title: Uptake and retention of androgens by the rat ventral prostate and consideration of their use as site directing agents.
abstract: Elucidation of the mechanism whereby androgens are accumulated selectively by the prostate may help in the design of drugs for the treatment of prostatic cancer. The uptake and retention of [3H]testosterone, following intraperitoneal injection, by various tissues in the 24 hr castrate rat has been studied over an extended time course. The selectivity with which prostate, as compared with blood or other tissues, accumulated 3H was shown to be dose-dependent. At a low dose (0.15 microgram), selective prostatic accumulation was greater in 24 hr castrate and diethylstilboestrol-treated rats than in normal animals. Testosterone, 5 alpha-dihydrotestosterone and oestradiol, radioactively labelled, were each administered to 24 hr castrate rats by intraperitoneal injection. Specific prostatic accumulation of radioactivity was more dependent on steroid structure at a low dose than at a high dose (0.6 mg) and at the low dose (0.15 microgram) followed the order testosterone greater than 5 alpha-dihydrotestosterone greater than or equal to oestradiol. This order was surprising in view of the androgen receptor binding affinities of these steroids. It is concluded that small quantities of material could be directed with the greatest specificity to the prostate of castrate or diethylstilboestrol-treated animals if attached to testosterone. Androgens would be more useful for site-directed radiopharmaceuticals than cytotoxic agents.
mesh_terms: D000728:Androgens / Q000378:metabolism*; D000818:Animals; D002369:Castration; D013196:Dihydrotestosterone / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism; D008297:Male; D009928:Organ Specificity; D011467:Prostate / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000188:drug therapy; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism; D013997:Time Factors
chemical_list: D000728:Androgens; D011956:Receptors, Cell Surface; D013196:Dihydrotestosterone; D013739:Testosterone; D004958:Estradiol