Role of Adrenal Steroid Metabolites in Osteoporosis in Patients with Autonomous Cortisol Secretion
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB61811 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR11282300_1.fastq.gz | Fastqsanger.gz | |||
| ERR11282300_2.fastq.gz | Fastqsanger.gz | |||
| ERR11282301_1.fastq.gz | Fastqsanger.gz | |||
| ERR11282301_2.fastq.gz | Fastqsanger.gz | |||
| ERR11282302_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 152 |
Similar Datasets
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.
2009-05-02 | GSE15918 | GEO
Project description:Glucocorticoids act through the glucocorticoid receptor (GR), a ligand activated transcription factor, to modulate gene expression profiles in target cells and tissues. The principal physiological glucocorticoid in humans, cortisol, is released in a pulsatile fashion from the adrenal gland, which results in oscillations in blood concentrations, with a period of 1 - 2 hours. The biological consequence of fluctuating cortisol concentrations has not been explored. To identify the role of cortisol concentration oscillations for target cell response a flow-through cell culture system was developed. Transcription profiling was performed in the absence and presence of cortisol. Cells were exposed to constant cortisol levels of 100ng/ml or 200 ng/ml or oscillating cortisol concentrations.
2010-07-10 | E-MEXP-2447 | biostudies-arrayexpress
Project description:The human adrenal glands are highly dynamic endocrine organs that are involved in the secretion of various hormones such as steroids and catecholamines. Here we present a single-nuclei and spatial transcriptomic analysis of healthy adult human adrenal glands to provide a complete adrenal gland atlas. With this, we show how such an atlas can be taken advantage when studying adrenocortical diseases, such as adrenocortical adenomas (ACA). Using nornal adrenal as reference, we showed a high intra-tumoural heterogeneity in the single-nuclei transcriptome of ACA, revealing the presence of specific cell populations associated with cortisol secretion and genetic background.
2023-01-01 | E-MTAB-12129 | biostudies-arrayexpress
Project description:RNA-seq analysis regarding adrenal gland contribution in mouse steroid synthesis
| PRJNA483136 | ENA
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.
2011-05-31 | E-GEOD-25138 | biostudies-arrayexpress
Project description:Duchenne muscular dystrophy is caused by genetic defects in the gene encoding dystrophin and leads to progressive muscle degeneration. Glucocorticoid steroids are current mainstay pharmacological regimen to decrease muscle inflammation and prolong the ambulatory period in these patients, but daily intake of glucocorticoids like prednisone and deflazacort causes adverse side effects like osteoporosis, adrenal suppression, insulin resistance and obesity. Intermittent steroid dosing has been proposed as alternative to maintain benefits and limit side effects, but a detailed understanding of the mechanisms underpinning the regimen-specific effects in muscle is still missing. Here we explore how once-daily versus once-weekly prednisone (4 week-long treatment) affect the epigenomic landscape in mdx mouse muscle (genetic model of Duchenne muscular dystrophy; DBA/2J background) through H3K27 acetylation profiles.
2019-11-30 | GSE137992 | GEO
Project description:Multipotent Schwann cell precursors generate steroid-producing cells of the adrenal cortex and chromaffin cells of the adrenal medulla
| PRJNA589040 | ENA
Project description:Human fetal adrenal glands are huge endocrine organ, produce prodigious quantities of dehydroepiandrosterone and its sulfate (DHEA/DHEAS), which is the most prominent precursor for steroid hormones, adrenal gonads dysfunction leads to states of virilization or effemination. However, for a long time the function of fetal adrenal in initial sex differentiation is unclear. Herein, we draw out a single-cell transcriptional landscape of human fetal adrenals and gonad from 6 to 14 gestational weeks (GW). We found that the adrenal glands begin to express CYP17A1 steroid-related enzyme much early than testis, subsequent testis steroid express pattern support de novo or halfway testosterone synthesis. Excepted steroidogenic cell, notably, the immune cells or neurocyte shows steroid metabolism or regulation ability, such as CD5L+ macrophage interacted with steroidogenic cell and SRD5A1+ AKR1C2+ chromaffin cells synthesis active testosterone DHT through backdoor pathway. Sex different were found at adrenal glands and gonad development: there is a small HSD3B2 peak occurs only in female adrenal glands around 10-12 GW within the time window of sex differentiation. SST expression levels or SST+ cells quantity in adrenal glands and gonads are different in two gender. Our research indicates that a sex different in spatial and temporal disparities steroidogenic regulatory networks in adrenal glands and gonads, facilitating further exploration of development and physiology of human adrenal glands.
2022-08-08 | GSE167860 | GEO