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

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 adre...

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Autores principales: Pecori Giraldi, Francesca, Sesta, Antonella, Tapella, Laura, Cassarino, Maria Francesca, Castelli, Luigi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275666/
https://www.ncbi.nlm.nih.gov/pubmed/34253781
http://dx.doi.org/10.1038/s41598-021-93672-0
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author Pecori Giraldi, Francesca
Sesta, Antonella
Tapella, Laura
Cassarino, Maria Francesca
Castelli, Luigi
author_facet Pecori Giraldi, Francesca
Sesta, Antonella
Tapella, Laura
Cassarino, Maria Francesca
Castelli, Luigi
author_sort Pecori Giraldi, Francesca
collection PubMed
description 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.
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spelling pubmed-82756662021-07-13 Dual effects of 9-cis retinoic acid on ACTH-dependent hyperplastic adrenal tissues Pecori Giraldi, Francesca Sesta, Antonella Tapella, Laura Cassarino, Maria Francesca Castelli, Luigi Sci Rep Article 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. Nature Publishing Group UK 2021-07-12 /pmc/articles/PMC8275666/ /pubmed/34253781 http://dx.doi.org/10.1038/s41598-021-93672-0 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Pecori Giraldi, Francesca
Sesta, Antonella
Tapella, Laura
Cassarino, Maria Francesca
Castelli, Luigi
Dual effects of 9-cis retinoic acid on ACTH-dependent hyperplastic adrenal tissues
title Dual effects of 9-cis retinoic acid on ACTH-dependent hyperplastic adrenal tissues
title_full Dual effects of 9-cis retinoic acid on ACTH-dependent hyperplastic adrenal tissues
title_fullStr Dual effects of 9-cis retinoic acid on ACTH-dependent hyperplastic adrenal tissues
title_full_unstemmed Dual effects of 9-cis retinoic acid on ACTH-dependent hyperplastic adrenal tissues
title_short Dual effects of 9-cis retinoic acid on ACTH-dependent hyperplastic adrenal tissues
title_sort dual effects of 9-cis retinoic acid on acth-dependent hyperplastic adrenal tissues
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275666/
https://www.ncbi.nlm.nih.gov/pubmed/34253781
http://dx.doi.org/10.1038/s41598-021-93672-0
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