INTRINSIC PULSATILITY OF ACTH RELEASE FROM THE HUMAN PITUITARY IN VITRO

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Abstract
SUMMARY: An in‐vitro perifusion system was used to investigate spontaneous ACTH release from human fetal (21–23 weeks gestation) and adult pituitaries. The pattern of ACTH release from fetal pituitaries (n= 7) exhibited a remarkable pulsatile character with a mean (± SEM) pulse interval of 11.3 ± 0.8 min. The mean pulse amplitude was 49.7 ± 6.3 pg, with a nadir to peak increment of 90.7 ± 10.4%. The mean ACTH release rate was 87.2±13.3 pg/2 min. Addition of the calcium chelator EGTA (4 nM) to the perifusion medium induced a significant (p±0.01) decrease in both ACTH release rate (from 102.0 ± 8.5 to 52.0 ± 9.9 pg/2 min) and ACTH pulse amplitude (from 57.7 ± 2.8 to 31.3 ± 4.6 pg) (n= 3). Administration of either 2 nM corticotrophin releasing factor (CRF) or 56 mM KCl induced 10‐ and 2‐fold increases in ACTH secretion, respectively (n= 2). Quarters of adult human pituitaries (n– 6) also secreted ACTH in a pulsatile fashion, with a pulse interval of 14.8±1.7 min, pulse amplitude of 86.7± 10.0 pg, nadir to peak increment of 84.5 ± 9.8%, and overall release rate of 167.2 ± 8.8 pg/2 min. These studies demonstrate that ACTH release from the isolated human pituitary in vitro is characterized by high frequency/low amplitude pulses, independent of hypothalamic stimulation. Accordingly, this spontaneous calcium‐dependent pulsatile ACTH release apparently reflects the activity of an intrinsic intrapituitary pulse‐generating mechanism.