title: Autocrine/paracrine regulatory mechanisms in adrenocortical neoplasms responsible for primary adrenal hypercorticism.
abstract: A wide variety of autocrine/paracrine bioactive signals are able to modulate corticosteroid secretion in the human adrenal gland. These regulatory factors, released in the vicinity of adrenocortical cells by diverse cell types comprising chromaffin cells, nerve terminals, cells of the immune system, endothelial cells, and adipocytes, include neuropeptides, biogenic amines, and cytokines. A growing body of evidence now suggests that paracrine mechanisms may also play an important role in the physiopathology of adrenocortical hyperplasias and tumors responsible for primary adrenal steroid excess. These intra-adrenal regulatory systems, although globally involving the same actors as those observed in the normal gland, display alterations at different levels, which reinforce the capacity of paracrine factors to stimulate the activity of adrenocortical cells. The main modifications in the adrenal local control systems reported by now include hyperplasia of cells producing the paracrine factors and abnormal expression of the latter and their receptors. Because steroid-secreting adrenal neoplasms are independent of the classical endocrine regulatory factors angiotensin II and ACTH, which are respectively suppressed by hyperaldosteronism and hypercortisolism, these lesions have long been considered as autonomous tissues. However, the presence of stimulatory substances within the neoplastic tissues suggests that steroid hypersecretion is driven by autocrine/paracrine loops that should be regarded as promising targets for pharmacological treatments of primary adrenal disorders. This new potential therapeutic approach may constitute an alternative to surgical removal of the lesions that is classically recommended in order to cure steroid excess.
authors: Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institut National de la Santé et de la Recherche Médicale Unité 982, 76821 Mont-Saint-Aignan, France.
authors: H
authors: H
authors: Lefebvre
authors: G
authors: G
authors: Prévost
authors: E
authors: E
authors: Louiset
mesh_terms: D000305:Adrenal Cortex Hormones / Q000096:biosynthesis; D000306:Adrenal Cortex Neoplasms / Q000150:complications / Q000503:physiopathology*; D000311:Adrenal Glands / Q000502:physiology / Q000503:physiopathology; D000308:Adrenocortical Hyperfunction / Q000209:etiology / Q000503:physiopathology*; D019898:Autocrine Communication / Q000502:physiology*; D006801:Humans; D019899:Paracrine Communication / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000502:physiology
chemical_list: D000305:Adrenal Cortex Hormones