Transgenic Hypersecretion of des(1-3) Human Insulin-Like Growth Factor I in Mouse Milk Has Limited Effects on the Gastrointestinal Tract in Suckling Pups

Manuscript received 8 July 1998. Initial reviews completed 31 July 1998. Revision accepted 30 September 1998.

USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, 1100 Bates Street, Houston, TX 77030-2600

We tested the hypothesis that chronic ingestion of increased concentrations of milk-borne des(1-3) human insulin-like growth factor-I (hIGF-I) stimulates gastrointestinal growth and development in suckling mice. We used a transgenic mouse with targeted, lactation-dependent, overexpression of des(1-3) hIGF-I in the mammary gland (IGF). Pups were suckled (7 pups per litter) from birth by either IGF (n = 3-6 litters) or control (n = 3-5 litters) dams. In IGF and control pups, we measured the growth (protein and DNA content) and protein synthesis rate (³H-phenylalanine incorporation) of gastrointestinal and visceral organs in 4-, 8-, 12-, 16- and 29-d-old pups. Des(1-3) hIGF-I in milk from IGF dams was 40-200-fold higher than mouse IGF in either IGF or control dams, but was not detected in the plasma of pups suckling IGF dams. Small intestinal weight, protein and DNA content at 8 and 16 d were greater in pups suckling IGF dams than control dams; protein synthesis was also greater in IGF pups at 8 d. Total intestinal lactase activity at 8 and 12 d of age tended to be higher (P < 0.10) in IGF than in control pups. Hypersecretion of des(1-3) hIGF-I in milk ingested by suckling mice pups had limited effects on the growth and maturation of the gastrointestinal tract. Moreover, there was little evidence that milk-borne IGF-I is absorbed into the circulation and stimulates visceral organ growth. This study also demonstrates the feasibility of using mammary-specific transgenes to increase the concentration of milk-borne growth factors to examine whether they affect the growth and development of the suckling neonate.

The Journal of Nutrition Vol. 129 No. 1 January 1999, pp. 51-56
Copyright ©1999 by the American Society for Nutritional Sciences

This article has been cited by other articles:

				D. L. Hadsell, D. T. Torres, N. A. Lawrence, J. George, A. F. Parlow, A. V. Lee, and M. L. Fiorotto Overexpression of Des(1-3) Insulin-Like Growth Factor 1 in the Mammary Glands of Transgenic Mice Delays the Loss of Milk Production with Prolonged Lactation Biol Reprod, December 1, 2005; 73(6): 1116 - 1125. [Abstract] [Full Text] [PDF]

				B. Roffler, A. Fah, S. N. Sauter, H. M. Hammon, P. Gallmann, G. Brem, and J. W. Blum Intestinal Morphology, Epithelial Cell Proliferation, and Absorptive Capacity in Neonatal Calves Fed Milk-Born Insulin-Like Growth Factor-I or a Colostrum Extract J Dairy Sci, May 1, 2003; 86(5): 1797 - 1806. [Abstract] [Full Text] [PDF]

				D. G. Burrin, B. Stoll, M. Z. Fan, M. A. Dudley, S. M. Donovan, and P. J. Reeds Oral IGF-I Alters the Posttranslational Processing but Not the Activity of Lactase-Phlorizin Hydrolase in Formula-Fed Neonatal Pigs J. Nutr., September 1, 2001; 131(9): 2235 - 2241. [Abstract] [Full Text] [PDF]

				R. J. Collier and D. E. Bauman Re: Re: Role of the Insulin-Like Growth Factors in Cancer Development and Progression J Natl Cancer Inst, June 6, 2001; 93(11): 876 - 876. [Full Text] [PDF]

				J. Pacha Development of Intestinal Transport Function in Mammals Physiol Rev, October 1, 2000; 80(4): 1633 - 1667. [Abstract] [Full Text] [PDF]

				H.-M. Lee, V. Udupi, E. W. Englander, S. Rajaraman, R. J. Coffey Jr., and G. H. Greeley Jr. Stimulatory Actions of Insulin-Like Growth Factor-I and Transforming Growth Factor-{alpha} on Intestinal Neurotensin and Peptide YY Endocrinology, September 1, 1999; 140(9): 4065 - 4069. [Abstract] [Full Text]

				A. N. Alexander and H. V. Carey Oral IGF-I enhances nutrient and electrolyte absorption in neonatal piglet intestine Am J Physiol Gastrointest Liver Physiol, September 1, 1999; 277(3): G619 - G625. [Abstract] [Full Text] [PDF]