Saturable transport of prolactin across the blood-brain barrier is independent of the prolactin receptor

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 112-141-Hypothalamus-Pituitary Development & Biology
Basic/Clinical
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-135
Rosemary S E Brown*1, William A Banks2, Nadine Binart3 and David R. Grattan1
1University of Otago, Dunedin, New Zealand, 2University of Washington School of Medicine, Seattle, WA, 3Universitť Paris-Sud, Le Kremlin BicÍtre, France
The anterior pituitary hormone, prolactin, crosses the blood-brain barrier (BBB) to exert critical physiological functions in the brain. However, the mechanism by which prolactin enters the brain is not completely understood. As a relatively large 23 kDa polypeptide, prolactin likely requires a transporter to cross the BBB and gain access to the brain. Prolactin is found in the cerebrospinal fluid (CSF), and levels in the CSF parallel those found in the blood. Extremely high levels of prolactin receptor are found in the choroid plexus, and it has been hypothesised that this receptor in the choroid plexus may serve as a transporter by binding to prolactin in the blood and secreting it into the CSF. The aim of this study was to test this hypothesis by measuring the transport of 125I-labelled prolactin into the brain of mice lacking the prolactin receptor (Prlr-/-) compared to wild-type controls (Prlr+/+). Mice were treated with bromocriptine (100ug/sc, 2 hours prior to anesthetisation), a D2 dopamine receptor agonist, to lower endogenous prolactin levels. Mice were anesthetised and 125I-labelled recombinant mouse prolactin (106 cpm) was injected into the left jugular vein. Blood samples from the right carotid artery and whole brains were collected at specific time points 1-15 minutes following injection, and the total radioactivity present in serum and whole brain was measured. The half-life clearance of prolactin from the blood was 6.7 minutes. We found that there was no change in the rate of 125I-labelled prolactin transport into the brain in Prlr-/- mice, compared to control mice. The transport of prolactin into the brain was saturable, with transport effectively blocked by unlabelled ovine prolactin. A very high dose of prolactin (1 mg prolactin injected, achieving blood levels 726.6 µg/ml prolactin) was required to block transport, however, suggesting that transport is unlikely to be saturated even at pathological levels of hyperprolactinaemia. These data suggest that the prolactin receptor is not required for transport of prolactin into the brain, but this function involves another, as yet unidentified, transporter molecule.

Nothing to Disclose: RSEB, WAB, NB, DRG

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