The expression of glucocorticoid and mineralocorticoid receptors in pituitary tumors causing Cushing’s disease and silent corticotroph tumors
ObjectivePituitary neuroendocrine corticotroph tumors commonly cause Cushing’s disease (CD) that results from increased adrenocorticotropic hormone (ACTH) secretion by the pituitary tumor and consequent increase of cortisol levels in blood. However, in some patients, corticotroph tumors remain clini...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-03-01
|
| Series: | Frontiers in Endocrinology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2023.1124646/full |
| _version_ | 1797857800366325760 |
|---|---|
| author | Paulina Kober Natalia Rusetska Beata J. Mossakowska Maria Maksymowicz Monika Pękul Grzegorz Zieliński Andrzej Styk Jacek Kunicki Łukasz Działach Przemysław Witek Mateusz Bujko |
| author_facet | Paulina Kober Natalia Rusetska Beata J. Mossakowska Maria Maksymowicz Monika Pękul Grzegorz Zieliński Andrzej Styk Jacek Kunicki Łukasz Działach Przemysław Witek Mateusz Bujko |
| author_sort | Paulina Kober |
| collection | DOAJ |
| description | ObjectivePituitary neuroendocrine corticotroph tumors commonly cause Cushing’s disease (CD) that results from increased adrenocorticotropic hormone (ACTH) secretion by the pituitary tumor and consequent increase of cortisol levels in blood. However, in some patients, corticotroph tumors remain clinically non-functioning. Cortisol secretion is regulated by the hypothalamic–pituitary–adrenal axis and includes a negative feedback between cortisol and ACTH secretion. Glucocorticoids reduce ACTH level both by hypothalamic regulation and acting on corticotrophs via glucocorticoid (GR) and mineralocorticoid (MR) receptors. The aim of the study was to determine the role of GR and MR expression at mRNA and protein levels in both functioning and silent corticotroph tumors.MethodsNinety-five patients were enrolled, including 70 with CD and 25 with silent corticotroph tumors. Gene expression levels of NR3C1 and NR3C2 coding for GR and MR, respectively, were determined with qRT-PCR in the two tumor types. GR and MR protein abundance was assessed with immunohistochemistry.ResultsBoth GR and MR were expressed in corticotroph tumors. Correlation between NR3C1 and NR3C2 expression levels was observed. NR3C1 expression was higher in silent than in functioning tumors. In CD patients NR3C1 and NR3C2 levels were negatively correlated with morning plasma ACTH levels and tumor size. Higher NR3C2 was confirmed in patients with remission after surgery and in densely granulated tumors. Expression of both genes and GR protein was higher in USP8-mutated tumors. Similar relationship between USP8 mutations and expression levels were observed in analysis of silent tumors that also revealed a negative correlation between GR and tumor size and higher NR3C1 expression in densely granulated tumors.ConclusionsAlthough the associations between gene/protein expression and patients clinical features are not strong, they consistently show an evident trend in which higher receptor expression corresponds to more favorable clinical characteristics. |
| first_indexed | 2024-04-09T21:02:40Z |
| format | Article |
| id | doaj.art-1a1d87f12f4d44ccbbb3de019e753037 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-09T21:02:40Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-1a1d87f12f4d44ccbbb3de019e7530372023-03-29T05:32:30ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-03-011410.3389/fendo.2023.11246461124646The expression of glucocorticoid and mineralocorticoid receptors in pituitary tumors causing Cushing’s disease and silent corticotroph tumorsPaulina Kober0Natalia Rusetska1Beata J. Mossakowska2Maria Maksymowicz3Monika Pękul4Grzegorz Zieliński5Andrzej Styk6Jacek Kunicki7Łukasz Działach8Przemysław Witek9Mateusz Bujko10Department of Molecular and Translational Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, PolandDepartment of Experimental