Possible role of cortisol in the stimulation of cortisol-binding capacity in the plasma of fetal sheep.

In sheep, the prepartum rise in fetal plasma cortisol (F) is associated with an increase in the corticosteroid-binding capacity (CBC) of the plasma. We examined whether CBC changed during preterm labor, induced by administering ACTH to the fetus, and we examined the role of F in such changes. Beginning on day 127, chronically catheterized fetal sheep were divided into six groups; 1) saline control infusions (n = 4); 2) pulsatile ACTH (P-ACTH; 66 ng/min for 15 min every 2 h; n = 5); 3) P-ACTH (as 2) plus metopirone (MET; 500 mg/24 h n = 5); 4) P-ACTH and MET (as 3) plus F (13.3 micrograms/min for 15 min every 2 h; n = 3); 5) P-ACTH and MET (as 3) plus F (133 micrograms/min for 15 min every 2 h; n = 4); 6) P-ACTH and MET (as 3) plus dexamethasone (0.56 micrograms/min for 15 min every 2 h for 50 h, then 5.6 micrograms/min for 15 min every 2 h until 100 h; n = 4). All infusions continued for 100 h. Fetal blood samples were collected at 8-h intervals for determination of plasma F concentration and CBC. Estrone and progesterone were measured in 8-h samples of maternal femoral arterial blood. P-ACTH resulted in a significant increase in CBC within 24 h; values at 72-96 h were 2- to 3-fold greater than controls. Rises in CBC were positively correlated with the changes in plasma F in the P-ACTH-treated fetuses and preceded changes in plasma progesterone or estrogens. MET treatment prevented the P-ACTH-induced increases in F and CBC. Exogenous F and dexamethasone overcame the MET-induced inhibition of P-ACTH-induced increases in CBC. We conclude that in fetal sheep 1) CBC is elevated by P-ACTH treatment; and 2) F may mediate this stimulation of its own binding protein.