Sex-steroid-dependent plasticity of brain-stem autonomic circuits

Erica L. Littlejohn, Stephanie Fedorchak, Carie R. Boychuk

Research output: Contribution to journalReview articlepeer-review

5 Scopus citations


In the central nervous system (CNS), nuclei of the brain stem play a critical role in the integration of peripheral sensory information and the regulation of autonomic output in mammalian physiology. The nucleus tractus solitarius of the brain stem acts as a relay center that receives peripheral sensory input from vagal afferents of the nodose ganglia, integrates information from within the brain stem and higher central centers, and then transmits autonomic efferent output through downstream premotor nuclei, such as the nucleus ambiguus, the dorsal motor nucleus of the vagus, and the rostral ventral lateral medulla. Although there is mounting evidence that sex and sex hormones modulate autonomic physiology at the level of the CNS, the mechanisms and neurocircuitry involved in producing these functional consequences are poorly understood. Of particular interest in this review is the role of estrogen, progesterone, and 5-reductase-dependent neurosteroid metabolites of progesterone (e.g., allopregnanolone) in the modulation of neurotransmission within brain-stem autonomic neurocircuits. This review will discuss our understanding of the actions and mechanisms of estrogen, progesterone, and neurosteroids at the cellular level of brain-stem nuclei. Understanding the complex interaction between sex hormones and neural signaling plasticity of the autonomic nervous system is essential to elucidating the role of sex in overall physiology and disease.

Original languageEnglish
Pages (from-to)R60-R68
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number1
StatePublished - Jul 2020

Bibliographical note

Funding Information:
regulatory response (CRR) to hypoglycemia is also blunted in women in part through blunted sympathetic activation (32, 98). However, complete autonomic blockade with trimethaphan significantly altered the CRR in women (51), indicating that the parasympathetic system likely plays a larger role compared with men. This conclusion is supported by preclinical models (59). Despite these sex differences in the CRR, there is no sex difference in the occurrence of hypoglycemia in patients with type 1 diabetes (32a), suggesting that women are likely protected from the effects of antecedent hypoglycemia on autonomic activity (32). Gastrointestinal function and disease is also markedly different between sexes and across the menstrual cycle (57) with notable differences in metabolic responses, including the use of different energy sources under normal, healthy conditions and during disease (72). Despite our understanding of the existence of sex differences throughout different autonomic functions, the neuromechanistic underpinning(s) of these differences is largely unexplored. Therefore, understanding the action of sex hormones on the regulation of autonomic circuits will be informative in our development of therapeutics to treat a wide array of autonomic dysfunction(s).

Publisher Copyright:
© 2020 the American Physiological Society


  • Autonomic
  • Estrogen
  • Neurosteroid
  • Progesterone
  • Sex

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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