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.
- prolactin receptor
- sensory neurones
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Endocrine and Autonomic Systems
- Cellular and Molecular Neuroscience