Limits to sustained energy intake. XXXIII. Thyroid hormones play important roles in milk production but do not define the heat dissipation limit in Swiss mice

The limits to sustained energy intake set physiological upper boundaries that affect many aspects of human and animal performance. The mechanisms underlying these limits however remain unclear. We exposed Swiss mice to either supplementary thyroid hormones (THs) or methimazole during lactation at 21 °C or 32.5 °C, and measured food intake, resting metabolic rate (RMR), milk energy output (MEO), serum THs and mammary gland gene expression of females, and litter size and mass of their offspring. Lactating females developed hyperthyroidism following exposure to supplementary THs at 21 °C, but they did not significantly change body temperature, asymptotic food intake, RMR or MEO, and litter and mass were unaffected. Hypothyroidism, induced by either methimazole or 32.5 °C exposure, significantly decreased asymptotic food intake, RMR and MEO, resulting in significantly decreased litter size and litter mass. Furthermore, gene expression of key genes in the mammary gland were significantly decreased by either methimazole or hot exposure, including gene expression of THs and prolactin receptors, and Stat5a and Stat5b. This suggests that endogenous THs are necessary to maintain sustained energy intake and milk energy output. Suppression of the thyroid axis seems to be an essential aspect of the mechanism by which mice at 32.5 °C reduce their lactation performance to avoid overheating. However, THs do not define the upper limit to sustained energy intake and milk energy output at peak lactation at 21 °C. Another, as yet unknown, factor, prevents supplementary thyroxine exerting any stimulatory metabolic impacts on lactating mice at 21 °C.