm1525. Epub 2006 Dec 31.


Metabolic hormones, such as leptin, alter the input organization of hypothalamic circuits, resulting in increased pro-opiomelanocortin (POMC) tone, followed by decreased food intake and adiposity. The gonadal steroid estradiol can also reduce appetite and adiposity, and it influences synaptic plasticity. Here we report that estradiol (E2) triggers a robust increase in the number of excitatory inputs to POMC neurons in the arcuate nucleus of wild-type rats and mice. This rearrangement of synapses in the arcuate nucleus is leptin independent because it also occurred in leptin-deficient (ob/ob) and leptin receptor-deficient (db/db) mice, and was paralleled by decreased food intake and body weight gain as well as increased energy expenditure. However, estrogen-induced decrease in body weight was dependent on Stat3 activation in the brain. These observations support the notion that synaptic plasticity of arcuate nucleus feeding circuits is an inherent element in body weight regulation and offer alternative approaches to reducing adiposity under conditions of failed leptin receptor signaling.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anorexia / chemically induced
  • Anorexia / physiopathology
  • Arcuate Nucleus of Hypothalamus / cytology
  • Arcuate Nucleus of Hypothalamus / physiology
  • Arcuate Nucleus of Hypothalamus / ultrastructure
  • Body Weight / drug effects
  • Estradiol / administration & dosage
  • Estradiol / pharmacology*
  • Estrogen Receptor alpha / genetics
  • Estrogen Receptor alpha / physiology
  • Excitatory Postsynaptic Potentials / drug effects
  • Female
  • Injections, Intraventricular
  • Leptin / genetics
  • Leptin / physiology
  • Male
  • Melanocortins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Obese
  • Microscopy, Electron
  • Neurons / cytology
  • Neurons / drug effects*
  • Neurons / metabolism
  • Obesity / genetics
  • Obesity / physiopathology*
  • Ovariectomy
  • Pro-Opiomelanocortin / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction / drug effects*


  • Estrogen Receptor alpha
  • Leptin
  • Melanocortins
  • STAT3 Transcription Factor
  • Estradiol
  • Pro-Opiomelanocortin