TSH-Dependent expression of the LDL receptor-associated protein (RAP) in thyroid epithelial cells.
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.
Botta
Roberta
R
Department of Endocrinology and Metabolism, University of Pisa, Via Paradisa 2, 56124, Pisa, Italy.
Lisi
Simonetta
S
Pinchera
Aldo
A
Segnani
Cristina
C
Cianferotti
Luisella
L
Altea
Maria Antonietta
MA
Menconi
Francesca
F
Mattii
Letizia
L
Corsini
Giovanni Umberto
GU
Marcocci
Claudio
C
Dolfi
Amelio
A
Bernardini
Nunzia
N
Marinò
Michele
M
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
D013956:Antithyroid Agents; D026563:LDL-Receptor Related Protein-Associated Protein; D010472:Perchlorates; D017670:Sodium Compounds; D008713:Methimazole; D013972:Thyrotropin; C031068:sodium perchlorate