Role of Adrenal Steroid Metabolites in Osteoporosis in Patients with Autonomous Cortisol Secretion
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PROVIDER: PRJEB61811 | ENA |
REPOSITORIES: ENA
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Project description:Background: Autonomous cortisol secretion (ACS), results from cortisol-producing adenomas (CPA), causes endogenous steroid-induced osteoporosis (SIOP). However, how other adrenal steroid metabolites affect bone status is unclear. Methods: ACS was diagnosed at serum cortisol after 1-mg dexamethasone suppression test (DST-cortisol) ≥ 1.8 g/dL. Using liquid chromatography-tandem mass spectrometry, we measured 21 plasma steroid metabolites in 73 patients with ACS and 85 with non-functioning adrenal tumors (NFAT). We also examined expression of steroidogenic enzymes and relevant steroid metabolites in some of CPA tissues. Results: In discriminant and principal component analysis, steroid profiles distinguished between the ACS and NFAT groups in premenopausal women. Premenopausal women with ACS exhibited higher levels of a mineralocorticoid metabolite; 11-deoxycorticosterone (11-DOC), with lower androgen metabolites; dehydroepiandrosterone-sulfate and androsterone-glucuronide. In premenopausal women with ACS, DST-cortisol was negatively correlated with trabecular bone score (TBS). Additionally, 11-DOC was negatively correlated with lumbar spine-bone mineral density (r = -0.603), while androsterone-glucuronide was positively correlated with TBS (r = 0.681), which was supported by Bayesian kernel machine regression analysis. There were no such correlations in postmenopausal women and men. The CPA tissues showed increased levels of 11-DOC, with increased expression of CYP21A2, which is essential for 11-DOC synthesis. The adrenal non-tumor tissues were atrophied with reduced expression of CYB5A, which is required for androgen synthesis. Conclusion: This study provides the first evidence that unbalanced production of adrenal steroid metabolites, which are derived from both adrenal tumors and non-tumor tissues, play a role in the pathogenesis of endogenous SIOP in premenopausal women with ACS.
2023-06-01 | E-MTAB-12895 | biostudies-arrayexpress
Project description:We performed mRNA-seq of a PRKACA-mutant adrenal tumor and demonstrated that the mutation is expressed at the mRNA level. Total RNA obtained from a cortisol-producing adrenal tumor with a PRKACA p.Leu206Arg mutation.
2014-04-15 | E-GEOD-56016 | biostudies-arrayexpress
Project description:ILLUMINATE (Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events), the phase 3 morbidity and mortality trial of torcetrapib, a cholesteryl ester transfer protein (CETP) inhibitor, identified previously undescribed changes in plasma levels of potassium, sodium, bicarbonate, and aldosterone. A key question after this trial is whether the failure of torcetrapib was a result of CETP inhibition or of some other pharmacology of the molecule. The direct effects of torcetrapib and related molecules on adrenal steroid production were assessed in cell culture using the H295R as well as the newly developed HAC15 human adrenal carcinoma cell lines. Torcetrapib induced the synthesis of both aldosterone and cortisol in these two in vitro cell systems. Analysis of steroidogenic gene expression indicated that torcetrapib significantly induced the expression of CYP11B2 and CYP11B1, two enzymes in the last step of aldosterone and cortisol biosynthesis pathway, respectively. Transcription profiling indicated that torcetrapib and angiotensin II share overlapping pathways in regulating adrenal steroid biosynthesis. Hormone-induced steroid production is mainly mediated by two messengers, calcium and cAMP. An increase of intracellular calcium was observed after torcetrapib treatment, whereas cAMP was unchanged. Consistent with intracellular calcium being the key mediator of torcetrapib’s effect in adrenal cells, calcium channel blockers completely blocked torcetrapib-induced corticoid release and calcium increase. A series of compounds structurally related to torcetrapib as well as structurally distinct compounds were profiled. The results indicate that the pressor and adrenal effects observed with torcetrapib and related molecules are independent of CETP inhibition.
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Project description:To gain insight into the adrenal stress response, we analyzed differential mRNA expression of genes associated with stress induced by aggressive behaviour in the pig In an animal experiment various levels of aggressive behaviour and stress were induced by mixing groups of unfamiliar pigs with different aggressiveness. To analyze adrenal stress response we selected two experimental groups for comparison, each comprising eight animals (n=16) which differed significantly in aggressive behaviour and plasma cortisol levels. To identify differentially expressed genes, we compared the adrenal transcriptome of these two groups of pigs, using the Affymetrix GeneChip porcine Genome Array.
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Project description:Multipotent Schwann cell precursors generate steroid-producing cells of the adrenal cortex and chromaffin cells of the adrenal medulla
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2022-08-08 | GSE167860 | GEO