Estrous cycle modulates fasting-induced torpor propensity via hypothalamic estrogen signalling

Abstract Torpor is a state of transient hypometabolism and hypothermia that is engaged by many species in adverse conditions such as food scarcity. Chemo- or optoactivation of neurons in the hypothalamic preoptic area (POA) drives torpor-like hypometabolism and hypothermia. Estrogens, principally estradiol, modulate thermogenesis and energy balance by central actions, and POA neurons express the canonical estrogen receptor ERα. We explored the role of POA estrogen signalling in fasting-induced torpor in the mouse. We found that torpor depth and duration vary across the estrus cycle in mice, whereby the torpor response is greatest during the diestrus phase in which circulating estradiol is at its peak. Exogenous estradiol lengthens torpor bouts in female mice, but not in males. Knockdown of ERα within the POA blunts torpor in female mice, suggesting that estradiol acting via ERα modulates the activity of hypothalamic neurons that generate torpor. We speculate that this cyclical oscillation in torpor propensity which is lowest in the estrous phase may be an adaptive change that preserves reproduction during periods of moderate environmental stress.