ALTERED EXPRESSION OF INSULIN-LIKE GROWTH-FACTOR-I (IGF-I) AND IGF BINDING-PROTEINS DURING RAT-THYROID HYPERPLASIA AND INVOLUTION

We have investigated changes in the synthesis and localization of insu lin-like growth factor (IGF)-I and IGF binding proteins (IGFBPs) in th yroid 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 re moved and thyroids examined 4 weeks later. Circulating T-4 levels beca me undetectable within two weeks of goitrogen administration while thy roid weight had increased five-fold. The thyroids continued to increas e in size up to 10 weeks, but at a slower growth rate. IGF-I mRNA, det ected by ribonuclease protection assay, was present in the control rat thyroid and increased in abundance after both 1 and 2 weeks of goitro gen administration. Levels of IGF-I mRNA showed a relative decline wit h 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 I GFBP-2 and -3 were elevated in the goitrous glands and remained so as long as goitrogen was administered, thereafter declining during thyroi d involution. IGF-I and IGFBP-2 and -3 mRNAs and synthesized peptides, detected by in situ hybridization and immunohistochemistry respective ly, were found to co-localize predominantly in follicular epithelial c ells. IGFBP-5 mRNA abundance was unaltered during goitre formation, bu t was increased in the involuting thyroid. Both IGFBP-5 mRNA and pepti de were localized to the parafollicular cells (C-cells) which were inc reased in number during involution. The results suggest that an increa sed 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 g rowth rate. The discrete expression of IGFBP-5 by C-cells suggests tha t it could contribute indirectly to goitre formation or involution by acting in a paracrine fashion.