title: Induction of adrenomedullin 2/intermedin expression by thyroid stimulating hormone in thyroid.
abstract: TSH is the important regulator of thyroid function but detailed molecular mechanisms have not been clarified. We first generated the iodine deficient (ID) rat in which goiter is induced by accelerated endogenous TSH secretion. The result of microarray analysis demonstrated markedly increased levels of adrenomedullin 2/intermedin (AM2/IMD) expression in the ID rat thyroid. AM2/IMD is a potent vasodilator. AM2/IMD mRNA expression was induced by TSH in a rat thyroid follicular cell line FRTL-5. Immunohistochemical analysis in human normal and Graves' disease thyroid revealed that AM2/IMD immunoreactivity was detected in follicular cells and more pronounced in Graves' disease. These results indicated that TSH induced AM2/IMD expression in the rat thyroid gland and it could locally work as a potent vasodilator, resulting in the expansion of thyroid inter-follicular capillaries. AM2/IMD could also contribute to facilitate thyroid hormone synthesis possibly via vasodilation effects and/or cAMP stimulating effects in the human thyroid gland.
authors.affiliation: Drug Discovery Department, ASKA Pharmaceutical Co., Ltd., Kawasaki, Japan; Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan. Electronic address: fukui-m@aska-pharma.co.jp.
authors.forename: Shuji
authors.initials: S
authors.lastname: Nagasaki
authors.affiliation: Safety Research Department, ASKA Pharmaceutical Co., Ltd., Kawasaki, Japan.
authors.forename: Motoko
authors.initials: M
authors.lastname: Fukui
authors.affiliation: Drug Discovery Department, ASKA Pharmaceutical Co., Ltd., Kawasaki, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Asano
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Ono
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Miki
authors.affiliation: Safety Research Department, ASKA Pharmaceutical Co., Ltd., Kawasaki, Japan.
authors.forename: Sei-ichi
authors.initials: S
authors.lastname: Araki
authors.affiliation: Safety Research Department, ASKA Pharmaceutical Co., Ltd., Kawasaki, Japan.
authors.forename: Mitsui
authors.initials: M
authors.lastname: Isobe
authors.affiliation: Department of Breast and Endocrine Surgery, Tohoku University Hospital, Sendai, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Nakashima
authors.affiliation: Department of Endocrinology and Applied Medical Science, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
authors.affiliation: Drug Discovery Department, ASKA Pharmaceutical Co., Ltd., Kawasaki, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Sato
mesh_terms: D000328:Adult; D000818:Animals; D002460:Cell Line; D000242:Cyclic AMP; D005260:Female; D005786:Gene Expression Regulation; D006111:Graves Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D036361:Peptide Hormones / Q000096:biosynthesis*; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D013961:Thyroid Gland / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D013972:Thyrotropin / Q000378:metabolism* / Q000494:pharmacology; D014664:Vasodilation
chemical_list: C484330:ADM2 protein, human; D036361:Peptide Hormones; D013972:Thyrotropin; D000242:Cyclic AMP
keywords: Adrenomedullin 2; Goiter; Immunohistochemistry; Intermedin; Iodine-deficiency