Tamoxifen alters hepatic cytochrome P450 enzyme expression and circulating growth hormone levels in intact male rats.
OBJECTIVE
To investigate the effects of acute tamoxifen treatment on hepatic cytochrome P450 (CYP) expression and circulating thyroid and growth hormone (GH) levels in intact adult male rats.


METHODS
Rats were injected subcutaneously with peanut oil (vehicle) or tamoxifen at a dosage of 20 or 200 mg/kg for 2 consecutive days. Blood for GH measurements was collected on day 34. Rats were sacrificed at 37 days after treatment, trunk blood was collected, and hepatic microsomes were prepared.


RESULTS
Mean body weight of rats treated with tamoxifen at 200 mg/kg was decreased compared to vehicle-treated rats throughout the 5-week period after treatment. Hepatic CYP2A1-dependent testosterone 7alpha-hydroxylase activity and CYP2A1 protein content were increased, whereas CYP2C11-mediated testosterone 2alpha- and 16alpha-hydroxylase activities and CYP2C11 protein content were decreased significantly following tamoxifen administration. Peak plasma GH levels were 60% lower and nadir plasma GH levels were 30% higher in tamoxifen-treated relative to vehicle-treated rats. In contrast, serum triiodothyronine and thyroxine levels were not affected by tamoxifen treatment.


CONCLUSIONS
Hepatic CYP enzyme expression was altered and body weight was decreased in adult male rats 5 weeks after treatment with tamoxifen. This alteration corresponded to changes in plasma GH levels.
Ickenstein
Ludger M
LM
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada, V6T 1Z3.
Holsmer
Susan L
SL
Bandiera
Stelvio M
SM
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004965:Estrogen Antagonists / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D013006:Growth Hormone / Q000097:blood*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D020318:Rats, Long-Evans; D013629:Tamoxifen / Q000494:pharmacology*; D013963:Thyroid Hormones / Q000097:blood
D004965:Estrogen Antagonists; D013963:Thyroid Hormones; D013629:Tamoxifen; D013006:Growth Hormone; D003577:Cytochrome P-450 Enzyme System