title: Estradiol stimulates an anti-translocation expression pattern of glucocorticoid co-regulators in a hippocampal cell model.
abstract: A consistent clinical finding in patients with major depressive disorder (MDD) is hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, the system in the body that facilitates the response to stress. It has been suggested that alterations in glucocorticoid receptor (GR)-mediated feedback prolong activation of the HPA axis, leading to the dysfunction observed in MDD. Additionally, the risk for developing MDD is heightened by several risk factors, namely gender, genetics and early life stress. Previous studies have demonstrated that GR translocation is sexually dimorphic and this difference may be facilitated by differential expression of GR co-regulators. The purpose of this study was to determine the extent to which ovarian hormones alter expression of GR and its co-regulators, Fkbp5 and Ppid, in HT-22 hippocampal neurons. The impact of corticosterone (cort), estradiol (E2), and progesterone (P4) treatments on the expression of the genes Nr3c1, Ppid, and Fkbp5 was assessed in HT-22 hippocampal neurons. Treatment of cells with increasing doses of cort increased the expression of Fkbp5, an effect that was potentiated by E2. Exposure of HT-22 cells to E2 decreased the expression of Ppid and simultaneous exposure to E2 and P4 had combinatory effects on Ppid expression. The effects of E2 on Ppid extend previous work which demonstrated that serum E2 concentrations correlate with hippocampal Ppid expression in female rats. The results presented here illustrate that E2 generates an anti-translocation pattern of GR co-regulators in hippocampal cells.
authors.affiliation: Department of Physiology, Emory University, Atlanta, GA, United States.
authors.forename: Sanjana A
authors.initials: SA
authors.lastname: Malviya
authors.forename: Sean D
authors.initials: SD
authors.lastname: Kelly
authors.forename: Megan M
authors.initials: MM
authors.lastname: Greenlee
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Eaton
authors.forename: Billie Jeanne
authors.initials: BJ
authors.lastname: Duke
authors.forename: Chase H
authors.initials: CH
authors.lastname: Bourke
authors.forename: Gretchen N
authors.initials: GN
authors.lastname: Neigh
mesh_terms: D000818:Animals; D002460:Cell Line; D003345:Corticosterone / Q000494:pharmacology; D021983:Cyclophilins / Q000235:genetics / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D022021:Tacrolimus Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000099159:Tacrolimus Binding Protein 5; D000097322:Peptidyl-Prolyl Isomerase D
chemical_list: D003345:Corticosterone; D021983:Cyclophilins; D004958:Estradiol; D011374:Progesterone; D011965:Receptors, Glucocorticoid; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5; C542344:NR3C1 protein, rat; C581109:Ppid protein, rat; D000097322:Peptidyl-Prolyl Isomerase D
keywords: Corticosterone; Estradiol; Fkbp5; Glucocorticoid receptor; HT-22; Nr3c1; Ppid; Progesterone
references.citation: J Affect Disord. 2003 Mar;74(1):5-13
references.pmid: 12646294
references.citation: JAMA. 2008 Mar 19;299(11):1291-305
references.pmid: 18349090
references.citation: Biol Psychiatry. 1998 Nov 1;44(9):798-811
references.pmid: 9807636
references.citation: Brain Res. 1988 Feb 2;440(1):67-78
references.pmid: 3359209
references.citation: Mol Cell Endocrinol. 2007 Sep 15;275(1-2):2-12
references.pmid: 17628337
references.citation: Steroids. 1991 Feb;56(2):52-8
references.pmid: 2020978
references.citation: J Neurosci Res. 2002 Feb 15;67(4):544-50
references.pmid: 11835321
references.citation: J Neurosci. 2009 Aug 26;29(34):10552-62
references.pmid: 19710308
references.citation: Physiol Behav. 2006 Feb 28;87(2):314-22
references.pmid: 16386277
references.citation: Ann N Y Acad Sci. 1998 May 1;840:33-44
references.pmid: 9629234
references.citation: Biochem Biophys Res Commun. 2001 Jun 1;284(1):219-25
references.pmid: 11374893
references.citation: J Neuroendocrinol. 2007 Feb;19(2):116-26
references.pmid: 17214874
references.citation: Cell Stress Chaperones. 2004 Autumn;9(3):243-52
references.pmid: 15544162
references.citation: ANS Adv Nurs Sci. 2005 Oct-Dec;28(4):364-75
references.pmid: 16292022
references.citation: Psychoneuroendocrinology. 2013 Jan;38(1):84-93
references.pmid: 22647578
references.citation: Endocrinology. 2012 Nov;153(11):5334-45
references.pmid: 22962255
references.citation: Brain Cogn. 2010 Feb;72(1):73-85
references.pmid: 19616355
references.citation: Endocrinology. 1992 Sep;131(3):1261-9
references.pmid: 1324155
references.citation: Cell Stress Chaperones. 2001 Jan;6(1):78-91
references.pmid: 11525247
references.citation: Biochem Pharmacol. 1983 May 1;32(9):1511-8
references.pmid: 6222739
references.citation: Horm Behav. 2012 Jan;61(1):91-9
references.pmid: 22134008
references.citation: Behav Brain Res. 2008 Mar 5;187(2):228-38
references.pmid: 17945360
references.citation: Proc Natl Acad Sci U S A. 2007 Mar 13;104(11):4688-93
references.pmid: 17360585
references.citation: Curr Top Med Chem. 2003;3(12):1348-57
references.pmid: 12871166
references.citation: Psychol Med. 2012 May;42(5):943-56
references.pmid: 21995950
references.citation: Psychopharmacology (Berl). 2011 Nov;218(1):303-12
references.pmid: 21509501
references.citation: Arch Gen Psychiatry. 1977 Jan;34(1):98-111
references.pmid: 319772
references.citation: Eur J Pharmacol. 2008 Apr 7;583(2-3):174-85
references.pmid: 18282566
references.citation: PLoS One. 2011 Feb 09;6(2):e16883
references.pmid: 21347384
references.citation: J Cell Biochem. 2005 May 15;95(2):302-12
references.pmid: 15778979
references.citation: Horm Behav. 1994 Dec;28(4):464-76
references.pmid: 7729815
references.citation: Horm Behav. 2011 Jun;60(1):112-20
references.pmid: 21466807
references.citation: Physiol Behav. 2009 May 25;97(2):250-8
references.pmid: 19275906
references.citation: Endocrinology. 2010 Sep;151(9):4332-43
references.pmid: 20668026
references.citation: Leukemia. 2004 Nov;18(11):1850-6
references.pmid: 15385927
references.citation: Steroids. 1994 Jul;59(7):436-42
references.pmid: 7974528
references.citation: J Neurosci. 1998 Sep 15;18(18):7462-73
references.pmid: 9736665
references.citation: Stress. 2004 Dec;7(4):209-19
references.pmid: 16019586
references.citation: Endocrinology. 1993 Jul;133(1):248-56
references.pmid: 8319574
references.citation: Psychoneuroendocrinology. 2009 Dec;34 Suppl 1:S186-95
references.pmid: 19560279
references.citation: Horm Behav. 2012 Aug;62(3):210-8
references.pmid: 22426413