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

Abstract 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...

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Autores principales:	Francesca Pecori Giraldi, Antonella Sesta, Laura Tapella, Maria Francesca Cassarino, Luigi Castelli
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5ef9d2bcf39a4ee0b8177dcff0ede382
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spelling	oai:doaj.org-article:5ef9d2bcf39a4ee0b8177dcff0ede3822021-12-02T16:14:03ZDual effects of 9-cis retinoic acid on ACTH-dependent hyperplastic adrenal tissues10.1038/s41598-021-93672-02045-2322https://doaj.org/article/5ef9d2bcf39a4ee0b8177dcff0ede3822021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93672-0https://doaj.org/toc/2045-2322Abstract 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.Francesca Pecori GiraldiAntonella SestaLaura TapellaMaria Francesca CassarinoLuigi CastelliNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Francesca Pecori Giraldi Antonella Sesta Laura Tapella Maria Francesca Cassarino Luigi Castelli Dual effects of 9-cis retinoic acid on ACTH-dependent hyperplastic adrenal tissues
description	Abstract 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.
format	article
author	Francesca Pecori Giraldi Antonella Sesta Laura Tapella Maria Francesca Cassarino Luigi Castelli
author_facet	Francesca Pecori Giraldi Antonella Sesta Laura Tapella Maria Francesca Cassarino Luigi Castelli
author_sort	Francesca Pecori Giraldi
title	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_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_sort	dual effects of 9-cis retinoic acid on acth-dependent hyperplastic adrenal tissues
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5ef9d2bcf39a4ee0b8177dcff0ede382
work_keys_str_mv	AT francescapecorigiraldi dualeffectsof9cisretinoicacidonacthdependenthyperplasticadrenaltissues AT antonellasesta dualeffectsof9cisretinoicacidonacthdependenthyperplasticadrenaltissues AT lauratapella dualeffectsof9cisretinoicacidonacthdependenthyperplasticadrenaltissues AT mariafrancescacassarino dualeffectsof9cisretinoicacidonacthdependenthyperplasticadrenaltissues AT luigicastelli dualeffectsof9cisretinoicacidonacthdependenthyperplasticadrenaltissues
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Dual effects of 9-cis retinoic acid on ACTH-dependent hyperplastic adrenal tissues

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