title: Thyroid dysfunction in megalin deficient mice.
abstract: 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.
authors.affiliation: Department of Endocrinology and Metabolism, University of Pisa, Via Paradisa 2, 56124 Pisa, Italy.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Lisi
authors.forename: Cristina
authors.initials: C
authors.lastname: Segnani
authors.forename: Letizia
authors.initials: L
authors.lastname: Mattii
authors.forename: Roberta
authors.initials: R
authors.lastname: Botta
authors.forename: Claudio
authors.initials: C
authors.lastname: Marcocci
authors.forename: Amelio
authors.initials: A
authors.lastname: Dolfi
authors.forename: Robert T
authors.initials: RT
authors.lastname: McCluskey
authors.forename: Aldo
authors.initials: A
authors.lastname: Pinchera
authors.forename: Nunzia
authors.initials: N
authors.lastname: Bernardini
authors.forename: Michele
authors.initials: M
authors.lastname: Marinò
mesh_terms: 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
chemical_list: D026561:Low Density Lipoprotein Receptor-Related Protein-2; D013963:Thyroid Hormones; D013972:Thyrotropin; D013954:Thyroglobulin; D013974:Thyroxine