Inherited endocrine diseases involving G proteins and G protein-coupled receptors

Research output: Chapter in Book/Report/Conference proceedingConference contribution

9 Citations (Scopus)

Abstract

Naturally occurring mutations in the G protein Gs-α subunit and in a number of G protein-coupled receptors (GPCRs) have been identified in human diseases. Loss-offunction mutations in GPCRs for various hormones lead to hormone resistance manifest as hypofunction of the gland expressing the affected GPCR. Conversely, GPCR gain-offunction mutations lead to hormone-independent activation and hyperfunction of the involved gland. Our laboratory has focused on the extracellular calcium-sensing GPCR (CaR) expressed primarily, but not exclusively, in parathyroid glands and kidney. Loss-offunction CaR mutations lead to a form of hyperparathyroidism, an apparent exception to the general pattern described above, but in fact reflecting resistance to the normal inhibition of parathyroid hormone secretion by the 'hormone' agonist, extracellular Ca2+. CaR gain-of function-mutations cause autosomal dominant hypocalcemia due to activation of the receptor at subphysiologic concentrations of serum Ca22+, leading to 'inappropriate' inhibition of parathyroid hormone secretion. I will describe our recent work that helps inform design of novel therapeutics targeting this important GPCR.

Original languageEnglish (US)
Title of host publicationEndocrine Development
Pages133-144
Number of pages12
Volume11
DOIs
StatePublished - 2007

Publication series

NameEndocrine Development
Volume11
ISSN (Print)14217082
ISSN (Electronic)16622979

Fingerprint

Endocrine System Diseases
G-Protein-Coupled Receptors
GTP-Binding Proteins
Mutation
Hormones
Parathyroid Hormone
Parathyroid Glands
Hyperparathyroidism
Protein Subunits
Calcium
Kidney
Serum

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Pediatrics, Perinatology, and Child Health
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Medicine(all)

Cite this

Spiegel, A. M. (2007). Inherited endocrine diseases involving G proteins and G protein-coupled receptors. In Endocrine Development (Vol. 11, pp. 133-144). (Endocrine Development; Vol. 11). https://doi.org/10.1159/000111069

Inherited endocrine diseases involving G proteins and G protein-coupled receptors. / Spiegel, Allen M.

Endocrine Development. Vol. 11 2007. p. 133-144 (Endocrine Development; Vol. 11).

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Spiegel, AM 2007, Inherited endocrine diseases involving G proteins and G protein-coupled receptors. in Endocrine Development. vol. 11, Endocrine Development, vol. 11, pp. 133-144. https://doi.org/10.1159/000111069
Spiegel, Allen M. / Inherited endocrine diseases involving G proteins and G protein-coupled receptors. Endocrine Development. Vol. 11 2007. pp. 133-144 (Endocrine Development).
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