Normal growth and development in the absence of hepatic insulin-like growth factor I

Normal growth and development in the absence of hepatic insulin-like growth factor I

^*Section on Cellular and Molecular Physiology, Molecular and Cellular Endocrinology Branch, and ^‡Laboratory of Biochemistry and Metabolism, National Institute of Diabetes and Digestive and Kidney Diseases, and ^†Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-1770

Communicated by J. E. Rall, National Institutes of Health, Bethesda, MD (received for review January 28, 1999)

Abstract

The somatomedin hypothesis proposed that insulin-like growth factor I (IGF-I) was a hepatically derived circulating mediator of growth hormone and is a crucial factor for postnatal growth and development. To reassess this hypothesis, we have used the Cre/loxP recombination system to delete the igf1 gene exclusively in the liver. igf1 gene deletion in the liver abrogated expression of igf1 mRNA and caused a dramatic reduction in circulating IGF-I levels. However, growth as determined by body weight, body length, and femoral length did not differ from wild-type littermates. Although our model proves that hepatic IGF-I is indeed the major contributor to circulating IGF-I levels in mice it challenges the concept that circulating IGF-I is crucial for normal postnatal growth. Rather, our model provides direct evidence for the importance of the autocrine/paracrine role of IGF-I.

Footnotes

↵ § To whom reprint requests should be addressed at: Molecular and Cellular Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Room 8D12, Building 10, Bethesda, MD 20892-1758. e-mail: derek{at}helix.nih.gov.
ABBREVIATIONS:

IGF,

insulin-like growth factor;

GH,

growth hormone;

KO,

knockout;

WT,

wild type