Transcriptome of the NR5A1 expressing pituitary gonadotropes
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE216466 | GEO | 2022/10/28
REPOSITORIES: GEO
Similar Datasets
Project description:Transcriptome of the NR5A1 expressing pituitary gonadotropes
| PRJNA893660 | ENA
Project description:NR5A1 is expressed in the pituitary gonadotropes and regulates their functional differentiation. We have previously identified a pituitary-specific enhancer region located in the 6th intron of the Nr5a1 gene. In this study, deletion of the pituitary enhancer by genome editing abolished the expression of NR5A1 in the pituitary gland, confirming the functional importance of the enhancer. Transcriptomic changes in the enhancer-deleted mouse pituitary were revealed in both males and females.
2022-10-28 | GSE216468 | GEO
Project description:Gonadotropin-releasing hormone (GnRH) governs reproduction in vertebrates by regulating pituitary gonadotropins. Zebrafish, however, is an exception as gnrh3–/– fish, which lack the hypophysiotropic GnRH3, are fertile, suggesting that zebrafish utilizes a Gnrh-independent mechanism to regulate reproduction. To elucidate the role of Gnrh3 and the Gnrh-independent mechanisms that regulate the pituitary gonadotropes, we profiled the gene expression in individual pituitary cells of wild-type and gnrh–/– adult female zebrafish and identified transcriptionally defined cell types. The classical Lh and Fsh gonadotropes expressed both gonadotropin beta subunits with a ratio of 13:1 (lhb:fshb) and 40:1 (fshb:lhb), respectively. We discovered that Lh gonadotropes predominantly express genes encoding receptors for Gnrh (gnrhr2), thyroid hormone, estrogen, dopamine, and steroidogenic factor 1 (SF1). No Gnrh receptor expression was enriched in Fsh gonadotropes, instead, the expression of cholecystokinin receptor (cckrb) and galanin receptor (gal1rb) were enriched in these cells. The hereditary loss of Gnrh3 gene resulted in downregulation of fshb in Lh gonadotropes. Likewise, targeted chemogenetic ablation of Gnrh3 neurons led to a decrease in the number of fshb+/lhb+ cells. Our studies suggest that Gnrh3 directly acts on Lh gonadotropes through Gnrhr2, but the outcome of this interaction is still unknown. Gnrh3 also regulates fshb expression, probably via a non-Gnrh receptor route. Altogether, while Lh secretion and synthesis are likely regulated by multiple factors in a Gnrh-independent manner, Gnrh3 seems to play a role in the cellular organization of the pituitary in zebrafish.
2024-11-20 | GSE272806 | GEO
Project description:Mammalian reproduction is dependent on the gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone, which are secreted by pituitary gonadotrope cells. The zinc-finger transcription factor, GATA2, was previously implicated in FSH production in male mice, although its mechanisms of action and role in females were not determined. To address these gaps in knowledge, we generated and analyzed gonadotrope-specific Gata2 knockout mice using the Cre-lox system. While conditional knockout (cKO) males exhibited ~50% reductions in serum FSH levels and pituitary FSHβ subunit (Fshb) expression relative to controls, FSH production was apparently normal in cKO females. RNA-seq analysis of purified gonadotropes from control and cKO males revealed a profound decrease in expression of gremlin (Grem1), a bone morphogenetic protein (BMP) antagonist. Grem1 was expressed in gonadotropes, but not other cell lineages, in the adult male mouse pituitary. Gata2, Grem1, and Fshb mRNA levels were significantly higher in pituitaries of wild-type males relative to females but decreased in males treated with estradiol and increased following ovariectomy in control but not cKO females. Recombinant gremlin stimulated Fshb expression in pituitary cultures from wild-type mice. Collectively, the data suggest that GATA2 promotes Grem1 expression in gonadotropes and that the gremlin protein potentiates FSH production. The mechanisms of gremlin action have not yet been established but may involve attenuation of BMP binding to activin type II receptors in gonadotropes, potentiating induction of Fshb transcription by activins or related ligands.
2022-07-14 | GSE189915 | GEO
Project description:Mammalian reproduction is dependent on the gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone, which are secreted by pituitary gonadotrope cells. The zinc-finger transcription factor, GATA2, was previously implicated in FSH production in male mice, although its mechanisms of action and role in females were not determined. To address these gaps in knowledge, we generated and analyzed gonadotrope-specific Gata2 knockout mice using the Cre-lox system. While conditional knockout (cKO) males exhibited ~50% reductions in serum FSH levels and pituitary FSHβ subunit (Fshb) expression relative to controls, FSH production was apparently normal in cKO females. RNA-seq analysis of purified gonadotropes from control and cKO males revealed a profound decrease in expression of gremlin (Grem1), a bone morphogenetic protein (BMP) antagonist. Grem1 was expressed in gonadotropes, but not other cell lineages, in the adult male mouse pituitary. Gata2, Grem1, and Fshb mRNA levels were significantly higher in pituitaries of wild-type males relative to females but decreased in males treated with estradiol and increased following ovariectomy in control but not cKO females. Recombinant gremlin stimulated Fshb expression in pituitary cultures from wild-type mice. Collectively, the data suggest that GATA2 promotes Grem1 expression in gonadotropes and that the gremlin protein potentiates FSH production. The mechanisms of gremlin action have not yet been established but may involve attenuation of BMP binding to activin type II receptors in gonadotropes, potentiating induction of Fshb transcription by activins or related ligands.
