Hypothyroidism induces Fos-like immunoreactivity in ventral medullary neurons that synthesize TRH

Altered thyroid statuses are associated with autonomic disorders. Thyrotrop in-releasing hormone (TRH) in medullary nuclei regulates vagal efferent act ivity. Induction of Fos-like immunoreactivity (IR) in medullary TRH-synthes izing neurons was investigated in 24-h fasted rats with different thyroid s tatuses. Hypo- and hyperthyroidism were induced by 6-N-propyl-2-thiouracil (PTU) in drinking water and a daily intraperitoneal injection of thyroxine (T-4; 10 mu g.100 g(-1).day(-1)), respectively, for 1-4 mk. The numbers of Fos-like IR positive neurons in the raphe pallidus, raphe obscurus, and par apyramidal regions, which were low in euthyroid rats (0-2/section), increas ed remarkably as the hypothyroidism progressed and were negatively correlat ed with serum T-4 levels. At the 4th wk, Fos-like IR positive neurons were 10- to 70-fold higher compared with euthyroid controls. Simultaneous T-4 re placement (2 mu g.100 g(-1).day(-1)) prevented the increases of Fos-like IR in PTU-treated rats. Hyperthyroidism did not change the number of Fos-like IR neurons in the raphe nuclei but reduced it in the parapyramidal regions . Double immunostaining revealed that most of the Fos-like IR induced by hy pothyroidism was located in the prepro-TRH IR positive neurons. The selecti ve and sustained induction of Fos-like IR in TRH-synthesizing neurons in ve ntral medullary nuclei by hypothyroidism indicates that these neurons play a role in the autonomic disorders observed in altered thyroid statuses.