The gsalpha gene: predominant maternal origin of transcription in human thyroid gland and gonads

• Published in: The journal of clinical endocrinology and metabolism 2002-10, Vol.87 (10), p.4736-4740
• Main Authors: Mantovani, Giovanna, Ballare, Emilia, Giammona, Enza, Beck-Peccoz, Paolo, Spada, Anna
• Format: Article
• Language: English
• Subjects: Adenoma - metabolism; Adenoma - secretion; Adrenal Glands - metabolism; Alleles; Exons; Female; Genomic Imprinting; Gonads - metabolism; Granulosa Cells - metabolism; GTP-Binding Protein alpha Subunits, Gs - genetics; Heterozygote; Human Growth Hormone - secretion; Humans; Lymphocytes - metabolism; Pituitary Gland - metabolism; Pituitary Neoplasms - metabolism; Pituitary Neoplasms - secretion; Polymerase Chain Reaction; Polymorphism, Genetic; Reverse Transcriptase Polymerase Chain Reaction; RNA - analysis; Thyroid Gland - metabolism; Transcription, Genetic
• ISSN: 0021-972X

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 alphas-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.