Mechanism for inhibitory effect of cannabidiol on microsomal testosterone oxidation in male rat liver

S. Narimatsu, K. Watanabe, I. Yamamoto, H. Yoshimura

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Effects of four cannabinoids [cannabidiol (CBD), Δ8-tetrahydrocannabinol, Δ9-tetrahydrocannabinol, and cannabinol] on hepatic microsomal oxidation of testosterone (17β-hydroxy-androst-4-ene-3-one) were examined in adult male rats. Only CBD (30 μM) competitively inhibited 2α-hydroxy-testosterone (2α-OH-T) and 16α-OH-T formation by hepatic microsomes but did not affect androstenedione (androst-4-ene-3, 17-dione) and 7α-OH-T formation. Kinetic analyses demonstrated that the inhibitory profile of CBD for testosterone oxidation was different from those of SKF 525-A, which caused competitive inhibition for 2α- and 16α-hydroxylations and noncompetitive inhibition for 6α-hydroxylation, and of metyrapone, which inhibited only 6β-hydroxylation competitively. CBD also suppressed formation of 2α-OH-T, 16α-OH-T, and androstenedione from testosterone, catalyzed by a reconstituted system containing hepatic cytochrome P-450 purified from phenobarbital-treated rats. Pretreatment of the rat with CBD (10 mg/kg, ip, once a day for 3 days) decreased testosterone oxidation at the 2α-, 16α-, and 17-positions and increased 7α-OH-T formation, while total cytochrome P-450 content was decreased. These results suggest that CBD suppresses hepatic testosterone oxidation at the 2α-, 16α-, and 17-positions through selective inhibition of the male-specific cytochrome P-450 in the adult male rat.

Original languageEnglish
Pages (from-to)880-889
Number of pages10
JournalDrug Metabolism and Disposition
Volume16
Issue number6
Publication statusPublished - 1988
Externally publishedYes

Fingerprint

Cannabidiol
Liver
Testosterone
Rats
Oxidation
Hydroxylation
Cytochrome P-450 Enzyme System
Dronabinol
Androstenedione
Cannabinol
Proadifen
Metyrapone
Cannabinoids
Phenobarbital
Microsomes
hydroxide ion
Kinetics

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Mechanism for inhibitory effect of cannabidiol on microsomal testosterone oxidation in male rat liver. / Narimatsu, S.; Watanabe, K.; Yamamoto, I.; Yoshimura, H.

In: Drug Metabolism and Disposition, Vol. 16, No. 6, 1988, p. 880-889.

Research output: Contribution to journalArticle

Narimatsu, S, Watanabe, K, Yamamoto, I & Yoshimura, H 1988, 'Mechanism for inhibitory effect of cannabidiol on microsomal testosterone oxidation in male rat liver', Drug Metabolism and Disposition, vol. 16, no. 6, pp. 880-889.
Narimatsu, S. ; Watanabe, K. ; Yamamoto, I. ; Yoshimura, H. / Mechanism for inhibitory effect of cannabidiol on microsomal testosterone oxidation in male rat liver. In: Drug Metabolism and Disposition. 1988 ; Vol. 16, No. 6. pp. 880-889.
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