Prolactin stimulation of parathyroid adenomas
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE32387 | GEO | 2012/05/01
SECONDARY ACCESSION(S): PRJNA147951
REPOSITORIES: GEO
Similar Datasets
Project description:Primary hyperparathyroidism is a common endocrine disorder frequently affecting postmenopausal women. In this study we have investigated expression of the prolactin receptor (PRLr) in a panel of 37 sporadic parathyroid tumours, as well as functionality in vitro in cultured parathyroid tumour cells. High levels of the prolactin receptor gene (PRLR) transcripts were demonstrated in parathyroid tissues as compared to other reference tissues and breast cancer cells. PRLr products of 60/70 kDa were highly expressed in all parathyroid tumours. In addition varying levels of the 80 kDa PRLr isoform, with known proliferative activity, were demonstrated. In parathyroid tumours PRLr immunoreactivity was observed in cytoplasm in all cases and in addition in the plasma membrane (n = 12) or enlarged lysosomes (n = 4). In normal parathyroid rim PRLr was expressed in cytoplasm and granulae. In in vitro studies of short-term cultured human parathyroid tumour cells prolactin stimulation was associated with transcriptional changes in JAK/STAT, RIG-I like receptor and type II interferon signaling pathways as documented by gene expression profiling. Moreover, PRLR gene expression in parathyroid tumors was significantly inversely correlated with plasma total Ca2+ levels. In conclusion, the prolactin receptor was found highly abundant in human parathyroid gland, parathyroid tumours, correlated with patient Ca2+ levels and functionally responsive to physiological levels of prolactin. These findings suggest a role for the prolactin receptor in human parathyroid adenomas. Expression profiling was done in parathyroid adenomas subjected to prolactin treatment in culture. In addition, corresponding paraffin sections were obtained for verification of PRLr expression by immunohistochemistry. 200 mg/L prolactin (recombinant humanM-BM- prolactin, Cat. No. JM-4687-50, MBL Woburn, MA) was added to 1M-CM-^W 10^6 attached parathyroid tumour cells. Cells were harvested using RNAlater (QIAGEN) and homogenized with QIAshredder for RNA extraction after 3 h and 24 h in culture, respectively. Negative controls were collected in parallel with each case at the same time points. RNA was extracted using QIA Cube, and quality assessed with Bioanalyser and Nanodrop. Expression array profiling and data analysis was done at the KI core facility Bioinformatics and Expression Analysis (BEA, Novum, Huddinge) using the Affymetrix platform and the TITAN ST 1.1 array. A total of 16 samples were analysed including 4 parathyroid adenomas cultured for 3 h or 24 h in the presence of prolactin plus control samples cultured in parallel without prolactin.
2012-04-30 | E-GEOD-32387 | biostudies-arrayexpress
Project description:Pancreatic islets adapt to insulin resistance of pregnancy by up regulating beta-cell proliferation and increase insulin secretion. Previously, we found that prolactin receptor (Prlr) signaling is important for this process, as heterozygous prolactin receptor-null (Prlr+/-) mice are glucose intolerant, had a lower number of beta cells and lower serum insulin levels than wild type mice during pregnancy. However, since Prlr expression is ubiquitous, to determine its beta-cell-specific effects, we generated a transgenic mouse with a floxed Prlr allele under the control of an inducible promoter, i.e. bPrlR-/- mice, allowing conditional deletion of Prlr from beta cells in adult mice. In this study, we found that beta-cell-specific Prlr reduction resulted in elevated blood glucose during pregnancy. Similar to our previous finding in mice with global Prlr reduction, beta-cell-specific Prlr loss led to a lower beta-cell mass and a lower in vivo insulin level during pregnancy. However, these islets do not have an intrinsic insulin secretion defect when tested in vitro. Interestingly, when we compared the islet gene expression profile, using islets isolated from mice with global versus beta-cell-specific Prlr reduction, we found differences in expression of genes that regulate apoptosis, synaptic vesicle function and neuronal development. Indeed, islets from pregnant Prlr+/- mice are more susceptible glucolipotoxicity than bPrlR+/- islets. These observations suggest that Prlr has both cell-autonomous and non-cell-autonomous effect on beta cells, beyond its regulation of pro-proliferative genes.
2020-08-25 | GSE156774 | GEO
Project description:Mouse models of prolactinoma can be useful to better understand molecular mechanisms involved in abnormal lactotroph cell proliferation and secretion. We have previously developed a prolactin receptor deficient (Prlr -/-) mouse, in which Prlr -/- females develop large secreting prolactinomas from 12 months of age with a penetrance of 100%, mimicking human aggressive densely granulated macroprolactinoma, a highly secreting subtype.
