Basal and Growth Hormone-Induced Hepatic Messenger Ribonucleic Acid Expression of Insulin-Like Growth Factor-I (IGF-I) and IGF-Binding Protein-3 Is Independent of Hyperinsulinemia and Increased Energy Status in the Genetically Obese Zucker Rat1

Genetically obese Zucker rats, like obese humans, have normal or elevated circulating insulin-like growth factor-I (IGF-I) levels in the presence of low GH secretion. Hyperinsulinemia, increased energy status, or other nutritional factors associated with obesity could be responsible for these findings directly by increasing hepatic IGF-I production at the transcriptional or posttranscriptional level. Alternatively, circulating IGF-I could be modulated indirectly by affecting its binding proteins. To further elucidate this point, we quantitated hepatic IGF-I, IGF binding protein-3 (IGFBP-3), and GH receptor messenger RNAs (mRNAs) expression in obese Zucker rats under different serum GH and insulin conditions using lean rats as controls. Eleven-week-old male rats were studied basally (intact) or after hypophysectomy (hx) at 9 weeks. In each condition, animals were killed before or 6 h after one dose of recombinant human GH (1.5 μg/g body weight ip). At this time, in addition to the mRNA expression of the ab...