Retinoic acid can enhance the stimulation by thyroid hormone of heme oxygenase activity in the liver of thyroidectomized rats.
The effects of retinoic acid (RA) (50 micrograms/100 g body wt. per day) on hepatic heme oxygenase activity, delta-aminolevulinate synthase (ALAS) activity and on cytochrome P-450 content were determined in thyroidectomized rats treated with T3 (10 micrograms/100 g body wt. per day) or diluent. RA, when administered for 3 days, failed to influence significantly the activity of either heme oxygenase or ALAS, however, the retinoid depleted hepatic cytochrome P-450 content by 17% (P less than 0.01) and microsomal heme content by 47% (P less than 0.001). T3 administration enhanced heme oxygenase activity by 72% (P less than 0.001) and ALAS activity by 251% (P less than 0.001) above levels in diluent treated controls and depleted cytochrome P-450 levels by 55% (P less than 0.001) and heme levels by 75% (P less than 0.001). When RA and T3 were administered together, the retinoid markedly enhanced the T3 stimulation of heme oxygenase activity; 173% above controls (P less than 0.001), and 61% above T3 alone (P less than 0.001). However, RA failed to influence the effect of T3 on ALAS activity or cytochrome P-450 depletion. The results indicate that RA can influence the levels of hepatic cytochrome P-450 and can modulate the stimulation of heme oxygenase activity by thyroid hormone in vivo.
Smith
T J
TJ
Department of Medicine, Albany Medical College, NY 12208.
Drummond
G S
GS
D000818:Animals; D002352:Carrier Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D006419:Heme Oxygenase (Decyclizing) / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains; D018168:Receptors, Retinoic Acid; D013965:Thyroidectomy; D014212:Tretinoin / Q000008:administration & dosage / Q000494:pharmacology*; D014284:Triiodothyronine / Q000008:administration & dosage / Q000494:pharmacology*
D002352:Carrier Proteins; D018168:Receptors, Retinoic Acid; D014284:Triiodothyronine; D014212:Tretinoin; D006419:Heme Oxygenase (Decyclizing)