{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T02:01:33Z","timestamp":1791684093965,"version":"4.3.4"},"reference-count":281,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T00:00:00Z","timestamp":1663200000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["P42ES04911, P30ES019776"],"award-info":[{"award-number":["P42ES04911, P30ES019776"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","award":["201908110055"],"award-info":[{"award-number":["201908110055"]}],"id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>\n                    Thyroid hormones (THs), including T4 and T3, are produced and released by the thyroid gland under the stimulation of thyroid-stimulating hormone (TSH). The homeostasis of THs is regulated\n                    <jats:italic>via<\/jats:italic>\n                    the coordination of the hypothalamic-pituitary-thyroid axis, plasma binding proteins, and local metabolism in tissues. TH synthesis and secretion in the thyrocytes-containing thyroid follicles are exquisitely regulated by an elaborate molecular network comprising enzymes, transporters, signal transduction machineries, and transcription factors. In this article, we synthesized the relevant literature, organized and dissected the complex intrathyroidal regulatory network into structures amenable to functional interpretation and systems-level modeling. Multiple intertwined feedforward and feedback motifs were identified and described, centering around the transcriptional and posttranslational regulations involved in TH synthesis and secretion, including those underpinning the Wolff-Chaikoff and Plummer effects and thyroglobulin-mediated feedback regulation. A more thorough characterization of the intrathyroidal network from a systems biology perspective, including its topology, constituent network motifs, and nonlinear quantitative properties, can help us to better understand and predict the thyroidal dynamics in response to physiological signals, therapeutic interventions, and environmental disruptions.\n                  <\/jats:p>","DOI":"10.3389\/fendo.2022.992883","type":"journal-article","created":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T02:19:41Z","timestamp":1663208381000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":58,"title":["Intrathyroidal feedforward and feedback network regulating thyroid hormone synthesis and secretion"],"prefix":"10.3389","volume":"13","author":[{"given":"Li","family":"Jing","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2016.174","article-title":"Thyroid hormones and cardiovascular disease","volume":"14","author":"Jabbar","year":"2017","journal-title":"Nat Rev Cardiol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1210\/js.2018-00423","article-title":"Thyroid hormone action and energy expenditure","volume":"3","author":"Yavuz","year":"2019","journal-title":"J Endocr Soc"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1093\/biolre\/ioy115","article-title":"Thyroid hormones and female 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