Changes in pituitary responses to synthetic ovine corticotrophin releasing factor in fetal sheep

Abstract

The rise in cortisol in fetal sheep during late pregnancy has been related to increased responsiveness of the adrenal to ACTH. Most reports have suggested that plasma ACTH concentrations rise coincident with or after the prepartum increase in cortisol. To reexamine the relationship of cortisol with basal immunoreactive ACTH (IR-ACTH) throughout the last 40 days of pregnancy and to determine changes in fetal pituitary responsiveness during this time, we measured basal and synthetic ovine corticotrophin-releasing factor (oCRF) (10 ng – 10 μg) induced rises in ACTH and cortisol in fetal sheep at days 110–115, 125–130, and 135–140 of pregnancy. The fetuses were catheterized on day 105–120 and entered spontaneous labour at > 140 days. Basal IR-ACTH (picograms per millilitre ± SEM) rose from 16.7 ± 2.9 pg/mL at day 110–115 to 34.8 ± 8.7 pg/mL at day 141–145. There was a significant effect of time on basal ACTH concentrations with a mean increase of approximately 5 pg ACTH per millilitre of plasma per 5-day sampling interval. Plasma cortisol changed gradually between day 110 and 125 of gestation and then more rapidly to term. At day 110–115 of gestation there was no significant change in plasma ACTH after 10 or 100 ng oCRF, but there was a significant increase in ACTH after 1 μg of oCRF. Plasma cortisol did not change after any CRF injection. The change in IR-ACTH after oCRF at day 125–130 of gestation was significantly greater than that at day 110–115. Plasma cortisol concentrations were elevated following 1- and 10-μg injections of oCRF. At day 135–140, significant rises in plasma ACTH were seen in response to 1 and 10 μg oCRF, but the response was less than that at day 125–130. In contrast, the response of plasma cortisol was significantly greater than at any of the other times in gestation. We conclude the following: (i) basal ACTH concentrations rise before the major prepartum increase in plasma cortisol; (ii) pituitary responsiveness to oCRF, measured as ACTH in plasma, increases between days 110–115 and 125–130 of gestation. The ACTH response decreased at day 135–140, perhaps reflecting negative feedback control by the rising basalcortisol concentrations; (iii) adrenal responsiveness increases progressively between days 110–115 and 135–140 of gestation, as reflected by changes in the plasmacortisol concentration in response to endogenously released ACTH.