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Pure Appl. Chem. Vol.
74, No. 6, pp. 881-890 (2002)
Pure and Applied Chemistry
Vol. 74, Issue 6
Cascade mechanism in a self-regulatory endocrine system. Modeling
pulsatile hormone secretion*
Thongchai Dumrongpokaphan and Yongwimon Lenbury**
Department of Mathematics, Faculty of Science, Mahidol
Abstract: Many endocrine systems have been found to
incorporate some form of cascade mechanism into their operation. Such
a mechanism involves an amplification system where an initial reaction
gives rise to the generation of multiple second reactions, each of which
sets off multiple third reactions, and so on. Examples will be presented,
with special attention paid to the hypothalamuspituitarytesticular
axis. The production and secretion of luteinizing hormone (LH) is governed
by the medial-basal region of the hypothalamus. It is well known that
the release of LH is a highly regulated process determined by negative
and positive feedback, as well as neural components. The presence of
gonadatropin-releasing hormone (GnRH) on specific adenohypophyseal cell
membrane receptors results in the release of LH, which is then transported
systemically to the Leydig cells of the testes. All the factors governing
the release of these hormones, as well as a biochemical description
of their actions, have not been completely elucidated, nor is the mechanism
behind the pulsatile fashion in which the decapeptide GnRH and LH are
released clearly explained. We describe how such a cascade mechanism
in a self-regulatory system may be modeled and analyzed by a singular
perturbation approach, identifying conditions that give rise to episodic
hormone secretion or activity. Insightful and valuable interpretations
can be made from such analysis of the cascade system.
* Plenary lecture presented at the International Conference
on Bioinformatics 2002: North-South Networking, Bangkok, Thailand, 6-8
February 2002. Other presentations are presented in this issue, pp.
** Corresponding author.
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