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Regulator of G protein signaling 5 is highly expressed in parathyroid tumors and inhibits signaling by the calcium-sensing receptor.

Publication ,  Journal Article
Koh, J; Dar, M; Untch, BR; Dixit, D; Shi, Y; Yang, Z; Adam, MA; Dressman, H; Wang, X; Gesty-Palmer, D; Marks, JR; Spurney, R; Druey, KM; Olson, JA
Published in: Mol Endocrinol
May 2011

The molecular mechanisms responsible for aberrant calcium signaling in parathyroid disease are poorly understood. The loss of appropriate calcium-responsive modulation of PTH secretion observed in parathyroid disease is commonly attributed to decreased expression of the calcium-sensing receptor (CaSR), a G protein-coupled receptor. However, CaSR expression is highly variable in parathyroid adenomas, and the lack of correlation between CaSR abundance and calcium-responsive PTH kinetics indicates that mechanisms independent of CaSR expression may contribute to aberrant calcium sensing in parathyroid disease. To gain a better understanding of parathyroid tumors and the molecular determinants that drive parathyroid adenoma development, we performed gene expression profiling on a panel of 64 normal and neoplastic parathyroid tissues. The microarray data revealed high-level expression of genes known to be involved in parathyroid biology (PTH, VDR, CGA, CaSR, and GCM2). Moreover, our screen identified regulator of G protein signaling 5 (RGS5) as a candidate inhibitor of CaSR signaling. We confirmed RGS5 to be highly expressed in parathyroid adenomas relative to matched-pair normal glands. Transient expression of RGS5 in cells stably expressing CaSR resulted in dose-dependent abrogation of calcium-stimulated inositol trisphosphate production and ERK1/2 phosphorylation. Furthermore, we found that RGS5-nullizygous mice display reduced plasma PTH levels, an outcome consistent with attenuated opposition to CaSR activity. Collectively, these data suggest that RGS5 can act as a physiological regulator of calcium sensing by CaSR in the parathyroid gland. The abnormally elevated expression of RGS5 observed in parathyroid adenomas could thus represent a novel mechanism of CaSR desensitization in patients with primary hyperparathyroidism.

Duke Scholars

Published In

Mol Endocrinol

DOI

EISSN

1944-9917

Publication Date

May 2011

Volume

25

Issue

5

Start / End Page

867 / 876

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • Signal Transduction
  • Receptors, Calcium-Sensing
  • RGS Proteins
  • Parathyroid Neoplasms
  • Parathyroid Hormone
  • Parathyroid Glands
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Koh, J., Dar, M., Untch, B. R., Dixit, D., Shi, Y., Yang, Z., … Olson, J. A. (2011). Regulator of G protein signaling 5 is highly expressed in parathyroid tumors and inhibits signaling by the calcium-sensing receptor. Mol Endocrinol, 25(5), 867–876. https://doi.org/10.1210/me.2010-0277
Koh, James, Moahad Dar, Brian R. Untch, Darshana Dixit, Yuhong Shi, Zhao Yang, Mohamed Abdelgadir Adam, et al. “Regulator of G protein signaling 5 is highly expressed in parathyroid tumors and inhibits signaling by the calcium-sensing receptor.Mol Endocrinol 25, no. 5 (May 2011): 867–76. https://doi.org/10.1210/me.2010-0277.
Koh J, Dar M, Untch BR, Dixit D, Shi Y, Yang Z, et al. Regulator of G protein signaling 5 is highly expressed in parathyroid tumors and inhibits signaling by the calcium-sensing receptor. Mol Endocrinol. 2011 May;25(5):867–76.
Koh, James, et al. “Regulator of G protein signaling 5 is highly expressed in parathyroid tumors and inhibits signaling by the calcium-sensing receptor.Mol Endocrinol, vol. 25, no. 5, May 2011, pp. 867–76. Pubmed, doi:10.1210/me.2010-0277.
Koh J, Dar M, Untch BR, Dixit D, Shi Y, Yang Z, Adam MA, Dressman H, Wang X, Gesty-Palmer D, Marks JR, Spurney R, Druey KM, Olson JA. Regulator of G protein signaling 5 is highly expressed in parathyroid tumors and inhibits signaling by the calcium-sensing receptor. Mol Endocrinol. 2011 May;25(5):867–876.

Published In

Mol Endocrinol

DOI

EISSN

1944-9917

Publication Date

May 2011

Volume

25

Issue

5

Start / End Page

867 / 876

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • Signal Transduction
  • Receptors, Calcium-Sensing
  • RGS Proteins
  • Parathyroid Neoplasms
  • Parathyroid Hormone
  • Parathyroid Glands
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice