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 alpha 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 I a patients, we investigated whether Galpha(s) is imprinted in thyroid. Examination of eight normal thyroids demonstrated significantly greater expression from the maternal GNAS1 allele, with paternal Got, transcripts accounting for only 25.9-40.4%. Expression of NESP55, XLalpha(s), and 1A was uniallelic. We conclude that Galpha(s) is incompletely imprinted in the thyroid, which provides an explanation for mild TSH resistance in PHP type 1a. (C) 2002 Elsevier Science (USA). All rights reserved.