We have investigated whether increasing gestational age has an effect on basal and K+- or CRF-stimulated ACTH secretion from slices of anterior pituitary from fetal sheep. We have also determined whether cortisol acts to inhibit basal or CRF-induced ACTH secretion from the fetal sheep pituitary between 106 and 144 days of gestation (term = 145 ± 3 days of gestation). Four slices were collected from each fetal sheep pituitary at 106-116 (n = 4 pituitaries), 120-124 (n = 4), 130–137 (n = 8) and 140-144 days (n = 11) and perifused with Krebs buffer bubbled with 95% O2 and 5% CO2 at 37°C. Slices were perifused for at least 120 min prior to one of the following treatments: K+ (100 mM); CRF (two separate boluses, 10 nM, administered 120 min apart); cortisol (100 nM, 30-min infusion), or cortisol (30-min infusion) with a CRF bolus administered 10 min after the start and 90 min after the end of the cortisol infusion. The basal output of ACTH (pg/mg/120 min) did not change significantly between 106 and 144 days of gestation. Bolus administration of K+ or CRF stimulated pituitary ACTH secretion above baseline values for 10 min at all ages. There was no significant difference with age, however, in the magnitude of the ACTH response in the first 10 min after K+ (106-116 days, 185.8 ± 71.1 pg/mg; 120-124 days, 186.4 ± 77.4 pg/mg; 130-137 days, 332.5 ± 185.7 pg/mg; 140-144 days, 123.7 ± 32.0 pg/mg) or CRF (106-116 days, 326.6 ± 193.4 pg/mg; 120-124 days, 389.0 ± 264.8 pg/mg; 130-137 days, 207.5 ± 153.2 pg/mg; 140-144 days, 160.5 ± 73.1 pg/mg). Between 100 and 116 days of gestation there was no change in ACTH secretion during infusion of cortisol, but 30 min after the end of the infusion, ACTH secretion increased significantly above pre-infusion values and this increase was sustained for a further 30 min. In contrast at all ages between 120 and 144 days, ACTH secretion decreased during the last 10 min of the cortisol infusion period and remained significantly lower than pre-infusion values for a further 30 min. There was no significant difference between the ACTH response to CRF administered in the presence or absence of cortisol (1,117.0 ± 809 vs. 302.4 ± 48.8%). The ACTH response (460.6 ± 112.5%) to CRF administered 90 min after the end of the cortisol infusion was, however, significantly greater than the ACTH response (152.8 ± 15.9%) to CRF administered in the absence of prior exposure to cortisol. We conclude that after 116 days of gestation, cortisol acts in the rapid and delayed time domains to inhibit the basal secretion of ACTH from the fetal sheep pituitary. These data support the possibility that cortisol acts to inhibit ACTH secreted as a consequence of paracrine stimulation of corticotropic cells within the fetal pituitary. We have also found that prior exposure to cortisol alters the subsequent secretory response of the fetal corticotropes to CRF.

Keywords:
Sheep fetus, Pituitary, ACTH, Cortisol
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© 1993 S. Karger AG, Basel
1993
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