Thyroid hormone (TH) is a key regulator of body temperature; however, its role in the tightly controlled maternal thermoregulatory system that safeguards fetal viability remains unknown. To address this gap, we investigated how maternal hyperthyroidism affects thermoregulation, metabolic tissues, and endocrine signaling in pregnant C57BL/6NCrl mice. Treatment with 3,3',5-Triiodo-L-thyronine (T3) from conception to late gestation initially elevated maternal core temperature, reflecting a hypothalamic pyrexic set-point. However, this effect was gradually attenuated towards term, permitting the normal prepartum drop in core body temperature. Despite elevated TH levels, brown and white adipose tissues showed no thermogenic activation, whereas skeletal muscle exhibited selective metabolic remodeling, including glycogen depletion and increased mitochondrial capacity in glycolytic muscles, without changes in SERCA2 expression. Notably, maternal T3 treatment further boosted the pregnancy-associated increase in FGF21, while adipose tissue remained non-thermogenic, indicating a role of TH-induced FGF21 in sustaining maternal metabolic requirements. Together, these findings reveal a hierarchical adaptation in which central TH effects are overridden, peripheral thermogenic activation is partially suppressed, and endocrine signaling is redirected to maintain maternal-fetal energy balance. In summary, this study identifies a pregnancy-specific mechanism that protects the fetus from hyperthermia while sustaining maternal metabolic demands, with important implications for thyroid dysfunction and fetal programming.
López-Alcántara et al. (Wed,) studied this question.