Estradiol enhances prostaglandin E2 receptor gene expression in luteinizing hormone-releasing hormone (LHRH) neurons and facilitates the LHRH response to PGE2 by activating a glia-to-neuron signaling pathway.
Prostaglandin E2 (PGE2) mediates the stimulatory effect of norepinephrine (NE) on the secretion of luteinizing hormone-releasing hormone (LHRH), the neuropeptide controlling reproductive function. In rodents, this facilitatory effect requires previous exposure to estradiol, suggesting that the steroid affects downstream components in the cascade that leads to PGE2-induced LHRH release. Because astroglia are the predominant cell type contacting LHRH-secreting nerve terminals, we investigated the involvement of hypothalamic astrocytes in the estradiol facilitation of PGE2-induced LHRH release. A subpopulation of LHRH neurons was found to express the mRNA encoding the PGE2 receptor subtype EP1-R, which is coupled to calcium mobilization. The LHRH-producing cell line GT1-1 also contains EP1-R mRNA and, to a lesser extent, the three alternatively spliced forms of EP3-R mRNA (alpha, beta, and gamma) that encode receptors linked to inhibition and stimulation of cAMP formation. Hypothalamic astrocytes treated with estradiol produced a conditioned medium that when applied to GT1-1 cells resulted in a selective upregulation of EP1-R and EP3gamma-R mRNAs. The conditioned medium also enhanced the LHRH response to EP1-R and EP3-R agonists and the cAMP response to EP3-R activation. Thus, one mechanism by which estradiol facilitates the effect of neurotransmitters acting via PGE2 to stimulate LHRH release is by enhancing the glial production of substances that upregulate PGE2 receptors on LHRH neurons. The existence of such a mechanism underscores the emerging importance of glial-neuronal communication in the control of brain neurosecretory activity.
Rage
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Division of Neuroscience, Oregon Regional Primate Research Center-Oregon Health Sciences University, Beaverton, Oregon 97006, USA.
Lee
B J
BJ
Ma
Y J
YJ
Ojeda
S R
SR
D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000502:physiology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D015232:Dinoprostone / Q000031:analogs & derivatives / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000145:classification / Q000235:genetics; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D010052:Ovariectomy; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018078:Receptors, Prostaglandin E / Q000096:biosynthesis* / Q000145:classification / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
C092396:17-phenyltrinorprostaglandin E2; D017077:Culture Media, Conditioned; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D018078:Receptors, Prostaglandin E; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D000242:Cyclic AMP; D015232:Dinoprostone; D009638:Norepinephrine