UCLA

Endothermy is an adaptation that can be traced back hundreds of millions of years and is critical for nearly every aspect of mammalian biology. Despite the advantages associated with a stable internal temperature, endothermy is energetically expensive. To conserve energy when food is scarce, many species of mammals, including mice, have evolved the ability to reversibly enter a regulated state of hypothermia and hypometabolism, known as torpor. While torpor effectively lowers metabolic demands, it comes with significant reproductive tradeoffs. As a result, organisms have evolved sophisticated strategies to balance torpor and reproduction, thereby maximizing their fitness. In Chapter 1, I review the current knowledge of the signaling networks underlying the bidirectional relationship between torpor and reproduction. In summary, little is known about the cues that influence the reproductive system during torpor and their mechanism of action, although hypothalamic kisspeptin neurons are well-positioned to act as integrators. Conversely, gonadal steroids attenuate torpor in multiple species, yet the signaling mechanisms underlying their effect remain unknown. Promising candidates, including the preoptic area, exist, yet there have been no studies to directly test these hypothesized targets. In Chapter 2, I confirm that circulating estrogens attenuate fasting-induced torpor in female mice and test the hypothesis that the preoptic area acts as a central mediator for their effects. In testing this hypothesis, I find that circulating estrogens alter the response properties of torpor-regulating neurons in the preoptic area yet require a peripheral signaling mechanism to drive torpor attenuation. Together, these works advance our understanding of the bidirectional relationship between torpor and reproduction in mammals and represent an important step towards the ultimate goal of manipulating these pathways to improve metabolic and reproductive health in humans.