Prolactin induces Egr-1 gene expression in cultured hypothalamic cells and in the rat hypothalamus.
Prolactin (PRL), the major lactogenic hormone, acts also as neuromodulator and regulator of neuronal and glial plasticity in the brain. There is an increase in synthesis and release of PRL within the hypothalamus during peripartum and in response to stress. To identify mechanisms by which PRL induces neuroplasticity, we studied the ability of PRL to induce the transcription factor Egr-1 in the hypothalamic cell line, 4B, in vitro, and in specific neuronal cell types of the hypothalamus in vivo. PRL induced Egr-1 mRNA expression in 4B cells, an effect which was prevented by the MEK inhibitor, U0126. In vivo, intracerebroventricular PRL (1 microg) increased Egr-1 mRNA levels in the hypothalamic paraventricular (PVN) and supraoptic nuclei (SON) of female rats. The increase in mRNA paralleled elevated Egr-1 protein expression in the PVN and SON. Double staining immunohistochemistry revealed Egr-1 localization in oxytocin neurons of the PVN and SON, but not in vasopressin neurons in these regions. In the dorsomedial PVN, a population of non-oxytocin or vasopressin cells localized in a region corresponding to corticotropin-releasing hormone neurons also showed marked Egr-1 immunoreactivity. The data suggest that PRL modulates plasticity in oxytocinergic neurons, through MAP kinase-dependent induction of Egr-1.
Blume
Annegret
A
Department of Behavioural and Molecular Neuroendocrinology, Institute of Zoology, University of Regensburg, Regensburg, Germany.
Torner
Luz
L
Liu
Ying
Y
Subburaju
Sivan
S
Aguilera
Greti
G
Neumann
Inga D
ID
D000818:Animals; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D051766:Early Growth Response Protein 1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics*; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000235:genetics*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010121:Oxytocin / Q000187:drug effects / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism* / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013495:Supraoptic Nucleus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D010121:Oxytocin; D011388:Prolactin; D003346:Corticotropin-Releasing Hormone