2018-02-21 | GSE100334 | GEO
Project description:ABSTRACT:Pregnancy requires a higher functional beta cell mass and this is associated with profound changes in the gene expression profile of pancreatic islets. Taking Tph1 as a sensitive marker for pregnancy-related islet mRNA expression in female mice, we previously identified prolactin receptors and placental lactogen as key signalling molecules. Since beta cells from male mice also express prolactin receptors, the question arose whether male and female islets have the same phenotypic resilience at the mRNA level during pregnancy. We addressed this question in vitro, by using islet tissue culture with placental lactogen and in vivo, by transplanting male or female islets into female acceptor mice. Additionally, the islet mRNA expression of pregnant prolactin receptor deficient mice was compared with that of their pregnant wild-type littermates. When cultured with placental lactogen, or transplanted in female recipients that became pregnant (day 12.5), male islets induced the ‘islet pregnancy gene signature’, which we defined as the 12 highest induced genes in non-transplanted female islets at day 12.5 of pregnancy. In addition, serotonin immunoreactivity was also induced in these male transplanted islets at day 12.5 of pregnancy. In order to investigate the importance of prolactin receptors in these mRNA changes we used a prolactin receptor deficient mouse model. For the 12 genes of the signature, which are highly induced in control pregnant mice, no significant induction of mRNA transcripts was found at day 9.5 of pregnancy. Together, our results support the key role of placental lactogen as a circulating factor that can trigger the pregnancy mRNA profile in male and female beta cells. Islets were isolated from non-prengant (NP) and pregnant (day 9.5) PRLR+/+ and PRLR-/- mice for RNA extraction and hybridization on Affymetrix microarrays. For every condition 3 biological replicates were used.
2015-03-31 | E-GEOD-59141 | biostudies-arrayexpress
Project description:This is an open-label, Phase I, dose-escalation study to determine the maximum tolerated dose (MTD) and the recommended phase two dose (RPTD), and to assess the safety, preliminary efficacy, and pharmacokinetic (PK) profile of ABBV-176 for participants with advanced solid tumors likely to express Prolactin Receptor (PRLR). The study will consist of 2 cohorts: Dose Escalation and Expanded Recommended Phase 2 Dose.
| 2243822 | ecrin-mdr-crc
Project description:Pituitary tumours are generally benign. However, many are invasive and some of these are aggressive with high proliferation and recurrence rates. Only metastatic tumours are considered malignant and are rare (0.2%). To identify molecular events associated with the aggressive and malignant phenotypes, we combined a comparative genomic hybridization and transcriptomic analysis of 13 prolactin (PRL) tumours classified as non-invasive (NI; n=5), invasive (I; n=2) or aggressive-invasive (AI; n=6). Each tumour showed copy number alterations which appeared to be varied and discrete in the NI and I tumour groups, and more numerous and extensive in the AI tumour group. Allelic loss within the p arm region of chromosome 11 was detected in five of the AI tumours. This region contains the cytobands 11p15.2, 11p15.1, 11p14.3, 11p14.2, 11p14.1, 11p13, 11p12 and 11p11.2. Furthermore, an allelic loss in the 11q arm was also observed in three of these five tumours, which were considered malignant based on the presence of metastases. The comparison of genomic and transcriptomic data showed that allelic loss impacted upon the expression of genes located in the imbalanced region. An original data filtering strategy allowed us to highlight five genes (DGKZ, CD44, TSG101, GTF2H1 and HTATIP2), within the missing 11p region, potentially responsible for triggering the aggressive and malignant phenotypes of PRL tumours. Our novel combined genomic and transcriptomic analysis underlines the importance of chromosome 11 allelic loss in aggressive and malignant PRL tumours and led us to propose a new strategy to find markers of progression in rare tumours. Transcriptomic analysis of Codelink Human Whole Genome Bioarray was performed for 13 prolactin tumors: 6 aggressive-invasive, 2 invasive, and 5 non-invasive.
2011-03-16 | E-GEOD-22812 | biostudies-arrayexpress
Project description:This a model from the article:
Mathematical modelling of prolactin-receptor interaction and the corollary for prolactin receptor gene expression in skin
Soboleva TK, Vetharaniam I, Nixon AJ, Montenegro R, Pearson AJ, Sneyd J. J Theor Biol.
