Gray, Colin Maurice; (1992) A study of the effects of androgens and other factors on cells derived from deer antler and mammalian bones. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Little is known of the direct effects of androgens on normal osteoblasts although in vivo studies have shown that gonadal steroids play an important role in the prevention of osteoporosis. This thesis has examined the action of the androgens testosterone and dihydrotestosterone, both alone and in combination with 1,25-dihydroxyvitamin on neonatal rat bone-derived cells, cultured from long bones and calvaria, in vitro. Androgens usually stimulated cell proliferation while 1,25-dihydroxyvitamin inhibited it. Androgens in combination with 1,25-dihydroxyvitamin D3, blunted the effect found with 1,25-dihydroxyvitamin alone. However, some populations of cells were unresponsive to androgens or were stimulated by 1,25-dihydroxyvitamin D3. These experiments provide evidence that bone contains a range of osteoblastic subpopulations which are directly affected by both androgens and 1,25-dihydroxyvitamin D3. Cells cultured from deer antler, a unique mammalian mineralised tissue normally only found in the male (except for reindeer/caribou), which can exhibit growth rates of up to 1.8cm/day in large species, were also studied in vitro, Antler-derived cells showed positive immunostaining for type 1 procollagen but not type 2. Most unusually for cells derived from 'bone', antler cells were almost completely devoid of alkaline phosphatase activity. There was also some weak staining of cells grown from antler 'woven bone' for factor VIII related antigen, a marker of the endothelial phenotype. The proliferation of cells derived from antler tips and 'woven bone' regions contrasted strongly with those grown from neonatal rat bone. Antler-derived cell proliferation was normally inhibited by androgens and 1,25- dihydroxyvitamin although some populations showed no effect or a small stimulation. Treatment of antler cells with 1,25-dihydroxyvitamin D3 normally increased protein synthesis. In contrast to the results obtained with steroids, the growth factors IGF-1, basic FGF, TGFfS and to a much lesser extent EOF significantly enhanced cell proliferation in 'serum-free' culture. This study shows that these growth factors may play an important role in rapid antler growth. Since antlers show such exceptional growth rates, an immunohistochemical study of innervation in growing antler tips was conducted. The sensory neuropeptides CGRP, and substance P were found to be present at the tip throughout antler development, showing that neural tissues are able to exhibit the same rapid growth of more than 1cm/day found in red deer antler.

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