Effects of local administration of GH and IGF-1 on longitudinal bone growth in rats

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Abstract
The effect of local administration of growth hormone (GH) and insulinlike growth factor 1 (IGF-1) on longitudinal bone growth was studied in the proximal tibia of hypophysectomized rats, by using the tetracycline method. Human GH (hGH) stimulated local bone growth when administered into the epiphysial growth plate, into the epiphysis through an implanted cannula, or into the knee joint intraarticularly. In contrast, hGH administration into the metaphysis did not cause such a stimulation. The effect of hGH was dose dependent, and the lowest daily dose of hGH that caused a stimulation was 50 ng. hGH produced by cloned bacteria was as effective as pituitary-derived hGH, excluding the possibility of a pituitary growth factor being the active compound. GH from other mammalian species (rat GH, ovine GH, and bacterially produced bovine GH) also stimulated local bone growth. Ovine prolactin (oPRL) stimulated local bone growth but the threshold dose of oPRL was approximately 100 times higher than that of hGH, suggesting that contamination of this preparation by GH may account for the stimulation. Reduced carboxymethylated human GH, that has a greatly reduced anabolic activity, did not stimulate local bone growth. Local administration of 5 micrograms of bacterially produced human IGF-1 per day produced a small but significant effect on unilateral bone growth. Simultaneous administration of hGH had no additive effect with, nor did it potentiate, the stimulatory effect of IGF-1. The present study confirms and extends earlier investigations, showing that local injection of GH at the site of the epiphysial growth plate stimulates unilateral bone growth. The study also shows that local administration of IGF-1 stimulates longitudinal bone growth.