Divergent changes in plasma acth and pituitary pomc mrna after cortisol administration to the ovine fetus in late gestation. Jeffray, T. M., S. G. Matthews, G. L. Hammond, and J. R. G. Challis. Departments of Physiology and Obstetrics and Gynaecology, The University of Toronto, Toronto, Ontario, Canada, Medical Research Council Group in Fetal and Neonatal Health and Development, Lawson Research Institute, and the Departments of Obstetrics and Gynaecology, and Physiology, The University of Western Ontario, London, Ontario, Canada. The London Regional Cancer Centre, Victoria Hospital, the Departments of Obstetrics and Gynaecology, Biochemistry, and Oncology, The University of Western Ontario, London, Ontario, Canada.
APStracts 4:0266E, 1997.
Plasma concentrations of cortisol and adrenocorticotrophic 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 on day 126.1 0.5 of gestation, and continued for 96 hours. 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 hours, and remained significantly elevated throughout the infusion period. Plasma immunoreactive (ir) -ACTH concentrations were significantly elevated in cortisol infused fetuses within 24-48 hours, and remained significantly higher than controls throughout the 96 hours 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 pro-opiomelanocortin (POMC) mRNA in the fetal pars distalis and pars intermedia were 96% and 38% lower, respectively, after 96 hours of cortisol infusion. Therefore, physiological elevations of plasma cortisol, in the late gestation ovine fetus, lead to increases in mean plasma ir-ACTH concentrations, but this is not associated with increases in fetal pituitary POMC mRNA levels. 

Received 16 September 1997; accepted in final form 18 November
1997.
APS Manuscript Number E439-7.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 12 December 1997