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.
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.
Project description:The regulation of pituitary function via the hypothalamus and via intra-pituitary connections represents a complex system. Though hormones secreted from the pituitary glands have been well studied, overall information of proteins expressed in the pituitary glands is very limited. Protein expression profiling of normal pituitary tissue may lead to discovery of novel proteins playing an important role in the physiology of pituitary glands and can lead to better understanding of pituitary gland diseases. We aimed to carry out systematic proteomic profiling of adenohypophysis from human pituitary glands using high-resolution Fourier transform mass spectrometer. A total of 2,175 proteins were identified in this study of which, 105 proteins were identified for the first time as compared to high throughput proteomic-based studies from human pituitary glands. The comprehensive list of proteins identified in this study will facilitate the better understanding the role of this important gland in health and disease.
Project description:Purpose: The transcriptome profiles were compared among groups of chronic stress exposure and control in two different breeds to identify genes and pathways related to response to chronic stress in the pituitary-adrenal axis. Methods: 6 male adult CFD and 6 Beagles were chosen at random with the similarities in good health, weight and other aspects. Separately, 3 of these two breeds were freely selected for the stress exposure via intermittent electrical stimulation and restraint stress, while the other 3 of these two breeds were non-disposed for normal control.The details for the disposal of dogs were: every morning dogs were restrained and electrical stimulations were exerted with a stable current of 10 mA for 6 s and then with a 6 s interval, lasting for 20 min every day. The duration of disposal was ten days.ll 12 dogs were killed by air embolism in the 11th day. Subsequently, pituitary and adrenal cortex tissues were fast collected and isolated for further high-sequencing. Results: 8 cDNA libraries were constructed for RNA-seq. A number of reads ranging from 53,295,978 to 65,414,932 was obtained in those 8 groups. About 10,000 genes and transcripts were annotated in each group. Besides,A total of 40, 346, 376, 69, 70, 38, 57, and 71 DEGs were detected in the contrasts of BP1_vs_BP2, CFDP1_vs_CFDP2, BP1_vs_CFDP1, BP2_vs_CFDP2, BAC1_vs_BAC2, CFDAC1_vs_CFDAC2, BAC1_vs_CFDAC1, and BAC2_vs_CFDAC2, respectively. Conclusions: Our results can contribute to a more comprehensive understanding about the genetic mechanisms of response to chronic stress in adrenal cortex and pituitary. Adrenal cortex and pituitary mRNA profiles of adult Chinese Field Dog and Beagle under chronic stress exposure and normal control, including BAC1 (Beagle adrenal cortex with disposal), BAC2 (Beagle adrenal cortex with non-disposal), BP1 (Beagle pituitary with disposal), BP2 (Beagle pituitary with non-disposal), CFDAC1 (Chinese Field Dog adrenal cortex with disposal), CFDAC2 (Chinese Field Dog adrenal cortex with non-disposal), CFDP1 (Chinese Field Dog pituitary with disposal), CFDP2 (Chinese Field Dog pituitary with non-disposal), were generated by deep sequencing, using Illumina Genome Analyzer IIx.
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.
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
Project description:Among female Long-Evans rats, mating enhances neurosteroid formation in the midbrain ventral tegmental area (independent of peripheral steroid-secreting glands, the ovaries and adrenals). The sources/targets for these actions are not well-understood. In Experiment 1, proestrous rats engaged in a mating paradigm, or did not, and had midbrains assessed via Affymetrix rat genome microarrays. In Experiment 2, the influence of gonadal and adrenal glands on the expression of these genes was assessed in rats that were proestrous, ovariectomized (OVX), or OVX and adrenalectomized (ADX). Microarrays revealed 53 target genes that were significantly up-regulated (> 2.0-fold change) in response to mating. Mating significantly enhanced midbrain mRNA expression of genes involved in hormonal and trophic actions: Gh1, S100g, and Klk1b3 in proestrous, but not OVX and/or ADX, rats; Fshb in all but OVX/ADX rats; and Lhb and Tshb in all rats. Thus, mating enhances midbrain gene expression, independent and dependent of, peripheral glands.
Project description:To explore individual variation in the biological response to cortisol, the main stress hormone, in pigs, we have developed a microarray analysis to study the kinetics of the response to an ACTH injection measured at 4 time points. ACTH is a hormone secreted by the pituitary gland and triggering the release of cortisol by the adrenal glands in response to a stress. The objective was to identify genes up- or down-regulated during the stress response triggered by cortisol in the whole blood.
Project description:In order to understand the role of Hippo pathway in mice adrenal glands, we inactivated lats1/2 in a transgenic mouse model using the cre recombinase system in aldosterone-producing zG cells. RNAseq analysis on whole adrenal glands were performed on male mice