HIF1α is an essential regulator of steroidogenesis in the adrenal gland
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PROVIDER: PRJNA644906 | ENA |
REPOSITORIES: ENA
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Project description:Hormones produced by the adrenal cortex are absolutely essential for numerous processes in living animals. Our research group investigated to what extend the central regulators of deprived oxygen, hypoxia inducible factors (HIFs), contribute to this steroidogenesis. For this, we developed a set of new transgenic mouse lines displaying modified HIF1α and HIF2α levels in cortical cells and revealed that HIF1α exclusively regulates the transcription of a majority of enzymes responsible for the production of glucocorticoids and mineralocorticoids as well as a consequent inflection of cytokines in circulation. These novel tools will be helpful to understand how sustained and chronic changes in adrenocortical hormones can impact during health and disease.
2020-07-09 | GSE154032 | GEO
Project description:Endogenous steroid hormones, especially glucocorticoids and mineralocorticoids, derive from the adrenal cortex, and drastic or sustained changes in their circulatory levels affect multiple organ systems. Although hypoxia signaling in steroidogenesis has been suggested, knowledge on the true impact of the HIFs (Hypoxia-Inducible Factors) in the adrenocortical cells of vertebrates is scant. By creating a unique set of transgenic mouse lines, we reveal a prominent role for HIF1α in the synthesis of virtually all steroids in vivo. Specifically, mice deficient in HIF1α in adrenocortical cells displayed enhanced levels of enzymes responsible for steroidogenesis and a cognate increase in circulatory steroid levels. These changes resulted in cytokine alterations and changes in the profile of circulatory mature hematopoietic cells. Conversely, HIF1α overexpression resulted in the opposite phenotype of insufficient steroid production due to impaired transcription of necessary enzymes. Based on these results, we propose HIF1α to be a vital regulator of steroidogenesis as its modulation in adrenocortical cells dramatically impacts hormone synthesis with systemic consequences. In addition, these mice can have potential clinical significances as they may serve as essential tools to understand the pathophysiology of hormone modulations in a number of diseases associated with metabolic syndrome, auto-immunity or even cancer.
| S-EPMC8038963 | biostudies-literature
Project description:Transcription factor GATA6 is expressed in the fetal and adult adrenal cortex and has been implicated in steroidogenesis. To characterize the role of GATA6 in adrenocortical development and function, we generated mice in which Gata6 was conditionally deleted using Cre-LoxP recombination with Sf1-cre. The adrenal glands of adult Gata6 conditional knockout (cKO) mice were small and had a thin cortex with thickened capsule. Cytomegalic changes were evident in the adrenal glands of fetal and adult cKO mice, and chromaffin cells were ectopically located at the periphery of the glands. The secretion of corticosterone in response to exogenous ACTH was blunted in cKO mice. Cells expressing gonadal-like markers, including Gata4, Amhr2, and Tcf21, accumulated in the adrenal capsule and subcapsule of cKO mice, suggesting aberrant adrenocortical progenitor/stem cell differentiation. Gonadectomy triggered the overexpression of sex steroidogenic differentiation markers, such as Lhcgr and Cyp17, in the adrenal glands of male and female cKO mice. Nulliparous female and orchiectomized male cKO mice lacked an adrenal X-zone. Microarray hybridization identified Pik3c2g as a novel X-zone marker that is downregulated in the adrenal glands of nulliparous female Gata6 cKO mice. Our findings offer genetic proof of the longstanding hypothesis that GATA6 regulates the differentiation of steroidogenic progenitors into corticoid-producing cells. 3 replicates from both conditional knockout of Gata6 in the adrenal gland and control adrenal glands from non-knockout mice were compared
2013-06-06 | E-GEOD-40398 | biostudies-arrayexpress
Project description:WGBS sequencing from adrenal gland tissue For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf
2019-03-03 | GSE127311 | GEO
Project description:WGBS sequencing from adrenal gland tissue For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf
2019-03-03 | GSE127282 | GEO
