Neuroestrogen, rapid action of estradiol, and GnRH neurons

Front Neuroendocrinol. 2012 Oct;33(4):364-75. doi: 10.1016/j.yfrne.2012.08.001. Epub 2012 Aug 30.


Estradiol plays a pivotal role in the control of GnRH neuronal function, hence female reproduction. A series of recent studies in our laboratory indicate that rapid excitatory actions of estradiol directly modify GnRH neuronal activity in primate GnRH neurons through GPR30 and STX-sensitive receptors. Similar rapid direct actions of estradiol through estrogen receptor beta are also described in mouse GnRH neurons. In this review, we propose two novel hypotheses as a possible physiological role of estradiol in primates. First, while ovarian estradiol initiates the preovulatory GnRH surge through interneurons expressing estrogen receptor alpha, rapid direct membrane-initiated action of estradiol may play a role in sustaining GnRH surge release for many hours. Second, locally produced neuroestrogens may contribute to pulsatile GnRH release. Either way, estradiol synthesized in interneurons in the hypothalamus may play a significant role in the control of the GnRH surge and/or pulsatility of GnRH release.

Publication types

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

MeSH terms

  • Animals
  • Estradiol / biosynthesis*
  • Estradiol / metabolism
  • Estradiol / physiology
  • Female
  • Gonadotropin-Releasing Hormone / biosynthesis*
  • Hypothalamus / metabolism*
  • Neurons / metabolism*
  • Receptors, Estrogen / metabolism*


  • Receptors, Estrogen
  • Gonadotropin-Releasing Hormone
  • Estradiol