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.
The best characterized effect of glucose-dependent insulinotropic polypeptide (GIP) is its stimulatory effect on insulin secretion by pancreatic beta-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 Cushing's syndrome; they were, however, also increased in some patients with non-GIP-dependent cortisol-secreting adenomas or with ACTH-dependent 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.
Baldacchino
Valérie
V
Laboratory of Endocrine Pathophysiology, Department of Medicine, Centre Hospitalier de l'Université de Montréal, Quebec, Canada.
Oble
Sylvie
S
Décarie
Patrick-Olivier
PO
Bourdeau
Isabelle
I
Hamet
Pavel
P
Tremblay
Johanne
J
Lacroix
André
A
D000311:Adrenal Glands / Q000378:metabolism*; D000328:Adult; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D016022:Case-Control Studies; D016384:Consensus Sequence; D003480:Cushing Syndrome / Q000235:genetics* / Q000378:metabolism*; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005333:Fetus / Q000378:metabolism; D015870:Gene Expression; D017930:Genes, Reporter; D006801:Humans; D056892:Mediator Complex; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011964:Receptors, Gastrointestinal Hormone / Q000235:genetics*; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D051705:Sp3 Transcription Factor; D014018:Tissue Distribution; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D004268:DNA-Binding Proteins; C492153:MED7 protein, human; D056892:Mediator Complex; D011964:Receptors, Gastrointestinal Hormone; C497121:SP3 protein, human; D016329:Sp1 Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors; D051705:Sp3 Transcription Factor; D004247:DNA; C041086:gastric inhibitory polypeptide receptor