Estrogenic Action in Stress-Induced Neuroendocrine Regulation of Energy Homeostasis

Abstract

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.

Sex differences and sex-specific regulation of motivated behavior by Melanin-concentrating hormone: a short review

“…Ovariectomized females sustain fasting activation levels, like intact males. This result supports the idea that developmental differences across sex are also critical for glucose-sensing functions [ 47 ], and that MCH neurons may also contribute to this process. Estrogen replacement in both sexes of gonadectomized rats allows MCH activity levels to quickly decrease to fed levels, similar to intact female rats.…”

Associations between a metal mixture and infant negative affectivity: Effect modification by prenatal cortisol and infant sex

“…Differing structure volumes, neuronal morphology, and synaptic connections lead to sexually dimorphic brain circuitry (Cosgrove et al, 2007; Schwarz & McCarthy, 2008). Starting in utero, sex hormones have organizational effects on the development of brain structures that control sexually dimorphic neuroendocrine responses and behaviors (Krolick & Shi, 2022). Interactions between the HPA axis and the hypothalamic–pituitary–gonadal (HPG) axis may underlie sex‐specific effects on behavior.…”

Preconceptional and in utero exposure of sheep to a real‐life environmental chemical mixture disrupts key markers of energy metabolism in male offspring

“…For this study, punches from the mPOA, AHA, PVN, rostral ARC, and caudal ARC were studied. These hypothalamic regions play pivotal roles in regulating energy metabolism 38,53 …”

“…To achieve this, we investigated the impact of gestational exposure to biosolids on offspring body weight (BW), plasma triglyceride (TG) levels, and the expression of key genes, with established roles in the regulation of metabolism, in the hypothalamus, liver, and adipose tissues (subcutaneous, visceral, and pericardial depots). The hypothalamic genes studied were ESR1 and LEPR in the medial preoptic area (mPOA), anterior hypothalamic area (AHA), and PVN [36][37][38] and ESR1, LEPR, NPY, and POMC in the rostral and caudal ARC. 36,39 The panel of markers assessed in the liver and adipose tissue were ZNF423 (a major determinant of preadipocyte commitment 40 ), LPL (important in the distribution of fatty acids and lipoproteins outside of the liver 41 ), PPARg (regulator of genes involved in lipid metabolism, obesity-induced inflammation, metabolic syndrome 42 ), ESR1, PPARGC1A (transcriptional coactivator that regulates energy production genes 43 ), DLK1 (inhibitor of adipogenesis and a preadipocyte marker 44,45 ) and LEPTIN (adipose signal, shown to be sensitive to EC exposure.…”