
Originally Posted by
Alpha-Male
Normal growth and development in the absence of hepatic insulin-like growth factor I
Shoshana Yakar*, Jun-Li Liu*, Bethel Stannard*, Andrew Butler*, Domenici Accili, Brian Sauer, and Derek LeRoith*,§
* 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, April 23, 1999 (received for review January 28, 1999)
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.
whether or not it's ever proven, inhibited igf-1 levels in my opinion are not optimal, especially when there are better alternatives.