Platelet-derived growth factor D expression in adrenal cells is modulated by corticosteroids: putative role in adrenal suppression



Parry, Christopher M ORCID: 0000-0002-0256-1325, Chan, Li F, Carr, Daniel F and Hawcutt, Daniel B ORCID: 0000-0002-8120-6507
(2023) Platelet-derived growth factor D expression in adrenal cells is modulated by corticosteroids: putative role in adrenal suppression. PEDIATRIC RESEARCH, 93 (1). pp. 97-101.

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Abstract

<h4>Background</h4>Adrenal suppression is a clinically concerning side effect of inhaled corticosteroid (ICS) treatment in patients with asthma. Increased susceptibility to ICS-induced adrenal suppression has previously been identified in those with the rs591118 polymorphism in platelet-derived growth factor D (PDGFD). The mechanism underpinning this relationship is not known.<h4>Methods</h4>H295R cells were genotyped for rs591118 using a validated Taqman PCR allelic discrimination assay. H295R cell viability was determined after treatment with beclometasone and fluticasone (range 0-330 μM). Cortisol was measured in cell culture medium using competitive enzyme immunoassay.<h4>Results</h4>PDGFD protein expression in H295R cells was confirmed using Western blotting. When ACTH and forskolin were added to H295R cells, a reduction in PDGFD expression was seen, which was then restored by incubation with prochloraz, a known inhibitor of steroidogenesis. A dose-dependent, decrease in PDGFD expression was observed with beclometasone (over a 24 h incubation period) but not with beclometasone incubations beyond 24 h nor with fluticasone (at 24 or 48 h).<h4>Conclusions</h4>H295R cells express PDGFD protein, which can be modulated by incubation with steroidogenesis agonists and antagonists and additionally with exogenous beclometasone.<h4>Impact</h4>PDGFD is expressed in the human adrenal cell line, H295R, and expression can be modulated by beclometasone as well as agonists/antagonists of steroidogenesis. This builds on previous research that identified a SNP in PDGFD (rs591118) as an independent risk factor for adrenal suppression in adults and children with obstructive airway disease treated with inhaled corticosteroids. First in vitro experiments to support a link between the PDGF and cortisol production pathways, supporting the hypothesis that PDGFD variants can affect an individual's sensitivity to corticosteroid-induced adrenal suppression.

Item Type: Article
Uncontrolled Keywords: Humans, Beclomethasone, Hydrocortisone, Adrenal Cortex Hormones, Platelet-Derived Growth Factor, Adult, Child, Fluticasone
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Clinical Directorate
Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Depositing User: Symplectic Admin
Date Deposited: 19 May 2022 14:20
Last Modified: 23 Feb 2023 05:19
DOI: 10.1038/s41390-022-02094-9
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3155157