Vieira, J Appl Bioinform Comput Biol 2012, 1:1

[Link]
Journal of Applied
Bioinformatics &
Computational Biology
Editorial a SciTechnol journal

Towards Validation of an 6

Endocrine Simulation Model

Biological Data
3
Amandio Vieira1*

From a biomedical engineering point of view, the bodys endocrine 0

network can be considered as a high-order feedback control system -3 0 3 6
based on chemical signals-hormones-produced by endocrine glands
and endocrine cells embedded in other body tissues. A large number of
-3
mathematical models have been developed to simulate subsystems of
Model Output
the bodys endocrine-metabolic network. These models, as with many
other in silicio representations of biological phenomena, require Figure 2: Summary plot of validation data for HPA axis hormones (triangles)
validation before they can be expanded in their core applications, and for the other endocrine-metabolic models (insulin-glucose, squares;
thyroid hormones, circles). Line represents absolute correlation between
and applied to novel biological simulations and response predictions. model output and biological data.
Such validation is normally done through comparisons with data
obtained directly in the related biological systems.
different behavioral and physiological of stresses [2-10], and are rep-
We have previously reported [1] modeling of the hypothalamus- resented by the mean +/- s.e.m of the data reported in these studies.
pituitary-adrenal (HPA) axis with three main hormones (Figure 1, For comparison with the HPA, results reported for two other
right panel), corticotropin-releasing hormone (CRH), adrenocorti- models involving (a) thyroid hormones [11] and (b) insulin [12] were
cotropic hormone (ACTH), and cortisol, as well as protein-bound estimated as follows:
cortisol parameters, based on a system of five differential equations.
We have more recently worked on validation of the model to include (a) fold-increases of TSH levels (Ts, thyroid stimulating
further simulation of circadian rhythms and induction of stress pa- hormone), and decreases of T4 levels (free T4), after iodine-loading
rameters (manuscript in preparation). In figure 1 (right panel), for simulation, (white circles)
example, a stress response output of the model (triangles) in terms of (b) fold-increases in glucose levels (G, 30:120 minute ratios for
fold increases in ACTH (A) and cortisol (C, or coriticosterone) levels G-loading simulation), and in insulin activity (I, 30 minute response
is compared to the range (solid lines) of responses obtained directly after G-loading simulation), (black squares)
from different biological systems. These ranges include a variety of
These values are also plotted in figure 1 (left panel) along with the
respective data ranges (single-dash lines for thyroid hormones, multi-
dash lines for insulin and glucose) obtained directly from different
8
biological systems: glucose and insulin ranges refer to levels after
Fold absolute change (points)

G-loading tests [12-14]; TSH and T4 ranges refer to levels after iodine
and ranges (rectangles)

6 supplementation [11,15]. Figure 2 shows a correlation composite of

I Hypothalamus
CORT
all three models-refer to respective original articles [1,11,12]for their
4
mathematical constructions; there is good correlation (R2=0.98)
between biological data (mean response values) and model output
TS C CRH
A G AVP data. In these examples representing different modeling approaches
2
T4 for the simulation of endocrine-metabolic subsystems, model
Adrenal
Anter. cortex response data for the given parameters are within, or close to, the
Pituitary ACTH
0 range calculated from experiments on biological systems.
Figure 1: Left panel: Stress-induced hormonal changes predicted by the HPA References
axis model (black triangles, A, C), and comparisons both with published data
for stress responses in biological systems (solid-line rectangles) and with other 1. Kyrylov V, Severyanova LA, Vieira A (2005) Modeling robust oscillatory
endocrine/metabolic models (see text for symbol definition related to the other behavior of the hypothalamic-pituitary-adrenal axis. IEEE Trans Biomed Eng
models). Right panel: Simplified schematic of HPA axis. 52: 1977-1983.
2. Gerra G, Zaimovic A, Mascetti GG, Gardini S, Zambelli U, et al. (2001)
Neuroendocrine responses to experimentally-induced psychological stress in
*Corresponding author: Amandio Vieira, PhD, Nutrition and Metabolism healthy humans. Psychoneuroendocrinology 26: 91-107.
Laboratory, Simon Fraser University, BPK9625-8888 University Drive, 3. Kudielka BM, Schommer NC, Hellhammer DH, Kirschbaum C (2004) Acute
Burnaby, BC, V5A 1S6, Canada, Tel: +1-778-782-425; Fax: +1-778-782- HPA axis responses, heart rate, and mood changes to psychosocial stress
3040; E-mail: avvieira@[Link] (TSST) in humans at different times of day. Psychoneuroendocrinology 29:
983-992.
Received: November 28, 2012 Accepted: December 06, 2012 Published:
December 07, 2012 4. Jeong KH, Jacobson L, Widmaier EP, Majzoub JA (1999) Normal suppression

