[en] The presence of corticotropin-releasing hormone (CRH) receptors has been previously demonstrated in corticotrophs from normal pituitaries using a method combining immunocytochemistry and liquid emulsion autoradiography. The aim of this study was to compare the characteristics of the 125I-Tyr0-hCRH binding in corticotrophs from normal pituitaries (three obtained at autopsy and one obtained at surgery) with corticotrophs from pituitary adenomas (six corticotroph adenomas responsible for Cushing's disease and two silent corticotroph adenomas secreting a biologically inactive ACTH molecule). In normal corticotrophs, the larger part of the 125I-Tyr0-hCRH binding was localised in patchy conglomerates at the centre of the cell and, to a much lesser degree, in a diffuse pattern at the cell periphery. In adenomatous corticotrophs, CRH receptor expression is disturbed both quantitatively and qualitatively. Except for a minority of cells in one adenoma, all adenomatous corticotrophs showed only peripherally bound 125I-Tyr0-hCRH and no centrally localised binding. Furthermore, adenomatous corticotrophs revealed a statistically significant lower signal intensity when compared to normal corticotrophs and a strongly negative correlation was found between the labelling area in adenomatous corticotrophs and both the basal and CRH-stimulated plasma ACTH levels. These findings suggest defective processing of CRH receptors and could be relevant to the sustained ACTH secretion by adenomatous corticotrophs in Cushing's disease and, more generally, provide an explanation to its pathology. The silent corticotrophs secreting a biologically inactive ACTH molecule were characterised by a very faint signal intensity, although present on almost every cell.
Disciplines :
Endocrinology, metabolism & nutrition
Author, co-author :
Abs, R.
Smets, G.
Vauquelin, G.
Verhelst, J.
Mahler, C.
Verlooy, J.
Stevenaert, Achille ; Centre Hospitalier Universitaire de Liège - CHU > Neurochirurgie
Wouters, L.
Borgers, M.
Beckers, Albert ; Université de Liège - ULiège > Département des sciences cliniques > Endocrinologie
Language :
English
Title :
125I-Tyr0-hCRH labelling characteristics of corticotropin-releasing hormone receptors: differences between normal and adenomatous corticotrophs.
Aguilera, G., Wynn, P. C., Harwood, J. P., Hauger, R. L., Millan, M. A., Grewe, C. and Catt, K. J. (1986) Receptor-mediated actions of corticotropin-releasing factor in pituitary gland and nervous system. Neuroendocrinology 43, 79-88.
Biller, B. M. K. (1994) Pathogenesis of pituitary Cushing's syndrome. Endocrinol. Metab. Clin. N. Am. 23, 547-554.
Childs, G. V., Morell, J. L., Niendorf, A. and Aguilera, G. (1986) Cytochemical studies of corticotropin-releasing factor (CRF) receptors in anterior lobe corticotropes: binding, glucocorticoid regulation, and endocytosis of [biotinyl-Ser1]CRF. Endocrinology 119, 2129-2142.
Chrousos, G. P., Schulte, H. M., Oldfield, E. H., Gold, P. W., Cutler, G. B. and Loriaux, D. L. (1984) The corticotropin-releasing factor stimulation test: an aid in the evaluation of patients with Cushing's syndrome. N. Engl. J. Med. 310, 622-626.
De Souza, E. B., Perrin, M. H., Rivier, J., Vale, W. W. and Kuhar, M. J. (1984) Corticotropin-releasing factor receptors in rat pituitary gland: autoradiographic localization. Brain Res. 296, 202-207.
De Souza, E. B., Perrin, M. H., Whitehouse, P. J., Rivier, J., Vale, W. W. and Kuhar, M. J. (1985) Corticotropin-releasing factor receptors in human pituitary gland: autoradiographic localization. Neuroendocrinology 40, 419-422.
Findling, J. W. and Doppman, J. L. (1994) Biochemical and radiologic diagnosis of Cushing's syndrome. Endocrinol. Metab. Clin. N. Am. 23, 511-537.
Grino, M., Guillaume, V., Boudouresque, F., Margioris, A. N., Grisoli, F., Jaquet, P., Oliver, C. and Conte-Devolx, B. (1988) Characterization of corticotropin-releasing hormone receptors on human pituitary corticotroph adenomas and their correlation with endogenous glucocorticoids. J. Clin. Endocrinol. Metab. 67, 279-283.
Heroux, J. A., Grigoriadis, D. B. and De Souza, E. B. (1991) Age-related decreases in corticotropin-releasing factor (CRF) receptors in rat brain and anterior pituitary gland. Brain Res. 542, 155-158.
Holmes, M. C., Catt, K. J. and Aguilera, G. (1987) Involvement of vasopressin in the down-regulation of pituitary corticotropin-releasing factor receptors after adrenalectomy. Endocrinology 121, 2093-2098.
Hsu, S.-M., Raine, L. and Fanger, H. (1981) A comparative study of the peroxidase-antiperoxidase method and an avidin-biotin complex method for studying polypeptide hormones with radioassay antibodies. Am. J. Clin. Pathol. 75, 734-738.
King, M. S. and Baertschi, A. J. (1990) The role of intracellular messengers in adrenocorticotropin secretion in vitro. Experientia 46, 26-40.
Kovacs, K., Horvath, E., Ryan, N. and Ezrin, C. (1980) Null cell adenoma of the pituitary. Virchows Arch. [A] 387, 165-174.
Leroux, P. and Pelletier, G. (1984) Radioautographic study of binding and internalisation of corticotropin-releasing factor by rat anterior pituitary corticotrophs. Endocrinology 114, 14-21.
Ratter, S. J., Lowry, P. J., Besser, G. M. and Rees, L. H. (1980) Chromatographic characterization of adrenocorticotrophin in human plasma. J. Endocrinol. 85, 359-369.
Reincke, M., Allolio, B., Saeger, W., Kaulen, D. and Winkelmann, W. (1987) A pituitary adenoma secreting high molecular weight adrenocorticotropin without evidence of Cushing's disease. J. Endocrinol. Metab. 65, 1296-1300.
Reisine, T. and Hoffman, A. (1983) Desensitization of corticotropin-releasing factor receptors. Biochem. Biophys. Res. Commun. 111, 919-925.
Reisine, T. and Affolter, H. U. (1987) Hormone receptor regulated proopiomelanocortin gene expression. Biochem. Pharmacol. 36, 191-195.
Smets, G., Vauquelin, G., Moons, L., Smitz, J., Klöppel, G. (1991) Receptors for corticotropin-releasing hormone in human pituitary: binding characteristics and autoradiographic localization to immunocytochemically defined proopiomelanocortin cells. J. Clin. Endocrinol. Metab. 73, 268-274.
Taylor, A. L. and Fishman, L. M. (1988) Corticotropin-releasing hormone. N. Engl. J. Med. 319, 213-222.
Wynn, P. C., Aguilera, G., Morell, J. and Catt, K. J. (1983) Proper ties and regulation of high-affinity pituitary receptors for corticotropin-releasing factor. Biochem. Biophys. Res. Commun. 110, 602-608.
Wynn, P. C., Harwood, P. J., Catt, K. J. and Aguilera, G. (1985) Regulation of corticotropin-releasing factor (CRF) receptors in the rat pituitary gland: effect of adrenalectomy on CRF receptors and corticotroph responses. Endocrinology 116, 1653-1659.