Prolactin-induced and neuronal activation in the brain of mother mice

Abstract

Nursing has important consequences on mothers. To separate the prolactin-mediated and the neuronally-mediated actions of nursing, neurons directly affected by prolactin were visualized using pSTAT5 immunohistochemistry in relation to Fos-expressing neurons in suckled mother mice. In response to pup exposure following 22-h pup deprivation, we found a markedly elevated number of pSTAT5-containing neurons in several brain regions, including the lateral septum, medial amygdaloid nucleus, subparafascicular area, caudal periaqueductal gray, dorsal raphe, lateral parabrachial nucleus, nucleus of the solitary tract, and the periventricular, medial preoptic, paraventricular, arcuate and ventromedial nuclei of the hypothalamus. Pup exposure also induced Fos expression in all of these brain regions except the arcuate and ventromedial hypothalamic nuclei. Bromocriptine treatment known to reduce prolactin levels eliminated pSTAT5 from most brain regions while it did not affect Fos activation following suckling. The degree of colocalization for pSTAT5 and Fos ranged from 8 to 80% in the different brain regions suggesting that most neurons responding to pup exposure in mother mice are driven either by prolactin or direct neuronal input from the pups, while the number of neurons affected by both types of inputs depends on the examined brain area. In addition, both pSTAT5 and Fos were also double-labeled with estrogen receptor alpha (ERα) in mother mice, which revealed a very high degree of colocalization between pSTAT5 and ERα with much less potential interaction between Fos- and ERα-containing neurons suggesting that estrogen-sensitive neurons are more likely to be affected by prolactin than by direct neuronal activation.

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).…”

“…as a marker of PRL action. 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.…”

“…Hence, phosphorylated STAT5 in the nucleus of a cell provides an excellent marker of signal transduction activated via this pathway and has been used to identify neurones responding to PRL. 25,[27][28][29][30][31][32] Signalling through the JAK/STAT pathway is attenuated by members of a family of cytokine-inducible suppressors of cytokine signalling proteins. 73 These proteins are activated by cytokines, including PRL, 74 and then act as intracellular feedback inhibitors of signalling, including in the brain.…”

Acute effects of prolactin on hypothalamic prolactin receptor expressing neurones in the mouse

“…Binding of prolactin to its receptor exerts co-ordinated effects on gene transcription dependent on phosphorylation of the STAT5 transcription factor. Utilising immunohistochemical labelling of phosphorylated STAT5 (pSTAT5) has therefore been an effective method of mapping prolactin-responsive cells [7][8][9][10]. In the central nervous system (CNS), prolactin-induced pSTAT5 is widely distributed in forebrain and brainstem areas [11].…”

“…The brain region key for this role is the MPOA, also host to prolactin-activated neurones [7]. Indeed, prolactin elicits marked effects on maternal behaviours through its receptors located in the MPOA [33], with a large number of neurones expressing pSTAT5 in response to prolactin [7,10]. A subset of MPOA neurones are also able to respond electrically to prolactin [18].…”