Endocrine Abstracts (2007) 14 S8.1

Autocrine-paracrine pathways in primary adrenal disorders

Hervé Lefebvre1, Vincent Contesse1, Dorthe Cartier1, Véronique Perraudin1, Catherine Delarue1, Hubert Vaudry1, Jérôme Bertherat2, Pierre-François Plouin3, Jean-Marc Kuhn4 & Estelle Louiset1


1INSERM U413, IFRMP23, Laboratory of Cellular and Molecular Neuroendocrinology, University of Rouen, Mont Saint Aignan, France; 2Department of Endocrinology, CHU Cochin & Institut Cochin, INSERM U567, CNRS UMR8104, IFR 116, University of Paris V-René Descartes, Paris, France; 3Hypertension Unit, European Hospital Georges Pompidou, University of Paris V-René Descartes, Paris, France; 4Department of Endocrinology, University Hospital of Rouen, Rouen, France.


It is now well demonstrated that, in the human adrenal gland, aldosterone and cortisol productions are stimulated by autocrine/paracrine factors, like serotonin (5-HT) and arginine vasopressin (AVP). Several data indicate that these signals may also be involved in the regulation of corticosteroidogenesis in adrenocortical hyperplasias and tumors. 5-HT is detected in clusters of steroidogenic cells in aldosterone-producing adrenocortical adenomas (APAs), and in both ACTH-independent macronodular adrenal hyperplasias (AIMAHs) and adenomas responsible for Cushing’s syndrome. In these lesions, 5-HT stimulates steroidogenesis through activation of overexpressed eutopic 5-HT4 and/or ectopic 5-HT7 receptors. Immunohistochemical studies have shown the occurrence of AVP in a subpopulation of steroidogenic cells in APAs and AIMAHs. In APAs, AVP activates aldosterone production through the eutopic V1a receptor whereas its stimulatory effect on cortisol secretion from AIMAH tissues is mediated by both overexpressed V1a and/or ectopic V1b and V2 receptors. Interestingly, administration of V1a antagonists to patients with APA induces an aldosterone response to the upright stimulation test, indicating that, in these tumors, inhibition of the vasopressinergic tone sensitizes the tissues to the action of posture-responsive hormones. Finally, the presence of ACTH has been observed in AIMAH tissues and the ACTH receptor antagonist corticostatin inhibits basal cortisol secretion from AIMAH explants, demonstrating that glucocorticoid production is dependent on the paracrine action of intraadrenal ACTH in some primary adrenal disorders causing Cushing’s syndrome. In conclusion, autocrine/paracrine regulatory factors are produced within adrenocortical hyperplasias and tumors in which they play an important role in the control of steroidogenesis. These local factors may therefore represent promising targets for the treatment of primary adrenal disorders. This work was supported by INSERM, the University Hospital of Rouen, the Conseil Régional de Haute-Normandie and the COMETE network (PHRC AOM 02068).

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