PMID- 15555924 OWN - NLM STAT- MEDLINE DCOM- 20050302 LR - 20141120 IS - 1044-7431 (Print) IS - 1044-7431 (Linking) VI - 27 IP - 4 DP - 2004 Dec TI - Estrogen deficiency leads to apoptosis in dopaminergic neurons in the medial preoptic area and arcuate nucleus of male mice. PG - 466-76 AB - The aromatase knockout (ArKO) mouse is unable to synthesize estrogens. Immunohistochemical studies on active caspase-3 and tyrosine hydroxylase (TH) revealed apoptosis of dopaminergic neurons in the medial preoptic area (MPO) and arcuate nucleus (Arc) of the hypothalamus of 1-year-old (1yo) male ArKO mice while no active caspase-3 was detected in wild type (WT). Furthermore, the number of TH-positive cells in the MPO and caudal Arc was significantly decreased in 1yo ArKO compared to WT. RNase protection assays support the presence of apoptosis in 1yo ArKO hypothalamus, revealing an up-regulation of pro-apoptotic genes: FASL, FADD, and caspase-8. Concomitantly, the ratio of bcl-2-related anti-apoptotic genes to pro-apoptotic genes in the hypothalamus of 1yo ArKO mice was significantly down-regulated. Previously, we have reported that no such changes were observed in the hypothalamus of female ArKO mice. Thus, we have provided direct evidence that estrogen is required to maintain the survival and functional integrity of dopaminergic neurons in the MPO and Arc of male, but not female mice. FAU - Hill, Rachel A AU - Hill RA AD - Prince Henry's Institute of Medical Research, Clayton 3168, VIC, Australia. FAU - Pompolo, Sueli AU - Pompolo S FAU - Jones, Margaret E E AU - Jones ME FAU - Simpson, Evan R AU - Simpson ER FAU - Boon, Wah Chin AU - Boon WC LA - eng GR - R37AG08174/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Mol Cell Neurosci JT - Molecular and cellular neurosciences JID - 9100095 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Estrogens) RN - 0 (Fadd protein, mouse) RN - 0 (Fas Ligand Protein) RN - 0 (Fas-Associated Death Domain Protein) RN - 0 (Fasl protein, mouse) RN - 0 (Membrane Glycoproteins) RN - 0 (RNA, Messenger) RN - EC 1.14.14.1 (Aromatase) RN - EC 1.14.16.2 (Tyrosine 3-Monooxygenase) RN - EC 3.4.22.- (Casp3 protein, mouse) RN - EC 3.4.22.- (Casp8 protein, mouse) RN - EC 3.4.22.- (Caspase 3) RN - EC 3.4.22.- (Caspase 8) RN - EC 3.4.22.- (Caspases) RN - VTD58H1Z2X (Dopamine) SB - IM MH - Adaptor Proteins, Signal Transducing/genetics MH - Animals MH - Apoptosis/*genetics MH - Arcuate Nucleus of Hypothalamus/pathology/*physiopathology MH - Aromatase/deficiency/genetics MH - Caspase 3 MH - Caspase 8 MH - Caspases/genetics/metabolism MH - Cell Count MH - Cell Survival/genetics MH - Dopamine/*metabolism MH - Down-Regulation/genetics MH - Estrogens/biosynthesis/*deficiency MH - Fas Ligand Protein MH - Fas-Associated Death Domain Protein MH - Genes, bcl-2/genetics MH - Male MH - Membrane Glycoproteins/genetics MH - Mice MH - Mice, Knockout MH - Nerve Degeneration/genetics/*metabolism MH - Preoptic Area/pathology/*physiopathology MH - RNA, Messenger/metabolism MH - Tyrosine 3-Monooxygenase/metabolism MH - Up-Regulation/genetics EDAT- 2004/11/24 09:00 MHDA- 2005/03/03 09:00 CRDT- 2004/11/24 09:00 PHST- 2004/01/08 00:00 [received] PHST- 2004/03/24 00:00 [revised] PHST- 2004/04/27 00:00 [accepted] PHST- 2004/11/24 09:00 [pubmed] PHST- 2005/03/03 09:00 [medline] PHST- 2004/11/24 09:00 [entrez] AID - S1044-7431(04)00174-5 [pii] AID - 10.1016/j.mcn.2004.04.012 [doi] PST - ppublish SO - Mol Cell Neurosci. 2004 Dec;27(4):466-76. doi: 10.1016/j.mcn.2004.04.012.