title: Altered expression of insulin-like growth factor-I (IGF-I) and IGF binding proteins during rat thyroid hyperplasia and involution.
abstract: We have investigated changes in the synthesis and localization of insulin-like growth factor (IGF)-I and IGF binding proteins (IGFBPs) in thyroid tissues during the induction of goitre in iodine-deficient rats, and during the subsequent involution of the gland following goitrogen withdrawal. Goitre was induced in adult rats by acute (1 or 2 weeks) or chronic (4 or 10 weeks) administration of methimazole together with a low iodine diet. After twelve weeks the goitrogenic stimuli were removed and thyroids examined 4 weeks later. Circulating T4 levels became undetectable within two weeks of goitrogen administration while thyroid weight had increased five-fold. The thyroids continued to increase in size up to 10 weeks, but at a slower growth rate. IGF-I mRNA, detected by ribonuclease protection assay, was present in the control rat thyroid and increased in abundance after both 1 and 2 weeks of goitrogen administration. Levels of IGF-I mRNA showed a relative decline with prolonged goitrogen administration, and following thyroid involution the hybridization signal was similar to that seen in control glands. Northern blot hybridization showed that IGFBP-2, -3 and -5 mRNAs were all present in growth-quiescent, control thyroids and those encoding IGFBP-2 and -3 were elevated in the goitrous glands and remained so as long as goitrogen was administered, thereafter declining during thyroid involution. IGF-I and IGFBP-2 and -3 mRNAs and synthesized peptides, detected by in situ hybridization and immunohistochemistry respectively, were found to co-localize predominantly in follicular epithelial cells. IGFBP-5 mRNA abundance was unaltered during goitre formation, but was increased in the involuting thyroid. Both IGFBP-5 mRNA and peptide were localized to the parafollicular cells (C-cells) which were increased in number during involution. The results suggest that an increased expression of IGF-1 may contribute to early goitre formation, but that a relative increase in the abundance of IGFBP-2 and -3 may limit IGF availability at later times, and facilitate a slowing of thyroid growth rate. The discrete expression of IGFBP-5 by C-cells suggests that it could contribute indirectly to goitre formation or involution by acting in a paracrine fashion.
authors.affiliation: MRC Group in Fetal and Neonatal Health and Development, Lawson Research Institute, St Joseph's Health Centre, London, Ontario, Canada.
authors.forename: I D
authors.initials: ID
authors.lastname: Phillips
authors.forename: G P
authors.initials: GP
authors.lastname: Becks
authors.forename: A
authors.initials: A
authors.lastname: Logan
authors.forename: J F
authors.initials: JF
authors.lastname: Wang
authors.forename: C
authors.initials: C
authors.lastname: Smith
authors.forename: D J
authors.initials: DJ
authors.lastname: Hill
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006042:Goiter / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D006965:Hyperplasia; D006984:Hypertrophy; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D018975:Insulin-Like Growth Factor Binding Protein 5; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D008713:Methimazole / Q000633:toxicity; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D013974:Thyroxine / Q000097:blood
chemical_list: D002352:Carrier Proteins; D018975:Insulin-Like Growth Factor Binding Protein 5; D012333:RNA, Messenger; D008713:Methimazole; D007334:Insulin-Like Growth Factor I; D013974:Thyroxine