Aberrant expression of human luteinizing hormone receptor by adrenocortical cells is sufficient to provoke both hyperplasia and Cushing's syndrome features

Autor: Michaël Thomas, Tânia Longo Mazzuco, Olivier Chabre, Jean-Jacques Feige
Přispěvatelé: Département de Diabétologie, Urologie, Néphrologie et Endocrinologie (CHU-Grenoble), CHU Grenoble, Angiogenèse hormono-régulée et angiogenèse tumorale, Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Feige, Jean-Jacques
Jazyk: angličtina
Rok vydání: 2006
Předmět:
MESH: Adrenal Hyperplasia
Congenital
Cell Transplantation
Endocrinology
Diabetes and Metabolism
Clinical Biochemistry
Biochemistry
MESH: Mice
Knockout
Human chorionic gonadotropin
MESH: Cushing Syndrome
Mice
Cushing syndrome
0302 clinical medicine
Endocrinology
Transduction
Genetic
MESH: Animals
Receptor
Cushing Syndrome
Cells
Cultured
Vasopressin receptor
Mice
Knockout
0303 health sciences
luteinizing hormone/choriogonadotropin receptor
Receptors
LH
MESH: Transduction
Genetic
Immunohistochemistry
DNA-Binding Proteins
MESH: Cattle
Phenotype
MESH: Retroviridae
MESH: Cell Transplantation
hormones
hormone substitutes
and hormone antagonists
Plasmids
MESH: Cells
Cultured
Cortisol secretion
medicine.medical_specialty
endocrine system
DNA
Complementary
030209 endocrinology & metabolism
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
Biology
MESH: Phenotype
03 medical and health sciences
MESH: Plasmids
Internal medicine
medicine
Animals
Humans
MESH: Receptors
LH
[SDV.BC] Life Sciences [q-bio]/Cellular Biology
MESH: Mice
030304 developmental biology
MESH: Humans
Adrenal Hyperplasia
Congenital
Biochemistry (medical)
MESH: Immunohistochemistry
MESH: DNA
Complementary
medicine.disease
Retroviridae
Macronodular Adrenal Hyperplasia
Adrenal Cortex
Cattle
Ectopic expression
MESH: Adrenal Cortex
MESH: DNA-Binding Proteins
Zdroj: Journal of Clinical Endocrinology and Metabolism
Journal of Clinical Endocrinology and Metabolism, 2006, 91 (1), pp.196-203. ⟨10.1210/jc.2005-1975⟩
Journal of Clinical Endocrinology and Metabolism, Endocrine Society, 2006, 91 (1), pp.196-203. ⟨10.1210/jc.2005-1975⟩
ISSN: 0021-972X
1945-7197
Popis: International audience; CONTEXT: Aberrant expression of LH/human chorionic gonadotropin (hCG) receptor has been suggested in several cases of bilateral macronodular adrenal hyperplasia with Cushing's syndrome. The cortisol production is then directly controlled by endogenous secretion of LH/hCG. However, the direct involvement of this aberrant LH/hCG receptor expression in the development of the hyperplasia has not been demonstrated. Moreover in most cases, whenever investigated, the aberrant expression of LH/hCG receptor has been associated with the ectopic expression of other G protein-coupled receptors such as gastric inhibitory polypeptide, serotonin, or vasopressin receptors. OBJECTIVE: The aim of this study was to explore the action of LH/hCG receptor on the development of adrenal hyperplasia. RESULTS: The ectopic expression of this single nonmutated gene transduced into bovine adrenocortical cells was sufficient to induce not only the aberrant cortisol secretion but also hyperproliferation and benign transformation. The cells were transplanted beneath the kidney capsule of adrenalectomized immunodeficient mice. Only the cells expressing the LH/hCG receptor gene formed an enlarged tissue with a high proliferation rate. The tissue expressing LH/hCG receptor was responsible for elevated plasma cortisol and decreased plasma ACTH levels in transplanted mice. These animals displayed physiological changes similar to those of patients with Cushing's syndrome, including muscle atrophy, thin skin, spleen atrophy, and hyperglycemia. CONCLUSIONS: These results demonstrate that a single genetic event such as the inappropriate expression of the nonmutated LH/hCG receptor gene is sufficient to initiate the phenotypic changes that cause the development of a benign adrenocortical tumor.
Databáze: OpenAIRE
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