Mutations in the Gs alpha gene causing hormone resistance

Giovanna Mantovani, Anna Spada

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

G-protein-coupled receptors (GPCRs) and G proteins mediate the effects of a number of hormones of relevance to endocrinology. Genes encoding these molecules may be targets of loss- or gain-of-function mutations, resulting in endocrine disorders. The only mutational change of G proteins so far unequivocally associated with endocrine disorders occurs in the Gsα gene (GNAS1, guanine nucleotide binding protein α stimulating activity polypeptide 1), which activates cyclic AMP (cAMP)-dependent pathways. Heterozygous loss-of-function mutations of GNAS1 in the active maternal allele cause resistance to hormones acting through Gsα-coupled GPCRs, whereas somatic gain-of-function mutations cause proliferation of endocrine cells recognizing cAMP as mitogen. This review will focus on inactivating mutations leading to hormone resistance syndromes, i.e., pseudohypoparathyroidism types Ia and Ib.

Original languageEnglish
Pages (from-to)501-513
Number of pages13
JournalBest Practice and Research: Clinical Endocrinology and Metabolism
Volume20
Issue number4
DOIs
Publication statusPublished - Dec 2006

Fingerprint

Hormones
Mutation
G-Protein-Coupled Receptors
GTP-Binding Proteins
Cyclic AMP
Genes
Pseudohypoparathyroidism
Endocrine Cells
Guanine Nucleotides
Endocrinology
Mitogens
Carrier Proteins
Alleles
Mothers
Peptides

Keywords

  • Albright's osteodystrophy
  • GNAS1
  • imprinting
  • pseudohypoparathyroidism

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Mutations in the Gs alpha gene causing hormone resistance. / Mantovani, Giovanna; Spada, Anna.

In: Best Practice and Research: Clinical Endocrinology and Metabolism, Vol. 20, No. 4, 12.2006, p. 501-513.

Research output: Contribution to journalArticle

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