Brain-derived estrogen and neural function

Darrell W. Brann, Yujiao Lu, Jing Wang, Quanguang Zhang, Roshni Thakkar, Gangadhara R. Sareddy, Uday P. Pratap, Rajeshwar R. Tekmal, Ratna K. Vadlamudi

Research output: Contribution to journalReview articlepeer-review

52 Scopus citations


Although classically known as an endocrine signal produced by the ovary, 17β-estradiol (E2) is also a neurosteroid produced in neurons and astrocytes in the brain of many different species. In this review, we provide a comprehensive overview of the localization, regulation, sex differences, and physiological/pathological roles of brain-derived E2 (BDE2). Much of what we know regarding the functional roles of BDE2 has come from studies using specific inhibitors of the E2 synthesis enzyme, aromatase, as well as the recent development of conditional forebrain neuron-specific and astrocyte-specific aromatase knockout mouse models. The evidence from these studies support a critical role for neuron-derived E2 (NDE2) in the regulation of synaptic plasticity, memory, socio-sexual behavior, sexual differentiation, reproduction, injury-induced reactive gliosis, and neuroprotection. Furthermore, we review evidence that astrocyte-derived E2 (ADE2) is induced following brain injury/ischemia, and plays a key role in reactive gliosis, neuroprotection, and cognitive preservation. Finally, we conclude by discussing the key controversies and challenges in this area, as well as potential future directions for the field.

Original languageEnglish (US)
Pages (from-to)793-817
Number of pages25
JournalNeuroscience and Biobehavioral Reviews
StatePublished - Jan 2022


  • 17β-Estradiol
  • Aromatase
  • Gliosis
  • Memory
  • Neuroprotection
  • Neurosteroid
  • Sexual behavior
  • Synaptic plasticity

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology
  • Cognitive Neuroscience
  • Behavioral Neuroscience


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