Project description:The extracellular matrix (ECM) comprises macromolecules that shape a complex three-dimensional network. Filling the intercellular space and playing a crucial role in the structure and function of tissues, ECM regulates essential cellular processes such as adhesion, differentiation, and cell signaling. In the human adrenal gland, composed of cortex and medulla surrounded by a capsule, the ECM has not yet been directly described, although its impact on the processes of proliferation and steroidogenesis of the adrenal cortex is recognized. This study proposes a comprehensive analysis aims to comprehensively analyze the ECM of the adult human adrenal cortex, which is separated into outer fraction (OF) and inner fraction (IF), by comparing their proteomic profiles. The study discusses the composition, spatial distribution, and relevance of differentially expressed ECM signatures of the adrenal cortex matrisome on adrenal structure and function. The findings were validated through database analysis (cross-validation), histochemical, and immunohistochemical approaches. A total of 121 ECM proteins were identified and categorized into glycoproteins, collagens, ECM regulators, proteoglycans, ECM-affiliated proteins, and secreted factors. Thirty-one ECM proteins were identified only in OF, 9 only in IF, and 81 were identified in common with both fractions. Additionally, 106 ECM proteins were cross-validated using Human matrisome DB 2.0 and the proteins differentially expressed in OF and IF, were identified. This study provides significant insights into the composition and regulation of the ECM in the human adrenal cortex, shedding light on the adrenal microenvironment and its role in the functioning, maintenance, and renewal of the adrenal gland.
2024-09-11 | PXD051801 | Pride
Project description:eCLIP control experiment on adrenal gland against HNRNPU For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf
2017-01-03 | GSE91477 | GEO
Project description:eCLIP experiment on adrenal gland from the GTEx collection against DGCR8 For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf
2021-06-15 | GSE177629 | GEO
Project description:Despite the ubiquitous function of macrophages across the body, the diversity, origin, and function of adrenal gland macrophages remain largely unknown. We defined the heterogeneity of adrenal gland immune cells using single-cell RNA sequencing and used genetic models to explore the developmental mechanisms yielding to macrophage diversity. We defined populations of monocyte-derived and embryonically seeded adrenal gland macrophages and identified a female-specific subset with low MHC-II expression. In adulthood, monocyte recruitment dominated adrenal gland macrophage maintenance in female mice, while self-proliferation was more important in males. Adrenal gland macrophage sub-tissular distribution followed a sex-dimorphic pattern, with MHC-IIlow macrophages located at the border between the cortex and the medulla. Macrophage sex dimorphism depended on the presence of the cortical Xzone. Forcing X-zone maintenance in males, or its degradation in females, directly impacted the presence of MHC-IIlow macrophages. Adrenal gland macrophage depletion resulted in altered tissue homeostasis, modulated lipid- metabolism and decreased local aldosterone production during stress exposure. Overall, these data explain the heterogeneity of adrenal gland macrophages and point toward sexrestricted distribution and functions of these cells.
2022-05-23 | GSE203095 | GEO
Project description:Despite the ubiquitous function of macrophages across the body, the diversity, origin, and function of adrenal gland macrophages remain largely unknown. We defined the heterogeneity of adrenal gland immune cells using single-cell RNA sequencing and used genetic models to explore the developmental mechanisms yielding to macrophage diversity. We defined populations of monocyte-derived and embryonically seeded adrenal gland macrophages and identified a female-specific subset with low MHC-II expression. In adulthood, monocyte recruitment dominated adrenal gland macrophage maintenance in female mice, while self-proliferation was more important in males. Adrenal gland macrophage sub-tissular distribution followed a sex-dimorphic pattern, with MHC-IIlow macrophages located at the border between the cortex and the medulla. Macrophage sex dimorphism depended on the presence of the cortical Xzone. Forcing X-zone maintenance in males, or its degradation in females, directly impacted the presence of MHC-IIlow macrophages. Adrenal gland macrophage depletion resulted in altered tissue homeostasis, modulated lipid- metabolism and decreased local aldosterone production during stress exposure. Overall, these data explain the heterogeneity of adrenal gland macrophages and point toward sexrestricted distribution and functions of these cells.
2022-05-23 | GSE203096 | GEO