Roles of Growth Hormone and Insulin-like Growth Factor 1 in Mouse Postnatal Growth

• Published in: Developmental biology Vol. 229; no. 1; pp. 141 - 162
• Main Authors: Lupu, Floria, Terwilliger, Joseph D., Lee, Kaechoong, Segre, Gino V., Efstratiadis, Argiris
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-01-2001
• Subjects: Animals; Base Sequence; Body Constitution; Bone Development; chondrocyte; Endocrine Glands - physiology; Gene Expression Regulation; growth; Growth - genetics; growth hormone; Growth Hormone - metabolism; growth hormone receptor; growth rate; growth retardation; insulin-like growth factor 1; Insulin-Like Growth Factor I - genetics; Mice; Mice, Mutant Strains; Molecular Sequence Data; Mutagenesis; Organ Size; ossification; Receptors, Somatotropin - genetics; RNA, Messenger - isolation & purification; Signal Transduction; Tissue Distribution; chondrocyte; growth hormone receptor; growth; growth rate; growth retardation; ossification; growth hormone; insulin-like growth factor 1
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1006/dbio.2000.9975

To examine the relationship between growth hormone (GH) and insulin-like growth factor 1 (IGF1) in controlling postnatal growth, we performed a comparative analysis of dwarfing phenotypes manifested in mouse mutants lacking GH receptor, IGF1, or both. This genetic study has provided conclusive evidence demonstrating that GH and IGF1 promote postnatal growth by both independent and common functions, as the growth retardation of double Ghr/Igf1 nullizygotes is more severe than that observed with either class of single mutant. In fact, the body weight of these double-mutant mice is only ∼17% of normal and, in absolute magnitude (∼5 g), only twice that of the smallest known mammal. Thus, the growth control pathway in which the components of the GH/IGF1 signaling systems participate constitutes the major determinant of body size. To complement this conclusion mainly based on extensive growth curve analyses, we also present details concerning the involvement of the GH/IGF1 axis in linear growth derived by a developmental study of long bone ossification in the mutants.