Estrogen Receptors Modulation of Anxiety-Like Behavior

Vitam Horm. 2017:103:27-52. doi: 10.1016/bs.vh.2016.08.004. Epub 2016 Oct 13.


Estrogens exert profound effects on the expression of anxiety in humans and rodents; however, the directionality of these effects varies considerably within both clinical and preclinical literature. It is believed that discrepancies regarding the nature of estrogens' effects on anxiety are attributable to the differential effects of specific estrogen receptor (ER) subtypes. In this chapter we will discuss the relative impact on anxiety and anxiety-like behavior of each of the three main ERs: ERα, which has a generally anxiogenic effect, ERβ, which has a generally anxiolytic effect, and the G-protein-coupled ER known as GPR30, which has been found to both increase and decrease anxiety-like behavior. In addition, we will describe the known mechanisms by which these receptor subtypes exert their influence on emotional responses, focusing on the hypothalamic-pituitary-adrenal axis and the oxytocinergic and serotonergic systems. The impact of estrogens on the expression of anxiety is likely the result of their combined effects on all of these neurobiological systems.

Keywords: Anxiety; Beta; Estradiol; Estrogen receptor alpha; GPR30; HPA; Oxytocin; Serotonin.

Publication types

  • Comparative Study
  • Review

MeSH terms

  • Active Transport, Cell Nucleus / drug effects
  • Animals
  • Anti-Anxiety Agents / pharmacology
  • Anti-Anxiety Agents / therapeutic use
  • Anxiety / drug therapy
  • Anxiety / metabolism*
  • Anxiety Disorders / drug therapy
  • Anxiety Disorders / metabolism*
  • Estrogen Receptor alpha / agonists*
  • Estrogen Receptor alpha / metabolism
  • Estrogen Receptor beta / agonists*
  • Estrogen Receptor beta / metabolism
  • Estrogens / metabolism*
  • Estrogens / pharmacology
  • Estrogens / therapeutic use
  • Humans
  • Hypothalamo-Hypophyseal System / drug effects
  • Hypothalamo-Hypophyseal System / metabolism
  • Nerve Tissue Proteins / agonists
  • Nerve Tissue Proteins / metabolism
  • Neurons / drug effects
  • Neurons / metabolism*
  • Oxytocin / metabolism
  • Pituitary-Adrenal System / drug effects
  • Pituitary-Adrenal System / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, G-Protein-Coupled / agonists*
  • Receptors, G-Protein-Coupled / metabolism
  • Receptors, Oxytocin / agonists
  • Receptors, Oxytocin / metabolism
  • Serotonergic Neurons / drug effects
  • Serotonergic Neurons / metabolism


  • Anti-Anxiety Agents
  • ESR1 protein, human
  • ESR2 protein, human
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Estrogens
  • GPER1 protein, human
  • Nerve Tissue Proteins
  • OXTR protein, human
  • Receptors, Estrogen
  • Receptors, G-Protein-Coupled
  • Receptors, Oxytocin
  • Oxytocin