Localization of thyroid hormone receptor beta2 in the ventral medullary neurons that synthesize thyrotropin-releasing hormone.
Altered thyroid statuses are associated with autonomic disorders. Thyrotropin-releasing hormone (TRH) synthesized in medullary raphe pallidus (Rpa), raphe obscurus (Rob) and the parapyramidal regions (PPR) regulates vagal and sympathetic preganglionic motoneurons. Hypothyroidism increased TRH gene expression and c-Fos immunoreactivity (IR) in these nuclei. Whether these increases represent a direct action of thyroid hormone was studied by detecting the presence of thyroid hormone receptor beta2 (TRbeta2) in pro-TRH-synthesizing neurons in the Rpa, Rob and the PPR using immunohistochemistry with specific TRbeta2 antiserum and in situ hybridization with digoxigenin-labeled pro-TRH cRNA probe. TRbeta2 IR was widely distributed throughout the medulla and primarily localized within the cell nuclei. Particularly intense immunostaining was presented in the Rpa, Rob and the PPR neurons. The combination of immunohistochemistry with in situ hybridization revealed that all pro-TRH mRNA-positive neurons in these ventral medullary nuclei were also TRbeta2 IR positive. The numbers of TRbeta2 IR-positive neurons in each nucleus were identical in both euthyroid rats and hypothyroid rats induced by 6-n-propyl-2-thiouracil in drinking water for 4 weeks. The finding that TRbeta2 localized in pro-TRH-synthesizing neurons in the ventral medullary nuclei provides an anatomical substrate for a direct thyroid hormone action on these neurons in the regulation of TRH gene expression, which may contribute to the altered autonomic activity in different thyroid statuses.
Yuan
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CURE:Digestive Diseases Research Center, Department of Medicine, Division of Digestive Diseases and Brain Research Institute, UCLA and VA Greater Los Angeles Healthcare System, Bldg 115, Room 203, 11301 Wilshire Blvd, Los Angeles, CA 90073, USA.
Yang
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D000818:Animals; D005246:Feedback / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D007037:Hypothyroidism / Q000378:metabolism; D008297:Male; D008526:Medulla Oblongata / Q000737:chemistry* / Q000166:cytology; D009474:Neurons / Q000737:chemistry* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011988:Receptors, Thyroid Hormone / Q000032:analysis*; D013973:Thyrotropin-Releasing Hormone / Q000235:genetics*; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D012333:RNA, Messenger; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; D013973:Thyrotropin-Releasing Hormone; D013974:Thyroxine