Estradiol-induced synaptic remodeling of tyrosine hydroxylase immunopositive neurons in the rat arcuate nucleus

Endocrinology. 2008 Aug;149(8):4137-41. doi: 10.1210/en.2007-1559. Epub 2008 Apr 17.


Gonadal steroids induce synaptic plasticity in several areas of the adult nervous system. In the arcuate nucleus of adult female rats, 17beta-estradiol triggers synaptic remodeling, resulting in a decrease in the number of inhibitory synaptic inputs, an increase in the number of excitatory synapses, and an enhancement of the frequency of neuronal firing. In the present paper, we studied the specificity of hormonal effects by determining the changes in synaptic connectivity of tyrosine hydroxylase (TH) immunoreactive (IR) neurons in the arcuate nucleus. We combined pre-embedding TH and post-embedding gamma-aminobutyric acid (GABA) immunostaining, and performed unbiased stereological measurements in gonadectomized and 17beta-estradiol-treated rats. We conclude that the synaptic connectivity of the TH-IR neurons is different from the other, nonlabeled population, and the response to estradiol is not uniform. TH-IR (dopaminergic) arcuate neurons of both male and female rats have more GABAergic (inhibitory) axosomatic inputs than the nondopaminergic population. Our study shows that the effect of 17beta-estradiol is sex and cell specific in the sense that not all arcuate neurons are affected by the structural synaptic remodeling. In ovariectomized females hormone treatment decreased the numerical density of GABAergic axosomatic synapses on TH-IR, but not on nondopaminergic, neurons, whereas in orchidectomized males, 17beta-estradiol treatment increased inhibitory synapses onto nondopaminergic neurons but did not affect the number of inhibitory terminals onto TH-IR neurons. The hormone-induced plastic changes in synaptic connectivity of TH-IR neurons may serve as the morphological basis for the cyclical regulation of the anterior pituitary.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arcuate Nucleus of Hypothalamus / drug effects*
  • Arcuate Nucleus of Hypothalamus / metabolism
  • Castration
  • Cell Count
  • Estradiol / pharmacology*
  • Female
  • Immunohistochemistry
  • Male
  • Neuronal Plasticity / drug effects*
  • Neurons / cytology
  • Neurons / drug effects*
  • Neurons / metabolism
  • Rats
  • Sex Characteristics
  • Synapses / drug effects
  • Synaptic Transmission / drug effects
  • Tyrosine 3-Monooxygenase / immunology
  • Tyrosine 3-Monooxygenase / metabolism*
  • gamma-Aminobutyric Acid / metabolism


  • Estradiol
  • gamma-Aminobutyric Acid
  • Tyrosine 3-Monooxygenase