Structure-activity relationship of the cholestatic activity of dihydrotestosterone glucuronide, allo bile acids and lithocholate

Mary Vore, Christopher Montgomery, Sherrie Durham, David Schlarman, William H. Elliot

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Dihydrotestosterone glucuronide (DHTG), a series of 5α-bile acids, or allo-bile acids (3α-hydroxy-5α-cholanic acid, 3-keto-5α-cholanic acid and 3β-hydroxy-5α-cholanic acid) and their normal bile acid analogues (3α-hydroxy-5β-cholanic acid or lithocholate, 3-keto-5β-cholanic acid and 3β-hydroxy-5β-cholanic acid) were administered intravenously to female rats in order to determine their effects on bile flow. All agents caused a rapid and profound inhibition of bile flow which was dose-dependent. The logarithm of the dose vs the cholestatic response curve for DHTG, the allo-bile acids and lithocholate were all parallel. DHTG was the most potent congener and was two times more potent than 3-keto-5α-cholanic acid and 5 times more potent than lithocholate. These data indicate that the glucuronic acid moiety and the trans configuration of the A and B rings of the steroid nucleus confer the greatest cholestatic potency.

Original languageEnglish
Pages (from-to)2033-2040
Number of pages8
JournalLife Sciences
Volume44
Issue number26
DOIs
StatePublished - 1989

Bibliographical note

Funding Information:
This work was supported by HD 13250 (M.V., C.M. and S.D.) and HL 07878 (D.S. and W.H.E.). D.S. was supported by NIH Grant T35HL-07846.

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (all)
  • Pharmacology, Toxicology and Pharmaceutics (all)

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