Figure 4.

Proposed model for hypothalamic-pituitary-liver feedback axis of GH secretion and how it is affected by liver-specific IGF-I deletion. Mice with liver-specific IGF-I KO (right panel) have increased GH secretion. Increased GH levels in turn enhance the liver weight. In male mice with depletion of liver-derived IGF-I, the enhanced GH trough levels feminize liver functions regulated by the sexual dimorphism of GH secretion in rodents. The mechanism by which lack of liver-derived IGF-I increases GH secretion seems to involve increased expression of GHRH and ghrelin receptors (right panel) and augmented responsiveness to these ligands at the level of the pituitary. There is no evidence that lack of liver-derived IGF-I enhances GH secretion via an effect on the hypothalamus, possibly because enhanced pituitary GH and local hypothalamic IGF-I secretion partly counteract the effects of lack of liver-derived IGF-I on the hypothalamus.