Liver-derived insulin-like growth factor I (IGF-I) is the principal source of IGF-I in blood but is not required for postnatal body growth in mice.

The body growth of animals is regulated by growth hormone and IGF-I. The classical theory of this regulation is that most IGF-I in the blood originates in the liver and that body growth is controlled by the concentration of IGF-I in the blood. We have abolished IGF-I production in the livers of mice by using the Cre/loxP recombination system. These mice demonstrated complete inactivation of the IGF-I gene in the hepatocytes. Although the liver accounts for less than 5% of body mass, the concentration of IGF-I in the serum was reduced by 75%. This finding confirms that the liver is the principal source of IGF-I in the blood. However, the reduction in serum IGF-I concentration had no discernible effect on postnatal body growth. We conclude that postnatal body growth is preserved despite complete absence of IGF-I production by the hepatocytes.

[1]  D. Leroith,et al.  Insulin-like growth factor-I affects perinatal lethality and postnatal development in a gene dosage-dependent manner: manipulation using the Cre/loxP system in transgenic mice. , 1998, Molecular endocrinology.

[2]  B. Sauer Inducible gene targeting in mice using the Cre/lox system. , 1998, Methods.

[3]  R. Hammer,et al.  Inducible inactivation of hepatic LRP gene by cre-mediated recombination confirms role of LRP in clearance of chylomicron remnants. , 1998, The Journal of clinical investigation.

[4]  C. Ohlsson,et al.  Growth hormone and bone. , 1998, Endocrine reviews.

[5]  M. Savage,et al.  Intrauterine growth retardation and postnatal growth failure associated with deletion of the insulin-like growth factor I gene. , 1996, The New England journal of medicine.

[6]  C. Stewart,et al.  Growth, differentiation, and survival: multiple physiological functions for insulin-like growth factors. , 1996, Physiological reviews.

[7]  P. Backeljauw,et al.  Prolonged treatment with recombinant insulin-like growth factor-I in children with growth hormone insensitivity syndrome--a clinical research center study. GHIS Collaborative Group. , 1996, The Journal of clinical endocrinology and metabolism.

[8]  M Aguet,et al.  Inducible gene targeting in mice , 1995, Science.

[9]  D. Clemmons,et al.  Insulin-like growth factors and their binding proteins: biological actions. , 1995, Endocrine reviews.

[10]  K. Rajewsky,et al.  Deletion of a DNA polymerase beta gene segment in T cells using cell type-specific gene targeting. , 1994, Science.

[11]  L. Powell-Braxton,et al.  IGF-I is required for normal embryonic growth in mice. , 1993, Genes & development.

[12]  J. Baker,et al.  Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r) , 1993, Cell.

[13]  Elizabeth J. Robertson,et al.  Role of insulin-like growth factors in embryonic and postnatal growth , 1993, Cell.

[14]  M. Berelowitz,et al.  Pituitary and hypothalamic insulin-like growth factor-I (IGF-I) and IGF-I receptor expression in food-deprived rats , 1993, Molecular and Cellular Endocrinology.

[15]  Z. Laron,et al.  Effects of insulin-like growth factor on linear growth, head circumference, and body fat in patients with Laron-type dwarfism , 1992, The Lancet.

[16]  L. Underwood,et al.  Effects of the infusion of insulin-like growth factor I in a child with growth hormone insensitivity syndrome (Laron dwarfism). , 1991, The New England journal of medicine.

[17]  R. Palmiter,et al.  Expression of insulin-like growth factor I stimulates normal somatic growth in growth hormone-deficient transgenic mice. , 1990, Endocrinology.

[18]  P. Rotwein,et al.  Insulin-like growth factors I and II. Peptide, messenger ribonucleic acid and gene structures, serum, and tissue concentrations. , 1989, Endocrine reviews.

[19]  E. Froesch,et al.  Recombinant human insulin-like growth factor I stimulates growth and has distinct effects on organ size in hypophysectomized rats. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[20]  R. Hammer,et al.  Growth allometry of the organs in giant transgenic mice. , 1987, Endocrinology.

[21]  A. Lindahl,et al.  Mechanism of the stimulatory effect of growth hormone on longitudinal bone growth. , 1987, Endocrine reviews.

[22]  S. M. Russell,et al.  Evidence suggesting that the direct growth-promoting effect of growth hormone on cartilage in vivo is mediated by local production of somatomedin. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[23]  J. Jansson,et al.  Growth hormone-releasing hormone. , 1986, Endocrine reviews.

[24]  M. Binoux,et al.  Analysis of serum insulin-like growth factor binding proteins using western blotting: use of the method for titration of the binding proteins and competitive binding studies. , 1986, Analytical biochemistry.

[25]  J. Jansson,et al.  Sexual dimorphism in the control of growth hormone secretion. , 1985, Endocrine reviews.

[26]  E. Froesch,et al.  Actions of insulin-like growth factors. , 1985, Annual review of physiology.

[27]  J. Jansson,et al.  Influence of gonadal steroids on age- and sex-related secretory patterns of growth hormone in the rat. , 1984, Endocrinology.

[28]  A. Stiles,et al.  Tissue concentrations of somatomedin C: further evidence for multiple sites of synthesis and paracrine or autocrine mechanisms of action. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[29]  J. Jansson,et al.  Growth hormone stimulates longitudinal bone growth directly. , 1982, Science.

[30]  M. Preece,et al.  Effect of bovine growth hormone and a partially pure preparation of somatomedin on various growth parameters in hypopituitary dwarf mice. , 1981, The Journal of endocrinology.

[31]  R. Schulte‐Hermann,et al.  Adaptive responses of rat liver to the gestagen and anti-androgen cyproterone acetate and other inducers. III. Cytological changes. , 1980, Chemico-biological interactions.

[32]  P. Seglen Preparation of rat liver cells. I. Effect of Ca 2+ on enzymatic dispersion of isolated, perfused liver. , 1972, Experimental cell research.