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As is widely recognised, the regulation of the body\u2019s energy status is a highly complex process involving numerous systems, hormones and neurotransmitters. Among the most important regulators of energy status, alongside the satiety and hunger centre located in the hypothalamus, is the HPT axis, which directly and indirectly affects the regulation of metabolism in all cells of the body. Therefore, it seems highly important to conduct studies aimed at elucidating how QRFP43 may impact the secretory activity of the HPT axis. The objective of this work was to investigate the role of QRFP43 in modulating HPT axis activity in sheep. The study examined mRNA and peptide expression of TRH and TSH in the hypothalamus and pituitary, as well as plasma concentrations of TSH, free T4 (FT4) and free T3 (FT3). Moreover, the relationship between QRFP34 and mRNA expression of the <jats:italic>Dio1<\/jats:italic>, <jats:italic>Dio2<\/jats:italic>, and <jats:italic>Dio3<\/jats:italic> genes was explored in selected tissues of the HPT axis. The animals (<jats:italic>n<\/jats:italic>\u2009=\u200948) were randomly divided into three experimental groups: a control group receiving an ICV infusion of Ringer-Locke solution, and two experimental groups receiving ICV infusions of QRFP43 at doses of 10 and 50\u00a0\u00b5g per day. Four 50-minute ICV infusions were administered to all sheep at 30\u00a0min intervals each of three consecutive days. Hypothalamic, pituitary and thyroid glands were collected and preserved for further immunohistochemical and molecular biological analyses. Additionally, blood samples were collected during the experiment for subsequent RIA determinations. In summary, the results of the experiment have indicated that QRFP43 modulates the secretory activity of the HPT axis at all organisational levels. Moreover, QRFP43 can alter the mRNA expression profiles of DIO1, DIO2 and DIO3 in HPT tissues, leading to discrete changes in the metabolism of the cells studied and their response to signals transmitted by T4 and T3.<\/jats:p>","DOI":"10.1038\/s41598-025-85693-w","type":"journal-article","created":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T08:54:57Z","timestamp":1736240097000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["QRFP43 modulates the activity of the hypothalamic-pituitary-thyroid axis in female sheep"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4782-3947","authenticated-orcid":false,"given":"Bartosz Jaros\u0142aw","family":"Przyby\u0142","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6385-8990","authenticated-orcid":false,"given":"Micha\u0142","family":"Szlis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5135-5328","authenticated-orcid":false,"given":"Anna","family":"Misztal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8288-1267","authenticated-orcid":false,"given":"Anna","family":"W\u00f3jcik-G\u0142adysz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,1,7]]},"reference":[{"key":"85693_CR1","doi-asserted-by":"publisher","first-page":"1550","DOI":"10.1523\/JNEUROSCI.20-04-01550.2000","volume":"20","author":"C Fekete","year":"2000","unstructured":"Fekete, C. et al. \u0391-Melanocyte-stimulating hormone is contained in nerve terminals innervating thyrotropin-releasing hormone-synthesizing neurons in the Hypothalamic Paraventricular Nucleus and prevents Fasting-Induced suppression of Prothyrotropin-releasing hormone gene E. 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Approval for the study was obtained from the Local Ethics Committee affiliated with the Warsaw University of Life Sciences (no. WAW2\/193\/2019), in compliance with the Polish Law for the Animal Care and Use of January 21, 2005, and the Polish Law for Animal Protection of September 16, 2011. Also presented experiment (design and all procedures) fulfil criteria of ARRIVE guidelines.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"The authors did not use any artificial intelligence-assisted technologies in the writing process.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declaration of generative AI and AI-assisted technologies in the writing process"}},{"value":"1: Primer3web, version 4.1.0; The Whitehead Institute, Cambridge, MA; . 2: The Rotor Gene 6000 software 1.7 containing Relative Expression Software (Qiagen GmbH, Hilden, Germany); software provided by the manufacturer. 3: Best-Keeper software; . 4: GraphPad Prism 5 (GraphPad Software Inc., La Jolla, CA); .","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Software used in experiments"}}],"article-number":"1085"}}