title: Estrogen receptor beta is essential for sprouting of nociceptive primary afferents and for morphogenesis and maintenance of the dorsal horn interneurons.
abstract: Estrogen is known to influence pain, but the specific roles of the two estrogen receptors (ERs) in the spinal cord are unknown. In the present study, we have examined the expression of ERalpha and ERbeta in the spinal cord and have looked for defects in pain pathways in ERbeta knockout (ERbeta(-/-)) mice. In the spinal cords of 10-month-old WT mice, ERbeta-positive cells were localized in lamina II, whereas ERalpha-positive cells were mainly localized in lamina I. In ERbeta(-/-) mice, there were higher levels of calcitonin gene-regulated peptide and substance P in spinal cord dorsal horn and isolectin B4 in the dorsal root ganglion. In the superficial layers of the spinal cord, there was a decrease in the number of calretinin (CR)-positive neurons, and in the outer layer II, there was a loss of calbindin-positive interneurons. During embryogenesis, ERbeta was first detectable in the spinal cord at embryonic day 13.5 (E13.5), and ERalpha was first detectable at E15.5. During middle and later embryonic stages, ERbeta was abundantly expressed in the superficial layers of the dorsal horn. ERalpha was also expressed in the dorsal horn but was limited to fewer neurons. Double staining for ERbeta and CR showed that, in the superficial dorsal horn of WT neonates [postnatal day 0 (P0)], most CR neurons also expressed ERbeta. At this stage, few CR-positive cells were detected in the dorsal horn of ERbeta(-/-) mice. Taken together, these findings suggest that, early in embryogenesis, ERbeta is involved in dorsal horn morphogenesis and in sensory afferent fiber projections to the dorsal horn and that ERbeta is essential for survival of dorsal horn interneurons throughout life.
authors: Division of Medical Nutrition, Department of Biosciences and Nutrition, Karolinska Institute, Novum, SE-141 86 Stockholm, Sweden.
authors: Xiaotang
authors: X
authors: Fan
authors: Hyun-Jin
authors: HJ
authors: Kim
authors: Margaret
authors: M
authors: Warner
authors: Jan-Ake
authors: JA
authors: Gustafsson
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D048430:Cell Shape; D047628:Estrogen Receptor alpha / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D007395:Interneurons / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D020671:Posterior Horn Cells / Q000166:cytology* / Q000196:embryology / Q000378:metabolism*; D013116:Spinal Cord / Q000196:embryology / Q000378:metabolism
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta
references: Brain. 1980 Dec;103(4):717-72
references: 7437888
references: Cell Tissue Res. 2001 May;304(2):193-214
references: 11396714
references: Neurosci Lett. 1983 Dec 30;43(2-3):149-54
references: 6672690
references: J Comp Neurol. 1987 Dec 15;266(3):332-59
references: 2447134
references: Cell Tissue Res. 1989 Jul;257(1):149-53
references: 2752404
references: J Neurophysiol. 1989 Jul;62(1):96-108
references: 2754484
references: Brain Res. 1989 Jul 3;491(1):33-44
references: 2765883
references: Brain Res Bull. 1989 Dec;23(6):493-508
references: 2611692
references: Brain Res. 1990 Mar 19;511(2):329-37
references: 2334851
references: Neuroscience. 1990;37(3):839-48
references: 2247226
references: Neuroscience. 1992;46(1):101-34
references: 1594096
references: Brain Res Bull. 1993;31(1-2):13-22
references: 7680942
references: Eur J Neurosci. 1993 Jul 1;5(7):782-94
references: 8281290
references: Brain Res Brain Res Rev. 1994 May;19(2):163-79
references: 8061685
references: J Biol Chem. 1997 Aug 8;272(32):19858-62
references: 9242648
references: Mol Endocrinol. 1997 Sep;11(10):1486-96
references: 9280064
references: J Comp Neurol. 1997 Dec 1;388(4):507-25
references: 9388012
references: Anat Embryol (Berl). 1999 May;199(5):379-90
references: 10221449
references: Endocr Rev. 1999 Jun;20(3):279-307
references: 10368772
references: Proc Natl Acad Sci U S A. 1999 Sep 14;96(19):10905-10
references: 10485924
references: J Neurosci. 2001 Aug 15;21(16):6077-85
references: 11487631
references: J Appl Physiol (1985). 2001 Dec;91(6):2785-801
references: 11717247
references: Proc Natl Acad Sci U S A. 2003 Jan 21;100(2):703-8
references: 12515851
references: J Neurosci. 2003 May 1;23(9):3908-15
references: 12736360
references: Int Rev Cytol. 2003;231:91-127
references: 14713004
references: Mol Interv. 2003 Aug;3(5):281-92
references: 14993442
references: J Neurophysiol. 2004 Jun;91(6):2413-21
references: 14749303
references: Neuroscience. 2004;126(2):391-403
references: 15207357
references: Mol Cell Biol. 2004 Sep;24(17):7681-94
references: 15314175
references: J Comp Neurol. 1979 Jul 15;186(2):117-31
references: 447880
references: J Comp Neurol. 2005 Jul 25;488(2):152-79
references: 15924341
references: Nat Rev Neurosci. 2005 Jul;6(7):507-20
references: 15995722
references: Eur J Neurosci. 2005 Sep;22(5):1149-57
references: 16176357
references: J Neurosci Res. 2005 Oct 15;82(2):283-93
references: 16130149
references: Horm Behav. 2006 Apr;49(4):441-9
references: 16257405
references: Brain Res. 2006 Apr 14;1083(1):39-49
references: 16542644
references: Hippocampus. 2006;16(5):453-63
references: 16526034
references: J Neurotrauma. 2006 Jun;23(6):830-52
references: 16774470
references: Curr Opin Neurobiol. 2006 Aug;16(4):460-6
references: 16828278
references: Eur J Pharmacol. 2006 Dec 28;553(1-3):146-8
references: 17056036
references: Proc Natl Acad Sci U S A. 2006 Dec 19;103(51):19338-43
references: 17159139
references: J Neurocytol. 2000 May-Jun;29(5-6):351-8
references: 11424951
references: Pain. 1999 Nov;83(2):243-8
references: 10534596
references: Cell Tissue Res. 1999 Oct;298(1):63-74
references: 10555540
references: Pain. 2000 Mar;85(1-2):273-81
references: 10692628
references: J Comp Neurol. 2000 Mar 13;418(3):281-98
references: 10701827
references: J Neurosci Res. 2000 Aug 1;61(3):329-37
references: 10900080
references: J Orofac Pain. 2000 Summer;14(3):169-84; discussion 184-95
references: 11203754
references: Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2792-6
references: 11226319
references: J Comp Neurol. 1983 Dec 10;221(3):313-28
references: 6197429