Dual effects of 9-cis retinoic acid on ACTH-dependent hyperplastic adrenal tissues

Autor:	Maria Francesca Cassarino, Laura Tapella, Luigi Castelli, Antonella Sesta, Francesca Pecori Giraldi
Jazyk:	angličtina
Rok vydání:	2021
Předmět:	0301 basic medicine Cortisol secretion medicine.medical_specialty endocrine system Adenoma Hydrocortisone Receptors Retinoic Acid Science Retinoic acid 030209 endocrinology & metabolism Tretinoin Article Translational Research Biomedical 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Endocrinology Downregulation and upregulation Adrenocorticotropic Hormone Internal medicine Adrenal Glands medicine Humans ACTH receptor Pituitary ACTH Hypersecretion Gene Incubation Cushing Syndrome Alitretinoin Adrenal gland diseases Multidisciplinary Translational research medicine.disease Retinoic acid receptor 030104 developmental biology chemistry Medicine hormones hormone substitutes and hormone antagonists
Zdroj:	Scientific Reports, Vol 11, Iss 1, Pp 1-8 (2021) Scientific Reports
ISSN:	2045-2322
Popis:	Retinoids play a pivotal role in adrenal development and differentiation. Recent clinical trials revealed therapeutic potential of both all-trans and 9-cis retinoic acid in patients with cortisol excess due to a pituitary ACTH-secreting adenoma and indicated that retinoids might act also on the adrenal. Aim of the present study was to evaluate the effect of 9-cis retinoic acid on adrenals from patients with ACTH-dependent Cushing’s syndrome. Adrenal specimens from six patients with Cushing’s disease were incubated with 10 nM–1 µM 9-cis retinoic acid with and without 10 nM ACTH. Cortisol secretion was measured by immunoassay and expression of genes involved in steroidogenesis as well as retinoic acid action were evaluated by real-time RT-PCR. Incubation with 10–100 nM 9-cis retinoic acid increased spontaneous cortisol secretion and expression of STAR and CYP17A. On the other hand, in wells treated with ACTH, 9-cis retinoic acid markedly diminished ACTH receptor upregulation and no stimulatory effect on cortisol secretion or steroidogenic enzyme synthesis was observed. ACTH itself increased ligand-induced retinoic acid receptor expression, possibly enhancing sensitivity to retinoic acid. Our findings indicate that the effect of 9-cis retinoic acid in presence of ACTH is distinct from unchallenged wells and support the hypothesis of a direct adrenal action in patients with Cushing’s disease.
Databáze:	OpenAIRE
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