Immunotherapy, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, PolandDepartment of Molecular and Translational Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, PolandDepartment of Cancer Pathomorphology, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, PolandDepartment of Cancer Pathomorphology, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, PolandDepartment of Neurosurgery, Military Institute of Medicine, Warsaw, PolandDepartment of Neurosurgery, Military Institute of Medicine, Warsaw, PolandDepartment of Neurosurgery, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, PolandDepartment of Internal Medicine, Endocrinology and Diabetes, Medical University of Warsaw, Warsaw, PolandDepartment of Internal Medicine, Endocrinology and Diabetes, Medical University of Warsaw, Warsaw, PolandDepartment of Molecular and Translational Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, PolandObjectivePituitary neuroendocrine corticotroph tumors commonly cause Cushing’s disease (CD) that results from increased adrenocorticotropic hormone (ACTH) secretion by the pituitary tumor and consequent increase of cortisol levels in blood. However, in some patients, corticotroph tumors remain clinically non-functioning. Cortisol secretion is regulated by the hypothalamic–pituitary–adrenal axis and includes a negative feedback between cortisol and ACTH secretion. Glucocorticoids reduce ACTH level both by hypothalamic regulation and acting on corticotrophs via glucocorticoid (GR) and mineralocorticoid (MR) receptors. The aim of the study was to determine the role of GR and MR expression at mRNA and protein levels in both functioning and silent corticotroph tumors.MethodsNinety-five patients were enrolled, including 70 with CD and 25 with silent corticotroph tumors. Gene expression levels of NR3C1 and NR3C2 coding for GR and MR, respectively, were determined with qRT-PCR in the two tumor types. GR and MR protein abundance was assessed with immunohistochemistry.ResultsBoth GR and MR were expressed in corticotroph tumors. Correlation between NR3C1 and NR3C2 expression levels was observed. NR3C1 expression was higher in silent than in functioning tumors. In CD patients NR3C1 and NR3C2 levels were negatively correlated with morning plasma ACTH levels and tumor size. Higher NR3C2 was confirmed in patients with remission after surgery and in densely granulated tumors. Expression of both genes and GR protein was higher in USP8-mutated tumors. Similar relationship between USP8 mutations and expression levels were observed in analysis of silent tumors that also revealed a negative correlation between GR and tumor size and higher NR3C1 expression in densely granulated tumors.ConclusionsAlthough the associations between gene/protein expression and patients clinical features are not strong, they consistently show an evident trend in which higher receptor expression corresponds to more favorable clinical characteristics.https://www.frontiersin.org/articles/10.3389/fendo.2023.1124646/fullpituitary neuroendocrine tumor (PitNET)Cushing’s disease (CD)silent corticotroph adenomaNR3C1NR3C2hypothalamic - pituitary - adrenal axis |
| spellingShingle | Paulina Kober Natalia Rusetska Beata J. Mossakowska Maria Maksymowicz Monika Pękul Grzegorz Zieliński Andrzej Styk Jacek Kunicki Łukasz Działach Przemysław Witek Mateusz Bujko The expression of glucocorticoid and mineralocorticoid receptors in pituitary tumors causing Cushing’s disease and silent corticotroph tumors Frontiers in Endocrinology pituitary neuroendocrine tumor (PitNET) Cushing’s disease (CD) silent corticotroph adenoma NR3C1 NR3C2 hypothalamic - pituitary - adrenal axis |
| title | The expression of glucocorticoid and mineralocorticoid receptors in pituitary tumors causing Cushing’s disease and silent corticotroph tumors |
| title_full | The expression of glucocorticoid and mineralocorticoid receptors in pituitary tumors causing Cushing’s disease and silent corticotroph tumors |
