PMID- 16204378 OWN - NLM STAT- MEDLINE DCOM- 20060420 LR - 20181113 IS - 0027-8424 (Print) IS - 1091-6490 (Electronic) IS - 0027-8424 (Linking) VI - 102 IP - 41 DP - 2005 Oct 11 TI - Sex differences in estrogenic regulation of neuronal activity in neonatal cultures of ventromedial nucleus of the hypothalamus. PG - 14907-12 AB - Estrogenic effects have been implicated in sexual differentiation of brain and behavior, in part by affecting neuronal activity in the ventromedial nucleus of the hypothalamus (VMN). We report here a remarkable sex difference in estrogenic regulation of neuronal activity in male vs. female neural networks. Spontaneous synaptic currents originating from a population of neurons were recorded in primary VMN cultures using the whole-cell patch-clamp technique. Treatment with 17beta-estradiol (E2, 10 nM) for 24 h induced opposite effects in the two sexes: the frequency of spontaneous synaptic events decreased significantly in neurons derived from males but increased in those from females. Interestingly, the 24-hour E2 effect was partially reversed by an acute application (5 min) of a second dose of E2 (10 nM), suggesting an interaction between extended (24-hr) and acute (5-min) effects of E2 in VMN neurons. To understand the underlying mechanism of this sexually dimorphic action of E2, we analyzed the E2 effect on GABAergic neurotransmission by recording miniature inhibitory postsynaptic currents. After 24-hour E2 treatment, both the amplitude and frequency of miniature inhibitory postsynaptic currents increased in neurons derived from males but decreased in those from females. These results suggest that E2-induced changes in GABAergic inhibition could at least partially explain E2 effects on neuronal activity. We conclude that E2 may have sexually dimorphic effects on the synaptic output of VMN neurons by modulating GABAergic neurotransmission. FAU - Zhou, Jin AU - Zhou J AD - Laboratory of Neurobiology and Behavior, The Rockefeller University, New York, NY 10021, USA. zhouj@rockefeller.edu FAU - Pfaff, Donald W AU - Pfaff DW FAU - Chen, Gong AU - Chen G LA - eng GR - R01 HD005751/HD/NICHD NIH HHS/United States GR - R37 HD005751/HD/NICHD NIH HHS/United States GR - HD-05751/HD/NICHD NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. DEP - 20051004 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 4TI98Z838E (Estradiol) SB - IM MH - Animals MH - Animals, Newborn MH - Estradiol/*pharmacology MH - Female MH - Male MH - Neurons/drug effects/*metabolism MH - Patch-Clamp Techniques MH - Rats MH - Rats, Sprague-Dawley MH - *Sex Characteristics MH - Synaptic Transmission/*drug effects MH - Time Factors MH - Ventromedial Hypothalamic Nucleus/drug effects/*metabolism PMC - PMC1253608 EDAT- 2005/10/06 09:00 MHDA- 2006/04/21 09:00 PMCR- 2006/04/11 CRDT- 2005/10/06 09:00 PHST- 2005/10/06 09:00 [pubmed] PHST- 2006/04/21 09:00 [medline] PHST- 2005/10/06 09:00 [entrez] PHST- 2006/04/11 00:00 [pmc-release] AID - 0507440102 [pii] AID - 010214907 [pii] AID - 10.1073/pnas.0507440102 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2005 Oct 11;102(41):14907-12. doi: 10.1073/pnas.0507440102. Epub 2005 Oct 4.