HORMONES AND AGING--PITUITARY-HYPOTHALAMIC FUNCTION IN EXPERIMENTAL ANIMALS

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In an investigation of the effects of age on tissue responses to hormones, young and old male mice were treated with rhGH, T, GH plus T, or placebo and mRNA extracts were prepared from various tissues and probed by Northern blotting, RNA'ase protection assay, or template specific quantitative PCR to quantify specific mRNA's for IGF-I,IGF-I receptor, IGF-I binding proteins 1 and 3, and elongation factor l-alpha as well as tissue specific differentiation factors and structural proteins (e.g. in muscle, myogenin and alpha-myosin heavy chain; in bone alpha- 1 procollagen). Pretreatment, IGF-I levels were significantly lower in old mice, and plasma T and the ratio of EF-1alpha/18S mRNA were reduced, but not significantly so. After rhGH treatment, IGF-I levels tended to increase, but this was significant only in old mice after 5 days. After 10 days, treatment with rhGH alone increased the ratio of EF-1alpha/18SmRNA similarly in mature and old mice, whereas treatment with T alone increased EF-1alpha/18S mRNA only in old mice. Combination treatment with rhGH + T increased EF-1alpha/l8S mRNA significantly after 5days in mature mice. These data suggest that, in male mice, EF-1alpha gene expression can be increased by GH or T, but with no additive response to GH + T. Aging appears to affect the pattern of this response. Continuation of this work should include estimation of IGF-I and IGF-I receptor protein by Western blotting and nuclear run-off assays to establish whether the increases observed in EF-1alpha represent regulation at the transcriptional level.