Combinatorial Expression of Phenotypes of Different Cell Lineages in the Rat and Mouse Pituitary

Denef, Carl; Pals, Katrien; Hauspie, Annelies; Vankelecom, Hugo; Seuntjens, Eve

doi:10.1196/annals.1327.010

Cited by 7 publications

(5 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…2a and 4a). Previous histological studies have described subpopulations of somatotropes in rat and pig [47][48][49] , including cells co-expressing Prl and Gh [50][51][52] . Recent scRNAseq analysis of murine pituitaries also resolved somatotrope sub-populations 1,53 .…”

Section: Discussionmentioning

confidence: 99%

Single nucleus multi-omics regulatory landscape of the murine pituitary

et al. 2021

View full text Add to dashboard Cite

To provide a multi-omics resource and investigate transcriptional regulatory mechanisms, we profile the transcriptome, chromatin accessibility, and methylation status of over 70,000 single nuclei (sn) from adult mouse pituitaries. Paired snRNAseq and snATACseq datasets from individual animals highlight a continuum between developmental epigenetically-encoded cell types and transcriptionally-determined transient cell states. Co-accessibility analysis-based identification of a putative Fshb cis-regulatory domain that overlaps the fertility-linked rs11031006 human polymorphism, followed by experimental validation illustrate the use of this resource for hypothesis generation. We also identify transcriptional and chromatin accessibility programs distinguishing each major cell type. Regulons, which are co-regulated gene sets sharing binding sites for a common transcription factor driver, recapitulate cell type clustering. We identify both cell type-specific and sex-specific regulons that are highly correlated with promoter accessibility, but not with methylation state, supporting the centrality of chromatin accessibility in shaping cell-defining transcriptional programs. The sn multi-omics atlas is accessible at snpituitaryatlas.princeton.edu.

show abstract

Section: Discussionmentioning

confidence: 99%

Single nucleus multi-omics regulatory landscape of the murine pituitary

et al. 2021

View full text Add to dashboard Cite

show abstract

“…However, Subburaju and Aguilera (Subburaju & Aguilera, 2007) found that only a minor proportion of BrdU labeled nuclei corresponded to cells stained with ACTH or the corticotroph precursor marker, T-pit (Pulichino et al, 2004). Reports of co-localization of ACTH in pituitary cell types other than corticotrophs, have suggested that mature pituitary cells can cross-differentiate (Denef et al, 2005). However, the lack of co-localization of BrdU stained nuclei in lactotrophs, thyrotrophs, somatotrophs or gonadotrophs, shown in this study is against this possibility.…”

Section: Alternative Actions Of Vp In the Pituitary On Mitogenesismentioning

confidence: 99%

The parvocellular vasopressinergic system and responsiveness of the hypothalamic pituitary adrenal axis during chronic stress

Aguilera

Subburaju

Young

et al. 2008

Progress in Brain Research

132

View full text Add to dashboard Cite

Vasopressin (VP) secreted from parvocellular neurons of the hypothalamic paraventricular nucleus (PVN) stimulates pituitary ACTH secretion, through interaction with receptors of the V1b subtype (V1bR) in the pituitary corticotroph, mainly by potentiating the stimulatory effects of corticotrophin releasing hormone (CRH). Chronic stress paradigms associated with corticotroph hyperresponsiveness lead to preferential expression of hypothalamic VP over CRH and upregulation of pituitary V1bR, suggesting that VP has a primary role during adaptation of the hypothalamic pituitary adrenal (HPA) axis to long-term stimulation. However, studies using pharmacological of genetic ablation of V1b receptors have shown that VP is required for full ACTH responses to some stressors, but not for the sensitization of ACTH responses to a novel stress observed during chronic stress. Studies using minipump infusion of a peptide V1 antagonist in long-term adrenalectomized rats have revealed that VP mediates proliferative responses in the pituitary. Nevertheless, only a minor proportion of cells undergoing mitogenesis co-express markers for differentiated corticotrophs or precursors, suggesting that new corticotrophs are recruited from yet undifferentiated cells. The overall evidence supports a limited role of VP regulating acute ACTH responses to some acute stressors and points to cell proliferation and pituitary remodeling as alternative roles for the marked increases in parvocellular vasopressinergic activity during prolonged activation of the HPA axis.

show abstract

“…Somatomammotropes and other co-secreting pituitary cells are a welldescribed phenomenon in normal mice, rats, and humans and in somatotropinomas, including the rat GH3 cell line [40][41][42] . Notably, the presence of important pools of cells secreting both GH and PRL has been repeatedly confirmed by single cell transcriptomic analysis [43][44][45] . As in other settings, increased body size and bone growth (vertebrae and long bones) due to GH/IGF-1 elevation was accompanied by decreased fat mass and increased lean mass in the Ghrhr Gpr101 mice versus wild-type controls (See Fig.…”

Section: Discussionmentioning

confidence: 85%

GPR101 drives growth hormone hypersecretion and gigantism in mice via constitutive activation of Gs and Gq/11

et al. 2020

View full text Add to dashboard Cite

Growth hormone (GH) is a key modulator of growth and GH over-secretion can lead to gigantism. One form is X-linked acrogigantism (X-LAG), in which infants develop GH-secreting pituitary tumors over-expressing the orphan G-protein coupled receptor, GPR101. The role of GPR101 in GH secretion remains obscure. We studied GPR101 signaling pathways and their effects in HEK293 and rat pituitary GH3 cell lines, human tumors and in transgenic mice with elevated somatotrope Gpr101 expression driven by the rat Ghrhr promoter (GhrhrGpr101). Here, we report that Gpr101 causes elevated GH/prolactin secretion in transgenic GhrhrGpr101 mice but without hyperplasia/tumorigenesis. We show that GPR101 constitutively activates not only Gs, but also Gq/11 and G12/13, which leads to GH secretion but not proliferation. These signatures of GPR101 signaling, notably PKC activation, are also present in human pituitary tumors with high GPR101 expression. These results underline a role for GPR101 in the regulation of somatotrope axis function.

show abstract

Combinatorial Expression of Phenotypes of Different Cell Lineages in the Rat and Mouse Pituitary

Cited by 7 publications

References 17 publications

Single nucleus multi-omics regulatory landscape of the murine pituitary

Single nucleus multi-omics regulatory landscape of the murine pituitary

The parvocellular vasopressinergic system and responsiveness of the hypothalamic pituitary adrenal axis during chronic stress

GPR101 drives growth hormone hypersecretion and gigantism in mice via constitutive activation of Gs and Gq/11

Contact Info

Product

Resources

About