Thyroid dysfunction in megalin deficient mice.
Megalin mediates transcytosis of thyroglobulin (Tg), the thyroid hormone precursor, resulting in its passage into the bloodstream. The process involves especially hormone-poor Tg, which may favour hormone secretion by preventing competition with hormone-rich Tg for proteolytic degradation. To gain more insight into the role of megalin, here we studied thyroid function and histology in megalin deficient mice compared with WT mice. As expected from the knowledge that megalin mediates Tg transcytosis, serum Tg levels were significantly reduced in homozygous (megalin-/-) mice, which, more importantly, were found to be hypothyroid, as demonstrated by significantly reduced serum free thyroxine and significantly increased serum thyroid stimulating hormone (TSH) levels. In heterozygous (megalin+/-) mice, in which megalin expression was normal, thyroid function was unaffected. Although the serological phenotype in megalin-/- mice was not associated with histological alterations or goiter, our results support a major role of megalin in thyroid hormone secretion.
Lisi
Simonetta
S
Department of Endocrinology and Metabolism, University of Pisa, Via Paradisa 2, 56124 Pisa, Italy.
Segnani
Cristina
C
Mattii
Letizia
L
Botta
Roberta
R
Marcocci
Claudio
C
Dolfi
Amelio
A
McCluskey
Robert T
RT
Pinchera
Aldo
A
Bernardini
Nunzia
N
Marinò
Michele
M
D000818:Animals; D006579:Heterozygote; D006720:Homozygote; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D013954:Thyroglobulin / Q000097:blood / Q000378:metabolism; D013961:Thyroid Gland / Q000378:metabolism / Q000503:physiopathology*; D013963:Thyroid Hormones / Q000097:blood / Q000378:metabolism; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood
D026561:Low Density Lipoprotein Receptor-Related Protein-2; D013963:Thyroid Hormones; D013972:Thyrotropin; D013954:Thyroglobulin; D013974:Thyroxine