Paternal imprinting of Gαs in the human thyroid as the basis of TSH resistance in pseudohypoparathyroidism type 1a

Emily L. Germain-Lee, Chang Lin Ding, Zhichao Deng, Janet L. Crane, Motoyasu Saji, Matthew D. Ringel, Michael A. Levine

Research output: Contribution to journalArticlepeer-review


Albright hereditary osteodystrophy (AHO) is characterized by multiple somatic defects secondary to mutations in the GNAS1 gene. AHO patients with mutations on maternally inherited alleles are resistant to multiple hormones (e.g., PTH, TSH), a variant termed pseudohypoparathyroidism (PHP) type 1a, due to presumed tissue-specific paternal imprinting of the α chain of Gs as demonstrated in murine renal proximal tubule and fat cells. Studies in human tissues thus far revealed imprinting only in pituitary. Because mild hypothyroidism due to TSH resistance occurs in most PHP type 1a patients, we investigated whether Gαs is imprinted in thyroid. Examination of eight normal thyroids demonstrated significantly greater expression from the maternal GNAS1 allele, with paternal Gαs transcripts accounting for only 25.9-40.4%. Expression of NESP55, XLαs, and 1A was uniallelic. We conclude that Gαs is incompletely imprinted in the thyroid, which provides an explanation for mild TSH resistance in PHP type 1a.

Original languageEnglish (US)
Pages (from-to)67-72
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number1
StatePublished - 2002


  • Albright hereditary osteodystrophy
  • G proteins
  • GNAS1
  • Genetics
  • Hormones
  • Imprinting
  • Pseudohypoparathyroidism

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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