Premium
The GnRH receptor gene is preferentially expressed in functioning gonadotroph adenomas and displays a Mae III polymorphism site
Author(s) -
Kottler MarieLaure,
SeretBégué Dominique,
Lahlou Najiba,
Assayag Michel,
Carré MarieClaude,
Lagarde JeanPierre,
Ajzenberg Christiane,
ChristinMaitre Sophie,
Bouchard Philippe,
Mikol Jacqueline,
Counis Raymond,
Warnet André
Publication year - 1998
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1046/j.1365-2265.1998.00500.x
Subject(s) - gnrhr , biology , microbiology and biotechnology , endocrinology , medicine , exon , single nucleotide polymorphism , gene , coding region , loss of heterozygosity , allele , genetics , genotype , gonadotropin releasing hormone , luteinizing hormone , hormone
OBJECTIVE Given the central role of the GnRH receptor (GnRHR) in the regulation of the gonadotrophin secretion, it might be implicated directly or indirectly in the pathogenesis of gonadotroph tumours. DESIGN We determined if GnRHR mRNA was expressed in gonadotroph tumours using RT‐PCR and analysed the GnRHR gene for the presence of mutations in its coding region, using direct sequencing of PCR products. Results were analysed according to the pattern of expression of α, β‐FSH and β‐LH subunit (SU) genes SUBJECTS RNA was extracted from 20 gonadotroph tumours identified by immunohistochemistry ( >10% of stained cells): 9 adenomas were functioning (high serum gonadotrophin levels), 3 were associated with high α‐SU levels and 8 were nonfunctioning. Genomic DNA was extracted from 64 normal subjects. RESULTS We found GnRHR mRNA in 12 tumours (60%): 8/9 functioning (88%), 1/3 α‐secreting (33%) and 3/8 nonfunctioning (37.5%) gonadotroph adenomas. There was a significant association between GnRHR expression and immunostaining for β‐FSH ( P = 0.014). The nucleotide sequence of the amplified products was identical to that of human pituitary except for the presence, in 3 functioning adenomas, of a silent C to T transition at nucleotide 453 encoding for the serine residue situated in the second intracellular loop at position 151. Heterozygosity provided evidence that both alleles were transcribed in these tumours. This substitution creates a Mae III restriction site. Genomic DNA from normal subjects were then tested for the presence of this new polymorphism. The frequency of the heterozygosity (18.7%) was not significantly different from that found in gonadotroph tumours (25%) and this new Mae III polymorphism site cannot be used as a tumoural marker. CONCLUSION 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.