title: Efficacy of protocols for induction of chronic hyperthyroidism in male and female mice.
abstract: Protocols for induction of hyperthyroidism in mice are highly variable and mostly involve short-term thyroid hormone (TH) treatment. In addition, little is known about a possible influence of sex on experimental TH manipulation. Here we analyzed the efficacy of intraperitoneal vs. oral levothyroxine (T4) administration to induce chronic hyperthyroidism in male and female mice and asked which T4 dosing intervals are required to achieve stable organ thyrotoxicosis. T4 was administered intraperitoneally or orally over a period of 6/7 weeks. Assessment included monitoring of body weight, TH serum concentrations, and serial quantitative TH target gene expression analysis in liver and heart. Our results show that both intraperitoneal and oral T4 treatment are reliable methods for induction of chronic hyperthyroidism in mice. Thereby T4 injection intervals should not exceed 48 h and oral levothyroxine should be administered continuously during experiments and up to sacrifice to ensure a hyperthyroid organ state. Furthermore, we found a sex-dependent variation in levothyroxine-induced TH serum state, with significantly higher T4 concentrations in female mice, while expression of investigated classical TH responsive genes in liver and heart did not vary with animal's sex. In summary, our study shows that common approaches for rendering rodents thyrotoxic can also be used for induction of chronic hyperthyroidism in male and female mice. Thereby T4 dosing intervals are critical as are read-out parameters to verify a chronic thyrotoxic organ state.
authors.affiliation: Department of Endocrinology and Metabolism, University Hospital Essen, University Duisburg-Essen, 45122, Essen, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Engels
authors.affiliation: Department of Endocrinology and Metabolism, University Hospital Essen, University Duisburg-Essen, 45122, Essen, Germany.
authors.forename: Helena
authors.initials: H
authors.lastname: Rakov
authors.affiliation: Department of Endocrinology and Metabolism, University Hospital Essen, University Duisburg-Essen, 45122, Essen, Germany.
authors.forename: Denise
authors.initials: D
authors.lastname: Zwanziger
authors.affiliation: Department of Endocrinology and Metabolism, University Hospital Essen, University Duisburg-Essen, 45122, Essen, Germany.
authors.forename: Georg Sebastian
authors.initials: GS
authors.lastname: Hönes
authors.affiliation: Department of Life Sciences and Chemistry, Jacobs University Bremen, 28759, Bremen, Germany.
authors.forename: Maren
authors.initials: M
authors.lastname: Rehders
authors.affiliation: Department of Life Sciences and Chemistry, Jacobs University Bremen, 28759, Bremen, Germany.
authors.forename: Klaudia
authors.initials: K
authors.lastname: Brix
authors.affiliation: Institut für Experimentelle Endokrinologie, Charité-Universitätsmedizin Berlin, 13353, Berlin, Germany.
authors.forename: Josef
authors.initials: J
authors.lastname: Köhrle
authors.affiliation: Department of Endocrinology and Metabolism, University Hospital Essen, University Duisburg-Essen, 45122, Essen, Germany.
authors.forename: Lars Christian
authors.initials: LC
authors.lastname: Möller
authors.affiliation: Department of Endocrinology and Metabolism, University Hospital Essen, University Duisburg-Essen, 45122, Essen, Germany. Dagmar.fuehrer@uk-essen.de.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Führer
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006980:Hyperthyroidism / Q000097:blood / Q000139:chemically induced*; D008297:Male; D051379:Mice; D012737:Sex Factors; D013974:Thyroxine
chemical_list: D013974:Thyroxine
keywords: Heart; Liver; Sex-difference; Target genes; Thyroid hormone action; Thyroid hormones; Thyrotoxicosis