Computational Biology and Chemistry 41 (2012) 10–17
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Computational Biology and Chemistry
jou rnal h omepa g e: www.elsevier.com/locate/compbiolchem
Stochastic synchronization of interacting pathways in testosterone model
Md. Jahoor Alam
a
, Gurumayum Reenaroy Devi
a
, R.K. Brojen Singh
a,∗
, R. Ramaswamy
b
,
Sonu Chand Thakur
a
, B. Indrajit Sharma
c
a
Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi 110025, India
b
School of Physical Sciences, Jawaharlal Nehru University, New Delhi 110067, India
c
Department of Physics, Assam University, Silchar 788 011, Assam, India
a r t i c l e i n f o
Article history:
Received 24 January 2012
Received in revised form 13 July 2012
Accepted 5 August 2012
Keywords:
Cell signaling
Synchronization
Coupling
Intercellular communication
Intracellular communication
a b s t r a c t
We examine the possibilities of various coupling mechanisms among a group of identical stochastic
oscillators via Chemical Langevin formalism where each oscillator is modeled by stochastic model of
testosterone (T) releasing pathway. Our results show that the rate of synchrony among the coupled oscil-
lators depends on various parameters namely fluctuating factor, coupling constants , and interestingly
on system size. The results show that synchronization is achieved much faster in classical deterministic
system rather than stochastic system. Then we do large scale simulation of such coupled pathways using
stochastic simulation algorithm and the detection of synchrony is measured by various order parameters
such as synchronization manifolds, phase plots etc and found that the proper synchrony of the oscillators
is maintained in different coupling mechanisms and support our theoretical claims. We also found that
the coupling constant follows power law behavior with the systems size (V) by ∼ AV
-
, where = 1
and A is a constant. We also examine the phase transition like behavior in all coupling mechanisms that
we have considered for simulation. The behavior of the system is also investigated at thermodynamic
limit; where V→ ∞, molecular population, N→ ∞ but
N
V
→ finite, to see the role of noise in information
processing and found the destructive role in the rate of synchronization.
© 2012 Elsevier Ltd. All rights reserved.
1. Introduction
The experimental observation of oscillation in testosterone
level in men (Murray, 2002) in the pathway of hypothalamic,
pituitary and leydig cells, is believed to be originated due to var-
ious feedback mechanisms involved in the pathway (Yen et al.,
1999). Following a central neuron system signal, the hypothal-
amic cells in the hypothalamus secret gonadotropin releasing
hormone (GnRH) and travel to reach pituitary gland via tuberoin-
fundibular pathway to activate the releasing of luteinizing hormone
(LH) from the pituitary cells (Heuett and Qian, 2006). The LH
diffuses through blood to activate testosterone (T) production
by the leydig cells in testes. Excess production of T is con-
trolled by a feedback mechanism which inhibits the secretion of
GnRH.
There have been various mathematical models (both determi-
nistic as well as stochastic) (Cartwright and Husain, 1986; Keenan
and Veldhuis, 1998; Keenan et al., 2000; Heuett and Qian, 2006) to
investigate and understand the origin of the oscillatory behaviour
of the testosterone level in male reproductive organ in human
being. Extensive study on the possibilities of oscillation in T without
∗
Corresponding author. Tel.: +91 11 2698 17171/4492; fax: +91 11 26983409.
E-mail addresses: brojen2k@yahoo.com, rk.brojen@gmail.com (R.K.B. Singh).
using experimental parameters, is also been done deterministi-
cally. The stochastic model to study various mechanisms involved
in this pathway gives us important insights, for example the oscil-
lation of T can be obtained with the experimental values of the
interacting or secreting hormones in the pathway etc and it is a
realistic model which consider various interaction events along
the pathway (Gillespie, 1977, 2007). Further, these models takes
into account the noise fluctuation systematically in the system
dynamics which enable to study the constructive role of noise such
as detection and amplification of weak signal which is known as
stochastic resonance (Hanggi, 2002). The Chemical Langevin Equa-
tion (CLE) formalism is a simple stochastic formalism which is
derived from the Chemical Master Equation (CME) under certain
realistic approaximations (Gillespie, 2000) and can describe well
the importance of noise (Gonze et al., 2003) associated with the
dynamics with order V
-1/2
.
A pathway which consists of a hypothalamic cell which release
GnRH, then a pituitary cell secreting LH activated by GnRH, a Leydig
cell which release T and control of T population by feedback mech-
anism, gives rise an oscillatory behaviour of T and therefore the
pathway can be taken as an oscillator. There are a number of such
identical pathways or oscillators which do the identical function in
releasing T hormone in testes. The basic issue we raise in this work
is the interaction of such identical pathways provided a central neu-
ron stimulus signal, to do the synchronous function of releasing T
1476-9271/$ – see front matter © 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.compbiolchem.2012.08.001