PMID- 17443789 OWN - NLM STAT- MEDLINE DCOM- 20070601 LR - 20131121 IS - 1932-8451 (Print) IS - 1932-8451 (Linking) VI - 67 IP - 3 DP - 2007 Feb 15 TI - Glutamate AMPA/kainate receptors, not GABA(A) receptors, mediate estradiol-induced sex differences in the hypothalamus. PG - 304-15 AB - Sex differences in brain morphology underlie physiological and behavioral differences between males and females. During the critical perinatal period for sexual differentiation in the rat, gonadal steroids act in a regionally specific manner to alter neuronal morphology. Using Golgi-Cox impregnation, we examined several parameters of neuronal morphology in postnatal day 2 (PN2) rats. We found that in the ventromedial nucleus of the hypothalamus (VMN) and in areas just dorsal and just lateral to the VMN that there was a sex difference in total dendritic spine number (males greater) that was abolished by treating female neonates with exogenous testosterone. Dendritic branching was similarly sexually differentiated and hormonally modulated in the VMN and dorsal to the VMN. We then used spinophilin, a protein that positively correlates with the amount of dendritic spines, to investigate the mechanisms underlying these sex differences. Estradiol, which mediates most aspects of masculinization and is the aromatized product of testosterone, increased spinophilin levels in female PN2 rats to that of males. Muscimol, an agonist at GABA(A) receptors, did not affect spinophilin protein levels in either male or female neonates. Kainic acid, an agonist at glutamatergic AMPA/kainate receptors, mimicked the effect of estradiol in females. Antagonizing AMPA/kainate receptors with NBQX prevented the estradiol-induced increase in spinophilin in females but did not affect spinophilin level in males. CI - (c) 2007 Wiley Periodicals, Inc. FAU - Todd, Brigitte J AU - Todd BJ AD - Department of Physiology, University of Maryland, Baltimore School of Medicine, Baltimore, Maryland 21201, USA. btodd@aecom.yu.edu FAU - Schwarz, Jaclyn M AU - Schwarz JM FAU - Mong, Jessica A AU - Mong JA FAU - McCarthy, Margaret M AU - McCarthy MM LA - eng GR - MH52716/MH/NIMH NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - Dev Neurobiol JT - Developmental neurobiology JID - 101300215 RN - 0 (Androgens) RN - 0 (Excitatory Amino Acid Antagonists) RN - 0 (Microfilament Proteins) RN - 0 (Nerve Tissue Proteins) RN - 0 (Quinoxalines) RN - 0 (Receptors, AMPA) RN - 0 (Receptors, GABA-A) RN - 0 (Receptors, Kainic Acid) RN - 0 (neurabin) RN - 118876-58-7 (2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline) RN - 3XMK78S47O (Testosterone) RN - SIV03811UC (Kainic Acid) SB - IM MH - Androgens/*pharmacology MH - Animals MH - Animals, Newborn MH - Dendrites/ultrastructure MH - Drug Interactions MH - Excitatory Amino Acid Antagonists/pharmacology MH - Female MH - Hypothalamus/cytology/*drug effects MH - Kainic Acid/pharmacology MH - Male MH - Microfilament Proteins/metabolism MH - Nerve Tissue Proteins/metabolism MH - Neurons/metabolism/ultrastructure MH - Pregnancy MH - Quinoxalines/pharmacology MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, AMPA/*physiology MH - Receptors, GABA-A/physiology MH - Receptors, Kainic Acid/*physiology MH - *Sex Characteristics MH - Silver Staining/methods MH - Testosterone/*pharmacology EDAT- 2007/04/20 09:00 MHDA- 2007/06/02 09:00 CRDT- 2007/04/20 09:00 PHST- 2007/04/20 09:00 [pubmed] PHST- 2007/06/02 09:00 [medline] PHST- 2007/04/20 09:00 [entrez] AID - 10.1002/dneu.20337 [doi] PST - ppublish SO - Dev Neurobiol. 2007 Feb 15;67(3):304-15. doi: 10.1002/dneu.20337.