Prolactin is involved in glial responses following a focal injury to the juvenile rat brain.
A cerebral growth hormone axis is activated following brain injury in the rat and treatment with growth hormone is neuroprotective. We have now investigated whether the closely related prolactin axis has similar properties following injury to the developing rat brain. From one day following a unilateral hypoxic ischemic injury, prolactin immunoreactivity was increased in the affected cortex parallel to the development of the injury (P<0.001). Initial prolactin and prolactin receptor staining on penumbral neurons progressively decreased whereas astrocytes remained strongly immunopositive. Reactive microglia also became strongly prolactin immunoreactive. Unlike growth hormone, central treatment with prolactin failed to rescue neurons in this paradigm. This was confirmed in vitro; rat prolactin failed to protect neurons under conditions for which growth hormone was neuroprotective. However, prolactin had trophic and pro-proliferative effects on glia (P<0.001). We confirmed the expression of the prolactin receptor in vitro by reverse transcriptase polymerase chain reaction, and show its strong association with astrocytes as compared with neurons by immunocytochemistry. In summary, we show for the first time that hypoxia ischemia induces a robust activation of the prolactin axis in regions of the cerebral cortex affected by injury. The lack of neuroprotective properties in vivo and in vitro indicates that, unlike growth hormone, prolactin is not directly involved in neuronal rescue in the injured brain. Its strong relation to glial reactions and its gliatrophic effects suggest that the prolactin axis is primarily involved in a gliogenic response during recovery from cerebral injury.
Möderscheim
T A E
TA
Liggins Institute, University of Auckland, 2-6 Park Avenue, Grafton, Auckland, New Zealand.
Gorba
T
T
Pathipati
P
P
Kokay
I C
IC
Grattan
D R
DR
Williams
C E
CE
Scheepens
A
A
D000818:Animals; D001930:Brain Injuries / Q000503:physiopathology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005333:Fetus; D013006:Growth Hormone / Q000494:pharmacology / Q000502:physiology; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology*; D011388:Prolactin / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D011981:Receptors, Prolactin / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology
D011981:Receptors, Prolactin; D011994:Recombinant Proteins; D011388:Prolactin; D013006:Growth Hormone