Distribution of Prolactin-Responsive Neurons in the Mouse Forebrain

Prolactin has numerous biological actions in the brain, and transgenic mice are increasingly being used to investigate these actions. The present study aimed to provide a detailed mapping of the prolactin-responsive neurons in the female mouse forebrain by describing the distribution of prolactin receptor mRNA by in situ hybridization, and measuring prolactin-induced phosphorylation of signal transducer and activation of transcription 5 (pSTAT5) by immunohistochemistry. For in situ hybridization, a probe designed to detect both long and short receptor isoforms showed mRNA expression in a heterogeneous manner within the forebrain. Strong expression was observed in the rostral hypothalamus, particularly in periventricular regions, as well as in the arcuate and ventromedial nuclei of the mediobasal hypothalamus. There was also significant expression in some nonhypothalamic regions, notably high expression in the choroid plexus, and lower levels of expression in the medial amygdala, bed nucleus of the stria terminalis, and lateral septum. Prolactin-induced pSTAT5, detected by immunohistochemistry, provided a functional index of prolactin receptor activation in neurons. Prolactin-induced pSTAT5 was only observed in areas containing prolactin receptor mRNA, and was particularly prominent in the rostral and mediobasal hypothalamus. Most other areas that contained prolactin receptor mRNA also showed positive signal for prolactin-induced pSTAT5. The major exceptions were paraventricular nucleus and median preoptic nucleus, in which prolactin receptor mRNA was observed, but no induction of pSTAT5 by prolactin. The data provide key neuroanatomical information facilitating the use of the mouse model for furthering our understanding of prolactin actions in the brain. J. Comp. Neurol. 518:92-102, 2010. (C) 2009 Wiley-Liss, Inc.