{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T20:15:12Z","timestamp":1774988112733,"version":"3.50.1"},"reference-count":41,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,4,6]],"date-time":"2023-04-06T00:00:00Z","timestamp":1680739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"publisher","award":["FGFZ-2022-0035"],"award-info":[{"award-number":["FGFZ-2022-0035"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Deuterium, a stable isotope of hydrogen, is abundant in organisms. It is known to produce various biological effects. However, its impact in thyroid hormone synthesis and secretion is poorly studied. The aim of this investigation was to evaluate the dynamics of thyroid hormones and pituitary thyroid-stimulating hormone secretion during bilateral shifts in deuterium supply and assess a possible role of the Na+\/I\u2212 symporter (NIS), the main iodide transporter, in altered thyroid function. The experiment was performed on adult male Wistar rats, which consumed deuterium-depleted ([D] = 10 ppm) and deuterium-enriched ([D] = 500,000 ppm) water for 21 days. The assessment of total thyroxine and triiodothyronine and their free fractions, as well as thyroid-stimulating hormone in blood serum, revealed the rapid response of the thyroid gland to shifts in the deuterium\/protium balance. The present investigation shows that the bilateral changes in the deuterium body content similarly modulate thyroid hormone production and functional activity of the pituitary gland, but the responses of the thyroid and pituitary glands differ. The response of the thyroid cells was to increase the synthesis of the hormones and the pituitary thyrotropes, in order to reduce the production of the thyroid-stimulating hormone. The evaluation of NIS serum levels found a gradual increase in the rats that consumed deuterium-enriched water and no differences in the group exposed to deuterium depletion. NIS levels in both groups did not correlate with thyroid hormones and pituitary thyroid-stimulating hormone production. The data obtained show that thyroid gland has a higher sensitivity to shifts in the deuterium body content than the hypothalamic\u2013pituitary complex, which responded later but similarly in the case of deuteration or deuterium depletion. It indicates a different sensitivity of the endocrine glands to alterations in deuterium content. It suggests that thyroid hormone production rate may depend on deuterium blood\/tissue and cytosol\/organelle gradients, which possibly disturb the secretory process independently of the NIS.<\/jats:p>","DOI":"10.3390\/ijms24076803","type":"journal-article","created":{"date-parts":[[2023,4,6]],"date-time":"2023-04-06T02:29:58Z","timestamp":1680748198000},"page":"6803","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Bilateral Shifts in Deuterium Supply Similarly Change Physiology of the Pituitary\u2013Thyroid Axis, but Differentially Influence Na+\/I\u2212 Symporter Production"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8239-5039","authenticated-orcid":false,"given":"Nataliya V.","family":"Yaglova","sequence":"first","affiliation":[{"name":"Laboratory of Endocrine System Development, A.P. Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution \u201cPetrovsky National Research Centre of Surgery\u201d, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergey S.","family":"Obernikhin","sequence":"additional","affiliation":[{"name":"Laboratory of Endocrine System Development, A.P. Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution \u201cPetrovsky National Research Centre of Surgery\u201d, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0504-1488","authenticated-orcid":false,"given":"Ekaterina P.","family":"Timokhina","sequence":"additional","affiliation":[{"name":"Laboratory of Endocrine System Development, A.P. Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution \u201cPetrovsky National Research Centre of Surgery\u201d, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentin V.","family":"Yaglov","sequence":"additional","affiliation":[{"name":"Laboratory of Endocrine System Development, A.P. Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution \u201cPetrovsky National Research Centre of Surgery\u201d, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dibakhan A.","family":"Tsomartova","sequence":"additional","affiliation":[{"name":"Laboratory of Endocrine System Development, A.P. Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution \u201cPetrovsky National Research Centre of Surgery\u201d, 119991 Moscow, Russia"},{"name":"Department of Human Anatomy and Histology, Federal State Funded Educational Institution, Higher Education I.M. Sechenov First Moscow State Medical University, 119435 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Svetlana V.","family":"Nazimova","sequence":"additional","affiliation":[{"name":"Laboratory of Endocrine System Development, A.P. Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution \u201cPetrovsky National Research Centre of Surgery\u201d, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elina S.","family":"Tsomartova","sequence":"additional","affiliation":[{"name":"Laboratory of Endocrine System Development, A.P. Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution \u201cPetrovsky National Research Centre of Surgery\u201d, 119991 Moscow, Russia"},{"name":"Department of Human Anatomy and Histology, Federal State Funded Educational Institution, Higher Education I.M. Sechenov First Moscow State Medical University, 119435 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina Y.","family":"Ivanova","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy and Histology, Federal State Funded Educational Institution, Higher Education I.M. Sechenov First Moscow State Medical University, 119435 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1046-6336","authenticated-orcid":false,"given":"Elizaveta V.","family":"Chereshneva","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy and Histology, Federal State Funded Educational Institution, Higher Education I.M. Sechenov First Moscow State Medical University, 119435 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatiana A.","family":"Lomanovskaya","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy and Histology, Federal State Funded Educational Institution, Higher Education I.M. Sechenov First Moscow State Medical University, 119435 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.gca.2007.10.003","article-title":"Turnover of oxygen and hydrogen isotopes in the body water, CO2, hair, and enamel of a small mammal","volume":"72","author":"Podlesak","year":"2008","journal-title":"Geochim. Cosmochim. Acta"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1002\/bies.20681","article-title":"Do \u201cheavy\u2019 eaters live longer?","volume":"29","author":"Shchepinov","year":"2007","journal-title":"Bioessays"},{"key":"ref_3","first-page":"1","article-title":"Pre-Clinical and Clinical Data Confirm the Anticancer Effect of Deuterium Depletion","volume":"2","author":"Somlyai","year":"2016","journal-title":"Biomacromol. J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/1073274821999655","article-title":"Deuterium Depletion Inhibits Cell Proliferation, RNA and Nuclear Membrane Turnover to Enhance Survival in Pancreatic Cancer","volume":"28","author":"Boros","year":"2021","journal-title":"Cancer Control"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1074\/mcp.RA120.002231","article-title":"Slight Deuterium Enrichment in Water Acts as an Antioxidant: Is Deuterium a Cell Growth Regulator?","volume":"19","author":"Zhang","year":"2020","journal-title":"Mol. Cell. Proteom."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"277","DOI":"10.3892\/etm_00000043","article-title":"Deuterium-depleted water inhibits human lung carcinoma cell growth by apoptosis","volume":"1","author":"Cong","year":"2010","journal-title":"Exp. Ther. Med."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Kravtsov, A., Kozin, S., Basov, A., Butina, E., Baryshev, M., Malyshko, V., Moiseev, A., Elkina, A., and Dzhimak, S. (2022). Reduction of Deuterium Level Supports Resistance of Neurons to Glucose Deprivation and Hypoxia: Study in Cultures of Neurons and on Animals. Molecules, 27.","DOI":"10.3390\/molecules27010243"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Yaglova, N.V., Timokhina, E.P., Obernikhin, S.S., and Yaglov, V.V. (2023). Emerging Role of Deuterium\/Protium Disbalance in Cell Cycle and Apoptosis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24043107"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1134\/S1607672915060071","article-title":"Content of deuterium in biological fluids and organs: Influence of deuterium depleted water on D\/H gradient and the process of adaptation","volume":"465","author":"Dzhimak","year":"2015","journal-title":"Dokl. Biochem. Biophys."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e0210","DOI":"10.15275\/rusomj.2020.0210","article-title":"Time-dependent effect of deuterium depletion on tumor growth and metastasis","volume":"9","author":"Yaglova","year":"2020","journal-title":"Russ. Open Med. J."},{"key":"ref_11","first-page":"85","article-title":"Isotope effects","volume":"Volume 2","author":"Nagy","year":"2013","journal-title":"Handbook of Nuclear Chemistry"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"809","DOI":"10.4103\/2230-8210.219335","article-title":"Incidence of Endocrine Disorders in Indian Adult Male Population","volume":"21","author":"Kumar","year":"2017","journal-title":"Indian J. Endocrinol. Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"694325","DOI":"10.3389\/fendo.2021.694325","article-title":"The Burden of Hormonal Disorders: A Worldwide Overview with a Particular Look in Italy","volume":"12","author":"Crafa","year":"2021","journal-title":"Front. Endocrinol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1007\/s10517-018-4005-1","article-title":"Sex Differences in the Production of SLC5A5, Thyroid Peroxidase, and Thyroid Hormones in Pubertal Rats Exposed to Endocrine Disruptor Dichlorodiphenyltrichloroethane (DDT) during Postnatal Ontogeny","volume":"164","author":"Yaglova","year":"2018","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"113215","DOI":"10.1016\/j.ecoenv.2022.113215","article-title":"Prenatal exposure to endocrine-disrupting chemicals and thyroid function in neonates: A systematic review and meta-analysis","volume":"231","author":"Sun","year":"2022","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1007\/s00702-020-02260-5","article-title":"Hypothyroidism after radiation exposure: Brief narrative review","volume":"127","author":"Reiners","year":"2020","journal-title":"J. Neural. Transm."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s13014-022-02028-z","article-title":"Predictors of radiation-induced hypothyroidism in nasopharyngeal carcinoma survivors after intensity-modulated radiotherapy","volume":"17","author":"Zhai","year":"2022","journal-title":"Radiat. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Hatch-McChesney, A., and Lieberman, H.R. (2022). Iodine and Iodine Deficiency: A Comprehensive Review of a Re-Emerging Issue. Nutrients, 14.","DOI":"10.3390\/nu14173474"},{"key":"ref_19","first-page":"11","article-title":"Studying of microbic synthesis of deuteriumlabelled l-phenylalanine by methylotrophic bacterium brevibacterium methylicum on media with differeny content of heavy water","volume":"4","author":"Mosin","year":"2012","journal-title":"Russ. J. Biopharmaceut."