Effect of retinoic acid on human adrenal corticosteroid synthesis

Retinoic acid has recently yielded promising results in the treatment of Cushing's disease, i.e., excess cortisol secretion due to a pituitary corticotropin (ACTH)-secreting adenoma. In addition to its effect on the tumoral corticotrope cell, clinical results suggest an additional adrenal site...

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Published in:Life sciences (1973) 2016-04, Vol.151, p.277-280
Main Authors: Sesta, Antonella, Cassarino, Maria Francesca, Tapella, Laura, Castelli, Luigi, Cavagnini, Francesco, Pecori Giraldi, Francesca
Format: Article
Language:English
Subjects:
Adrenal
Adrenal Glands - drug effects
Adrenal Glands - metabolism
Adrenocorticotropic Hormone - antagonists & inhibitors
Adrenocorticotropic Hormone - pharmacology
Cholesterol Side-Chain Cleavage Enzyme - biosynthesis
Cortisol
Cushing's syndrome
Dose-Response Relationship, Drug
Gene Expression - drug effects
Humans
Hydrocortisone - biosynthesis
Hydrocortisone - secretion
MC2R
Phosphoproteins - biosynthesis
Primary Cell Culture
Receptor, Melanocortin, Type 1 - biosynthesis
Retinoic acid
STAR
Tretinoin - pharmacology
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Summary:Retinoic acid has recently yielded promising results in the treatment of Cushing's disease, i.e., excess cortisol secretion due to a pituitary corticotropin (ACTH)-secreting adenoma. In addition to its effect on the tumoral corticotrope cell, clinical results suggest an additional adrenal site of action. Aim of this study was to evaluate whether retinoic acid modulates cortisol synthesis and secretion by human adrenals in vitro. Primary cultures from 10 human adrenals specimens were incubated with 10nM, 100nM and 1μM retinoic acid with and without 10nM ACTH for 24h. Cortisol levels were measured by radioimmunoassay and CYP11A1, STAR and MC2R gene expression analyzed by real-time PCR. Retinoic acid increased cortisol secretion (149.5±33.01%, 151.3±49.45% and 129.3±8.32% control secretion for 10nM, 100nM and 1μM respectively, p
ISSN:0024-3205
1879-0631
DOI:10.1016/j.lfs.2016.03.023