TY - JOUR
T1 - Mechanism for inhibitory effect of cannabidiol on microsomal testosterone oxidation in male rat liver
AU - Narimatsu, S.
AU - Watanabe, K.
AU - Yamamoto, I.
AU - Yoshimura, H.
PY - 1988/12/1
Y1 - 1988/12/1
N2 - 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.
AB - 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.
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M3 - Article
C2 - 2907469
AN - SCOPUS:0024268447
SN - 0090-9556
VL - 16
SP - 880
EP - 889
JO - Drug Metabolism and Disposition
JF - Drug Metabolism and Disposition
IS - 6
ER -