A Signaling Network of Thyroid-Stimulating Hormone.

Human thyroid stimulating hormone (TSH) is a glycoprotein secreted by the anterior part of the pituitary gland. TSH plays an important physiological role in the regulation of hypothalamic-pituitary-thyroid axis by modulating the release of the thyroid hormones from the thyroid gland. It induces iodine uptake by the thyroid, promotes thyroid epithelial differentiation and growth, and protects thyroid cells from apoptosis. Impairment of TSH signal transduction pathway leads to thyroid disorders such as goitre, hypothyroidism and hyperthyroidism, which can have complex clinical manifestations. TSH signaling is largely effected through two separate pathways, the adenylate cyclase and the phospholipase C pathways. In spite of its biomedical importance, a concise signaling map of TSH pathway is not available in the public domain. Therefore, we have generated a detailed signaling map of TSH pathway by systematically cataloging the molecular reactions induced by TSH including protein-protein interactions, post-translational modifications, protein translocation events and activation/inhibition reactions. We have cataloged 40 molecular association events, 42 enzyme-substrate reactions and 16 protein translocation events in TSH signaling pathway resource. Additionally, we have documented 208 genes, which are differentially regulated by TSH. We have provided the details of TSH pathway through NetPath (http://www.netpath.org), which is a publicly available resource for human signaling pathways developed by our group. We have also depicted the map of TSH signaling using NetSlim criteria (http://www.netpath.org/netslim/) and provided pathway maps in Wikipathways (http://www.wikipathways.org/). We anticipate that the availability of TSH pathway as a community resource will enhance further biomedical investigations into the function and effects of this important hormone.