Estrogenic Action in Stress-Induced Neuroendocrine Regulation of Energy Homeostasis

Estrogens are among important contributing factors to many sex differences in neuroendocrine regulation of energy homeostasis induced by stress. Research in this field is warranted since chronic stress-related psychiatric and metabolic disturbances continue to be top health concerns, and sex differences are witnessed in these aspects. For example, chronic stress disrupts energy homeostasis, leading to negative consequences in the regulation of emotion and metabolism. Females are known to be more vulnerable to the psychological consequences of stress, such as depression and anxiety, whereas males are more vulnerable to the metabolic consequences of stress. Sex differences that exist in the susceptibility to various stress-induced disorders have led researchers to hypothesize that gonadal hormones are regulatory factors that should be considered in stress studies. Further, estrogens are heavily recognized for their protective effects on metabolic dysregulation, such as anti-obesogenic and glucose-sensing effects. Perturbations to energy homeostasis using laboratory rodents, such as physiological stress or over-/under- feeding dietary regimen prevalent in today’s society, offer hints to the underlying mechanisms of estrogenic actions. Metabolic effects of estrogens primarily work through estrogen receptor α (ERα), which is differentially expressed between the sexes in hypothalamic nuclei regulating energy metabolism and in extrahypothalamic limbic regions that are not typically associated with energy homeostasis. In this review, we discuss estrogenic actions implicated in stress-induced sex-distinct metabolic disorders.