Specific binding of [3H]-16β-hydroxydehydroepiandrosterone by rat kidney

Daniel T. Matulich, John D. Baxter, Celso Gomez-Sanchez, O. Bryan Holland

Research output: Contribution to journalArticle

Abstract

16β-Hydroxydehydroepiandrosterone (16β-OH-DHEA) can influence electrolyte excretion in the rat and has been reported to be elevated in the urine of patients with low-renin essential hypertension. This steroid does not bind to the mineralocorticoid receptors in rat or human kidney that bind aldosterone and other sodium-retaining steroids. Thus, actions of 16β-OH-DHEA may be mediated through other binding sites. To obtain a direct indication of how cells interact with 16β-OH-DHEA, we studied the binding of the radioactively labeled steroid. Limited capacity binding of [3H]-16β-OH-DHEA was demonstrated after incubating the steroid with kidney slices at 37°C (apparent equilibrium dissociation constant (KD approximately 0.3 μM) or cytosol at 0°C (KD approximately 3 μM). Specific binding activity by kidney cytosol was respectively 6-fold and 40-fold greater than by liver or brain cytosol. Nonradioactive testosterone, progesterone and the spironolacton SC14266 had detectable but weak activities (as compared with non-radioactive 16β-OH-DHEA) for inhibition of [3H]-16β-OH-DHEA. No significant competition was observed with androstenediol, aldosterone, deoxycorticosterone, corticosterone and 16-oxo-androstenediol at concentrations to 10 μM. A heat-dependent nuclear transfer mechanism for 16β-OH-DHEA was not observed. Thus, limited capacity binding sites exist in rat kidney which can recognize 16β-OH-DHEA. The sites are distinguishable from the previously characterized mineralocorticoid, glucocorticoid and androgen receptors, and differ from known steroid receptors in that they lack an obvious nuclear transfer mechanism. The physiological role of the binding sites detected in these studies is not known.

Original languageEnglish (US)
Pages (from-to)285-289
Number of pages5
JournalJournal of Steroid Biochemistry
Volume10
Issue number3
DOIs
StatePublished - Mar 1979

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ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology

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