Growth hormone, insulin-like growth factor I, and motoneuron size

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Abstract

In this study we asked whether growth hormone (GH) and one of its key mediators, insulin-like growth factor I (IGF-I), influence spinal motoneuron size in conjunction with whole body size. We present evidence that GH has such a role, possibly without the mediation of IGF-I. Both lumbar motoneuron and body size were found to be increased relative to littermate controls in transgenic mice overexpressing GH, while body size, but not motoneuron size, was increased in mice overexpressing IGF-I. GH overexpression coordinately increased nucleolar, nuclear, and cell body size in lumbar spinal motoneurons, so that their normal size relationships were preserved in the transgenic mice. In addition, spinal cord and brain weights were significantly increased in both types of transgenic animal. We conclude that GH can regulate motoneuron, central nervous system, and body size in the same animal, and that IGF-I can mimic the effects of GH on at least two of these three parameters.

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Most cited references 54

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Insulin-like growth factor I increases brain growth and central nervous system myelination in transgenic mice.

Richard Behringer, Alexander M Carson, Carly McMorris … (1993)

Insulin-like growth factor I (IGF-I) is a potent regulator of oligodendrocyte development and myelination in vitro, but its effect on myelination in vivo has never been tested directly. Therefore, we examined brain growth and myelination in a transgenic mouse line that overexpresses IGF-I. By postnatal day 55, when brain growth and myelination are essentially complete in normal mice, the brains of transgenic mice were 55% larger than those of controls owing to an increase in cell size and apparently in cell number. Most or all brain structures appeared to be affected. At the same time, total myelin content of the transgenic mice was 130% greater than that of controls. Oligodendrocyte number as a percentage of total cell number was not increased in the transgenic mouse brains; the increase in myelin content was primarily the result of an increase in myelin production per oligodendrocyte. These findings indicate that IGF-I is a potent inducer of brain growth and myelination in vivo.

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Growth enhancement of transgenic mice expressing human insulin-like growth factor I.

Rachel R. Hammer, Stephanie Mathews, Trevor G. Bell … (1988)

A line of transgenic mice carrying a chimeric gene composed of human insulin-like growth factor I (IGF-I) coding sequences fused to the mouse metallothionein I promoter was generated to study the effects of chronically elevated exposure to IGF-I. Mice in this line overexpress IGF-I in most tissues studied and have circulating IGF-I levels 1.5 times the normal value. This results in a growth response manifested by a 1.3-fold increase in weight as a result of selective organomegaly without an apparent increase in skeletal growth. In addition, expression of the endogenous GH and IGF-I genes is inhibited. These results are consistent with IGF-I playing an important role in the control of somatic growth.