ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2008) 16 P60

Intraadrenal production of ACTH in macronodular bilateral adrenal hyperplasia causing Cushing's syndrome: its role in the physiopathology of hypercortisolism

Estelle Louiset1, Céline Duparc1, Lionel Groussin2, Jérôme Bertherat2, Xavier Bertagna2, Jean-Marc Kuhn3 & Hervé Lefebvre1

1INSERM U413, University of Rouen, Mont-Saint-Aignan, France; 2INSERM U567, CNRS UMR8104, Department of Endocrinology-Metabolism-Cancer, Institut Cochin, Université Paris V René Descartes, Paris, France; 3Department of Endocrinology, Institute for Biomedical Research, Rouen University Hospital, University of Rouen, Rouen, France.

Illicit expression of membrane receptors for circulating regulatory factors, such as GIP and LH receptors, has been well documented in ACTH-independent macronodular adrenal hyperplasias (AIMAHs) causing Cushing’s syndrome. In addition, we have observed an abnormal expression of serotonin, arginine vasopressin and ACTH in a subpopulation of steroidogenic cells in two AIMAH tissues. The aim of the present study was: (i) to investigate the presence of ACTH by immunohistochemistry in eleven additional AIMAHs; (ii) to detect ACTH release by the tissue fragments, (iii) to determine whether ACTH secretion can be modulated by activation of illicit receptors, and (iv) to examine the role of local production of ACTH in the control of steroidogenesis.

ACTH-like immunoreactivity was detected in AIMAH tissues, suggesting that this regulatory signal may act through autocrine/paracrine mechanisms to stimulate cortisol secretion. Perifusion experiments demonstrated that adrenal slices spontaneously released detectable amounts of ACTH. In addition, ACTH secretion was significantly increased by GIP and hCG in tissues derived from patients with food-dependent and LH-sensitive hypercortisolism. The ACTH receptor antagonists corticostatin and ACTH (7–38) reduced basal and ACTH-induced cortisol production from the hyperplasia tissues. These data indicate that, in AIMAH tissues, ACTH released by a subpopulation of adrenocortical cells exerts an intraadrenal stimulatory tone on cortisol secretion.

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