Prolactin Signalling in the Arcuate Nucleus During Pregnancy and Lactation

Abstract

Prolactin is a pleiotropic hormone secreted by the anterior pituitary gland with numerous functions throughout the body. Prolactin regulates its own release via a “short-loop” feedback mechanism mediated by dopaminergic neurons located in the arcuate nucleus. These neurons release dopamine into the median eminence through the portal blood system to the anterior pituitary gland, where it inhibits further PRL release. During late-pregnancy and lactation, elevated levels of prolactin are required; therefore changes in this regulatory system are essential. Such alterations may arise due to changes in the characteristics of these neurons, whereby they cease producing dopamine in response to prolactin. Interestingly, previous findings in rats suggest they also start expressing the opioid peptide enkephalin at this time.

This thesis aims to extend these observations into a mouse model by investigating tyrosine hydroxylase (dopamine synthesising enzyme) and proenkephalin A mRNA levels in the arcuate nucleus of late pregnant and lactating mice. Tyrosine hydroxylase mRNA levels were reduced (to approximately 4-fold to that seen in diestrus, n=8-12) and proenkephalin A mRNA levels were increased (from about 10-fold diestrus levels during late-pregnancy to about 5-fold during lactation, n=8-12) under these conditions. Furthermore, these changes were maintained following 24 h of pup removal. Immunohistochemistry was used to show that there was an increased number of enkephalin-expressing cells in the arcuate nucleus of mice during late-pregnancy (rising from approximately 2 cells per section during diestrus to 40 cells per section in late-pregnancy, n=6). This increase in the number of enkephalin-expressing cells was not seen in late-pregnant mice lacking in neuronal expression of the prolactin receptor.

These studies have therefore confirmed and extended the previous observations made in rats and provided the first evidence that neuronally expressed prolactin receptors are essential for modulating the prolactin feedback pathway during late-pregnancy and lactation.