title: The synthesis and testing of E-17 alpha-(2-iodovinyl)-5 alpha-dihydrotestosterone and Z-17 alpha-(2-iodovinyl)-5 alpha-dihydrotestosterone as gamma-emitting ligands for the androgen receptor.
abstract: Two iodinated steroids, E-17 alpha-(2-iodovinyl)-5 alpha-dihydrotestosterone and Z-17 alpha-(2-iodovinyl)-5 alpha-dihydrotestosterone were synthesized in a search for a gamma-emitting androgen that binds with high affinity to the androgen receptor. Such compounds would be extremely useful research tools for studies of androgen responsive tissues and as in vivo probes of androgen responsive tumors such as prostate cancer. These 17 alpha-iodovinyl steroids were synthesized because many 17 alpha-substituents do not interfere markedly with binding to the androgen receptor and because similar analogs of other steroids, estrogens and progestins, have been shown to have the requisite properties for ligands to those receptors. Both of these potential ligands were tested for their ability to compete with [3H]R1881 for binding to the androgen receptor in cytosols from prostate, hypothalamus and pituitary. The relative binding affinities ranged between 5 and 20%, depending upon the tissue and steroid. In order to test the two ligands directly, they were both synthesized labelled with 125I and tested for binding to the androgen receptor in prostatic cytosol and in vivo for specific concentration in androgen responsive tissues. While there was considerable binding in the prostatic cytosol, it was not specific because 5 alpha-dihydrotestosterone did not compete. Likewise in the in vivo experiment there was no evidence for androgen receptor mediated concentration of the tracers. While on the basis of relative binding affinity, these 2 steroids appeared to be good candidates for androgen receptor ligands, neither were useful for this purpose. These results contribute new information which will be valuable in the design of other gamma-emitting androgens and emphasises that, in this process, other factors such as metabolism and nonspecific binding must be considered.
authors.affiliation: Department of Chemistry, College at Old Westbury, State University of New York 11568.
authors.forename: R M
authors.initials: RM
authors.lastname: Hoyte
authors.forename: N J
authors.initials: NJ
authors.lastname: MacLusky
authors.forename: R B
authors.initials: RB
authors.lastname: Hochberg
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D055598:Chemical Phenomena; D002621:Chemistry; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D013196:Dihydrotestosterone / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D066298:In Vitro Techniques; D007536:Isomerism; D008297:Male; D010902:Pituitary Gland / Q000378:metabolism; D011467:Prostate / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011944:Receptors, Androgen / Q000378:metabolism*
chemical_list: D011944:Receptors, Androgen; D013196:Dihydrotestosterone; C064824:17-(2-iodovinyl)dihydrotestosterone