title: Excess TSH causes abnormal skeletal development in young mice with hypothyroidism via suppressive effects on the growth plate.
abstract: Hypothyroidism in the young leads to irreversible growth failure. hyt/hyt Mice have a nonfunctional TSH receptor (TSHR) and are severely hypothyroid, but growth retardation was not observed in adult mice. We found that epiphysial cartilage as well as cultured chondrocytes expressed functional TSHR at levels comparable to that seen in the thyroid, and that addition of TSH to cultured chondrocytes suppressed expression of chondrocyte differentiation marker genes such as Sox-9 and type IIa collagen. Next, we compared the long bone phenotypes of two distinct mouse models of hypothyroidism: thyroidectomized (THYx) mice and hyt/hyt mice. Although both THYx and hyt/hyt mice were severely hypothyroid and had similar serum Ca(2+) and growth hormone levels, the tibia was shorter and the proliferating and hypertrophic zones in the growth plate was significantly narrower in THYx mice than in hyt/hyt mice. Supplementation of hyt/hyt mice thyroid hormone resulted in a wider growth plate compared with that of wild-type mice. Expressions of chondrocyte differentiation marker genes Sox-9 and type IIa collagen in growth plate from THYx mice were 52 and 60% lower than those of hyt/hyt mice, respectively. High serum TSH causes abnormal skeletal development in young mice with hypothyroidism via suppressive effects on the growth plate.
authors.affiliation: Third Department of Internal Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo City, Yamanashi, Japan.
authors.forename: Toyoshi
authors.initials: T
authors.lastname: Endo
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D019902:Chondrocytes; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D005260:Female; D006132:Growth Plate / Q000378:metabolism*; D007037:Hypothyroidism / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism; D013972:Thyrotropin / Q000378:metabolism*; D013974:Thyroxine / Q000097:blood; D013977:Tibia / Q000002:abnormalities*; D014284:Triiodothyronine / Q000097:blood
chemical_list: C447413:Col2a1 protein, mouse; D024043:Collagen Type II; D012333:RNA, Messenger; D011988:Receptors, Thyroid Hormone; D055758:SOX9 Transcription Factor; D014284:Triiodothyronine; D013972:Thyrotropin; D013974:Thyroxine
keywords: TSH receptor; chondrocyte; growth plate; hypothyroidism; hyt mouse