I-125 TYR(0)-HCRH LABELING CHARACTERISTICS OF CORTICOTROPIN-RELEASINGHORMONE RECEPTORS - DIFFERENCES BETWEEN NORMAL AND ADENOMATOUS CORTICOTROPHS

The presence of corticotropin-releasing hormone (CRH) receptors has be en previously demonstrated in corticotrophs From normal pituitaries us ing a method combining immunocytochemistry and liquid emulsion autorad iography. The aim of this study was to compare the characteristics of the I-125-Tyr(0)-hCRH binding in corticotrophs from normal pituitaries (three obtained at autopsy and one obtained at surgery) with corticot rophs from pituitary adenomas (six corticotroph adenomas responsible f or Cushing's disease and two silent corticotroph adenomas secreting a biologically inactive ACTH molecule). In normal corticotrophs, the lar ger part of the I-125-Tyr(0)-hCRH binding was localised in patchy cong lomerates 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 qualitati vely. Except for a minority of cells in one adenoma, all adenomatous c orticotrophs showed only peripherally bound I-125-Tyr(0)hCRH and no ce ntrally localised binding. Furthermore, adenomatous corticotrophs reve aled 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 b asal and CRH-stimulated plasma ACTH levels. These findings suggest def ective processing of CRH receptors and could be relevant to the sustai ned ACTH secretion by adenomatous corticotrophs in Cushing's disease a nd, more generally, provide an explanation to its pathology. Thr silen t corticotrophs secreting a biologically inactive ACTH molecule were c haracterised by a very faint signal intensity, although present on alm ost every cell. (C) 1997 Elsevier Science Ltd. All rights reserved.