Similar Datasets
Project description:Translation Regulation of the Prolactin Receptor Defines Sexually Dimorphic Pain Responses to Prolactin
| PRJNA497998 | ENA
Project description:Chronic pain is a major health care problem with great social and economic consequences. Although the medial prefrontal cortex (mPFC) and the thalamus have been implicated in regulating pain, whether and how these regions may involve in pain chronification process have remained largely unknown. Here, we show that Foxp2+ neurons in mPFC, which are corticothalamic (CT) neurons representing the major mPFC output to thalamus, are deactivated in chronic inflammatory pain. Interestingly, prolonged, but not short-term, inactivation of the Foxp2+ neurons in mPFC increases the sensitivity to noxious stimulations. Conversely, chemogenetic activation of this neuronal cluster induces robust antinociceptive effects in both naïve mice and mice with chronic inflammatory pain. Furthermore, we found that the mPFC Foxp2+ neurons project to several thalamic relay nuclei and that activation of the mPFC to the parataenial nucleus of thalamus (PTN) circuit relieves pain. Finally, RNA-seq of the mPFC Foxp2+ neurons revealed that many genes related to neuronal activity are dysregulated in mice with chronic inflammatory pain. Collectively, our studies revealed that Foxp2+ neurons in mPFC that project to thalamus play a critical role in somatosensory processing and pain chronification.
2023-09-16 | GSE243136 | 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.
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
Project description:We aim to determine blood transcriptome-based molecular signature of acute coronary syndrome (ACS), and to identify novel serum biomarkers for early stage ST-segment-elevation myocardial infarction (STEMI) We obtained peripheral blood from the patients with ACS who visited emergency department within 4 hours after the onset of chest pain: ST-elevation myocardial infarction (STEMI, n=7), Non-ST-elevation MI (NSTEMI, n=10) and unstable angina (UA, n=9), and normal control (n=7)
2015-05-23 | E-GEOD-60993 | biostudies-arrayexpress
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:Human infants are born to breastfeed. While 50% of lactating persons report struggling to make enough milk, there are no governmentally-approved drugs to enhance lactation1. Here, we engineer a variant of the naturally-occurring driver of lactation, the hormone Prolactin, to increase its serum half-life and produce a viable drug candidate. Our engineered variant,Prolactin-eXtra Long-acting(Prolactin-XL), is comprised of endogenously active human prolactin fused to an engineered human IgG1 Fc domain designed to overcome the unique drug development challenges specific to the lactating person-infant dyad. Our Prolactin-XL has a serum half-life of 70.9h in mice, 2,625-fold longer than endogenously active prolactin alone (70.9h v. 0.027h). We demonstrate that Prolactin-XL increases milk production and restores growth of pups fed by dams with pharmacologically-ablated lactation. We show that Prolactin-XL-enhanced lactation is accompanied by reversible, alveolar cell-driven changes in mammary gland morphology. Prolactin-XL treatment was associated with no identifiable pathology or adverse side effect in the lactating mice or nursing pups. This work establishes long-acting prolactins as a potentially powerful pharmacologic means to combat insufficient lactation. Implications for future research in lactating mammary gland biology and a potential preclinical path for developing Prolactin-XL for use in lactating persons are discussed.
2024-07-16 | GSE270276 | GEO
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.
2012-05-01 | GSE32387 | GEO
Project description:The exact role of prolactin on breast cancer still remains unclear. Clues supportive or unsurpportive for prolactin to be cancer driver are confusing. To clarify the role of autocrine prolactin of breast cancer cells on cancer development, we construct T47D cells overexpressing prolactin.
2023-03-01 | GSE221394 | GEO
Project description:Genomics of Pain - Resilience to Pain
| PRJNA498369 | ENA