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Series GSE121645 Query DataSets for GSE121645
Status Public on Mar 01, 2019
Title Translation Regulation of the Prolactin Receptor Defines Sexually Dimorphic Pain Responses to Prolactin
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary 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.
Overall design Paw and DRG tissue from 3 males and 3 females are sequenced
Contributor(s) Patil M, Hovhannisyan AH, Mecklenburg J, Zou Y, Wangzhou A, Goffin V, Grattan D, Boehm U, Lai Z, Dussor G, Price TJ, Akopian AN
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Submission date Oct 23, 2018
Last update date Mar 02, 2019
Contact name Theodore J Price
Organization name University of Texas at Dallas
Street address 800 W Campbell Rd.
City Richardson
State/province TX
ZIP/Postal code 75080
Country USA
Platforms (1)
GPL21493 Illumina HiSeq 3000 (Mus musculus)
Samples (12)
GSM3440940 Male_paw_Veh1
GSM3440941 Male_paw_Veh2
GSM3440942 Male_paw_Veh3
BioProject PRJNA497998
SRA SRP166419

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE121645_RAW.tar 1.1 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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