Physiological control of pituitary hormone secretory-burst mass, frequency, and waveform: a statistical formulation and analysis.
The present study investigates the time-varying control of pituitary hormone secretion over the day and night (D/N). To this end, we implemented an analytical platform designed to reconstruct simultaneously 1) basal (nonpulsatile) secretion, 2) single or dual secretory-burst waveforms, 3) random effects on burst amplitude, 4) stochastic pulse-renewal properties, 5) biexponential elimination kinetics, and 6) experimental uncertainty. The statistical solution is conditioned on a priori pulse-onset times, which are estimated in the first stage. Primary data composed of thyrotropin (TSH) concentrations were monitored over 24 h in 27 healthy adults. According to statistical criteria, 21/27 profiles favored a dual compared with single secretory-burst waveform. An objectively defined waveform change point (D/N boundary) emerged at 2046 (+/-23 min), after which 1) the mass of TSH released per burst increases by 2.1-fold (P < 0.001), 2) TSH secretory-burst frequency rises by 1.2-fold (P < 0.001), 3) the latency to maximal TSH secretion within a burst decreases by 67% (P < 0.001), 4) variability in secretory-burst shape diminishes by 50% (P < 0.001), and 5) basal TSH secretion declines by 17% (P < 0.002). In contrast, the regularity of successive burst times and the slow-phase half-life are stable. In conclusion, nycthemeral mechanisms govern TSH secretory-burst mass, frequency, waveform, and variability but not evidently TSH elimination kinetics or the pulse-timing process. Further studies will be required to assess the generality of the foregoing distinctive control mechanisms in other hypothalamo-pituitary axes.
Division of Endocrinology and Metabolism, Dept. of Internal Medicine, Mayo Medical School and Graduate School of Medicine, General Clinical Research Center, Mayo Clinic, Rochester, MN 55905, USA. veldhuis.johannes@mayo.edu
Daniel M
DM
Keenan
Ferdinand
F
Roelfsema
Nienke
N
Biermasz
Johannes D
JD
Veldhuis
D000328:Adult; D000368:Aged; D025461:Feedback, Physiological / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010903:Pituitary Gland, Anterior / Q000378:metabolism* / Q000502:physiology; D011673:Pulsatile Flow; D013269:Stochastic Processes; D013972:Thyrotropin / Q000378:metabolism*
D013972:Thyrotropin