Liver-derived IGF-I regulates GH secretion at the pituitary level in mice

We have reported that liver-specific deletion of IGF-I in mice (LI-IGF-I-/- ) results in decreased circulating IGF-I and increased GH levels. In the pr esent study, we determined how elimination of hepatic IGF-I modifies the hy pothalamic-pituitary GH axis to enhance GH secretion. The pituitary mRNA le vels of GH releasing factor (GHRF) receptor and GH secretagogue (GHS) recep tor were increased in LI-IGF-I-/- mice, and in line with this, their GH res ponse to ip injections of GHRF and GHS was increased. Expression of mRNA fo r pituitary somatostatin receptors, hypothalamic GHRF, somatostatin, and ne uropeptide Y was not altered in LI-IGF-I-/- mice, whereas hypothalamic IGF- I expression was increased. Changes in hepatic expression of major urinary protein and the PRL receptor in male LI-IGF-I-/- mice indicated an altered GH release pattern most consistent with enhanced GH trough levels. Liver we ight was enhanced in LI-IGF-I-/- mice of both genders. In conclusion, loss of liver-derived IGF-I enhances GH release by increasing expression of pitu itary GHRF and GHS receptors. The enhanced GH release in turn affects sever al liver parameters, in line with the existence of a pituitary-liver axis.