Adrenocortical overexpression of gastric inhibitory polypeptide receptor underlies food-dependent Cushing's syndrome

被引:75
作者
N'Diaye, N
Tremblay, J
Hamet, P
De Herder, WW
Lacroix, A
机构
[1] Ctr Hosp Univ Montreal, Res Ctr, Div Endocrinol, Montreal, PQ H2W 1T8, Canada
[2] Ctr Hosp Univ Montreal, Res Ctr, Dept Med, Montreal, PQ H2W 1T8, Canada
[3] Univ Rotterdam Hosp, Dept Internal Med, Rotterdam, Netherlands
关键词
D O I
10.1210/jc.83.8.2781
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Abnormal responsiveness of adrenocortical cells to gastric inhibitory polypeptide (GIP) in food-dependent Cushing's syndrome suggested that adrenal expression of ectopic, overexpressed, or mutated GIP receptor (GIPR) underlies this syndrome. The expression of GIPR was studied by RT-PCR in human adrenal tissues from two patients with GIP-dependent Cushing's syndrome (adenoma, bilateral hyperplasia), five fetal or adult controls, one patient with Cushing's disease, and four patients with non-food-dependent cortisol-secreting adenomas or bilateral hyperplasias and compared to that in normal pancreas. Hybridization of the RT-PCR-amplified ribonucleic acids with the human GIPR complementary DNA showed an overexpression of GIPR in the adrenals of the two GIP-dependent Cushing's syndrome patients compared to that in normal adrenal tissues (2-3 orders of magnitude) or pancreas (10-fold); no signal could be seen in adrenal adenomas or macronodular hyperplasia from cases of non-food-dependent Cushing's syndrome. No mutation of the GIPR was identified by sequencing the full-length receptor in GIP-dependent adrenal tissue. New alternative spliced isoforms of the GIPR were found, but are identical in GIP-dependent and normal adrenal tissues. Incubation of adrenal cells with GIP stimulates cortisol secretion in GIP-dependent, but not in normal fetal, adult, or non-food-dependent Cushing's syndrome, adrenals. We conclude that the GIPR overexpression and its coupling to steroidogenesis underlie GIP-dependent Cushing's syndrome.
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页码:2781 / 2785
页数:5
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