TY - JOUR
T1 - Thyroid regeneration
T2 - Characterization of clear cells after partial thyroidectomy
AU - Ozaki, Takashi
AU - Matsubara, Tsutomu
AU - Seo, Daekwan
AU - Okamoto, Minoru
AU - Nagashima, Kunio
AU - Sasaki, Yoshihito
AU - Hayase, Suguru
AU - Murata, Tsubasa
AU - Liao, Xiao Hui
AU - Hanson, Jeffrey
AU - Rodriguez-Canales, Jaime
AU - Thorgeirsson, Snorri S.
AU - Kakudo, Kennichi
AU - Refetoff, Samuel
AU - Kimura, Shioko
PY - 2012/5
Y1 - 2012/5
N2 - Although having the capacity to grow in responseto a stimulus that perturbs the pituitary-thyroid axis, the thyroid gland is considered not a regenerative organ. In this study, partial thyroidectomy (PTx) was used to produce a condition for thyroid regeneration. In the intact thyroid gland, the central areas of both lobes served as the proliferative centers where microfollicles, and bromodeoxyuridine (Brd U)-positive and/or C cells, were localized. Two weeks after PTx, the number of Brd U-positive cells and cells with clear or faintly eosinophilic cytoplasm were markedly increased in the central area and continuous to the cut edge. Clear cells were scant in the cytoplasm, as determined by electron microscopy; some retained the characteristics of calcitonin-producing C cells by having neuroendocrine granules, whereas others retained follicular cell-specific features, such as the juxtaposition to a lumen with microvilli. Some cells were Brd U-positive and expressed Foxa2, the definitive endoderm lineage marker. Serum TSH levels drastically changed due to the thyroidectomy-induced acute reduction in T 4-generating tissue, resulting in a goitrogenesis setting. Microarray followed by pathway analysis revealed that the expression of genes involved in embryonic development and cancer was affected by PTx. The results suggest that both C cells and follicular cells may be altered by PTx to become immature cells or immature cells that might be derived from stem/progenitor cells on their way to differentiation into C cells or follicular cells. These immature clear cells may participate in the repair and/or regeneration of the thyroid gland.
AB - Although having the capacity to grow in responseto a stimulus that perturbs the pituitary-thyroid axis, the thyroid gland is considered not a regenerative organ. In this study, partial thyroidectomy (PTx) was used to produce a condition for thyroid regeneration. In the intact thyroid gland, the central areas of both lobes served as the proliferative centers where microfollicles, and bromodeoxyuridine (Brd U)-positive and/or C cells, were localized. Two weeks after PTx, the number of Brd U-positive cells and cells with clear or faintly eosinophilic cytoplasm were markedly increased in the central area and continuous to the cut edge. Clear cells were scant in the cytoplasm, as determined by electron microscopy; some retained the characteristics of calcitonin-producing C cells by having neuroendocrine granules, whereas others retained follicular cell-specific features, such as the juxtaposition to a lumen with microvilli. Some cells were Brd U-positive and expressed Foxa2, the definitive endoderm lineage marker. Serum TSH levels drastically changed due to the thyroidectomy-induced acute reduction in T 4-generating tissue, resulting in a goitrogenesis setting. Microarray followed by pathway analysis revealed that the expression of genes involved in embryonic development and cancer was affected by PTx. The results suggest that both C cells and follicular cells may be altered by PTx to become immature cells or immature cells that might be derived from stem/progenitor cells on their way to differentiation into C cells or follicular cells. These immature clear cells may participate in the repair and/or regeneration of the thyroid gland.
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U2 - 10.1210/en.2011-1365
DO - 10.1210/en.2011-1365
M3 - Article
C2 - 22454152
AN - SCOPUS:84860346864
SN - 0013-7227
VL - 153
SP - 2514
EP - 2525
JO - Endocrinology
JF - Endocrinology
IS - 5
ER -