Insulin-like growth factor-II messenger ribonucleic acid expression in fetal tissues of the sheep during late gestation: effects of cortisol.
Using RNase protection analysis, insulin-like growth factor-II (IGF-II) mRNA levels were measured in various tissues from fetal sheep during late gestation (term, 146 +/- 2 days) and after experimental manipulation of fetal plasma cortisol levels. No gestational trend in IGF-II mRNA levels was observed in the fetal lung, kidney, or skeletal muscle. However, in the fetal liver, there was a marked decline in IGF-II mRNA abundance immediately before term, which closely paralleled the normal prepartum surge in fetal plasma cortisol. This decrease in hepatic IGF-II mRNA levels toward term was prevented when the cortisol surge was abolished by fetal adrenalectomy and was stimulated prematurely in fetuses younger than 130 days by exogenous infusion of cortisol. Hepatic and renal IGF-II mRNA abundances were also reduced when fetal cortisol levels were raised endogenously by maternal fasting in late gestation. Muscle IGF-II mRNA levels were reduced by fetal cortisol infusion, but not by maternal fasting, and were higher in adrenalectomized than in intact fetuses in late gestation. No change in IGF-II mRNA levels were observed in the fetal lung in response to altering the fetal cortisol level either exogenously or endogenously. When the data from all fetuses were combined regardless of treatment or gestational age, there was a significant inverse correlation between the plasma cortisol level in utero and IGF-II mRNA abundance in the fetal liver (P < 0.001), but not in any of the other fetal tissues studied. These findings show that cortisol suppresses IGF-II gene expression in the liver of the sheep fetus and indicate that the developmental change in hepatic IGF status toward term may be due to the prepartum cortisol surge.
Li
J
J
Department of Cellular Physiology, Institute of Animal Physiology and Genetics Research, Babraham, Cambridge, United Kingdom.
Saunders
J C
JC
Gilmour
R S
RS
Silver
M
M
Fowden
A L
AL
D000311:Adrenal Glands / Q000196:embryology / Q000601:surgery; D000315:Adrenalectomy; D000818:Animals; D001483:Base Sequence; D005215:Fasting; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D005333:Fetus / Q000378:metabolism*; D015870:Gene Expression; D005865:Gestational Age; D006854:Hydrocortisone / Q000097:blood / Q000494:pharmacology*; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D007668:Kidney / Q000196:embryology / Q000378:metabolism; D008099:Liver / Q000196:embryology / Q000378:metabolism; D008168:Lung / Q000196:embryology / Q000378:metabolism; D008969:Molecular Sequence Data; D009132:Muscles / Q000196:embryology / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism*; D012756:Sheep
D012333:RNA, Messenger; D007335:Insulin-Like Growth Factor II; D006854:Hydrocortisone