Effects of growth hormone and insulinlike growth factor-I on body growth and adult bone metabolism

The anabolic action of growth hormone (GH) on bone is well demonstrated by the short stature and delayed bone maturation in children with GH deficienc y and in acromegalic patients with increased cortical bone mass. The body g rowth is regulated by growth hormone and insulin-like growth factor-I (IGF- I). The classic somatomedin hypothesis of this regulation is that most IGF- I in the blood originates in the liver and that body growth is controlled b y the concentration of IGF-I in the blood. We have recently abolished IGF-I production in the livers of mice by using the Cre/loxP recombination syste m. The mice, in which IGF-I production had been inactivated in the liver, d isplayed a more than 80% reduction in serum IGF-I. In contrast, they demons trated a normal postnatal growth, indicating that extrahepatic, autocrine/p aracrine-acting IGF-I is the main determinant of postnatal growth. GH is al so important for normal adult bone remodeling. Adults with GH deficiency ha ve reduced bone mass, and GH treatment increases bone mass in GH-deficient adults. Future clinical studies will determine whether some patients with d ecreased bone mass for other reasons will benefit from treatment with GH al one or in combination with other treatments. (C) 2000 Lippincott Williams & Wilkins, Inc.