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Circadian, continued treatment with melatonin during the dark cycle produces changes
in the blood level of thyroid hormones in aging mice. Thyroid-stimulating hormone
(TSH) and thyrotropin-releasing hormone (TRH) antagonize the involution of the thymus
produced by prednisolone. This effect of TRH does not seem thyroid dependent. TRH
restores antibody production in non-responder athymic nude mice but does not exert
this effect in neonatally thymectomized mice. Moreover, this activity does not correlate
with thyroxine levels. TRH exerts a powerful protective effect in mice challenged
with encephalomyocarditis (EMC) virus. Presumably pineal melatonin exerts its varied
regulatory functions via hypothalamic TRH.