Direct effects of tamoxifen on growth hormone secretion by pituitary cells in vitro.
There is now strong evidence to suggest that insulin-like growth factor I (IGF-I) plays an important role in breast cancer proliferation. Recently we observed that tamoxifen-treated stage I breast cancer patients have serum IGF-I levels significantly lower than placebo-treated patients. Since IGF-I is growth hormone (GH) dependent, we have tested the hypothesis that tamoxifen alters serum IGF-I levels through direct inhibition of GH secretion. Immature lamb pituitary cultures were examined for acute (3 h) or chronic (1-6 day) effects of the drug, using doses (0.1-10 mumol/l) based on known steady state levels in patients on tamoxifen therapy (0.31-3.1 mumol/l). Tamoxifen had a direct, dose-related, inhibitory effect on GH release from pituitary somatotropes, during acute as well as chronic treatment. The 10 mumol/l dose consistently decreased both basal and growth hormone releasing factor stimulated GH release. These in vitro data are consistent with our hypothesis that tamoxifen suppresses serum IGF-I levels by acting at the pituitary to inhibit GH release.
Endocrine Research Laboratory, Montreal Children's Hospital, Quebec, Canada.
S A
SA
Malaab
M N
MN
Pollak
C G
CG
Goodyer
D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis / Q000187:drug effects; D013006:Growth Hormone / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D007700:Kinetics; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism; D011506:Proteins / Q000032:analysis; D012756:Sheep; D013004:Somatostatin / Q000494:pharmacology; D013268:Stimulation, Chemical; D013629:Tamoxifen / Q000494:pharmacology*; D013997:Time Factors
D011506:Proteins; D013629:Tamoxifen; D013004:Somatostatin; D011388:Prolactin; D007986:Luteinizing Hormone; D013006:Growth Hormone; D004247:DNA; D013007:Growth Hormone-Releasing Hormone