},{"key":"ref_20","first-page":"390","article-title":"Activation of Na,K-ATPase by small concentrations of D2O, inhibition by high concentrations","volume":"23","author":"Lobyshev","year":"1978","journal-title":"Biofizika"},{"key":"ref_21","first-page":"595","article-title":"D2O as a modifier of ionic specificity of Na, K-ATPase","volume":"27","author":"Lobyshev","year":"1982","journal-title":"Biofizika"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1002\/bies.201600040","article-title":"Can heavy isotopes increase lifespan? Studies of relative abundance in various organisms reveal chemical perspectives on aging","volume":"38","author":"Li","year":"2016","journal-title":"Bioessays"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1134\/S0006350918050111","article-title":"The reversible effect of deuteration on tissue fluid and biopolymers in normal and tumor tissues of mice","volume":"63","author":"Kosenkov","year":"2018","journal-title":"Biophysics"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1007\/s10517-021-05208-1","article-title":"Response of Pituitary-Thyroid Axis to a Short-Term Shift in Deuterium Content in the Body","volume":"171","author":"Yaglova","year":"2021","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2373","DOI":"10.1074\/mcp.RA119.001455","article-title":"Anticancer Effect of Deuterium Depleted Water\u2014Redox Disbalance Leads to Oxidative Stress","volume":"18","author":"Zhang","year":"2019","journal-title":"Mol. Cell. Proteom."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0014-5793(93)81479-J","article-title":"Naturally occurring deuterium is essential for the normal growth rate of cells","volume":"317","author":"Somlyai","year":"1993","journal-title":"FEBS Lett."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.mce.2011.05.047","article-title":"Cell biology of H2O2 generation in the thyroid: Investigation of the control of dual oxidases (DUOX) activity in intact ex vivo thyroid tissue and cell lines","volume":"343","author":"Massart","year":"2011","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1210\/endo.137.3.8603567","article-title":"The Ca2+- and reduced nicotinamide adenine dinucleotide phosphate-dependent hydrogen peroxide generating system is induced by thyrotropin in porcine thyroid cells","volume":"137","author":"Carvalho","year":"1996","journal-title":"Endocrinology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3066","DOI":"10.1002\/anie.201107334","article-title":"On the interpretation of deuterium kinetic isotope effects in C-H bond functionalizations by transition-metal complexes","volume":"51","author":"Simmons","year":"2012","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6528106","DOI":"10.1155\/2019\/6528106","article-title":"Deuterium Incorporation Protects Cells from Oxidative Damage","volume":"2019","author":"Sestili","year":"2019","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1530\/JOE-17-0111","article-title":"Hypophysectomy abolishes rhythms in rat thyroid hormones but not in the thyroid clock","volume":"233","author":"Fahrenkrug","year":"2017","journal-title":"J. Endocrinol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1038\/nrendo.2014.78","article-title":"Circadian clock control of endocrine factors","volume":"10","author":"Gamble","year":"2014","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"107","DOI":"10.17816\/PAVLOVJ20133107-113","article-title":"The infradian rthythms of cortisol and thyroid hormones at woman of reproductive age","volume":"21","author":"Diatroptov","year":"2013","journal-title":"I.P. Pavlov Russ. Med. Biol. Her."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.1210\/endo-120-5-1742","article-title":"Thyroid hormone-binding proteins in plasma facilitate uniform distribution of thyroxine within tissues: A perfused rat liver study","volume":"120","author":"Mendel","year":"1987","journal-title":"Endocrinology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5357","DOI":"10.1111\/j.1742-4658.2009.07245.x","article-title":"Evolutionary changes to transthyretin: Developmentally regulated and tissue-specific gene expression","volume":"276","author":"Yamauchi","year":"2009","journal-title":"FEBS J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/0304-4157(93)90017-I","article-title":"Iodide transport in the thyroid gland","volume":"1154","author":"Carrasco","year":"1993","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1210\/er.2001-0029","article-title":"The sodium\/iodide Symporter (NIS): Characterization, regulation, and medical significance","volume":"24","author":"Dohan","year":"2003","journal-title":"Endocr. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1210\/er.2012-1036","article-title":"The Na+\/I\u2212 Symporter (NIS): Mechanism and Medical Impact","volume":"35","author":"Portulano","year":"2014","journal-title":"Endocr. Rev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s10517-015-3136-x","article-title":"Mechanisms of Disruptive Action of Dichlorodiphenyltrichloroethane (DDT) on the Function of Thyroid Follicular Epitheliocytes","volume":"160","author":"Yaglova","year":"2015","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/1687-9856-2014-8","article-title":"Iodide transport: Implications for health and disease","volume":"2014","author":"Pesce","year":"2014","journal-title":"Int. J. Pediatr. Endocrinol."},{"key":"ref_41","first-page":"4","article-title":"Biological effects of deuteronation: ATP synthase as an example","volume":"22","author":"Olgun","year":"2007","journal-title":"Theor. Biol. Med. Model."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/7\/6803\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:10:45Z","timestamp":1760123445000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/7\/6803"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,6]]},"references-count":41,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["ijms24076803"],"URL":"https:\/\/doi.org\/10.3390\/ijms24076803","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,6]]}}}