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IN‐VIVO METABOLITES OF SPIRONOLACTONE AND POTASSIUM CANRENOATE: DETERMINATION OF POTENTIAL ANTI‐ANDROGENIC ACTIVITY BY A MOUSE KIDNEY CYTOSOL RECEPTOR ASSAY
Author(s) -
ARMANINI D.,
KARBOWIAK ISABELLA,
GOI ANNA,
MANTERO F.,
FUNDER J. W.
Publication year - 1985
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.1985.tb01090.x
Subject(s) - endocrinology , medicine , spironolactone , androgen receptor , chemistry , androgen , receptor , in vivo , antiandrogen , kidney , bioassay , testosterone (patch) , biology , aldosterone , hormone , genetics , microbiology and biotechnology , prostate cancer , cancer
SUMMARY We have established a sensitive and specific radioreceptor assay for androgen receptor active materials in plasma, using tritiated methyltrienolone ([ 3 H]R 1881) as tracer, and spayed mouse kidney cytosol receptor as the binding species. On radioreceptor assay, plasma from mice chronically administered spironolactone contained ˜ 10 times higher levels of androgen receptor active material than from mice administered potassium canrenoate. In parallel bioassays (antagonism of the effect of testosterone on seminal vesicle weight), spironolactone was >4 times as potent an antiandrogen as potassium canrenoate. Administered potassium canrenoate circulates as canrenoic acid, in equilibrium with its lactonized congener canrenone. Since over 80% of administered spironolactone is irreversibly converted to canrenone/canrenoic acid, its much higher anti‐androgen activity on radioreceptor assay and bioassay may point to the generation of unidentified, minor metabolites with very high affinity for androgen receptors and/or a very long plasma half‐life.