title: Role of ACTH in the Interactive/Paracrine Regulation of Adrenal Steroid Secretion in Physiological and Pathophysiological Conditions.
abstract: In the normal human adrenal gland, steroid secretion is regulated by a complex network of autocrine/paracrine interactions involving bioactive signals released by endothelial cells, nerve terminals, chromaffin cells, immunocompetent cells, and adrenocortical cells themselves. ACTH can be locally produced by medullary chromaffin cells and is, therefore, a major mediator of the corticomedullary functional interplay. Plasma ACTH also triggers the release of angiogenic and vasoactive agents from adrenocortical cells and adrenal mast cells and, thus, indirectly regulates steroid production through modulation of the adrenal blood flow. Adrenocortical neoplasms associated with steroid hypersecretion exhibit molecular and cellular defects that tend to reinforce the influence of paracrine regulatory loops on corticosteroidogenesis. Especially, ACTH has been found to be abnormally synthesized in bilateral macronodular adrenal hyperplasia responsible for hypercortisolism. In these tissues, ACTH is detected in a subpopulation of adrenocortical cells that express gonadal markers. This observation suggests that ectopic production of ACTH may result from impaired embryogenesis leading to abnormal maturation of the adrenogonadal primordium. Globally, the current literature indicates that ACTH is a major player in the autocrine/paracrine processes occurring in the adrenal gland in both physiological and pathological conditions.
authors.affiliation: U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, INSERM, Institute for Research and Innovation in Biomedicine, Mont-Saint-Aignan, France; Normandie Université, UNIROUEN, Rouen, France; Department of Endocrinology, Diabetes and Metabolic Diseases, University Hospital of Rouen, Rouen, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Lefebvre
authors.affiliation: U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, INSERM, Institute for Research and Innovation in Biomedicine, Mont-Saint-Aignan, France; Normandie Université, UNIROUEN, Rouen, France.
authors.forename: Michaël
authors.initials: M
authors.lastname: Thomas
authors.affiliation: U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, INSERM, Institute for Research and Innovation in Biomedicine, Mont-Saint-Aignan, France; Normandie Université, UNIROUEN, Rouen, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Duparc
authors.affiliation: U1016, INSERM, Institut Cochin, Paris, France; Department of Endocrinology and Metabolic Diseases, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Bertherat
authors.affiliation: U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, INSERM, Institute for Research and Innovation in Biomedicine, Mont-Saint-Aignan, France; Normandie Université, UNIROUEN, Rouen, France.
authors.forename: Estelle
authors.initials: E
authors.lastname: Louiset
keywords: ACTH; Cushing’s syndrome; VEGF; adrenocortical cells; aldosterone; aldosterone-producing adenoma; cortisol; hyperplasia