The effects of chronically elevated plasma cortisol on the bioactive and immunoreactive corticotropin secretory responses to hemorrhage in the fetal sheep at 0.70 gestation.

OBJECTIVE

Our purpose was to test the hypothesis that a long-term physiologic elevation of plasma cortisol would not alter the basal plasma concentrations of immunoreactive and bioactive corticotropin, yet it would evoke an increase in the ratio of bioactive to immunoreactive corticotropin secreted during stress. We define immunoreactive corticotropin (i.e., immunoreactive corticotropin-like activity) as that material obtained from plasma that displaces the binding of tracer quantities of iodine 125-labeled corticotropin from antisera directed toward the 6-24 portion of the corticotropin (1-39) molecule, whereas bioactive corticotropin (i.e., bioactive corticotropin-like activity) is defined as that material obtained from plasma that stimulates the secretion of corticosterone from dispersed rat adrenal cells in comparison to known concentrations of synthetic corticotropin (1-39).

STUDY DESIGN

We studied the plasma immunoreactive and bioactive corticotropin response to hemorrhage in eight vehicle- and 10 cortisol-treated fetal sheep at 101 +/- 1 days of gestation. At 94 +/- 1 days of gestation each fetus began receiving a 6-day continuous infusion of either vehicle or cortisol. During the last 10 minutes of the infusion about 30% of the estimated blood volume was withdrawn from the fetuses.

RESULTS

Basal plasma cortisol was significantly higher in the cortisol group (20.6 +/- 2.3 ng/ml vs 2.7 +/- 0.3 ng/ml). Basal plasma immunoreactive ACTH and bioactive corticotropin were not significantly different between groups. In both groups the plasma immunoreactive corticotropin significantly increased during hemorrhage, although the increase in the cortisol group (32 +/- 8 to 40 +/- 8 pg/ml) was significantly less than that in the vehicle group (45 +/- 14 to 86 +/- 28 pg/ml). In contrast, plasma bioactive corticotropin increased significantly during hemorrhage in the vehicle group (10 +/- 1 to 16 +/- 3 pg/ml) alone.

CONCLUSIONS

In the early-gestation fetal sheep a chronic elevation of plasma cortisol does not significantly lower basal plasma immunoreactive and bioactive corticotropin. Nevertheless, it (1) attenuates the immunoreactive corticotropin response and (2) abolishes the bioactive corticotropin response to hemorrhage. It is possible that some of the negative feedback effects of plasma cortisol on corticotropin release occur at the posttranslational level.