CHANGES IN HEPATIC INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN-1, PROTEIN-2 AND PROTEIN-3 MESSENGER-RNA LEVELS IN RATS WITH ALTERED THYROID STATUS

Changes in thyroid status have a major effect on the GH/insulin-like g rowth factor (IGF) axis. The majority of IGF in the circulation is bou nd to specific IGF-binding proteins (IGFBPs) of which six have been cl oned and sequenced. We have studied changes in hepatic gene expression of IGFBP-1, -2 and -3, in male Wistar rats rendered hyperthyroid (thy roxine, 200 mug/kg per day) or hypothyroid (propylthiouracil, 0.1% dai ly). Littermates of the same age were used as controls (n = 6 in each group). Thyroxine was measured by radioimmunoassay, and hepatic IGFBP- 1, -2 and -3 mRNA levels by Northern blot analysis using specific rat cDNA probes with a 28S ribosomal probe as a loading control. Mean +/- S.E.M. thyroxine levels were 247.0 +/- 44.5 (hyperthyroid group), <9.0 (hypothyroid group) and 76.0 +/- 4.5 nmol/l (control group). IGFBP-1 and -2 mRNA levels in the hypothyroid animals compared with the contro ls were significantly increased, but similar levels of expression were found in thyrotoxic and control rats. IGFBP-3 mRNA levels in hypothyr oid animals were decreased, and increased in thyrotoxic animals. Thus, in the adult rat, hypothyroidism is associated with increased hepatic IGFBP-1 and -2 gene expression, but decreased IGFBP-3 gene expression , while in thyrotoxicosis there are normal IGFBP-1 and -2 mRNA levels but increased IGFBP-3 gene expression. These results suggest that ther e is specific and different transcriptional regulation for IGFBP-1, -2 and -3 in hypo- and hyperthyroid rats.