Effects of cycloheximide on hepatic and uterine insulin-like growth factor-I mRNA.
To investigate differences in growth hormone (GH) and estrogen activation of insulin-like growth factor-I (IGF-I) expression, we have examined the effects of cycloheximide on hepatic and uterine IGF-I mRNA abundance in response to GH and 17 beta-estradiol (E2) respectively. In hypophysectomized (hypox) rats a single injection of GH significantly increased hepatic IGF-I mRNA 3.65 +/- 0.68-fold, P less than 0.005, 6 h after injection. Administration of cycloheximide 30 min prior to GH injection completely abolished this response. In contrast, in pituitary intact rats killed 6 h after administration of cycloheximide, hepatic IGF-I mRNA abundance was not significantly different from untreated control rats although the serum IGF-I concentration was significantly reduced; 119.9 +/- 11.8 vs. 270.2 +/- 48.7 ng/ml, P less than 0.005. In immature rats, injection of E2 (1 micrograms/100 g body weight) significantly increased uterine IGF-I mRNA 4.1 +/- 0.4-fold. Cycloheximide did not block the E2-induced increase in IGF-I mRNA but rather significantly enhanced the IGF-I response. These data indicate that continuing protein synthesis is required for GH induction of hepatic IGF-I mRNA in the hypox rat but is not required for E2 induction of uterine IGF-I mRNA. Furthermore, in pituitary-intact rats protein synthesis is not required for maintenance of hepatic IGF-I mRNA levels.
Murphy
L J
LJ
Department of Internal Medicine, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Luo
J M
JM
D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology*; D004958:Estradiol / Q000502:physiology; D005260:Female; D013006:Growth Hormone / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000097:blood / Q000235:genetics*; D008099:Liver / Q000187:drug effects*; D008297:Male; D009693:Nucleic Acid Hybridization; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000302:isolation & purification; D051381:Rats; D011919:Rats, Inbred Strains; D015398:Signal Transduction / Q000187:drug effects; D013002:Somatomedins / Q000235:genetics*; D014599:Uterus / Q000187:drug effects*
D012333:RNA, Messenger; D013002:Somatomedins; D004958:Estradiol; D012313:RNA; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D003513:Cycloheximide