The GnRH receptor gene is preferentially expressed in functioning gonadotroph adenomas and displays a <i>Mae</i> III polymorphism site

Kottler, Marie‐Laure; Seret‐Bégué, Dominique; Lahlou, Najiba; Assayag, Michel; Carré, Marie-Claude; Lagarde, Jean‐Pierre; Ajzenberg, C.; Christin-Maître, Sophie; Bouchard, Philippe; Mikol, Jacqueline; Counis, Raymond; Warnet, A

doi:10.1046/j.1365-2265.1998.00500.x

Cited by 20 publications

(11 citation statements)

References 44 publications

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“…We identified a silent polymorphism at nucleotide 453 (14), different from that recently described by Grosse et al (17) at nucleotide 150 in exon 1 and creating an MaeIII restriction site. The observed heterozygosity was low (18%) and was in agreement with the Hardy-Weinberg equilibrium.…”

Section: Discussioncontrasting

confidence: 41%

“…Given its central role in the regulation of gonadotropin secretion, GnRHR may possibly be implicated, directly or indirectly, in putative pathological processes such as a lower (11,12) or higher (13,14) production of gonadotropins or alteration of their regulation. We therefore determined the nucleotide sequences of introns flanking the exon boundaries in order to design three sets of primers in the intronic sequences to study the GnRHR at the DNA level.…”

Section: Introductionmentioning

confidence: 99%

“…Exon 1 displays a silent C to T transition at nucleotide 453, which is a part of a codon for a serine residue, situated in the second intracellular loop at position 151. The C453T transition created a new MaeIII site within exon 1 (14). The allele frequency of the former polymorphism was evaluated in DNA extracted from lymphocytes (genomic DNA) obtained from 92 healthy unrelated French Caucasians.…”

Section: Genomic Amplification Of the Introns And Sequencingmentioning

confidence: 99%

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Tissue-specific pattern of variant transcripts of the human gonadotropin-releasing hormone receptor gene

Kottler

Bergametti²,

Carre³

et al. 1999

European Journal of Endocrinology

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The expression pattern of the GnRH receptor was investigated in a variety of normal and neoplastic human tissues by RT-PCR-Southern blotting. In addition to the full-length cDNA (sb1), we identified two other transcripts: the first (sb2) was characterized by a 128 bp deletion as previously described; the second was an unexpected finding composed of a shorter cDNA (sb3), the sequence of which revealed a 220 bp deletion corresponding in size to exon 2. These three transcripts were found in normal pituitary and pituitary adenomas, and in granulosa tumors, but not in testis, where sb2 was lacking. Only sb1 was expressed in normal, fibrocystic and malignant breast tissue. No transcript with a full-length region was found in endometrium, intestine or lymphocytes. This is the first report that shows that splicing of the gonadotropin-releasing hormone receptor gene is tissue dependent.We also determined the intron-exon nucleotide sequence of the gene and identified an MaeIII polymorphic site in exon 1 created by a silent C453T transition found in 10% of unrelated French whites.

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Section: Discussioncontrasting

confidence: 41%

Section: Introductionmentioning

confidence: 99%

Section: Genomic Amplification Of the Introns And Sequencingmentioning

confidence: 99%

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Tissue-specific pattern of variant transcripts of the human gonadotropin-releasing hormone receptor gene

Kottler

Bergametti²,

Carre³

et al. 1999

European Journal of Endocrinology

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“…Annealing temperature (8C) Amplicon size (bp) at nucleotide position 453 was investigated by restriction analysis using MaeIII (30). This polymorphism was found to be mostly heterozygous, with the same allelic frequency in both patients and controls (Table 4).…”

Section: Primermentioning

confidence: 99%

Role of sequence variations of the GnRH receptor and G protein-coupled receptor 54 gene in male idiopathic hypogonadotropic hypogonadism

