Because steroids are lipophilic, they diffuse easily through the cell membranes, and therefore have a very large distribution volume. In their target tissues, steroids are concentrated by an uptake mechanism which relies on their binding to intracellular proteins (or " receptors ", see below). High concentration of steroids are also found in adipose tissue, although this is not a target for hormone action. In the human male, adipose tissue contains aromatase activity, and seems to be the main source of androgen-derived estrogens found in the circulation. But most of the peripheral metabolism occurs in the liver and to some extent in the kidneys, which are the major sites of hormone inactivation and elimination, or catabolism (see below).
The C-terminal AF-2 transactivation domain is highly conserved within the nuclear receptor superfamily 31 and is recognized by various transcriptional coactivators. 32 , 33 AF-2 is localized to the most C-terminal end of the E domain. A third transactivation domain called AF-2a or tau2 has been localized to the N-terminal region of the LBD of ERα 31 and GR. 34 Deletion experiments revealed a role for AF-2a and the DBD in targeting rat GR to the nuclear matrix, 35 an interconnected ribonuclear-protein network within the nucleus that is thought to play an important roles in transcription of active genes by stabilizing the assembly of the transcriptional machinery. 36