Grant: Operating Grant

Sex hormone-binding globulin (SHBG) transports sex steroids (androgens and estrogens) in the blood and regulates their access to tissues. In humans, the liver produces the SHBG that circulates in the blood. However, SHBG is also produced by sex steroid-sensitive cells of the kidney and small intestine and remains inside these cells, and a truncated SHBG is produced in developing sperm. This proposal sets out to determine how the human SHBG gene is regulated in these specialized cell types, how it accumulates within some cells, and what impact this has on controlling the local actions of sex steroids. We have also identified new genetic variants in the human SHBG gene and will define how these alter the production and function of SHBG in the blood and in sperm. Understanding how SHBG expression is controlled in different cells, and how SHBG acts locally within tissues and specific cell types will provide insight into SHBG's broader physiological roles. Importantly, this will be help establish how SHBG polymorphisms can be used to predict disease risk, and how abnormalities in SHBG production and/or function may contribute to the etiology of specific diseases.