Mechanisms of Transient Signaling via Short and Long Prolactin Receptor Isoforms in Female and Male Sensory Neurons

Abstract

Background: Prolactin regulates the activity of nociceptors in pain conditions. Results: Prolactin regulation of sensory neurons is acute and mediated via PI3K and PKC⑀ following activation of prolactin receptor short isoform. Prolactin receptor short isoform actions are inhibited by the long isoform. Conclusion: Prolactin receptor short isoform mediates transient sensitization of nociceptors. Significance: The proposed mechanism could underlie prolactin involvement in hyperalgesia/pain.

Prolactin receptor in regulation of neuronal excitability and channels

“…Evaluation of human dental pulp tissue that is innervated by the trigeminal nerve, showed that PRLR-L is mostly absent in afferent nerves, but is present in the myelin sheath of peripheral glia that surrounds nerves. 40 In contrast, the use of isoform-specific human antibodies, showed that both PRLR-S1a and 1b were present in both nerve axoplasm and glia. 40 In the female rat dorsal The enteric nervous system ?…”

“…40 In contrast, the use of isoform-specific human antibodies, showed that both PRLR-S1a and 1b were present in both nerve axoplasm and glia. 40 In the female rat dorsal The enteric nervous system ?…”

“…7,8 A PRLR antibody, which does not discriminate between the different forms of PRLR, labels 50-60% of neurons in female rat trigeminal ganglia (TG) and a majority of the satellite glial cells (SGC) surrounding neuronal cell bodies. 40 However, use of in situ hybridization showed that PRLR-L is only present in 3-5% of male and female rat TG neurons thus suggesting that much of the PRLR immunoreactivity is due to PRLR-S. Evaluation of human dental pulp tissue that is innervated by the trigeminal nerve, showed that PRLR-L is mostly absent in afferent nerves, but is present in the myelin sheath of peripheral glia that surrounds nerves.…”

“…Results of other studies show that PRLR is also highly expressed in neurons within the hypothalamic arcuate nucleus (ARN) and anteroventral periventricular nucleus (AVPV), in addition to the expressions seen in sensory ganglia. 40,45 In this respect, it comes as no surprise that a majority of studies on regulation of neuronal functions by PRL have been done on neurons from ARN, AVPV, DRG and TG.…”

“…7,29,[36][37][38][39][40] Dual regulation of extra-pituitary PRL by estrogen and pathological condition is not well studied. Therefore, direct measurements on alterations in PRL concentrations in relevant parts of the nervous system triggered by pathological conditions are important to consider.…”