| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on June 7, 2004
Accepted on January 28, 2005
Department of Endocrinology, William Harvey Research Institute, Barts & the London, Queen Mary University of London, London EC1A 7BE, UK; Department of Endocrinology, King's College Hospital, London, Department of Clinical Biochemistry, Barts & The London NHS Trust, Haartman Institute of Pathology, University of Helsinki, Finland
* To whom correspondence should be addressed. E-mail: a.j.clark{at}qmul.ac.uk.
Context: Cortisol secretion is usually under the control of ACTH. However, cortisol secretion occurs in response to gastric inhibitory polypeptide (GIP) in rare cases of food-dependent Cushing's syndrome (CS).
Objective: We have investigated whether chronic ACTH stimulation or activation of the ACTH signaling pathway might be associated with GIPR expression.
Design: Reverse transcriptase PCR (RTPCR) analysis and primary culture of hyperplastic adrenals.
Patients: All patients presented with CS: 20 unilateral adrenal adenomas, 5 Cushing's disease, 1 food-dependent CS.
Results: RTPCR revealed GIPR expression in all hyperplastic adrenals studied. No RTPCR product could be detected in 2 normal adrenals or 20 hyperfunctioning adrenal adenomas. Primary culture revealed a significant cAMP response to ACTH in all adrenals available for study (EC50 8.1x10-10M in normals, 4.7x10-10M in Cushing's disease, 4.4x10-10M in food-dependent disease). However, cultures taken from all 4 ACTH-dependant and the 1 food-dependant hyperplastic adrenals studied, were also responsive to GIP (EC50 for cAMP 1.3x10-9M in Cushing's disease, 4.1x10-10M in food-dependent disease).
Fasting cortisol levels were low in the case of food-dependant Cushing's, rising post-prandially as predicted. However, there was no trend toward low fasting, or high post-prandial cortisols in the other cases, suggesting that the presence of detectable GIPR alone, albeit with definite function in vitro, is not sufficient to cause clinically food-dependent Cushing's syndrome.
Conclusions: These data are consistent with the hypothesis that chronic ACTH stimulation or constitutive activation of the ACTH signaling pathway may be associated with aberrant GIPR expression, and suggest one mechanism for the pathogenesis of this phenomenon.
This article has been cited by other articles:
 |
|
 |
|
  D Vezzosi, D Cartier, C Regnier, P Otal, A Bennet, F Parmentier, M Plantavid, A Lacroix, H Lefebvre, and P Caron Familial adrenocorticotropin-independent macronodular adrenal hyperplasia with aberrant serotonin and vasopressin adrenal receptors Eur. J. Endocrinol., January 1, 2007; 156(1): 21 - 31. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Lampron, I. Bourdeau, P. Hamet, J. Tremblay, and A. Lacroix Whole Genome Expression Profiling of Glucose-Dependent Insulinotropic Peptide (GIP)- and Adrenocorticotropin-Dependent Adrenal Hyperplasias Reveals Novel Targets for the Study of GIP-Dependent Cushing's Syndrome J. Clin. Endocrinol. Metab., September 1, 2006; 91(9): 3611 - 3618. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Basu, R. Singh, A. Basu, C.M. Johnson, and R. A. Rizza Effect of Nutrient Ingestion on Total-Body and Splanchnic Cortisol Production in Humans Diabetes, March 1, 2006; 55(3): 667 - 674. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Saner-Amigh, B. A. Mayhew, F. Mantero, F. Schiavi, P. C. White, C. V. Rao, and W. E. Rainey Elevated Expression of Luteinizing Hormone Receptor in Aldosterone-Producing Adenomas J. Clin. Endocrinol. Metab., March 1, 2006; 91(3): 1136 - 1142. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. L. Mazzuco, O. Chabre, N. Sturm, J.-J. Feige, and M. Thomas Ectopic Expression of the Gastric Inhibitory Polypeptide Receptor Gene Is a Sufficient Genetic Event to Induce Benign Adrenocortical Tumor in a Xenotransplantation Model Endocrinology, February 1, 2006; 147(2): 782 - 790. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Baldacchino, S. Oble, P.-O. Decarie, I. Bourdeau, P. Hamet, J. Tremblay, and A. Lacroix 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 J. Mol. Endocrinol., August 1, 2005; 35(1): 61 - 71. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
