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The Influence of the Anabolic Agent, Oxandrolone, Upon the Expression of Procollagen Types I and III mRNA in Human Fibroblasts Cultured on Collagen or Plastic
Abstract & Introduction
Abstract
The repair process entails the reestablishment of a connective tissue matrix, a scar, where collagen is the major matrix component. Collagen deposition is critical for the initial gains in wound breaking strength and makes up the extracellular matrix of granulation tissue. The systemic administration of anabolic steroid reportedly enhances wound repair through the expansion of collagen synthesis and deposition. Do human dermal fibroblasts receiving an anabolic steroid, oxandrolone, increase their expression of procollagen mRNA? Human dermal fibroblasts were grown on collagen-coated or uncoated plastic dishes in the presence of ascorbic acid to optimize collagen processing. By Northern Blot analysis, fibroblasts growing on collagen expressed less types I and III procollagen mRNA, reduced by 49 percent and 91 percent respectively, compared to fibroblasts growing on plastic. Fibroblasts growing on plastic and receiving oxandrolone (3g/mL) showed a minimal change in procollagen mRNA expression. However, oxandrolone stimulated expression of type III procollagen mRNA 11-fold and type I procollagen mRNA doubled in fibroblasts maintained on collagen, relative to control fibroblasts maintained on collagen. A collagen substrate inhibits types I and III procollagen mRNA expression in fibroblasts. The anabolic steroid, oxandrolone, antagonizes such collagen substrate inhibition of procollagen mRNA expression, stimulating procollagen mRNA expression to levels of fibroblasts growing on plastic. These findings suggest that oxandrolone may directly enhance wound healing by increasing the expression of procollagen mRNA in fibroblasts associated with a collagen matrix analogous to the healing wound.
Introduction
Patients who have lost weight unintentionally or who are nutritionally depleted are at increased risk for the formation of pressure ulcers. Similarly, pressure ulcers in such patients present a significant clinical challenge as these patients experience ongoing catabolism with continued nutritional decline. Bodily resources tend to be conserved for vital organ function and overall survival mechanisms rather than being applied toward wound repair. [1] In-vivo studies report that anabolic steroids promote wound healing. [2-6] Clinically, anabolic steroids restore lean body mass and muscle lost as a consequence of severe trauma, including burns or chronic infections, such as HIV. [7-10] In vitro, anabolic steroid stimulates protein synthesis in a variety of cell types, including dermal fibroblasts. [11] In wounded rats, anabolic steroids stimulate wound closure, reepithelialization and granulation tissue deposition, and gain in wound breaking strength. [1,5,12,13] Anabolic steroids can stimulate protein synthesis by enhancing the cellular uptake of amino acids. [14,15] There is also evidence that anabolic steroids directly stimulate mRNA transcription.16 Fibroblasts have a high density of anabolic steroid receptors on their surface and are thus expected to respond to added anabolic steroid. [17] The hypothesis that anabolic steroid increases fibroblast expression of procollagen mRNA warrants investigation.
The influence of the surrounding extracellular matrix on the expression of procollagen mRNA in dermal fibroblasts is also examined. Fibroblasts grown on collagen synthesize about 20 percent of the level of collagen they synthesize when grown on plastic. [18] This apparent inhibition of collagen synthesis by fibroblasts in a collagen-rich environment is analogous to the bed of a maturing granulation tissue. On the other hand, the collagen-free plastic is comparable to a new wound. The effects that anabolic steroids have on procollagen mRNA expression in fibroblasts grown on collagen are unknown. Will the inclusion of oxandrolone, an anabolic steroid, [19] antagonize the inhibition of collagen synthesis by fibroblasts maintained on collagen? More specifically, will oxandrolone increase the expression of procollagen genes in cultured dermal fibroblasts?
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