We have recently discovered a receptor for human plasma testosterone-estradiol-binding globulin (TeBG) in human prostatic membranes. We plan to study the structure of this receptor and to investigate the binding reaction in some detail. TeBG binds a variety of androgens and estrogens: we will determine if the interaction of TeBG with its receptor is influenced by the particular steroid which is bound to it. We will purify the receptor from human prostatic membranes and examine its subunit structure. The binding site will be probed using both monoclonal antibodies and the technique of affinity labeling. Aspects of the physiology of the receptor system will be examined in cultured cells. The possible transport of TeBG into cells by the receptor will be examined as will the influence of estrogens and androgens on this transport. We will examine known effects of androgens and estrogens in cultured cells and determine in what ways these effects are altered by the binding of these steroids to TeBG. In addition, any effects which TeBG stripped of steroids might have on these cells will be sought. TeBG binds androgens and estrogens with high affinity. An understanding of the physiology and pathophysiology of these steroid hormones is not possible without an understanding of their binding to TeBG; the presence of a TeBG receptor now complicates this understanding and it is our purpose to begin to explore the entire TeBG-steroid-receptor system. The clinical importance of these investigations ranges from an understanding of carcinoma of the prostate to hirsutism in women.
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