The Role and Regulation of Corticotropin in the Fetal Sheep

The activity of the fetal sheep adrenal increases in the last few days of gestation and this increase clearly initiates the mechanisms of parturition. The factors that stimulate the increased activity are however undefined. The most likely factor is corticotropin (ACTH) secreted from the fetal pituitary. The problems associated with the measurement of corticotropin in fetal plasma and the interpretation of the significance of currently available data are discussed. The two major experimental models used for investigation of the fetal hypothalamohypophysial-adrenal axis are the hypophysectomized and the pituitary-stalksectioned fetus with indwelling vascular catheters. Baseline endocrine data for these preparations are given. Experiments designed to calculate fetal blood production rates for corticotropin are described and the observed value of about 50 ng/h at a corticotropin concentration of 100 pg/ml in fetal plasma is considerably less than the amounts generally used when corticotropin is infused into fetuses to initiate delivery. Experiments in which 1 μg synthetic corticotropin (Synacthen)/h was infused into hypophysectomized and stalk-sectioned fetuses to induce delivery are described. The problem of the existence and physiological significance of negative and positive feedback loops within the fetal hypothalomo-hypophysial-adrenal axis are discussed. Finally, factors which may play a role in the development of fetal adrenal sensitivity to corticotropin and the increased cortisol secretion are discussed.