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Am J Physiol Regul Integr Comp Physiol 285: R664-R673, 2003. First published May 8, 2003; doi:10.1152/ajpregu.00195.2003
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COMPLEX FUNCTION OF THE CENTRAL NERVOUS SYSTEM, SLEEP AND LOCOMOTION

Physiological control of pituitary hormone secretory-burst mass, frequency, and waveform: a statistical formulation and analysis

Daniel M. Keenan,1 Ferdinand Roelfsema,2 Nienke Biermasz,2 and Johannes D. Veldhuis3

1Department of Statistics, University of Virginia, Charlottesville, Virginia 22904; 2Department of Internal Medicine, Leiden University, Rapenburg 70, NA-2300 RA Leiden, The Netherlands; and 3Division of Endocrinology and Metabolism, Department of Internal Medicine, Mayo Medical School and Graduate School of Medicine, General Clinical Research Center, Mayo Clinic, Rochester, Minnesota 55905

Submitted 11 April 2003 ; accepted in final form 5 May 2003

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.

secretion; thyrotrope; hypothalamus; pulsatility



Address for reprint requests and other correspondence: J. D. Veldhuis, 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 (E-mail: veldhuis.johannes{at}mayo.edu).




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