Tuning the brain for motherhood: prolactin-like central signalling in virgin, pregnant, and lactating female mice

Abstract

Prolactin is fundamental for the expression of maternal behaviour. In virgin female rats, prolactin administered upon steroid hormone priming accelerates the onset of maternal care. By contrast, the role of prolactin in mice maternal behaviour remains unclear. This study aims at characterizing central prolactin activity patterns in female mice and their variation through pregnancy and lactation. This was revealed by immunoreactivity of phosphorylated (active) signal transducer and activator of transcription 5 (pSTAT5-ir), a key molecule in the signalling cascade of prolactin receptors. We also evaluated non-hypophyseal lactogenic activity during pregnancy by administering bromocriptine, which suppresses hypophyseal prolactin release. Late-pregnant and lactating females showed significantly increased pSTAT5-ir resulting in a widespread pattern of immunostaining with minor variations between pregnant and lactating animals, which comprises nuclei of the sociosexual and maternal brain, including telencephalic (septum, nucleus of the stria terminalis, and amygdala), hypothalamic (preoptic, paraventricular, supraoptic, and ventromedial), and midbrain (periaqueductal grey) regions. During late pregnancy, this pattern was not affected by the administration of bromocriptine, suggesting it to be elicited mostly by non-hypophyseal lactogenic agents, likely placental lactogens. Virgin females displayed, instead, a variable pattern of pSTAT5-ir restricted to a subset of the brain nuclei labelled in pregnant and lactating mice. A hormonal substitution experiment confirmed that estradiol and progesterone contribute to the variability found in virgin females. Our results reflect how the shaping of the maternal brain takes place prior to parturition and suggest that lactogenic agents are important candidates in the development of maternal behaviours already during pregnancy.

30 years after: CNS actions of prolactin: Sources, mechanisms and physiological significance

“…There is ample evidence for expression of the PRL receptor throughout a number of brain regions, using binding assays, 18 immunohistochemistry 19-21 and in situ hybridisation. 25,[27][28][29][30][31][32] These data are consistent with the model proposed above in that PRL is transported into the brain in a dispersed manner from cerebral microvasculature, simultaneously activating neurones at a wide range of target sites. 26 These studies have provided a consistent picture of the widespread distribution of PRL receptors in the brain, not only particularly in medial periventricular hypothalamic nuclei from the preoptic region through to the caudal ARC, but also in a number of extrahypothalamic regions such as the bed nucleus of the stria terminalis and the posterodorsal medial amygdala ( Figure 3).…”

The role of prolactin in the suppression of Crh mRNA expression during pregnancy and lactation in the mouse

“…These data compliment previous findings in the rat where central down‐regulation of prolactin receptors enhanced stress‐induced ACTH and oxytocin release . Recently, we have shown that the CRH neurones are not directly regulated by prolactin; however, there are many non‐CRH prolactin‐responsive cells both within and outside the PVN that might mediate an indirect action of prolactin upon the CRH neurones . One possible candidate within the PVN for mediating prolactin actions upon CRH neurones is oxytocin.…”

“…Prolactin receptor‐mediated signalling is markedly up‐regulated in the mouse brain during both pregnancy and lactation, including within the limbic and hypothalamic regions known to participate in the processing of stress information. This sustained elevation in prolactin receptor activation is achieved through the actions of prolactin and/or placental lactogen .…”

Prolactin maintains transient melanin‐concentrating hormone expression in the medial preoptic area during established lactation

“…The detection of immunopositive pSTAT5 is used as a surrogate marker of the long form of the Prlr because the available antibodies to the long form of the Prlr are often not sufficiently sensitive . Low numbers of cells immunopositive for pSTAT5 have previously been detected in the mPOA of virgin mice, with the number increasing in both pregnant and early lactating mice . We have now demonstrated that a significant proportion of the immunopositive MCH cells found in the mPOA are also immunopositive for pSTAT5 in response to prolactin administration, but not vehicle, 4 hours after treatment with bromocriptine on the morning of day 19 of lactation only.…”