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1 Statistics, University of Virginia, Charlottesville, VA, USA
2 Internal Medicine, Leiden University, Leiden, The Netherlands
3 Endocrinology and Metabolism, Internal Medicine, Mayo Medical School and Graduate School of MedicineMayo Clinic, Rochester, MN, USA
* To whom correspondence should be addressed. E-mail: veldhuis.johannes{at}mayo.edu.
The present study investigates the time-varying control of pituitary-hormone secretion over the day and night (D/N). To this end, we implement an analytical platform designed to reconstruct simultaneously: (a) basal (nonpulsatile) secretion; (b) single or dual secretory burst-waveform representation of pulsatile release; (c) random effects on burst amplitude; (d) stochastic pulse-renewal properties; (e) biexponential elimination kinetics; and (f) experimental uncertainty. The statistical solution is conditioned on a priori pulse-onset times, which are estimated in the first stage. Primary data comprised frequently (10-min) sampled serum thyrotropin (TSH) concentrations monitored over 24 hr in 27 healthy men and women. According to the Akaike information criterion, 21/27 TSH release profiles favored a dual compared with single secretory-burst waveform representation. Under this structure, an objectively defined waveform changepoint (D/N boundary) emerges at 2046 h (± 23 min), after which: (a) the mass of TSH released per burst increases by 2.1-fold [P < 0.001]; (b) TSH secretory-burst frequency rises by 1.2-fold [P < 0.001]; (c) the latency to maximal TSH secretion within a burst decreases by 67% [P < 0.001]; (d) intersubject variability in secretory-burst shape diminishes by 50% [P < 0.001]; and (e) basal TSH secretion declines by 17% [P < 0.002]. In contrast, the statistical regularity of successive burst times and the slow-phase half-life of TSH are stable across 24 hr. In conclusion, nycthemeral mechanisms govern each of TSH secretory-burst mass, frequency, waveform shape and intersubject variability, but not evidently TSH elimination kinetics or the primary pulse-timing process. Further studies will be required to assess the generality of the foregoing distinctive control mechanisms in other hypothalamo-pituitary axes.
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