PITUITARY AND PERIPHERAL THYROID-HORMONE RESPONSES TO THYROTROPIN-RELEASING-HORMONE DURING SUSTAINED SLEEP-DEPRIVATION IN FREELY MOVING RATS

Sleep deprivation is associated with poor cognitive ability and impair ed physical health, but the ways in which the brain and body become co mpromised are not understood. In sleep-deprived rats, plasma total T-4 and T-3 concentrations decline progressively to 78% and 47% below bas eline values, respectively, brown adipose tissue 5'-deiodinase type II activity increases 100-fold, and serum TSH values are unknown. The pr ogressive decline in plasma thyroid hormones is associated with a deep negative energy balance despite normal or increased food intake and m alnutrition-like symptoms that eventuate in hypothermia and lethal sys temic infections. The purpose of the present experiment was to evaluat e the probable causes of the low plasma total T-4 during sleep depriva tion by measuring the free hormone concentration to minimize binding i rregularities and by challenging the pituitary-thyroid axis with iv TR H to determine both 1) the pituitary release of TSH and 2) the thyroid al response of free T-4 (FT4) and free T-3 (FT3) release to the TSH in crement. Sleep-deprived rats were awake 91% of the total time compared with 63% of the total time in yoked control rats and 50% of the total time during the baseline period. Cage control comparison rats were pe rmitted to sleep normally. Sustained sleep deprivation resulted in a d ecline from baseline in plasma FT4 of 73 +/- 6% and FT3 of 45 +/- 12%, which were similar to the declines in total hormone concentrations ob served previously; nonstimulated TSH was unchanged. In the yoked and c age control groups, FT4 also declined, but much less than that of the sleep-deprived group. The relative changes in free compared with total hormone concentrations over the study were also less parallel than th ose in the sleep-deprived group. The plasma TSH response to TRH was si milar in all groups across experimental days. The plasma FT4 and FT3 c oncentrations in sleep-deprived rats increased after TRH-stimulated TS H release to an extent comparable to control values. Taken together, l ow basal FT4 and FT3 hormone concentrations and unchanged TSH and thyr oidal responses to TRH suggest a pituitary or hypothalamic contributio n to the hypothyroxinemia during sleep deprivation.