Medicina
Daniel J. Vis1,2,3*, Johan A. Westerhuis2,3, Huub C. J. Hoefsloot2,3, Ferdinand Roelfsema4, Margriet M. W. B. Hendriks1,3., Age K. Smilde2,3.
1 Department of Metabolic Diseases, University Medical Center Utrecht, Utrecht, The Netherlands, 2 Biosystems Data Analysis, Swammerdam Institute for Life Sciences, University ofAmsterdam, Amsterdam, The Netherlands, 3 Netherlands Metabolomics Centre, Leiden, The Netherlands, 4 Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands
Abstract
The regulatory mechanisms underlying pulsatile secretion are complex, especially as it is partly controlled by other hormones and the combined action of multiple agents. Regulatoryrelations between hormones are not directly observable but may be deduced from time series measurements of plasma hormone concentrations. Variation in plasma hormone levels are the resultant of secretion and clearance from the circulation. A strategy is proposed to extract inhibition, activation, thresholds and circadian synchronicity from concentration data, using particular association methods.Time delayed associations between hormone concentrations and/or extracted secretion pulse profiles reveal the information on regulatory mechanisms. The above mentioned regulatory mechanisms are illustrated with simulated data. Additionally, data from a lean cohort of healthy control subjects is used to illustrate activation (ACTH and cortisol) and circadian synchronicity (ACTH and TSH) in realdata. The simulation and the real data both consist of 145 equidistant samples per individual, matching a 24-hr time span with 10 minute intervals. The results of the simulation and the real data are in concordance.
Citation: Vis DJ, Westerhuis JA, Hoefsloot HCJ, Roelfsema F, Hendriks MMWB, et al. (2012) Detecting Regulatory Mechanisms in Endocrine Time Series Measurements. PLoS ONE 7(3): e32985.doi:10.1371/journal.pone.0032985 Editor: Thomas Preiss, The John Curtin School of Medical Research, Australia Received June 20, 2011; Accepted February 6, 2012; Published March 26, 2012 Copyright: ß 2012 Vis et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium,provided the original author and source are credited. Funding: TNO Quality of Life supported this research from the systems biology program (www.tno.nl). The Netherlands Metabolomics Center, which is part of the Netherlands Genomics Initiative of the Netherlands Organization for Scientific Research (http://www.metabolomicscentre.nl/). The funders had no role in study design, data collection andanalysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: science@danielvis.nl . These authors contributed equally to this work.
Introduction
Hormones are important agents in the regulation of physiological processes. Endocrine glands, producing hormones [1,2], often secrete their product in shortwell-synchronized bursts, referred to as episodic secretion [3]. The episodic secretion depends on the circadian rhythm but also involves a strong stochastic component [4–6]. Secretion results in changes in hormone levels, usually leading to critical modulation of tissue function triggering the secretion of other hormones. Hormones can thus be seen as an ensemble of initiators and inhibitors thatcritically modulate physiological processes. This paper refers to regulatory mechanisms in the strict context of actions between hormones, which can be initiatory, inhibitory or both. It has been shown [1,7] that these regulatory relations between hormones are subject to the physiological state, e.g., age, gender, lifestyle and pathology, and thus exhibit some inter- and intra-individual variability....
Regístrate para leer el documento completo.