Sex-hormone-binding Globulin: a Biomarker for Anabolic Abuse

The most widely used substances to improve performance in human and equine athletes are anabolic steroids, such as testosterone. These are a subgroup of steroid hormones, which are a large group of lipids that play a key role in the physiology of mammalian species. The vast majority of steroids are found in circulation bound to carrier proteins with only a small portion free in circulation. In mammals studied to date, the main carrier proteins are albumin, which binds steroids with low affinity and specificity and sex steroid binding globulin (SHBG), which binds sex steroids with high affinity and specificity. SHBG acts as a transporter of androgens and estrogens in blood and due to its high affinity and specificity, the concentration of SHBG in blood appear to be a major factor regulating bioavailability of steroids in circulation by controlling the concentration of free steroid available to interact with steroid receptors in target tissues. Although there are several naturally produced steroids that have anabolic activity, there are a large number of synthetically modified anabolic agents. Because current regulatory testing involves specific identification of these anabolic agents, regulatory bodies are frequently one step behind the synthetic chemist in their attempt to identify these substances. A number of studies in humans and food-producing animals indicate that concentrations of circulating SHBG are reduced with the administration of a number of exogenous anabolic steroids for a prolong period of time even after withdrawal of the anabolic agents. Therefore, changes in SHBG concentrations can be used as an indirect biological indicator for administration of exogenous growth promoting anabolic agents without direct knowledge or identification of the agent(s) administered. This approach offers the advantages of screening for a large group of anabolic steroids with one biomarker and to potentially respond to new or exotic anabolic androgens which may not yet be characterized by regulatory authorities. In recent years, the world anti-doping agency proposed the use of the “athlete biological passport” (ABP) to determine if an athlete had manipulated his/her physiological variables using illegal substances, without necessarily detecting a particular substance or method. The ABP relies on establishing biomarkers of doping which are abnormal changes in physiological parameters that occur as the result of the use of illegal drugs. In the proposed research, we will characterize SHBG in the horse; develop equine-specific immunoassays for SHBG. With this assay we will characterize normal physiological concentration of SHBG for stallions and mares during the different stages of their sexual development and under different physiological conditions such as pregnancy or orchiectomy. Finally, we will evaluate the effects of exogenous anabolic steroids such as testosterone, Winstrol or Equipoise on circulating concentrations of SHBG as a potential biomarker for administration of these agents.