The Sp transcription factors are involved in the cellular expression of the human glucose-dependent insulinotropic polypeptide receptor gene and overexpressed in adrenals of patients with Cushing's syndrome

被引:23
作者
Baldacchino, V
Oble, S
Décarie, PO
Bourdeau, I
Hamet, P
Tremblay, J
Lacroix, A
机构
[1] Ctr Hosp Univ Montreal, Hotel Dieu, Lab Endocrine Pathophysiol, Montreal, PQ H2W 1T7, Canada
[2] Ctr Hosp Univ Montreal, Hotel Dieu, Lab Cellular Biol Hypertens & Mol Med, Montreal, PQ H2W 1T7, Canada
[3] Ctr Hosp Univ Montreal, Hotel Dieu, Dept Med, Montreal, PQ H2W 1T7, Canada
关键词
D O I
10.1677/jme.1.01765
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The best characterized effect of glucose-dependent insulinotropic polypeptide (GIP) is its stimulatory effect on insulin secretion by pancreatic P-cells. Recently, it was demonstrated that some cases of primary adrenal Cushing ' s syndrome were secondary to the ectopic expression of non-mutated GIP receptor (GIP-R) in bilateral adrenal hyperplasias or unilateral adrenal adenomas, resulting in food-dependent steroidogenesis. Using a human multiple-expression tissue array, GIP-R was found to be expressed in a large number of human adult and fetal tissues, but not in the adrenal gland. The analysis of the promoter region of human (h) GIP-R gene revealed six consensus sequences important in regulating the reporter gene activity and capable of binding to Sp1 and Sp3 transcription factors. Data obtained by gene array and semi-quantitative RT-PCR showed an increase in the expression of Sp3 and CRSP9 (co-regulator of Sp1 transcription factor, subunit 9) in the adrenal adenomas or bilateral macronodular hyperplasias of patients with GIP-dependent Cushings syndrome; they were, however, also increased in some patients with non-GIP-dependent cortisol-secreting adenomas or with ACTH-depenclent Cushing ' s disease. This study represents the first step in our understanding of the mechanisms involved in the regulation of the expression of the hGIP-R gene.
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页码:61 / 71
页数:11
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