(2005) 234(2); 289-98 15757685
,
Abstract:
A mathematical model of prolactin regulating its own receptors was developed, and compared with experimental data on a qualitative level. The model incorporates the kinetics of prolactin-receptor interactions and subsequent signalling by prolactin-receptor dimers to regulate the production of receptor mRNA and hence the receptor population. The model relates changes in plasma prolactin concentration to prolactin receptor (PRLR) gene expression, and can be used for predictive purposes. The cell signalling that leads to the activation of target genes, and the mechanisms for regulation of transcription, were treated empirically in the model. The model's parameters were adjusted so that model simulations agreed with experimentally observed responses to administration of prolactin in sheep. In particular, the model correctly predicts insensitivity of receptor mRNA regulation to a series of subcutaneous injections of prolactin, versus sensitivity to prolonged infusion of prolactin. In the latter case, response was an acute down-regulation followed by a prolonged up-regulation of mRNA, with the magnitude of the up-regulation increasing with the duration of infusion period. The model demonstrates the feasibility of predicting the in vivo response of prolactin target genes to external manipulation of plasma prolactin, and could provide a useful tool for identifying optimal prolactin treatments for desirable outcomes.
This model was taken from the CellML repository
and automatically converted to SBML.
The original model was:
soboleva, vetharaniam, nixon, montenegro, pearson, sneyd, 2005, version01
The original CellML model was created by:
Lloyd, Catherine, May
c.lloyd(at)auckland.ac.nz
The University of Auckland
Auckland Bioengineering Institute
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
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In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not..
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2005-01-01 | MODEL7896869925 | BioModels
Project description:Transcriptional control by gonadal hormone nuclear receptors is the foundation for sex-dependent physiological processes, including pain. Our current findings point to sex-dependent translation control as a new mechanism for sexual dimorphisms in pain. We show that hindpaw or spinal administration of exogenous prolactin (PRL) induces thermal and mechanical hyperalgesia in a female-selective fashion. Unexpectedly, PCR and transcriptomic analysis of hindpaw and dorsal root ganglion (DRG) tissues reveal no differences in PRL receptor (Prlr) mRNA between sexes. Variance in overall hindpaw and DRG transcriptomes between females and males were minor. We find that Prlr mRNA and protein is mainly expressed by peptidergic nociceptors as shown by profiling using Prlr reporter mice and electrophysiology, but there are far more peptidergic neurons with functional Prlr in females than in males. In line with this, exogenous PRL increased excitability only in female neurons. Moreover, in male DRG neurons, 6-24 hr estrogen exposure establishes PRL sensitivity in Prlr mRNA+ male neurons that do not show PRL responses under other conditions. PRL-induced behavioral hypersensitivity as well as sensitivity to PRL in female DRG neurons can be ablated by treatment with cap-dependent translation inhibitor 4EGI-1. Spinal cord immunohistochemistry of Prlr reporter mice highlight that Prlr protein is only found in female DRG neurons, but Prlr mRNA localizes to central terminals of male and female sensory neurons. Based on these findings, we propose a novel mechanism for sex-dependent regulation Prlr mRNA translation that renders female DRG neurons uniquely responsive to PRL.
2019-03-01 | GSE121645 | GEO
Project description:Transcriptional control by gonadal hormone nuclear receptors is the foundation for sex-dependent physiological processes, including pain. Our current findings point to sex-dependent translation control as a new mechanism for sexual dimorphisms in pain. We show that hindpaw or spinal administration of exogenous prolactin (PRL) induces thermal and mechanical hyperalgesia in a female-selective fashion. Unexpectedly, PCR and transcriptomic analysis of hindpaw and dorsal root ganglion (DRG) tissues reveal no differences in PRL receptor (Prlr) mRNA between sexes. Variance in overall hindpaw and DRG transcriptomes between females and males were minor. We find that Prlr mRNA and protein is mainly expressed by peptidergic nociceptors as shown by profiling using Prlr reporter mice and electrophysiology, but there are far more peptidergic neurons with functional Prlr in females than in males. In line with this, exogenous PRL increased excitability only in female neurons. Moreover, in male DRG neurons, 6-24 hr estrogen exposure establishes PRL sensitivity in Prlr mRNA+ male neurons that do not show PRL responses under other conditions. PRL-induced behavioral hypersensitivity as well as sensitivity to PRL in female DRG neurons can be ablated by treatment with cap-dependent translation inhibitor 4EGI-1. Spinal cord immunohistochemistry of Prlr reporter mice highlight that Prlr protein is only found in female DRG neurons, but Prlr mRNA localizes to central terminals of male and female sensory neurons. Based on these findings, we propose a novel mechanism for sex-dependent regulation Prlr mRNA translation that renders female DRG neurons uniquely responsive to PRL.
2023-11-17 | GSE161826 | GEO