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Mice Deficient in Liver Production of Insulin-Like Growth Factor I Display Sexual Dimorphism in Growth Hormone-Stimulated Postnatal Growth

Clinical Endocrinology Branch, NIDDK, National Institutes of Health, 10/8D12, 10 Center Drive, Bethesda, Maryland 20892-1758

Address all correspondence and requests for reprints to: Derek LeRoith, M.D., Ph.D., CEB/NIDDK, Building 10, Room 8D12, National Institutes of Health, 10 Center Drive, Bethesda, Maryland 20892-1758. E-mail: Derek{at}helix.nih.gov

Insulin-like growth factor I (IGF-I) is essential for normal intrauterine and postnatal growth and development. Using the Cre/loxP-induced conditional knockout system, we have established a liver-specific IGF-I-deficient (LID) mouse model. Circulating IGF-I levels were decreased by approximately75% without any apparent effect on their growth and development. To determine the role of extra-hepatic IGF-I in GH-induced postnatal growth, we tested the effects of GH on growth rates in these mice. Female, but not male, LID mice displayed significantly accelerated growth rates in response to daily injections of GH for 5 weeks. The GH-induced peripubertal growth in female LID mice was not affected by ovariectomy, nor did castration change the growth pattern in male LID mice. Thus, factors other than gonadal steroids mediate this sexual dimorphism. We postulate that the sexual dimorphic response to GH observed in LID mice may be related to genetically programmed differences in GH secretion patterns.

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