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The expression of the ACTH receptor
Elias, L. L. K; Clark, A. J. L.
Afiliação
  • Elias, L. L. K; Universidade de Säo Paulo. Faculdade de Medicina de Ribeiräo Preto. Departamento de Clínica Médica. Divisäo de Endocrinologia. Ribeiräo Preto. BR
  • Clark, A. J. L; St. Bartholomew's and the Royal London School of Medicine and Dentistry. Department of Chemical Endocrinology. Molecular Endocrinology Laboratory. London. GB
Braz. j. med. biol. res ; 33(10): 1245-8, Oct. 2000.
Artigo em Inglês | LILACS | ID: lil-270221
Biblioteca responsável: BR1.1
RESUMO
Adrenal glucocorticoid secretion is regulated by adrenocorticotropic hormone (ACTH) acting through a specific cell membrane receptor (ACTH-R). The ACTH-R is a member of the G protein superfamily-coupled receptors and belongs to the subfamily of melanocortin receptors. The ACTH-R is mainly expressed in the adrenocortical cells showing a restricted tissue specificity, although ACTH is recognized by the other four melanocortin receptors. The cloning of the ACTH-R was followed by the study of this gene in human diseases such as familial glucocorticoid deficiency (FGD) and adrenocortical tumors. FGD is a rare autosomal recessive disease characterized by glucocorticoid deficiency, elevated plasma ACTH levels and preserved renin/aldosterone secretion. This disorder has been ascribed to an impaired adrenal responsiveness to ACTH due to a defective ACTH-R, a defect in intracellular signal transduction or an abnormality in adrenal cortical development. Mutations of the ACTH-R have been described in patients with FGD in segregation with the disease. The functional characterization of these mutations has been prevented by difficulties in expressing human ACTH-R in cells that lack endogenous melanocortin receptor activity. To overcome these difficulties we used Y6 cells, a mutant variant of the Y1 cell line, which possesses a non-expressed ACTH-R gene allowing the functional study without any background activity. Our results demonstrated that the several mutations of the ACTH-R found in FGD result in an impaired cAMP response or loss of sensitivity to ACTH stimulation. An ACTH-binding study showed an impairment of ligand binding with loss of the high affinity site in most of the mutations studied.
Assuntos
Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: LILACS Assunto principal: Receptores da Corticotropina Limite: Humanos Idioma: Inglês Revista: Braz. j. med. biol. res Assunto da revista: Biologia / Medicina Ano de publicação: 2000 Tipo de documento: Artigo / Congresso e conferência País de afiliação: Brasil / Reino Unido Instituição/País de afiliação: St. Bartholomew's and the Royal London School of Medicine and Dentistry/GB / Universidade de Säo Paulo/BR

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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: LILACS Assunto principal: Receptores da Corticotropina Limite: Humanos Idioma: Inglês Revista: Braz. j. med. biol. res Assunto da revista: Biologia / Medicina Ano de publicação: 2000 Tipo de documento: Artigo / Congresso e conferência País de afiliação: Brasil / Reino Unido Instituição/País de afiliação: St. Bartholomew's and the Royal London School of Medicine and Dentistry/GB / Universidade de Säo Paulo/BR
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