Endocrinology, Vol 123, 433-437, Copyright © 1988 by Endocrine Society

ARTICLES

Expression of insulin-like growth factor I in transgenic mice with elevated levels of growth hormone is correlated with growth

LS Mathews, RE Hammer, RL Brinster and RD Palmiter
Department of Biochemistry, University of Washington, Seattle 98195.

To study the role of insulin-like growth factor I (IGF-I) in mediating the growth-promoting function of GH, IGF-I expression was assayed in transgenic mice carrying either GH or GRF fusion genes. These mice exhibit enhanced growth as a result of high level ectopic expression of GH and have 2-fold elevation of both hepatic IGF-I mRNA levels and circulating IGF-I levels. Hepatic IGF-I mRNA levels are low at birth regardless of GH levels; they increase approximately 10-fold during postnatal development and become GH inducible 2 weeks after birth. The ontogeny of circulating IGF-I is similar. Accelerated growth in transgenic mice with GH fusion genes commences 3 weeks after birth despite high circulating GH levels at least as early as birth. In addition, endogenous mouse GH-secreting somatotroph cells in the pituitary are present in normal numbers at 3 weeks, but are undetectable 4 weeks after birth. Because the time at which IGF-I expression becomes GH responsive slightly precedes both the initiation of accelerated growth and the time when endogenous GH disappears, we conclude that IGF-I is directly involved in mediating the GH signal and that delayed induction of IGF-I gene expression is responsible, at least in part, for the delayed onset of other GH-responsive events.

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