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The Journal of Clinical Endocrinology & Metabolism Vol. 87, No. 10 4736-4740
Copyright © 2002 by The Endocrine Society

Original Article

The Gs{alpha} Gene: Predominant Maternal Origin of Transcription in Human Thyroid Gland and Gonads

Giovanna Mantovani, Emilia Ballare, Enza Giammona, Paolo Beck-Peccoz and Anna Spada

Institute of Endocrine Sciences-University of Milan (G.M., E.B., P.B.-P., A.S.), Ospedale Maggiore IRCCS, Milan; and Istituto Auxologico Italiano IRCCS (E.G.), Milan, Italy

Address all correspondence and requests for reprints to: Anna Spada, M.D., Istituto di Scienze Endocrine-Università di Milano, Padiglione Granelli, Via Francesco Sforza, 35, 20122 Milan, Italy. E-mail: anna.spada{at}unimi.it.

Abstract

Mutations in the guanine nucleotide binding {alpha}-subunit 1 gene (GNAS1) cause Albright’s hereditary osteodistrophy, and the parent of transmission determines variable phenotypic expression of the disease. This has suggested that GNAS1 may be under tissue-specific imprinting control, although studies so far available have failed to clearly define the pattern of GNAS1 expression in humans. To establish if GNAS1 is imprinted in human endocrine tissues, we selected 14 thyroid, 10 granulosa cell, 13 pituitary (3 normal glands, 7 GH-secreting adenomas, and 3 nonfunctioning adenomas), 3 adrenal, and 11 lymphocyte samples shown to be heterozygous for a known polymorphism in exon 5. RNA from these tissues was analyzed by RT-PCR, and expression from both parental alleles was evaluated by enzymatic digestion and subsequent quantification of the resulting fragments. The parental origin of Gs{alpha} was assessed by evaluating neuroendocrine secretory protein 55 and extra large {alpha}s-like protein transcripts, which have been shown to be monoallelically and parent-specifically expressed from the maternal and paternal allele, respectively. By this approach, the great majority of thyroid (n = 12), ovarian (n = 7), and pituitary (n = 11) samples showed an almost exclusive or significantly predominant expression of the maternal allele over the paternal one, whereas in lymphocyte and adrenal samples both alleles were equally expressed. Our results provide evidence for a predominant maternal origin of GNAS1 transcripts in different human adult endocrine tissues, particularly thyroid, ovary, and pituitary, and strongly suggest that this mechanism may play a crucial role in the determination of the phenotypic expression of Albright’s hereditary osteodistrophy.




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