title: Detecting regulatory mechanisms in endocrine time series measurements.
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. Regulatory relations 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 real data. 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.
authors.affiliation: Department of Metabolic Diseases, University Medical Center Utrecht, Utrecht, The Netherlands. science@danielvis.nl
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Vis
authors.forename: Johan A
authors.initials: JA
authors.lastname: Westerhuis
authors.forename: Huub C J
authors.initials: HC
authors.lastname: Hoefsloot
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Roelfsema
authors.forename: Margriet M W B
authors.initials: MM
authors.lastname: Hendriks
authors.forename: Age K
authors.initials: AK
authors.lastname: Smilde
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000465:Algorithms; D002940:Circadian Rhythm / Q000502:physiology*; D015331:Cohort Studies; D004703:Endocrine System / Q000378:metabolism* / Q000502:physiology*; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006728:Hormones / Q000097:blood*; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D013739:Testosterone / Q000097:blood; D013997:Time Factors
chemical_list: D006728:Hormones; D019382:Human Growth Hormone; D013739:Testosterone; D004958:Estradiol; D000324:Adrenocorticotropic Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone