Decreased thyroid follicle size in dwarf mice may suggest the role of growth hormone signaling in thyroid growth regulation

Abstract

BackgroundAltered somatotrophic signaling is among the most important potential mechanisms of extended longevity. Ames dwarf (df/df) mice are homozygous for mutation at the Prop-1 gene, leading to a lack of growth hormone (GH), prolactin and thyroid stimulating hormone (TSH). Mice homozygous for targeted disruption of the growth hormone receptor/growth hormone binding protein gene are known as GH receptor knockout (GHRKO) mice or “Laron dwarf”. Both, df/df and GHRKO mice, are characterized by reduced body size, low plasma insulin and insulin-like growth factor-I (IGF-I), remarkably extended longevity, and severe (in df/df mice) or mild (in GHRKO mice) thyroid hypofunction. Recently, by crossing df/df and GHRKO mice, double-mutant Ames dwarf/GHRKO (df/KO) mice were created. Interestingly, these mice are smaller than Ames dwarfs or GHRKOs, and also have reduced insulin and IGF-I levels. The aim of the study was to investigate if and to what extent certain thyroid morphological parameters, such as inner follicular surface area, inner follicular perimeter, as well as the follicular epithelium thickness are changed in the examined dwarf mice.MethodsThis quantification was performed in thyroids collected from df/df, GHRKO and df/KO female mice, at approximately 5–6 months of age. We used a computerized plotting programme that combines a live microscopic image of the slide with an operator-generated overlay.ResultsInner follicular surface area and inner follicular perimeter were decreased in all examined kinds of dwarf mice as compared to normal animals. Furthermore, decreases in these two parameters were more pronounced in df/df and df/KO than in GHRKO mice. Concerning the follicular epithelium thickness, only a tendency towards decrease of this parameter was found in all three kinds of dwarf mice.ConclusionsParameters characterizing thyroid follicle size are decreased in all three examined models of dwarf mice, which may explain decreased thyroid hormone levels in both basal mutants (Ames dwarfs and GHRKOs). df/df mutation seems to predominate over GHRKO genetic intervention concerning their effects on thyroid growth. Beside TSH, also GH signaling seems to constitute a crucial element in the regulation of thyroid growth and, possibly, function.

TSH-independent release of thyroid hormones through cold exposure in aging rats

“…However, young rats did not show any significant morphologic or functional change despite exposure to cold, but they still had higher active follicle ratio and thyroid hormone levels than old rats. The differences in the thyroid function changes after cold exposure between young and old rats indicate that aging rats respond first to the cold rather than the young ones because the former have reduced ability to produce metabolic heat through lowering of the basal metabolic rate compared with the latter; moreover, although cold adaptation of the thyroid occurs first in aging rats [ 17 – 21 ], their heat production capacity is likely to be still insufficient compared with the young rats [ 22 , 23 ].…”

Gene expression of key regulators of mitochondrial biogenesis is sex dependent in mice with growth hormone receptor deletion in liver

“…We have previously shown increased expression of key regulators of mitochondrial biogenesis, including PGC1α, AMPK, SIRT1, eNOS and MFN2 in the kidneys and heart of GHRKO mice [ 11 - 13 ]. Moreover, GHRKO mice have decreased levels of pro-apoptotic factors [ 13 - 16 ] and decreased thyroid follicle size [ 17 ] with mild thyroid hypofunction. Interestingly, preservation of cognitive function in aging GHRKO mice was also observed [ 10 ].…”

The thyroid gland and the process of aging; what is new?

“…For example, a very severe thyroid hypofunction with reduced core body temperature, as observed in Ames dwarf (df/df) and Snell mice (characterized by mutations at the Prop-1 and Pit-1 gene, respectively, and demonstrating a lack of growth hormone (GH), prolactin and TSH), is considered to substantially contribute to remarkable longevity in these rodents [40]. Furthermore, severe hypothyroid Ames dwarfs and mice with targeted disruption of the growth hormone receptor/growth hormone binding protein gene (GH receptor knockout; GHRKO) with mild thyroid hypofunction, have decreased thyroid follicle size which may explain decreased thyroid hormone levels in these mutants [43]. …”