Abstract
BackgroundGrowth hormone (GH) plays an incompletely understood role in the development of the central nervous system (CNS). In this study, we use transgenic mice expressing a growth hormone antagonist (GHA) to explore the role of GH in regulating postnatal brain, spinal cord and body growth into adulthood. The GHA transgene encodes a protein that inhibits the binding of GH to its receptor, specifically antagonizing the trophic effects of endogenous GH.ResultsBefore 50 days of postnatal age, GHA reduces spinal cord weight more than brain weight, but less than body weight. Thereafter, GHA ceases to inhibit the increase in body weight, which approaches control levels by day 150. In contrast, GHA continues to act on the CNS after day 50, reducing spinal cord growth to a greater extent and for a longer duration than brain growth.ConclusionsJudging from its inhibition by GHA, GH differentially affects the magnitude, velocity and duration of postnatal growth of the brain, spinal cord and body. GH promotes body enlargement more than CNS growth early in postnatal life. Later, its CNS effects are most obvious in the spinal cord, which continues to exhibit GH dependence well into adulthood. As normal CNS growth slows, so does its inhibition by GHA, suggesting that reduced trophic effects of GH contribute to the postnatal slowing of CNS growth. GHA is a highly useful tool for studying the role of endogenous GH on organ-specific growth during aging.
Highlights
Growth hormone (GH) plays an incompletely understood role in the development of the central nervous system (CNS)
By postnatal day 50, male and female mice had achieved slightly over three-quarters of the body weight achieved at 150 days (Fig. 1)
Because growth hormone antagonist (GHA) antagonizes the action of GH at the GH receptor, we infer that endogenous GH must differentially influence their growth
Summary
Growth hormone (GH) plays an incompletely understood role in the development of the central nervous system (CNS). We use transgenic mice expressing a growth hormone antagonist (GHA) to explore the role of GH in regulating postnatal brain, spinal cord and body growth into adulthood. Human brain weight increases 3–4 fold between birth and maturity [1], while the spinal cord enlarges about 10 times postnatally [2]. Transgenic mice have been especially useful in demonstrating the role of GH in CNS growth [6,7,8,9]. Strong evidence for a trophic role of GH in brain growth has come from transgenic mice whose somatotropes were selectively destroyed after birth by the expression of a GH promoter-driven diphtheria toxin transgene [6,10,11].
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