| title_fullStr | The expression of glucocorticoid and mineralocorticoid receptors in pituitary tumors causing Cushing’s disease and silent corticotroph tumors |
| title_full_unstemmed | The expression of glucocorticoid and mineralocorticoid receptors in pituitary tumors causing Cushing’s disease and silent corticotroph tumors |
| title_short | The expression of glucocorticoid and mineralocorticoid receptors in pituitary tumors causing Cushing’s disease and silent corticotroph tumors |
| title_sort | expression of glucocorticoid and mineralocorticoid receptors in pituitary tumors causing cushing s disease and silent corticotroph tumors |
| topic | pituitary neuroendocrine tumor (PitNET) Cushing’s disease (CD) silent corticotroph adenoma NR3C1 NR3C2 hypothalamic - pituitary - adrenal axis |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1124646/full |
| work_keys_str_mv | AT paulinakober theexpressionofglucocorticoidandmineralocorticoidreceptorsinpituitarytumorscausingcushingsdiseaseandsilentcorticotrophtumors AT nataliarusetska theexpressionofglucocorticoidandmineralocorticoidreceptorsinpituitarytumorscausingcushingsdiseaseandsilentcorticotrophtumors AT beatajmossakowska theexpressionofglucocorticoidandmineralocorticoidreceptorsinpituitarytumorscausingcushingsdiseaseandsilentcorticotrophtumors AT mariamaksymowicz theexpressionofglucocorticoidandmineralocorticoidreceptorsinpituitarytumorscausingcushingsdiseaseandsilentcorticotrophtumors AT monikapekul theexpressionofglucocorticoidandmineralocorticoidreceptorsinpituitarytumorscausingcushingsdiseaseandsilentcorticotrophtumors AT grzegorzzielinski theexpressionofglucocorticoidandmineralocorticoidreceptorsinpituitarytumorscausingcushingsdiseaseandsilentcorticotrophtumors AT andrzejstyk theexpressionofglucocorticoidandmineralocorticoidreceptorsinpituitarytumorscausingcushingsdiseaseandsilentcorticotrophtumors AT jacekkunicki theexpressionofglucocorticoidandmineralocorticoidreceptorsinpituitarytumorscausingcushingsdiseaseandsilentcorticotrophtumors AT łukaszdziałach theexpressionofglucocorticoidandmineralocorticoidreceptorsinpituitarytumorscausingcushingsdiseaseandsilentcorticotrophtumors AT przemysławwitek theexpressionofglucocorticoidandmineralocorticoidreceptorsinpituitarytumorscausingcushingsdiseaseandsilentcorticotrophtumors AT mateuszbujko theexpressionofglucocorticoidandmineralocorticoidreceptorsinpituitarytumorscausingcushingsdiseaseandsilentcorticotrophtumors AT paulinakober expressionofglucocorticoidandmineralocorticoidreceptorsinpituitarytumorscausingcushingsdiseaseandsilentcorticotrophtumors AT nataliarusetska expressionofglucocorticoidandmineralocorticoidreceptorsinpituitarytumorscausingcushingsdiseaseandsilentcorticotrophtumors AT beatajmossakowska expressionofglucocorticoidandmineralocorticoidreceptorsinpituitarytumorscausingcushingsdiseaseandsilentcorticotrophtumors AT mariamaksymowicz expressionofglucocorticoidandmineralocorticoidreceptorsinpituitarytumorscausingcushingsdiseaseandsilentcorticotrophtumors AT monikapekul expressionofglucocorticoidandmineralocorticoidreceptorsinpituitarytumorscausingcushingsdiseaseandsilentcorticotrophtumors AT grzegorzzielinski expressionofglucocorticoidandmineralocorticoidreceptorsinpituitarytumorscausingcushingsdiseaseandsilentcorticotrophtumors AT andrzejstyk expressionofglucocorticoidandmineralocorticoidreceptorsinpituitarytumorscausingcushingsdiseaseandsilentcorticotrophtumors AT jacekkunicki expressionofglucocorticoidandmineralocorticoidreceptorsinpituitarytumorscausingcushingsdiseaseandsilentcorticotrophtumors AT łukaszdziałach expressionofglucocorticoidandmineralocorticoidreceptorsinpituitarytumorscausingcushingsdiseaseandsilentcorticotrophtumors AT przemysławwitek expressionofglucocorticoidandmineralocorticoidreceptorsinpituitarytumorscausingcushingsdiseaseandsilentcorticotrophtumors AT mateuszbujko expressionofglucocorticoidandmineralocorticoidreceptorsinpituitarytumorscausingcushingsdiseaseandsilentcorticotrophtumors |