Hypothyroidism induces Fos-like immunoreactivity in ventral medullary neurons that synthesize TRH.
Altered thyroid statuses are associated with autonomic disorders. Thyrotropin-releasing hormone (TRH) in medullary nuclei regulates vagal efferent activity. Induction of Fos-like immunoreactivity (IR) in medullary TRH-synthesizing neurons was investigated in 24-h fasted rats with different thyroid statuses. 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 microgram. 100 g(-1). day(-1)), respectively, for 1-4 wk. The numbers of Fos-like IR positive neurons in the raphe pallidus, raphe obscurus, and parapyramidal regions, which were low in euthyroid rats (0-2/section), increased remarkably as the hypothyroidism progressed and were negatively correlated 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) replacement (2 microgram. 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 hypothyroidism was located in the prepro-TRH IR positive neurons. The selective and sustained induction of Fos-like IR in TRH-synthesizing neurons in ventral medullary nuclei by hypothyroidism indicates that these neurons play a role in the autonomic disorders observed in altered thyroid statuses.
Yuan
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CURE: Digestive Diseases Research Center, West Los Angeles Veterans Affairs Medical Center, Department of Medicine, Division of Digestive Diseases and Brain Research Institute, University of California Los Angeles, USA.
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D000818:Animals; D000906:Antibodies; D013956:Antithyroid Agents; D002452:Cell Count; D007037:Hypothyroidism / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology*; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D011441:Propylthiouracil; D011498:Protein Precursors / Q000032:analysis / Q000276:immunology; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000096:biosynthesis* / Q000276:immunology; D011903:Raphe Nuclei / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013973:Thyrotropin-Releasing Hormone / Q000032:analysis / Q000096:biosynthesis* / Q000276:immunology; D013974:Thyroxine / Q000096:biosynthesis / Q000097:blood
D000906:Antibodies; D013956:Antithyroid Agents; D011498:Protein Precursors; D016760:Proto-Oncogene Proteins c-fos; C063596:prepro-thyrotropin-releasing hormone; D013973:Thyrotropin-Releasing Hormone; D011441:Propylthiouracil; D013974:Thyroxine