All articles published in Journal of Applied Bioinformatics & Computational Biology are the property of SciTechnol, and is
International Publisher of Science, protected by copyright laws. Copyright 2012, SciTechnol, All Rights Reserved.
Technology and Medicine
Citation: Vieira A (2012) Towards Validation of an Endocrine Simulation Model. J Appl Bioinform Comput Biol 1:1.

doi:[Link]

of the reproductive axis following stress in corticotropin-releasing hormone- Prenatal stress alters circadian activity of hypothalamo-pituitary-adrenal
deficient mice. Endocrinology 140: 1702-1708. axis and hippocampal corticosteroid receptors in adult rats of both gender. J
Neurobiol 40: 302-315.
5. Parker KJ, Schatzberg AF, Lyons DM (2003) Neuroendocrine aspects of
hypercortisolism in major depression. Horm Behav 43: 60-66. 11. eker O, Barlas Y, Alagl F (2012) Modelling the dynamics of thyroid
hormones and related disorders. MSc Thesis, Bogazici University.
6. Tuchscherer M, Kanitz E, Puppe B, Tuchscherer A, Stabenow B (2004)
Effects of postnatal social isolation on hormonal and immune responses of 12. Cobelli C, Mari A (1983) Validation of mathematical models of complex
pigs to an acute endotoxin challenge. Physiol Behav 82: 503-511. endocrine-metabolic systems. A case study on a model of glucose regulation.
Med Biol Eng Comput 21: 390-399.
7. Poore KR, Fowden AL (2003) The effect of birth weight on hypothalamo-
pituitary-adrenal axis function in juvenile and adult pigs. J Physiol 547: 107- 13. Stickle DF, Reynolds MA, Morris MD, Quon MJ (1999) Dynamic changes in
116. plasma proinsulin/insulin ratio during insulin secretion influence correlation
between radioimmunoassay (RIA) and IMX measurements of insulin. Clin
8. Bloomfield FH, Oliver MH, Giannoulias CD, Gluckman PD, Harding JE, Chim Acta 284: 1-13.
et al. (2003) Brief undernutrition in late-gestation sheep programs the
hypothalamic-pituitary-adrenal axis in adult offspring. Endocrinol 144: 2933- 14. Haugaard SB, Andersen O, Flyvbjerg A, Orskov H, Madsbad S, et al. (2006)
2940. Growth factors, glucose and insulin kinetics after low dose growth hormone
therapy in HIV-lipodystrophy. J Infect 52: 389-398.
9. Demitrack MA, Dale JK, Straus SE, Laue L, Listwak SJ, et al. (1991) Evidence
for impaired activation of the hypothalamic-pituitary-adrenal axis in patients 15. Namba H, Yamashita S, Kimura H, Yokoyama N, Usa T, et al. (1993)
with chronic fatigue syndrome. J Clin Endocrin Metab 73: 1224-1234. Evidence of thyroid volume increase in normal subjects receiving excess
iodide. J Clin Endocrinol Metab 76: 605-608.
10. Koehl M, Darnaudery M, Dulluc J, Van Reeth O, Le Moal M, et al. (1999)

Author Affiliation Top

Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby,
1

BC, Canada

Submit your next manuscript and get advantages of SciTechnol

submissions
50 Journals
21 Day rapid review process
1000 Editorial team
2 Million readers
More than 5000
Publication immediately after acceptance
Quality and quick editorial, review processing

Submit your next manuscript at [Link]/submission

Volume 1 Issue 1 1000e103 Page 2 of 2