Investigation into the ability of the androgen receptor (AR) to alter skeletal muscle growth

Raising intact male pigs for market rather than castrating them neonatally is potentially the simplest method of improving lean carcass percentage. Despite economic advantages, these animals display “boar taint,” an unpleasant odor in the meat of intact male pigs. Alternate strategies to improve meat quality (and quantity) have been delayed due to the lack of understanding of the mechanisms that stimulate muscle growth. It has been long known that males have the potential to grow faster and to a greater capacity than females. Early work has suggested that the male steroid hormone testosterone is responsible for the distinct growth patterns; unfortunately it has been implicated in the “boar taint” phenomenon. Again, the interaction of testosterone and muscle growth has not been clearly defined.; The purpose of this research is to investigate the relationship among androgens, the androgen receptor (AR), and muscle growth. Methods to stimulate mitogenic activity via natural hormone stimulation and genetic alteration will be examined as a potential model to increase the efficiency of muscle potential. Natural modifications in the androgen receptor have proven to alter the cycle of the cells and exploration into this abnormality has demonstrated that mutations in the AR alter steroid binding capabilities. Utilizing the concept of mutations to alter binding characteristics, a mutated AR was created and its ability to induce expression of an androgen-sensitive reporter gene was measured.; When transfected to HeLa cells, the mutated AR was able to significantly (P < 0.01) increase expression of the reporter gene over that of the wild type AR when treated with androgens and estrogens. Transfection of the mutant AR into myoblast cell lines from both mouse and rat species resulted in an increase in expression of the reporter gene that is consistent with the data from HeLa cells. Overexpression of the wild type AR into myoblasts and treatment with testosterone induced both proliferation and differentiation of the cells in excess of those expressing endogenous AR. Transgenic mice overexpressing the mutated AR were produced at a 9% efficiency, but due to lack of expression of the transgene, no increased muscle mass phenotype was detected.