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"Access of plasma steroids to target tissues and cells
While measurements of free steroid concentrations remain the most robust indicator of the biological activities of plasma steroids (Vermeulen et al. 1999), adoption of the free hormone hypothesis as a universal explanation for how steroids access their target cells in different tissues and organ systems is overly simplistic (Mendel 1989). This is because steroid-target cells in multicellular organ systems are often compartmentalized and separated from the blood vasculature. Moreover, tissues and organ systems vary enormously in terms of their vascular permeability and the nature of their blood supply, including blood flow and transit time. Extreme examples include the highly fenestrated aspect of the blood vasculature in the liver, where hepatocytes are essentially bathed in blood, vs cells within the brain and testis that are separated by blood barriers. In addition, sex steroid-sensitive epithelial cells in organs such as the prostate, breast, and endometrium are separated from blood capillaries by complex basement membranes, and are compartmentalized together with other cell types (e.g., stroma and adipocytes), in which steroids may either act directly or are metabolically converted into more active hormones in intracrine or paracrine fashions. Thus, the locations of target cells in relation to the blood supply, the endothelial vascular permeability, the composition of the extravascular fluids and extracellular matrix, as well as the juxtaposition of different cell types within a tissue all dictate the ultimate ability of steroids to access their target cells. This review provides examples of how albumin, CBG, and SHBG function in concert with each other, as well as separately, to control the actions of steroid hormones in both the blood and extravascular tissue compartments."
