Uncovering the mechanisms of estrogen effects on hippocampal function

Front Neuroendocrinol. 2008 May;29(2):219-37. doi: 10.1016/j.yfrne.2007.08.006. Epub 2007 Oct 15.


Estrogens have direct effects on the brain areas controlling cognition. One of the most studied of these regions is the dorsal hippocampal formation, which governs the formation of spatial and episodic memories. In laboratory animals, most investigators report that estrogen enhances synaptic plasticity and improves performance on hippocampal-dependent cognitive behaviors. This review summarizes work conducted in our laboratory and others toward identifying estrogen's actions in the hippocampal formation, and the mechanisms for these actions. Physiologic and pharmacologic estrogen affects cognitive behavior in mammals, which may be applicable to human health and disease. The effects of estrogen in the hippocampal formation that lead to modulation of hippocampal function include effects on cell morphology, synapse formation, signaling, and excitability that have been studied in laboratory mice, rats, and primates. Finally, estrogen may signal through both nuclear and extranuclear hippocampal estrogen receptors to achieve its downstream effects.

Publication types

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

MeSH terms

  • Acetylcholine / physiology
  • Aging / physiology
  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / physiology
  • Cognition / drug effects
  • Cyclic AMP Response Element-Binding Protein / physiology
  • Estradiol / pharmacology
  • Estrogens / physiology*
  • Estrous Cycle / physiology
  • Female
  • Genome
  • Hippocampus / drug effects*
  • Hippocampus / physiology*
  • Humans
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology
  • Mitogen-Activated Protein Kinase Kinases / physiology
  • Nerve Growth Factors / physiology
  • Neurotransmitter Agents / physiology
  • Ovariectomy
  • Ovary / physiology
  • Postmenopause / physiology
  • Prefrontal Cortex / physiology
  • Receptors, Estrogen / physiology*
  • Receptors, N-Methyl-D-Aspartate / physiology
  • gamma-Aminobutyric Acid / physiology


  • Cyclic AMP Response Element-Binding Protein
  • Estrogens
  • Nerve Growth Factors
  • Neurotransmitter Agents
  • Receptors, Estrogen
  • Receptors, N-Methyl-D-Aspartate
  • Estradiol
  • gamma-Aminobutyric Acid
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Mitogen-Activated Protein Kinase Kinases
  • Acetylcholine