Sex and estrous cycle influence fasting-induced torpor via hypothalamic estrogen signalling

Torpor is a state of transient hypometabolism and hypothermia that is engaged by many species in adverse conditions such as food scarcity. Neurons in the hypothalamic preoptic area (POA) are capable of driving entry into torpor when activated. Estrogens, principally estradiol, are capable of modulating thermogenesis and energy balance by central actions, and POA neurons express the canonical estrogen receptor ERα. We find 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. Torpor responses are longer and deeper in female mice compared to males, and this is potentiated by exogenous estradiol, which lengthens torpor bouts in female mice, but not 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 in periods of moderate environmental stress.