2022-07-14 | GSE190064 | GEO
Project description:Mammalian reproduction is dependent on the gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone, which are secreted by pituitary gonadotrope cells. The zinc-finger transcription factor, GATA2, was previously implicated in FSH production in male mice, although its mechanisms of action and role in females were not determined. To address these gaps in knowledge, we generated and analyzed gonadotrope-specific Gata2 knockout mice using the Cre-lox system. While conditional knockout (cKO) males exhibited ~50% reductions in serum FSH levels and pituitary FSHβ subunit (Fshb) expression relative to controls, FSH production was apparently normal in cKO females. RNA-seq analysis of purified gonadotropes from control and cKO males revealed a profound decrease in expression of gremlin (Grem1), a bone morphogenetic protein (BMP) antagonist. Grem1 was expressed in gonadotropes, but not other cell lineages, in the adult male mouse pituitary. Gata2, Grem1, and Fshb mRNA levels were significantly higher in pituitaries of wild-type males relative to females but decreased in males treated with estradiol and increased following ovariectomy in control but not cKO females. Recombinant gremlin stimulated Fshb expression in pituitary cultures from wild-type mice. Collectively, the data suggest that GATA2 promotes Grem1 expression in gonadotropes and that the gremlin protein potentiates FSH production. The mechanisms of gremlin action have not yet been established but may involve attenuation of BMP binding to activin type II receptors in gonadotropes, potentiating induction of Fshb transcription by activins or related ligands.
2022-07-14 | GSE190060 | GEO
Project description:Transcriptomic changes in the pituitary when pituitary enhancer of the Nr5a1 gene is deleted
| PRJNA893668 | ENA
Project description:The inhibins control reproduction by suppressing follicle-stimulating hormone synthesis by pituitary gonadotrope cells. The recently discovered inhibin B co-receptor mediating this inhibition, TGFBR3L, is selectively and highly expressed in gonadotropes in both mice and humans. We sought to characterize mechanisms controlling cell-specific Tgfbr3l/TGFBR3L transcription. We identified two steroidogenic factor 1 (SF-1) cis-elements in the proximal Tgfbr3l promoter in mice. Using single-nucleus ATAC-seq we find that gonadotrope-specific SF-1 (Nr5a1) knockout mice, which exhibit hypogonadotropic hypogonadism, display, contrary to controls, closed chromatin in the promoter region of theTgfbr3l gene in gonadotropes. These, and other, data collectively indicate that SF-1 directly regulates Tgfbr3l/TGFBR3L transcription, contributing to gonadotrope-specific expression of the gene.
2023-03-13 | GSE198907 | GEO
Project description:The pituitary tumors (PA) arise in adenohypophyseal cells and are the second most common tumor in central nervous system. Reflective of their monoclonal cell of origin these tumors could be classified according to the hormone that they produce. The mutational and copy number variation burden in these tumors are scarce, indicating other molecular events are involved in pituitary tumorigenesis. Here we show throughout transcriptome and methylome analysis that there are three readily distinctive molecular signatures. The first group is comprised by the gonadotropes, null cell and silent corticotroph PA, the second group comprised by ACTH PA and the group cluster together the TSH-, PRL- and GH- PA. These groups showed CACNA2D4, EPHA4 and SLIT1 gene up-regulation, respectively. Pathway enrichment analysis support the previous observations. The calcium signaling pathway is characteristic for gonadotropes null cell and silent corticotroph, the Renin-Angiotensin system for the ACTH PA and the Fatty acid metabolisms for the TSH-, PRL-, GH- cluster. The analysis of scRNA-seq from non-tumoral pituitary tissue revealed that these three groups originate since the pituitary development/embryogenesis. The immune cell infiltration landscape revealed that PA could be potentially infiltrated by NK and mast cells. Taken together these results correlate with the expression of the NR5A1, TBX19 and POU1F1 transcription factors, which drive pituitary embryogenesis and theoretically tumorigenesis and potentially indicates three divergent cell precursors cells. We used microarrays to detail the molecular alteration in PA compared to non-tumoral gland.
2020-11-16 | GSE147786 | GEO
Project description:Identifying the early gene program induced by GnRH would help understand how GnRH-activated signaling pathways modulate gonadotrope secretory response. We previously analyzed GnRH-induced early genes in LbT2 cells, however these lack GnRH self-potentiation, a physiological attribute of gonadotropes. To minimize cellular heterogeneity, rat primary pituitary cultures were enriched for gonadotropes by 40-60% using a sedimentation gradient. Given the limited number of gonadotropes, RNA was amplified prior to microarray analysis. Thirty-three genes were up-regulated 40 minutes after GnRH stimulation. Real-time PCR confirmed regulation of several transcripts including fosB, c-fos, egr-2 and rap1b, a small GTPase and member of the Ras family. GnRH stimulated rap1b gene expression in gonadotropes, measured by a sensitive single cell assay. Immunocytochemistry revealed increased Rap1 protein in GnRH-stimulated gonadotropes. These data establish rap1b as a novel gene rapidly induced by GnRH and a candidate to modulate gonadotropin secretion in rat gonadotropes. Primary rat gonadotrope cells were exposed to 10 nM GnRH for 40 min, then harvested and processed for RNA extraction using a Qiagen RNeasy mini kit (Qiagen, Valencia, CA). A total of 12 Affymetrix Rat Expression Array 230 v2.0, namely 6 GnRH-treated and 6 vehicle-treated samples, each containing 31,000 gene clusters, were used. Data analysis was performed by Affymetrix GeneChip Operating System (GCOS). A gene was considered to be up-regulated by GnRH if there is at least 50% concordance across multiple pairwise comparisons of GnRH- vs. vehicle-treated microarrays, and if the fold-change was at least 1.50.
2011-08-16 | E-GEOD-31399 | biostudies-arrayexpress