Glucocorticoid receptor gene polymorphisms in ACTH-secreting pituitary tumours.
OBJECTIVE
The inhibitory action of glucocorticoids on the hypothalamic-pituitary axis is disrupted in ACTH-secreting pituitary tumours. The molecular events leading to the development of these tumours and their relative resistance to glucocorticoids are unknown. We investigated the presence of mutations and polymorphisms of the glucocorticoid receptor (GR) gene in corticotropinoma and their possible relationship with the tissue-specific resistance to glucocorticoids.


METHODS
DNA or RNA was extracted from 18 corticotropinomas and the GR gene was amplified by the polymerase chain reaction (PCR) or reverse transcriptase-PCR followed by automated direct sequencing.


RESULTS
We did not identify any mutation in the coding region and the exon-intron boundary regions of the GR gene. The polymorphism AAT > AGT at codon 363 (N363S) was found in 17% and the polymorphism AAT > AAC at codon 766 (N766N) in 11% of tumours, both in heterozygous state. The polymorphisms at codons 22 and 23, at introns 3 and 4, and at codon 618, previously described in normal population, were not observed.


CONCLUSIONS
Our results show that GR gene mutations are rare and unlikely to contribute to the glucocorticoid resistance observed in corticotropinomas. Polymorphisms in the GR gene might confer a selective advantage to tumorigenesis in corticotropinoma. However, there was no relationship between GR gene polymorphism and clinical presentation, tumour size or surgery outcome, suggesting that tumour growth may not be directly related to alterations of the GR gene structure.
Antonini
S R R
SR
Department of Paediatrics, School of Medicine of Ribeirao Preto-USP, Ribeirao Preto, Brazil.
Latronico
A C
AC
Elias
L L K
LL
Cukiert
A
A
Machado
H R
HR
Liberman
B
B
Mendonca
B B
BB
Moreira
A C
AC
Castro
M
M
D000236:Adenoma / Q000235:genetics* / Q000378:metabolism* / Q000601:surgery; D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000328:Adult; D002675:Child, Preschool; D003480:Cushing Syndrome / Q000235:genetics / Q000601:surgery; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000601:surgery; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D017422:Sequence Analysis, DNA
D011965:Receptors, Glucocorticoid; D000324:Adrenocorticotropic Hormone