Intrinsic pulsatility of ACTH release from the human pituitary in vitro

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 less than 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.