Role of caveolin-1 in thyroid phenotype, cell homeostasis, and hormone synthesis: in vivo study of caveolin-1 knockout mice.
In human thyroid, caveolin-1 is localized at the apex of thyrocytes, but its role there remains unknown. Using immunohistochemistry, (127)I imaging, transmission electron microscopy, immunogold electron microscopy, and quantification of H(2)O(2), we found that in caveolin-1 knockout mice thyroid cell homeostasis was disrupted, with evidence of oxidative stress, cell damage, and apoptosis. An even more striking phenotype was the absence of thyroglobulin and iodine in one-half of the follicular lumina and their presence in the cytosol, suggesting that the iodide organification and binding to thyroglobulin were intracellular rather than at the apical membrane/extracellular colloid interface. The latter abnormality may be secondary to the observed mislocalization of the thyroid hormone synthesis machinery (dual oxidases, thyroperoxidase) in the cytosol. Nevertheless, the overall uptake of radioiodide, its organification, and secretion as thyroid hormones were comparable to those of wild-type mice, suggesting adequate compensation by the normal TSH retrocontrol. Accordingly, the levels of free thyroxine and TSH were normal. Only the levels of free triiodothyronine showed a slight decrease in caveolin-1 knockout mice. However, when TSH levels were increased through low-iodine chow and sodium perchlorate, the induced goiter was more prominent in caveolin-1 knockout mice. We conclude that caveolin-1 plays a role in proper thyroid hormone synthesis as well as in cell number homeostasis. Our study demonstrates for the first time a physiological function of caveolin-1 in the thyroid gland. Because the expression and subcellular localization of caveolin-1 were similar between normal human and murine thyroids, our findings in caveolin-1 knockout mice may have direct relevance to the human counterpart.
Senou
Maximin
M
Unité de Morphologie Expérimentale, Université Catholique de Louvain, Brussels, Belgium.
Costa
Maria José
MJ
Massart
Claude
C
Thimmesch
Matthieu
M
Khalifa
Céline
C
Poncin
Sylvie
S
Boucquey
Marie
M
Gérard
Anne-Catherine
AC
Audinot
Jean-Nicolas
JN
Dessy
Chantal
C
Ruf
Jean
J
Feron
Olivier
O
Devuyst
Olivier
O
Guiot
Yves
Y
Dumont
Jacques Emile
JE
Van Sande
Jacqueline
J
Many
Marie-Christine
MC
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D016466:CHO Cells; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D054879:Halogenation / Q000235:genetics; D006706:Homeostasis / Q000235:genetics*; D006861:Hydrogen Peroxide / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000235:genetics; D010641:Phenotype; D013961:Thyroid Gland / Q000002:abnormalities / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D013963:Thyroid Hormones / Q000096:biosynthesis*
D051242:Caveolin 1; D013963:Thyroid Hormones; D006861:Hydrogen Peroxide