Estradiol Protects Hypothalamic Neurons Against Insulin Resistance

Oline K. Rønnekleiv, Martin J. Kelly

Research output: Chapter in Book/Report/Conference proceedingChapter


Obesity is a worldwide health problem that leads to a number of serious diseases of which metabolic syndrome associated with insulin and leptin resistance is of the most serious. Males exhibit a higher incidence of metabolic syndrome than women in early adult life, but this sex difference diminishes sharply in hypoestrogenic states as during menopause. Importantly the gonadal hormone 17β-estradiol (E2) has been found to protect obese females against insulin resistance during the reproductive years by actions on hypothalamic anorexigenic and orexigenic neurons. Thus E2 helps maintain the insulin-mediated excitation of canonical transient receptor potential 5 (TRPC 5) channels in proopiomelanocortin (POMC) neurons and the hyperpolarizing effects of insulin via activation of KATP channels in neuropeptide Y/agouti-related peptide (NPY/AgRP) neurons in obese females, but not in obese males. These studies, therefore, have identified a sex difference in the hypothalamic development of insulin resistance with obesity, which will be the topic of this review.

Original languageEnglish (US)
Title of host publicationStress
Subtitle of host publicationGenetics, Epigenetics and Genomics Volume 4: Handbook of Stress
Number of pages8
ISBN (Electronic)9780128131565
StatePublished - Jan 1 2020


  • 17β-Estradiol
  • Hypothalamus
  • Insulin signaling
  • K channel
  • Obesity
  • TRPC 5 channel

ASJC Scopus subject areas

  • Neuroscience(all)


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