Low-dose cortisol infusion increases plasma corticosteroid-binding globulin (CBG) and the amount of hepatic CBG mRNA in fetal sheep on day 100 of gestation.
Synthetic glucocorticoids stimulate the production of corticosteroid-binding globulin (CBG) by the liver of the sheep fetus near term (day 145). We have examined whether physiological changes in plasma cortisol alter plasma CBG concentrations, patterns of glycosylation and the amount of hepatic CBG mRNA at earlier times during pregnancy (day 100), prior to the activation of fetal hypothalamic-pituitary-adrenal function. Cortisol was infused into chronically catheterized sheep fetuses in amounts that raised the plasma cortisol concentration by about 15 nmol/l. This treatment resulted in a significant increase in the plasma corticosteroid-binding capacity and in the amount of CBG mRNA in the fetal liver, but did not alter the proportion of CBG retained using Concanavalin A chromatography. We conclude that the CBG gene in the liver of fetal sheep responds to physiological changes in plasma concentration of cortisol and we speculate that the rise in plasma CBG concentration is important in diminishing the negative feedback effect of circulating cortisol on the fetal pituitary and hypothalamus.
Berdusco
E T
ET
MRC Group in Fetal and Neonatal Health and Development, Lawson Research Institute, St Joseph's Health Centre, London, Ontario, Canada.
Milne
W K
WK
Challis
J R
JR
D000818:Animals; D015152:Blotting, Northern; D002847:Chromatography, Agarose; D005260:Female; D005312:Fetal Blood / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D006854:Hydrocortisone / Q000097:blood / Q000494:pharmacology*; D008099:Liver / Q000196:embryology / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D012756:Sheep / Q000196:embryology* / Q000378:metabolism; D013268:Stimulation, Chemical; D014156:Transcortin / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D014156:Transcortin; D006854:Hydrocortisone