Structure, function, and regulation of androgen-binding protein/sex hormone-binding globulin.

Despite over 20 years of research, the functions of ABP and SHBG remain elusive. The major reason for this lack of knowledge has been the unavailability of natural mutants with clinical defects for study. There is strong evidence that these binding proteins do act to modulate the gene regulatory actions of nuclear sex steroid receptors by controlling the availability of androgens and estrogens. In plasma, SHBG controls the metabolic clearance rate of sex steroids. In addition there is strong evidence that they have a much broader function. The identification of plasma membrane receptors in target tissues and the finding of homologous domains in several developmental proteins support other functions. Moreover, other experiments suggest the proteins may actually be hormones or growth factors. These findings are not compatible with a model that has the proteins only regulating free steroid hormone levels. Obviously, much more experimentation will be necessary to reveal the functions of ABP and SHBG. The recent discoveries have offered several clues to their functions and open new routes for study. These experiments, coupled with newly developed techniques, such as gene knockout by homologous recombination, make one optimistic that the functions of these unique proteins will be deciphered in the near future.