Dr. Clark has received a research planning grant to explore the use of anabolic steroids as a means to examine the relationship between brain and behavior. Until recently, the mechanism of steroid action was thought to require genomic activity. Steroids, such as testosterone, estrogen and corticosterone, are lipid soluble compounds that readily enter all cells. Within target tissues, such as the brain, uterus and prostate, the cells contain intracellular protein receptors that bind the hormone. The steroid-receptor complexes interact with the nuclear DNA and initiate RNA and protein synthesis. This increase and/or decrease in protein synthesis mediate the physiological and behavioral responses to the hormone. Recently, membrane binding of steroid hormones has been proposed as an alternative mechanism to explain some biological functions that occur too rapidly for genomic activation. Because the family of anabolic steroids have a different chemical structure and metabolic properties, these compounds may be ideal to investigate this alternative mechanism of steroid action. Dr. Clark will carry out a series of studies to determine the ability of anabolic steroids to bind to intracellular and membrane receptors. Anabolic steroids were initially developed for medicinal purposes and were used for the treatment of hypogonadal dysfunction in men, initiation of delayed puberty and growth production. Although these synthetic compounds were synthesized to have maximal effects on protein synthesis and muscle growth, they also have androgenic or masculinizing effects. Therefore, Dr. Clark will examine how these synthetic compounds modulate the biochemical and behavioral action of naturally occurring androgens and estrogens. Anabolic abuse by athletics is receiving international attention. Although little is known about the mechanisms of action, it is clear that these drugs have harmful side-effects, especially on muscle, liver and cardiovascular functions. The results from these types of studies will provide needed important about how these compounds are working.
