Divergent changes in plasma ACTH and pituitary POMC mRNA after cortisol administration to late-gestation ovine fetus.
Plasma concentrations of cortisol and adrenocorticotropic hormone (ACTH) rise in the late-gestation sheep fetus at approximately the same time as there is an increase in the plasma levels of corticosteroid-binding globulin (CBG). We hypothesized that intrafetal cortisol infusion during late pregnancy would stimulate an increase in fetal plasma CBG, which in turn would bind cortisol and diminish glucocorticoid negative-feedback regulation of the fetal pituitary, leading to an increase in plasma ACTH concentrations. Cortisol was infused into chronically catheterized fetal sheep beginning at 126.1 +/- 0.5 days of gestation and continued for 96 h. Control fetuses were infused with saline. In cortisol-infused fetuses, the plasma cortisol concentrations rose significantly from control levels (4.4 +/- 0.6 ng/ml) to 19.3 +/- 3.1 ng/ml within 24 h and remained significantly elevated throughout the infusion period. Plasma immunoreactive (i.r.) ACTH concentrations were significantly elevated in cortisol-infused fetuses within 24-48 h and remained significantly higher than in controls throughout the 96-h experimental period. Plasma free cortisol concentrations increased 10-fold and remained significantly elevated in cortisol-infused animals, despite a rise in plasma corticosteroid-binding capacity. Levels of pituitary proopiomelanocortin (POMC) mRNA in the fetal pars distalis and pars intermedia were 96 and 38% lower, respectively, after 96 h of cortisol infusion. Therefore physiological elevations of plasma cortisol, in the late-gestation ovine fetus, lead to increases in mean plasma irACTH concentrations, but this is not associated with increases in fetal pituitary POMC mRNA levels.
Jeffray
T M
TM
Department of Physiology, University of Toronto, Ontario, Canada.
Matthews
S G
SG
Hammond
G L
GL
Challis
J R
JR
D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000818:Animals; D001784:Blood Gas Analysis; D002352:Carrier Proteins / Q000096:biosynthesis; D005260:Female; D005865:Gestational Age; D006854:Hydrocortisone / Q000097:blood / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D010902:Pituitary Gland / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000097:blood*; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D012756:Sheep
D002352:Carrier Proteins; D012333:RNA, Messenger; C027091:cortisol binding globulin; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone