Corvol P, Michaud A, Menard J, Freifeld M, Mahoudeau J
Endocrinology. 1975 Jul;97(1):52-8. doi: 10.1210/endo-97-1-52.
Spirolactones are aldosterone antagonists which inhibit the binding of aldosterone to the renal mineralocorticoid receptor. These molecules also possess an antiandrogenic effect which could be due, among other possibilities, to a peripheral antagonism of androgens. This hypothesis has been tested in the present study. From in vivo experiments, spironolactone K+ canrenoate appear to inhibit the binding of [3H]5alpha-dihydrotestosterone [3H]DHT to the cytosolic and nuclear receptor of the rat ventral prostate. The doses used are in the same range as those used for demonstrating the antimineralocorticoid effect of these molecules. In vitro incubations and in vitro displacement studies show that spironolactone and K+ canrenoate are respectively about 20 and 100 times less effective than DHT in displacing 50 percent of 5 times 10- minus 10 M [3H]DHT from its receptor. Spirolactones are also able to compete with [3H]DHT for the specific 8 S cytosolic receptor. Neither spironolactone nor K+ canrenoate decreases prostatic 5alpha-reductase activity, even at a concentration as high as 10- minus 5 M. It seems likely that spirolactones, besides their action on testosterone biosynthesis, exert their antiandrogenic activity via a peripheral androgen antagonism.
螺内酯是醛固酮拮抗剂，可抑制醛固酮与肾脏盐皮质激素受体的结合。这些分子还具有抗雄激素作用，其原因可能是多方面的，其中一种可能性是对雄激素的外周拮抗作用。本研究对这一假说进行了验证。在体内实验中，螺内酯钾盐坎利酸钾似乎能抑制[³H]5α-双氢睾酮（[³H]DHT）与大鼠腹侧前列腺胞质和核受体的结合。所用剂量与用于证明这些分子抗盐皮质激素作用的剂量范围相同。体外孵育和体外置换研究表明，在从其受体上置换50%的5×10⁻¹⁰ M [³H]DHT时，螺内酯和钾盐坎利酸钾的效力分别比DHT低约20倍和100倍。螺内酯还能够与[³H]DHT竞争特异性的8S胞质受体。即使在高达10⁻⁵ M的浓度下，螺内酯和钾盐坎利酸钾也不会降低前列腺5α-还原酶的活性。除了对睾酮生物合成的作用外，螺内酯似乎还通过外周雄激素拮抗作用发挥其抗雄激素活性。
