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Pure Appl. Chem., 2002, Vol. 74, No. 6, pp. 881-890

Cascade mechanism in a self-regulatory endocrine system. Modeling pulsatile hormone secretion

Thongchai Dumrongpokaphan and Yongwimon Lenbury*

Department of Mathematics, Faculty of Science, Mahidol University, Thailand

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.