Prolactin transport into mouse brain is independent of prolactin receptor

Abstract

The anterior pituitary hormone prolactin exerts important physiologic actions in the brain. However, the mechanism by which prolactin crosses the blood-brain barrier and enters the brain is not completely understood. On the basis of high expression of the prolactin receptor in the choroid plexus, it has been hypothesized that the receptor may bind to prolactin in the blood and translocate it into the cerebrospinal fluid (CSF). This study aimed to test this hypothesis by investigating transport of ). Peripherally administered prolactin rapidly activates brain neurons, as evidenced by prolactin-induced phosphorylation of signal transducer and activator of transcription 5 (pSTAT5) in neurons within 30 min of administration. The transport of prolactin into the brain was saturable, with transport effectively blocked only by a very high dose of unlabeled ovine prolactin. Transport was regulated, as in lactating mice with chronically elevated levels of prolactin, the rate of 125 I-prolactin transport into the brain was significantly increased compared to nonlactating controls. There was no change in the rate of 125 Iprolactin transport into the brain in PRLR 2/2 mice lacking functional prolactin receptors compared to control mice, indicating transport is independent of the prolactin receptor. These data suggest that prolactin transport into the brain involves another as yet unidentified transporter molecule. Because CSF levels of 125 I-prolactin were very low, even up to 90 min after administration, the data suggest that CSF is not the major route by which blood prolactin gains access to neurons in the brain.-Brown, R.

Effects of Prolactin and Lactation on A15 Dopamine Neurones in the Rostral Preoptic Area of Female Mice

“…Moreover, there is significant activation of this population during lactation that is likely prolactin-mediated, with large increases in pSTAT5 labelling and increased dopamine turnover in the regions surrounding the OVLT and in the rPOA during lactation. Prolactin of pituitary origin appears to be the major factor mediating these actions because prolactin is known to enter the cerebrospinal fluid from the peripheral circulation through a saturable, carrier-mediated transport system (29-31), which we have recently shown to be independent of the prolactin receptor (32). This is illustrated by the fact that prolactin-induced pSTAT in the A15 neurones is seen following peripheral administration of exogenous prolactin, and that pSTAT5 in response to endogenous prolactin, such as during lactation, is lost when pituitary prolactin is inhibited by treatment with bromocriptine.…”

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

“…This is likely related to their role in PRL transport to the brain (Mangurian et al 1992; but see Brown et al 2015). In addition, in pregnant/lactating females, quite abundant cell labelling was present in the cerebral hemispheres (septum, amygdala, extended amygdala, and, to a lesser extent, cortex), diencephalon (mainly in the hypothalamus, but also in some thalamic and pretectal nuclei), midbrain (periaqueductal grey and laterodorsal tegmentum) and hindbrain.…”

Prolactin: Friend or Foe in Central Nervous System Autoimmune Inflammation?

“…Circulating PRL can cross the blood-brain barrier; however, its transport into the brain does not depend on PRLR but is mediated by a still-unidentified transport molecule [20]. …”