PMID- 18480251 OWN - NLM STAT- MEDLINE DCOM- 20080624 LR - 20211020 IS - 1091-6490 (Electronic) IS - 0027-8424 (Print) IS - 0027-8424 (Linking) VI - 105 IP - 20 DP - 2008 May 20 TI - Estradiol modulation of phenylephrine-induced excitatory responses in ventromedial hypothalamic neurons of female rats. PG - 7333-8 LID - 10.1073/pnas.0802760105 [doi] AB - Estrogens act within the ventromedial nucleus of the hypothalamus (VMN) to facilitate lordosis behavior. Estradiol treatment in vivo induces alpha(1b)-adrenoreceptor mRNA and increases the density of alpha(1B)-adrenoreceptor binding in the hypothalamus. Activation of hypothalamic alpha(1)-adrenoceptors also facilitates estrogen-dependent lordosis. To investigate the cellular mechanisms of adrenergic effects on VMN neurons, whole-cell patch-clamp recordings were carried out on hypothalamic slices from control and estradiol-treated female rats. In control slices, bath application of the alpha(1)-agonist phenylephrine (PHE; 10 microM) depolarized 10 of 25 neurons (40%), hyperpolarized three neurons (12%), and had no effect on 12 neurons (48%). The depolarization was associated with decreased membrane conductance, and this current had a reversal potential close to the K(+) equilibrium potential. The alpha(1b)-receptor antagonist chloroethylclonidine (10 microM) blocked the depolarization produced by PHE in all cells. From estradiol-treated rats, significantly more neurons in slices depolarized (71%) and fewer neurons showed no response (17%) to PHE. PHE-induced depolarizations were significantly attenuated with 4-aminopyridine (5 mM) but unaffected by tetraethylammonium chloride (20 mM) or blockers of Na(+) and Ca(2+) channels. These data indicate that alpha(1)-adrenoceptors depolarize VMN neurons by reducing membrane conductance for K(+). Estradiol amplifies alpha(1b)-adrenergic signaling by increasing the proportion of VMN neurons that respond to stimulation of alpha(1b)-adrenergic receptors, which is expected in turn to promote lordosis. FAU - Lee, Anna W AU - Lee AW AD - Laboratory of Neurobiology and Behavior, The Rockefeller University, New York, NY 10065, USA. leeaw@rockefeller.edu FAU - Kyrozis, Andreas AU - Kyrozis A FAU - Chevaleyre, Vivien AU - Chevaleyre V FAU - Kow, Lee-Ming AU - Kow LM FAU - Devidze, Nino AU - Devidze N FAU - Zhang, Qiuyu AU - Zhang Q FAU - Etgen, Anne M AU - Etgen AM FAU - Pfaff, Donald W AU - Pfaff DW LA - eng GR - HD05751/HD/NICHD NIH HHS/United States GR - R37 HD005751/HD/NICHD NIH HHS/United States GR - MH38273/MH/NIMH NIH HHS/United States GR - R37 MH041414/MH/NIMH NIH HHS/United States GR - R01 MH038273/MH/NIMH NIH HHS/United States GR - R37 MH41414/MH/NIMH NIH HHS/United States GR - R01 HD005751/HD/NICHD NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20080514 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 - 0 (Estrogens) RN - 0 (Potassium Channels) RN - 1WS297W6MV (Phenylephrine) RN - 4TI98Z838E (Estradiol) RN - 66-40-0 (Tetraethylammonium) RN - BH3B64OKL9 (4-Aminopyridine) RN - X4W3ENH1CV (Norepinephrine) SB - IM MH - 4-Aminopyridine/chemistry MH - Animals MH - Electrophysiology/methods MH - Estradiol/*pharmacology MH - Estrogens/metabolism MH - Female MH - Hypothalamus/*pathology MH - Neurons/metabolism MH - Norepinephrine/*pharmacology MH - Patch-Clamp Techniques MH - Phenylephrine/*pharmacology MH - Potassium Channels/chemistry MH - Rats MH - Tetraethylammonium/chemistry MH - Ventromedial Hypothalamic Nucleus/*pathology PMC - PMC2438250 COIS- The authors declare no conflict of interest. EDAT- 2008/05/16 09:00 MHDA- 2008/06/25 09:00 PMCR- 2008/11/20 CRDT- 2008/05/16 09:00 PHST- 2008/05/16 09:00 [pubmed] PHST- 2008/06/25 09:00 [medline] PHST- 2008/05/16 09:00 [entrez] PHST- 2008/11/20 00:00 [pmc-release] AID - 0802760105 [pii] AID - 0367 [pii] AID - 10.1073/pnas.0802760105 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2008 May 20;105(20):7333-8. doi: 10.1073/pnas.0802760105. Epub 2008 May 14.