Effect of thyroid status on release of hypothalamic thyrotropin-releasing hormone

Previous studies have shown that hyperthyroidism induced in rats by daily administration of 10 micrograms T4 per 100 g BW for 8 days resulted in a 45% decrease in TRH release into hypophysial portal blood, whereas induction of hypothyroidism by administration of methimazole (MMI; 0.05% in drinking water) for 8 days led to a small but insignificant increase of hypothalamic TRH release. We now show that even prolonged MMI administration (3 weeks) does not affect TRH release. Hypothalamic fragments of rats treated with T4 as above for 3 weeks secreted 40% less TRH than hypothalami of euthyroid rats (P less than 0.05). Secretion of TRH from hypothalamic fragments of rats treated for 3 weeks with MMI as above did not differ from euthyroid controls. Addition of 10 nM T3 did not effect TRH secretion from hypothyroid hypothalami. Secretion of TRH was increased several-fold by 56 mM K+ through a calcium dependent mechanism, without significant differences between hypothalami of eu-, hypo- or hyperthyroid rats. In conclusion, both in vivo and in vitro hypothalamic TRH release is decreased in hyperthyroidism, whereas short- or long-term hypothyroidism induced by MMI does not increase TRH release. These findings suggest a negative feedback of thyroid hormone at the hypothalamic level.