CALCITONIN-SECRETING CELLS OF THE THYROID EXPRESS AN EXTRACELLULAR CALCIUM RECEPTOR GENE

被引:202
作者
GARRETT, JE
TAMIR, H
KIFOR, O
SIMIN, RT
ROGERS, KV
MITHAL, A
GAGEL, RF
BROWN, EM
机构
[1] COLUMBIA UNIV, COLL PHYS & SURG, DEPT ANAT & CELL BIOL, NEW YORK, NY 10032 USA
[2] NEW YORK STATE PSYCHIAT INST & HOSP, DIV NEUROSCI, NEW YORK, NY USA
[3] UNIV TEXAS, MD ANDERSON CANC CTR, ENDOCRINOL SECT, HOUSTON, TX 77030 USA
[4] BRIGHAM & WOMENS HOSP, DEPT MED, DIV ENDOCRINE HYPERTENS, BOSTON, MA 02115 USA
关键词
D O I
10.1210/en.136.11.5202
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Calcitonin (CT) secretion by parafollicular cells of the thyroid (C cells) is regulated by small changes in the concentration of extracellular calcium ([Ca2+](e)). Elevation of [Ca2+](e) elicits a rise in the C cell cytoplasmic calcium concentration and stimulates CT release. The molecular entity through which C cells detect changes in [Ca2+](e) and modulate hormone secretion is unknown. Recently, an extracellular calcium-sensing receptor (CaR) complementary DNA. was isolated from bovine parathyroid gland. To assess whether parathyroid cells and C cells use similar mechanisms to detect changes in ambient Ca2+, rat, human, and sheep C cells were examined for expression of the parathyroid CaR or a related receptor isoform. Reverse transcription-polymerase chain reaction analysis identified CaR transcripts in rat and human thyroid gland. Northern blot analysis demonstrated CaR messenger RNA. (mRNA) in rat thyroid gland, a human medullary thyroid carcinoma (MTC) isolate, and a highly enriched preparation of sheep C cells. Rat MTC 44-2 cells, a cell line responsive to changes in [Ca2+](e), express abundant levels of CaR mRNA. Human TT cells, a C cell line lacking the extracellular calcium-sensing function, have undetectable levels of CaR mRNA by Northern blot analysis. Western blot analysis, using antiserum specific to the parathyroid CaR, detected CaR protein in rMTC 44-2, but not TT cells. Immunostaining of both dispersed sheep C cells and rat thyroid gland sections identified C cell-specific expression of the CaR protein, and in situ hybridization analysis confirmed the C cell-specific expression of CaR mRNA in the intact rat thyroid. The nucleotide sequence of the coding region of the rMTC 44-2 CaR transcript was found to encode the same CaR protein as that expressed in the parathyroid and kidney. The results demonstrate that C cells express the same extracellular calcium-sensing receptor that is found in parathyroid and kidney, and the presence of this receptor protein in C cell lines correlates with the extracellular calcium-sensing function. This CaR is likely to represent the primary molecular entity through which C cells detect changes in [Ca2+](e) and control CT release, suggesting that activation of the same receptor can either stimulate or inhibit hormone secretion in different cell types.
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页码:5202 / 5211
页数:10
相关论文
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