Prolactin receptor expression in mouse dorsal root ganglia neuronal subtypes is sex-dependent

Mayur Patil, Anahit H. Hovhannisyan, Andi Wangzhou, Jennifer Mecklenburg, Wouter Koek, Vincent Goffin, David Grattan, Ulrich Boehm, Gregory Dussor, Theodore J. Price, Armen N. Akopian

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Sensory neurones exhibit sex-dependent responsiveness to prolactin (PRL). This could contribute to sexual dimorphism in pathological pain conditions. The present study aimed to determine the mechanisms underlying sex-dependent PRL sensitivity in sensory neurones. A quantitative reverse transcriptase-polymerase chain reaction shows that prolactin receptor (Prlr) long and short isoform mRNAs are expressed at comparable levels in female and male mouse dorsal root ganglia (DRG). In Prlrcre/+;Rosa26LSL-tDTomato/+ reporter mice, percentages of Prlr+ sensory neurones in female and male DRG are also similar. Characterisation of Prlr+ DRG neurones using immunohistochemistry and electrophysiology revealed that Prlr+ DRG neurones are mainly peptidergic nociceptors in females and males. However, sensory neurone type-dependent expression of Prlr is sex dimorphic. Thus, Prlr+ populations fell into three small- and two medium-large-sized sensory neuronal groups. Prlr+ DRG neurones are predominantly medium-large sized in males and are proportionally more comprised of small-sized sensory neurones in females. Specifically, Prlr+/IB4+/CGRP+ neurones are four- to five-fold higher in numbers in female DRG. By contrast, Prlr+/IB4/CGRP+/5HT3a+/NPYR2 are predominant in male DRG. Prlr+/IB4/CGRP, Prlr+/IB4/CGRP+ and Prlr+/IB4/CGRP+/NPYR2+ neurones are evenly encountered in female and male DRG. These differences were confirmed using an independently generated single-cell sequencing dataset. Overall, we propose a novel mechanism by which sensory neurone type-dependent expression of Prlr could explain the unique sex dimorphism in responsiveness of nociceptors to PRL.

Original languageEnglish (US)
Article numbere12759
JournalJournal of Neuroendocrinology
Volume31
Issue number8
DOIs
StatePublished - Jan 1 2019

Keywords

  • electrophysiology
  • nociception
  • prolactin
  • prolactin receptor
  • sensory neurones

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

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    Patil, M., Hovhannisyan, A. H., Wangzhou, A., Mecklenburg, J., Koek, W., Goffin, V., Grattan, D., Boehm, U., Dussor, G., Price, T. J., & Akopian, A. N. (2019). Prolactin receptor expression in mouse dorsal root ganglia neuronal subtypes is sex-dependent. Journal of Neuroendocrinology, 31(8), [e12759]. https://doi.org/10.1111/jne.12759