Leptin Receptor Ablation in Anterior Pituitary Somatotropes Reveals Broad Transcriptomic Changes and Sex-Specific Signaling Pathways
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ABSTRACT:
PROVIDER: PRJNA1157429 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR30559055.fastq.gz | Fastqsanger.gz | |||
| SRR30559056.fastq.gz | Fastqsanger.gz | |||
| SRR30559057.fastq.gz | Fastqsanger.gz | |||
| SRR30559058.fastq.gz | Fastqsanger.gz | |||
| SRR30559059.fastq.gz | Fastqsanger.gz |
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Project description:Anterior pituitary somatotropes utilize metabolic signals from the adipokine leptin to optimize responses to the body’s nutritional state via expression of growth hormone (GH), growth hormone releasing hormone receptors (GHRHR) and their transcriptional regulator POU1F1. To identify the mechanism underlying leptin action upon somatotropes, we analyzed single cell transcriptomes of pituitaries from somatotropes lacking leptin receptors (LEPR-null) compared with control pituitaries. Computational clustering of results identified all common pituitay cell types plus 5 undefined (UND) clusters. Differentially expressed genes (DEGs) (Log2FC0.58; adjusted p<0.055 thresholds) in mutant males revealed effects upon both transcriptional and mRNA translation regulators, but not direct effects upon hormone mRNA expression. Dysfunction in the male mutant LEPR-null somatotrope cluster was indicated by down-regulated genes in key transcriptional and second messenger signaling pathways, which were mostly upregulated in mutant females. Furthermore, mutant female somatotrope dysfunction was indicataed by an increase in markers for pituitary stem and/or progenitor cells (e.g.Sox9) and also increases (0.67-2.6-fold) in non-somatotrope hormone DEGs, e.g. Pomc, Lhb, Tshb, Cga, and/or Prl in female somatotrope, lactotrope, thyrotrope, corticotrope, and the UND3 clusters. Gh mRNA was decreased in mutant female somatotrope, UND2 and UND3 clusters. Collectively the increases in multihormonal expression did not coincide with increased expression of receptors for their releasing hormones. This and the presence of Sox9 suggested that the female somatotropes presented an immature gene signature. Collectively, these data point to a trophic role for leptin in the differentiation and/or maturation of somatotropes through regulatory pathways that are unique to each sex.
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Project description:This SuperSeries is composed of the following subset Series:; GSE4028: Effects of diethylstilbestrol (DES) on the anterior pituitary gland of the ACI, Copenhagen and Brown Norway Rat. GSE4080: Effect of DES-treated Ept congenic rat lines on gene expression in the anterior pituitary gland. GSE4081: Expression QTL (eQTL) mapping in the anterior pituitary gland using DES-treated COPxACI F2 rats. Experiment Overall Design: Refer to individual Series
2008-06-12 | E-GEOD-4083 | biostudies-arrayexpress
Project description:This study provides a comprehensive proteomic analysis of five matched pairs of the anterior and posterior lobe of the pituitary, which was used to study the proteomic signature specific to both anterior and posterior lobes. Anterior Lobe n=5 Posterior Lobe n=5 A441 PT441 A442 PT442 A457 PT457 A459 PT459 A460 PT460
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Project description:The mouse pituitary gland undergoes vivid maturation immediately after birth. During this process, the local stem cell compartment shows signs of activation including elevated abundance and expression of stemness pathways when compared to adult pituitary stem cells. In addition, we found that the neonatal pituitary displays high regeneration efficiency, as occurring following diphtheria toxin (DT)-triggered endocrine cell-ablation injury using the GHCre/iDTR mouse model (expressing Cre recombinase under control of the growth hormone (Gh) promoter, as well as Cre-inducible (floxed) DT receptor (iDTR)). This regeneration is more pronounced than in older mice, which is in line with the activated (stem cell) nature of the neonatal gland. However, it is not known what molecular mechanisms underlie the stem cell activation status in the neonatal gland. Here, we set out to decode the stem cells’ phenotype during the neonatal pituitary maturation stage starting from single cell RNA-sequencing (scRNA-seq) interrogations of neonatal (postnatal day 7, PD7) normal (undamaged) and damaged pituitary (more specifically, its major endocrine anterior lobe).
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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.
