title: TSH-Dependent expression of the LDL receptor-associated protein (RAP) in thyroid epithelial cells.
abstract: The low density lipoprotein (LDL) receptor-associated protein (RAP) is an endoplasmic reticulum (ER)-resident molecular chaperone for several LDL receptor family members and it also binds to thyroglobulin (Tg), the thyroid hormone precursor. Disruption of the RAP gene in thyrocytes results in impaired Tg secretion. To gain further insights into the function of RAP in the thyroid, we investigated whether its expression in thyrocytes is regulated by thyroid-stimulating hormone (TSH), a feature common to all proteins involved in thyroid hormone secretion. We found by immunofluorescence that in FRTL-5 cells cultured in the presence of TSH, RAP is expressed intracellularly. The levels of expression increased after exposure to TSH, beginning at 48 hours, in a concentration-dependent manner as observed by immunofluorescence and Western blotting. Expression of RAP was also increased by TSH in primary cultures of human thyrocytes as observed by Western blotting. In hypothyroid mice with high serum TSH, RAP was markedly increased compared with euthyroid mice as observed by immunohistochemistry and Western blotting. Based on these findings, we concluded that RAP is expressed by thyrocytes in a TSH-dependent manner, both in cultured thyroid cells and in vivo.
authors.affiliation: Department of Endocrinology and Metabolism, University of Pisa, Via Paradisa 2, 56124, Pisa, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Botta
authors.forename: Simonetta
authors.initials: S
authors.lastname: Lisi
authors.forename: Aldo
authors.initials: A
authors.lastname: Pinchera
authors.forename: Cristina
authors.initials: C
authors.lastname: Segnani
authors.forename: Luisella
authors.initials: L
authors.lastname: Cianferotti
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Altea
authors.forename: Francesca
authors.initials: F
authors.lastname: Menconi
authors.forename: Letizia
authors.initials: L
authors.lastname: Mattii
authors.forename: Giovanni Umberto
authors.initials: GU
authors.lastname: Corsini
authors.forename: Claudio
authors.initials: C
authors.lastname: Marcocci
authors.forename: Amelio
authors.initials: A
authors.lastname: Dolfi
authors.forename: Nunzia
authors.initials: N
authors.lastname: Bernardini
authors.forename: Michele
authors.initials: M
authors.lastname: Marinò
mesh_terms: D000818:Animals; D013956:Antithyroid Agents / Q000494:pharmacology; D015153:Blotting, Western; D019556:COS Cells; D002522:Chlorocebus aethiops; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007037:Hypothyroidism / Q000139:chemically induced / Q000378:metabolism; D026563:LDL-Receptor Related Protein-Associated Protein / Q000378:metabolism*; D008713:Methimazole / Q000494:pharmacology; D051379:Mice; D010472:Perchlorates / Q000494:pharmacology; D051381:Rats; D017670:Sodium Compounds / Q000494:pharmacology; D013961:Thyroid Gland / Q000166:cytology* / Q000378:metabolism; D013972:Thyrotropin / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D013956:Antithyroid Agents; D026563:LDL-Receptor Related Protein-Associated Protein; D010472:Perchlorates; D017670:Sodium Compounds; D008713:Methimazole; D013972:Thyrotropin; C031068:sodium perchlorate