SC 25152: A potent mineralocorticoid antagonist with reduced affinity for the 5α-dihydrotestosterone receptor of human and rat prostate

G. B. Cutler, J. C. Pita, S. M. Rifka, R. H. Menard, M. A. Sauer, Donald (Lynn) Loriaux

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

It has previously been shown that spironolactone possesses antiandrogenic activity in the rat and interacts with rat prostate 5-dihydrotestosterone cytoplasmic receptors to block the nuclear uptake of this hormone. Current evidence suggests that this androgen receptor interaction may be an important mechanism through which spironolactone causes endocrine side effects in rat and man. The authors have analyzed the interactions of several spirolactone analogs with the androgen receptor of human and rat prostate and the mineralocorticoid receptor of human and rat kidney. One analog SC 25152, was found to have considerably reduced affinity for the prostate 5α-dihydrotestosterone receptor [K(a)=24±1% and 19±6% (mean ± SE) in the human and rat, respectively, of the K(a) for spironolactone] while maintaining similar affinity for the mineralocorticoid receptors of human and rat kidney [K(a)=113±37% and 86±7% (mean ± SE), respectively, of the K(a) for spironolactone]. These findings would predict this analog to have reduced antiandrogenicity at equivalent therapeutic doses.

Original languageEnglish (US)
Pages (from-to)171-175
Number of pages5
JournalJournal of Clinical Endocrinology and Metabolism
Volume47
Issue number1
StatePublished - 1978
Externally publishedYes

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Mineralocorticoid Receptor Antagonists
Spironolactone
Rats
Prostate
Androgen Receptors
Mineralocorticoid Receptors
Kidney
Dihydrotestosterone
Cytoplasmic and Nuclear Receptors
human AR protein
SC 25152
Hormones

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

SC 25152 : A potent mineralocorticoid antagonist with reduced affinity for the 5α-dihydrotestosterone receptor of human and rat prostate. / Cutler, G. B.; Pita, J. C.; Rifka, S. M.; Menard, R. H.; Sauer, M. A.; Loriaux, Donald (Lynn).

In: Journal of Clinical Endocrinology and Metabolism, Vol. 47, No. 1, 1978, p. 171-175.

Research output: Contribution to journalArticle

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AU - Sauer, M. A.

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