Sex hormone binding globulin in men: the free hormone hypothesis revisited during aging and endocrine disorders

Sex hormones (with testosterone as main male sex hormone) belong to the family of steroid hormones. Only the ‘free’ (unbound) fraction is active, but in the circulation these hormones are mainly bound to proteins, with sex hormone binding globulin (SHBG) as most important player. Concentrations of SHBG and thus biological availability of sex steroids change considerably, not only during disease but also during aging. Moreover, the assessment of biological activity of sex steroids in serum is currently undeveloped. The question whether and how physicians should measure either serum total or free testosterone or both in male patients remains unanswered. Likewise, the current use of calculated serum free sex steroid concentrations and their associations with clinical parameters in epidemiological studies is questioned. The real impact of changes in SHBG and hereby biological activity of sex steroids on age-related diseases such as osteoporosis also is still not completely understood. 

In this project we will introduce new methods for measurement of bioavailability and biological activity of sex steroids in serum of normal men as well as men suffering from different hormonal diseases (thyroid disease, type 2 diabetes, obesity). We will also study a new transgenic mouse model which produces high concentrations of human SHBG. This project will therefore increase our knowledge with respect to the biological role of sex steroids in men.