Lanfranco

Gromoll²,

Eckardstein³

et al. 2005

eur j endocrinol

113

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Objective: To determine the frequency of mutations of the gonadotropin-releasing hormone receptor (GnRHR) and of the G protein-coupled receptor 54 (GPR54) genes in normosmic idiopathic hypogonadotropic hypogonadism (IHH). Methods: In a retrospective study we analyzed the GnRHR and the GPR54 genes of 45 IHH patients and 50 controls. Genomic DNA was amplified by PCR to obtain partially overlapping amplicons encompassing the exon -intron boundaries of the GnRHR and GPR54 genes and analyzed by single-stranded conformation polymorphism gel electrophoresis and/or DNA sequencing. Results: One heterozygous R262Q mutation of the GnRHR gene was identified in one patient with familial IHH. The silent single-nucleotide polymorphism (SNP) 453C . T occurred at the same frequency in patients and controls. One patient with sporadic IHH and consanguineous parents showed a novel homozygous sequence variation of the GPR54 gene (1001_1002insC) resulting in an open reading frame shift and elongation of 43 amino acids with an increased number of proline residues in the intracellular receptor domain. This patient had delayed puberty, low testosterone (3.4 nmol/l), and low-normal LH and FSH levels responsive to GnRH. Pulsatile GnRH administration normalized testosterone levels and induced spermatogenesis sufficiently to induce a pregnancy with assisted reproduction. Two common SNPs in exon 1 and exon 5 of the GPR54 gene showed similar frequency distribution and hormonal profiles in IHH and controls. Conclusions: Mutations of the GnRHR and of the GPR54 gene are rare in IHH and should be investigated especially in cases with autosomal recessive transmission. Common SNPs of the GnRHR and GPR54 genes do not play any role in IHH.European Journal of Endocrinology 153 845-852

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“…(GnRH) receptor gene is mainly expressed in functioning compared to nonfunctioning gonadotroph adenomas, no coding-region mutations have been identified (12). Surgical removal of the adenoma remains the optimal approach, and when successful, it leads to restoration of normal gonadotropin secretion.…”

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confidence: 99%

Secondary Polycythemia Attributed To An Incidentally Discovered Luteinizing Hormone–Secreting Pituitary Adenoma: A Case Report

Angelousi

Nikolopoulos

Kolomodi

et al. 2017

AACE Clinical Case Reports

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Objective: Polycythemia is a rare and often unrecognized manifestation of a functional gonadotroph adenoma. Although silent gonadotroph macroadenomas are relatively common, functional gonadotroph adenomas are rare.Methods: We report a case of a 66-year-old patient treated for chronic idiopathic polycythemia for at least 10 years, in whom a large pituitary lesion in a cerebral computed tomography (CT) scan was incidentally discovered in a cerebral computed tomography (CT) scan.Results: The patient presented with nasal erythromelalgia and facial erythrosis while being treated with hydroxyurea for primary polycythemia. CT findings and biochemical analyses revealed a large pituitary tumor and increased testosterone and luteinizing hormone (LH) levels. Following resection of the tumor, immunostaining confirmed positive staining for follicle-stimulating hormone and LH, leading to the diagnosis of a functional gonadotroph adenoma. Due to persistent radiologic and biochemical disease after surgical resection, tumoral and secretory control was achieved with combination treatment with long-acting octreotide and cabergolide. Polycythemia was resolved after the initiation of the treatment for the gonadotroph adenoma. Conclusion:This case of a rare LH-secreting pituitary adenoma illustrates that physicians should be aware of rare causes of polycythemia. Testosterone measurement should always be considered, especially in cases of polycythemia of unknown origin. In our case, the combination of treatment with somatostatin analogues and dopaminergic agonists was efficacious in reducing both the secretory and tumoral component that led to resolution of polycythemia.(AACE Clinical Case Rep. 2017;3:e54-e58) Abbreviations: FSΗ = follicle-stimulating hormone; Hb = hemoglobin; Hct = hematocrit; IHC = immunohistochemistry; LAR = long-acting release; LH = luteinizing hormone; MRI = magnetic resonance imaging

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The GnRH receptor gene is preferentially expressed in functioning gonadotroph adenomas and displays a Mae III polymorphism site

Abstract: The GnRHR gene is preferentially expressed in functioning rather than in nonfunctioning gonadotroph adenomas, but no mutations altering the coding region of the gene were found to further substantiate its role in the pathogenesis of gonadotroph tumours.

Cited by 20 publications

References 44 publications

Tissue-specific pattern of variant transcripts of the human gonadotropin-releasing hormone receptor gene

Tissue-specific pattern of variant transcripts of the human gonadotropin-releasing hormone receptor gene

Role of sequence variations of the GnRH receptor and G protein-coupled receptor 54 gene in male idiopathic hypogonadotropic hypogonadism

Secondary Polycythemia Attributed To An Incidentally Discovered Luteinizing Hormone–Secreting Pituitary Adenoma: A Case Report

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