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Leptin Receptor Ablation in Anterior Pituitary Somatotropes Reveals Broad Transcriptomic Changes and Sex-Specific Signaling Pathways

ABSTRACT: Leptin Receptor Ablation in Anterior Pituitary Somatotropes Reveals Broad Transcriptomic Changes and Sex-Specific Signaling Pathways

PROVIDER: PRJNA1157429 | ENA |

REPOSITORIES: ENA

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			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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Leptin Receptor Ablation in Anterior Pituitary Somatotropes Reveals Broad Transcriptomic Changes and Sex-Specific Signaling Pathways

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) (Log2FC0.58; 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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Transcription profiling of rat anterior pituitary gland response to diethylstilbestrol

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

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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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