Research article summary (published 19 Oct 2009):

Prostaglandin E2-induced masculinization of brain and behavior requires protein kinase A, AMPA/kainate, and metabotropic glutamate receptor signaling.

Full Abstract

Prostaglandin E(2) (PGE(2)) mediates the masculinization of adult sex behavior in rats in response to the surge in serum testosterone at approximately birth. Measures of behavioral masculinization correlate with a twofold increase in spinophilin protein and the density of dendritic spines in the medial preoptic area (POA). Of the four receptors for PGE(2), EP(2) and EP(4) are required for the masculinization of behavior by PGE(2). EP(2) and EP(4) couple to G(s)-proteins, activating protein kinase A (PKA). By using H89 (N-[2-(p-bromo-cinnamylamino)-ethyl]-5-isoquinoline-sulfon-amide 2HCl) and Ht31, disruptors of PKA signaling, we have determined that PKA signaling is required for the masculinization of behavior by PGE(2). Glutamatergic signaling often mediates PGE(2) signaling; therefore, we tested whether inhibition of AMPA/kainate and metabotropic glutamate receptor (mGluR) signaling prevents PGE(2)-induced behavioral masculinization and whether activation of glutamate receptors mimics PGE(2). Females treated neonatally with NBQX (2,3-dihydroxy-6-nitro-7-sulfonyl-benzo[f]quinoxaline) plus LY341495 [(2S)-2-amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid] combined (AMPA/kainate and mGluR inhibitors, respectively) before PGE(2) did not exhibit as many mounts or intromission-like behaviors or initiate these behaviors as quickly as animals treated with PGE(2) alone. Animals neonatally treated with kainate, (+/-)-1-amino-1,3-cyclopentanedicarboxylic acid (ACPD) (type I mGluR agonist), or the two combined mounted as frequently and initiated mounting behavior as quickly as those given PGE(2). Ht31 does not prevent the masculinization of behavior by ACPD plus kainate cotreatment; rather, the coadministration of NBQX plus LY341495 prevents the forskolin-induced formation of POA dendritic spine-like processes. We conclude that PKA, AMPA/kainate, and metabotropic glutamate receptor signaling are necessary for the effects of PGE(2), that each receptor individually suffices to organize behavior, and that PKA is upstream of the glutamate receptors.

Author information

Author/s: Wright, Christopher L (CL); McCarthy, Margaret M (MM);

Affiliation: Program in Neuroscience, University of Maryland, Baltimore, School of Medicine, Baltimore, Maryland 21201, USA.

Grants: R01 MH052716 (Agency:NIMH NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural

Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci), published in United States. (Language: eng)

Reference: 2009-Oct; vol 29 (issue 42) : pp 13274-82

Dates: Created 2009/10/22; Completed 2009/11/06;

PMID: 19846715, status: MEDLINE (last retrieval date: 11/6/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals Animals, Newborn Cells, Cultured Cyclic AMP-Dependent Protein Kinases - metabolism Dinoprostone - pharmacology Drug Combinations Drug Interactions Excitatory Amino Acid Antagonists - pharmacology Female Isoquinolines - pharmacology Male Microfilament Proteins - metabolism Nerve Tissue Proteins - metabolism Neurites - drug effects

Neurons - cytology; drug effects Oxytocics - pharmacology Pregnancy Preoptic Area - cytology; drug effects; growth & development; metabolism Protein Kinase Inhibitors - pharmacology Proteins - pharmacology Rats Rats, Sprague-Dawley Reaction Time - drug effects Receptors, Metabotropic Glutamate - metabolism Sexual Behavior, Animal - drug effects Signal Transduction - drug effects Sulfonamides - pharmacology alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid - metabolism

Associated Chemicals: Drug Combinations (0) ; Excitatory Amino Acid Antagonists (0) ; Ht 31 protein, synthetic (0) ; Isoquinolines (0) ; Microfilament Proteins (0) ; Nerve Tissue Proteins (0) ; Oxytocics (0) ; Protein Kinase Inhibitors (0) ; Proteins (0) ; Receptors, Metabotropic Glutamate (0) ; Sulfonamides (0) ; neurabin (0) ; H 89 (127243-85-0) ; Dinoprostone (363-24-6) ; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (77521-29-0) ; Cyclic AMP-Dependent Protein Kinases (EC 2.7.11.11)

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