title: Sex-specific phenotypes of hyperthyroidism and hypothyroidism in mice.
abstract: BACKGROUND
  Thyroid dysfunction is more common in the female population, however, the impact of sex on disease characteristics has rarely been addressed. Using a murine model, we asked whether sex has an influence on phenotypes, thyroid hormone status, and thyroid hormone tissue response in hyper- and hypothyroidism.
  
  
  METHODS
  Hypo- and hyperthyroidism were induced in 5-month-old female and male wildtype C57BL/6N mice, by LoI/MMI/ClO4 (-) or T4 i.p. treatment over 7 weeks, and control animals underwent sham treatment (N = 8 animals/sex/treatment). Animals were investigated for impact of sex on body weight, food and water intake, body temperature, heart rate, behaviour (locomotor activity, motor coordination, and strength), liver function, serum thyroid hormone status, and cellular TH effects on gene expression in brown adipose tissue, heart, and liver.
  
  
  RESULTS
  Male and female mice showed significant differences in behavioural, functional, metabolic, biochemical, and molecular traits of hyper- and hypothyroidism. Hyperthyroidism resulted in increased locomotor activity in female mice but decreased muscle strength and motor coordination preferably in male animals. Hypothyroidism led to increased water intake in male but not female mice and significantly higher serum cholesterol in male mice. Natural sex differences in body temperature, body weight gain, food and water intake were preserved under hyperthyroid conditions. In contrast, natural sex differences in heart rate disappeared with TH excess and deprivation. The variations of hyper- or hypothyroid traits of male and female mice were not explained by classical T3/T4 serum state. TH serum concentrations were significantly increased in female mice under hyperthyroidism, but no sex differences were found under eu- or hypothyroid conditions. Interestingly, analysis of expression of TH target genes and TH transporters revealed little sex dependency in heart, while sex differences in target genes were present in liver and brown adipose tissue in line with altered functional and metabolic traits of hyper- and hypothyroidism.
  
  
  CONCLUSIONS
  These data demonstrate that the phenotypes of hypo- and hyperthyroidism differ between male and female mice and indicate that sex is an important modifier of phenotypic manifestations.
authors: Division of Laboratory Research Department of Endocrinology and Metabolism, Clinical Chemistry, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany.
authors: Helena
authors: H
authors: Rakov
authors: Division of Laboratory Research Department of Endocrinology and Metabolism, Clinical Chemistry, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany.
authors: Kathrin
authors: K
authors: Engels
authors: Division of Laboratory Research Department of Endocrinology and Metabolism, Clinical Chemistry, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany.
authors: Georg Sebastian
authors: GS
authors: Hönes
authors: Charité-Universitätsmedizin Berlin, Institute of Experimental Endocrinology, 13353 Berlin, Germany.
authors: Karl-Heinz
authors: KH
authors: Strucksberg
authors: Division of Laboratory Research Department of Endocrinology and Metabolism, Clinical Chemistry, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany.
authors: Lars Christian
authors: LC
authors: Moeller
authors: Charité-Universitätsmedizin Berlin, Institute of Experimental Endocrinology, 13353 Berlin, Germany.
authors: Josef
authors: J
authors: Köhrle
authors: Division of Laboratory Research Department of Endocrinology and Metabolism, Clinical Chemistry, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany.
authors: Denise
authors: D
authors: Zwanziger
authors: Division of Laboratory Research Department of Endocrinology and Metabolism, Clinical Chemistry, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany.
authors: Dagmar
authors: D
authors: Führer
keywords: Hyperthyroidism; Hypothyroidism; Mice; Sex difference; Sex steroid hormone; Thyroid hormone action; Thyroid hormone transport