Abstract
Thyroid hormone secretion pathway is one of the important pathways that regulates growth, development and is considered critical for brain, skeletal development and maturation. Autoimmune Thyroid Disease (AITD) results in damage of the thyroid gland altering the normal secretion of thyroid hormones causing hypothyroidism (Hashimoto’s thyroiditis) or hyperthyroidism (graves’ disease). A map of molecular interaction of the thyroid stimulating hormone receptor has been created using systems biology graphical notation language with the help of CellDesigner 4.1 and converted into BioPax 2.8.2 pathways description format. In the current state the map contains 9 compartment, 32 simple and complex protein, 18 small molecules, 3 ions and 35 chemical reactions. The network contains more details about Thyroid hormones, Thyroxin (T4) and Triiodothyronin (T3), secretion pathway than existing large scale real pathways. Simulation was done in order to understand the time-dependent behavior of TSH, T3 and T4 by taking 16 different cases related thyroid disorder. The simulation patterns are invariable after passing with certain period, it does not deviate the simulation pattern of pathways. This study helps in identification of novel targets related with different types of thyroid disorder. To anticipate potential drug targets by system-wide analysis of the metabolic network for the effective treatment of thyroid disorder, the model can be useful.
Highlights
Autoimmune thyroid disease (AITD) is a common organ specific autoimmune disorder affecting thyroid gland mostly in women [1]
This autoimmunity to thyroid is the result of interaction of many genetic and environmental factors which renders Thyroid Stimulating Antibodies (TSAbs) and Thyroid Blocking Antibodies (TBABs) to compete with Thyroid Stimulating Hormone (TSH) for binding with thyroid stimulating hormone receptor and do not let the TSH to bind with its receptor resulting in hyper or hyposecretion of thyroid hormones [2,3]
A study has shown that TSH binding based on TSHR sequences recognized by the antibodies and suggested 3 distinct TSH binding regions in the TSHR: aa 246–260, 277–296, and 381–385
Summary
Autoimmune thyroid disease (AITD) is a common organ specific autoimmune disorder affecting thyroid gland mostly in women [1]. Thyroid gland is affected by autoimmunity in which the immune system which is “self-defense mechanism” attacks and damages the thyroid of an individual This autoimmunity to thyroid is the result of interaction of many genetic and environmental factors which renders Thyroid Stimulating Antibodies (TSAbs) and Thyroid Blocking Antibodies (TBABs) to compete with Thyroid Stimulating Hormone (TSH) for binding with thyroid stimulating hormone receptor and do not let the TSH to bind with its receptor resulting in hyper or hyposecretion of thyroid hormones [2,3]. The diagnosis and therapy of Graves’ disease required better understanding of molecular interaction between TSHR auto antibodies and the TSHR [5].Various information related to thyroid disorders were retrieved from different literature for the simulation of thyroid model [6,7,8,9,10]
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