Reduction of thyroid hormone may participate in the modulation of cytochromes P450 2C11 and 3A2 by retinol.
Both hypothyroidism and retinol supplementation in rats induce CYP 3A2 and suppress CYP 2C11. Therefore studies were performed to evaluate the role of thyroid hormones in the modulation of P450 expression by retinol. Adult male Sprague-Dawley rats were given retinol as a single oral dose of 75 mg/kg. Rats were killed and hepatic microsomes prepared at 24, 48, 72, and 96 hr following treatment. The catalytic activity of 2C11 was reduced maximally by retinol at 48 hr (by 30%) whereas 3A2 activity was elevated maximally at 24 hr (by 30%). The serum concentration of testosterone was not altered at any time point. However, retinol produced a decline in the concentration of thyroxine by 35% and 43% at 24 and 48 hr, respectively. These data suggest that administration of large doses of retinol may alter hepatic microsomal enzyme expression by perturbation of plasma thyroid hormone levels.
Badger
D
D
Department of Pharmacology and Toxicology, The University of Arizona, Tucson 85721, USA.
Kraner
J
J
Fraser
D
D
Hoglen
N
N
Halpert
J
J
Sipes
I G
IG
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000187:drug effects* / Q000378:metabolism; D013739:Testosterone / Q000097:blood; D013963:Thyroid Hormones / Q000097:blood / Q000502:physiology*; D014801:Vitamin A / Q000494:pharmacology*
D013963:Thyroid Hormones; D014801:Vitamin A; D013739:Testosterone; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; D039181:Steroid 16-alpha-Hydroxylase; C022657:steroid hormone 6-beta-hydroxylase