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2024-07-04 | PXD042011 | Pride
Project description:Anterior pituitary cells are highly active with regards to protein synthesis and secretion, processes which depend heavily on mitochondrial ATP production and functional endoplasmic reticula. It is well known that obesity adds an allostatic overload to tissues, requiring them to adapt to inflammation and oxidative stress. Therefore, we hypothesized that the pituitary is highly vulnerable to the stress of high fat diet-induced weight gain. In this study, we utilized a 10-15 week high fat diet (HFD, 60%) plus a thermoneutral housing paradigm, testing both male and female FVB.129P mice. We quantified serum hormones and cytokines, characterized the metabolic phenotype, and defined changes in the pituitary transcriptome using single-cell RNA-seq. Weight gain was significant by 3 weeks in HFD mice, and by 10 weeks all HFD groups had gained 20 g. HFD females (15 weeks) had increased energy expenditure and decreased activity. All HFD groups showed increases in serum leptin, Il-6, resistin, MCP-1, and TNFα. HFD males had increased insulin; both HFD males and females had increased TSH, and HFD females had decreased serum prolactin and growth hormone (GH) pulse amplitude. Pituitary scRNA-seq revealed modest or no changes in pituitary cell gene expression in the different cell types from HFD males after 10 or 15 weeks or HFD females after 10 weeks. However, females exposed to a HFD for 15 weeks showed significant numbers of differentially expressed genes in lactotropes and stem cells. Pathway analyses identified a reduction in pathways that supported protein translation, ribosome biogenesis, and oxidative phosphorylation, indicating mitochondrial dysfunction. Collectively, these studies reveal that pituitary cells from males are more resilient to the oxidative stress of obesity than females and identify the most vulnerable pituitary cell populations in females.
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Project description:Anterior pituitary glands were isolated from 21 week old male rats treated for 12 weeks with the synthetic estrogen diethylstilbestrol (DES). 43 COPxACI F2 animals were selected based on pituitary weight phenotypic extremes: 22 highest and 21 lowest pituitary weights in our F2 population. Expression profiles were determined using Affymetrix Rat Genome 230 v. 2.0 arrays. In conjunction with genomewide genotypes available for these 43 animals, linkage analysis was done using mRNA abundance of each transcript on the array as a separate quantitative phenotype. These arrays provide a resource for expression QTL (eQTL) mapping on a genomewide level in the pituitary gland. Experiment Overall Design: 43 samples from anterior pituitary gland were analyzed. COPxACI F2 male animals were treated with DES for 12 weeks, starting at 9 weeks of age. Pituitary glands were harvested and weighed at sacrifice (21 weeks of age). The 43 samples were selected for pituitary weight phenotypic extremes: 22 highest and 21 lowest pituitary weights in our F2 population. Genomewide genotypes are available for these animals and in conjunction with the array data, genomewide expression QTL (eQTL) mapping was done.
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Project description:Anterior pituitary glands were isolated from 21 week old male rats treated for 12 weeks with the synthetic estrogen diethylstilbestrol (DES). Three biological replicates were prepared for each of 4 congenic lines: Ept1, Ept2, Ept6, and Ept9. Congenic rat lines were constructed by introgressing COP alleles onto an ACI background within a given Ept locus. Expression profiles were determined using Affymetrix Rat Genome 230 v. 2.0 arrays. Comparison of congenic rats with the ACI and COP parental strains (see series GSE4028) will allow identification of genes whose expression is influenced by an estrogen-induced pituitary tumor (Ept) QTL. Experiment Overall Design: 12 samples from anterior pituitary gland were analyzed. For each of 4 congenic rat lines (Ept1, Ept2, Ept6, Ept9) there were 3 biological replicates of DES-treated male animals. Congenic animals were constructed by introgressing COP alleles onto an ACI background. This was done within the linkage interval for a given Ept locus. These congenic samples can be compared to the ACI and COP parental strains (see GSE4028) to determine expression differences due to a particular chromosomal region, or QTL.
2008-06-12 | E-GEOD-4080 | biostudies-arrayexpress
Project description:Anterior pituitary glands were isolated from 21 week old male rats treated for 12 weeks with the synthetic estrogen diethylstilbestrol (DES). 43 COPxACI F2 animals were selected based on pituitary weight phenotypic extremes: 22 highest and 21 lowest pituitary weights in our F2 population. Expression profiles were determined using Affymetrix Rat Genome 230 v. 2.0 arrays. In conjunction with genomewide genotypes available for these 43 animals, linkage analysis was done using mRNA abundance of each transcript on the array as a separate quantitative phenotype. These arrays provide a resource for expression QTL (eQTL) mapping on a genomewide level in the pituitary gland. Keywords: Estrogen Response
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