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