Advertisement
Original article| Volume 48, ISSUE 8, P854-860, October 15, 2000

Download started.

Ok

Effects of estradiol and progesterone administration on human serotonin 2A receptor binding: a PET study

  • Eydie L. Moses
    Correspondence
    Address reprint requests to Eydie Moses, M.D., NIMH Clinical Research Fellow, Magee-Women’s Hospital, Department of OB-GYN/RS, 300 Halket Street, Pittsburgh PA 15213-3180
    Affiliations
    Department of Psychiatry, University of Pittsburgh, Magee-Women’s Research Institute, Pittsburgh, Pennsylvania, USA (ELM, WCD, GS, MAB, SLB)
    Search for articles by this author
  • Wayne C. Drevets
    Affiliations
    Department of Psychiatry, University of Pittsburgh, Magee-Women’s Research Institute, Pittsburgh, Pennsylvania, USA (ELM, WCD, GS, MAB, SLB)

    Department of Radiology, University of Pittsburgh, Magee-Women’s Research Institute, Pittsburgh, Pennsylvania, USA (WCD, CAM, PJG, BL)
    Search for articles by this author
  • Gwenn Smith
    Affiliations
    Department of Psychiatry, University of Pittsburgh, Magee-Women’s Research Institute, Pittsburgh, Pennsylvania, USA (ELM, WCD, GS, MAB, SLB)

    Psychiatry Research and Neuroscience Research Center, North Shore–Long Island Jewish Health Care System, Glen Oaks, New York, USA (GS)
    Search for articles by this author
  • Chester A. Mathis
    Affiliations
    Department of Radiology, University of Pittsburgh, Magee-Women’s Research Institute, Pittsburgh, Pennsylvania, USA (WCD, CAM, PJG, BL)
    Search for articles by this author
  • Brinda N. Kalro
    Affiliations
    Department of Ob/Gyn/ReproSci, University of Pittsburgh, Magee-Women’s Research Institute, Pittsburgh, Pennsylvania, USA (BNK, TLL, SLB)
    Search for articles by this author
  • Meryl A. Butters
    Affiliations
    Department of Psychiatry, University of Pittsburgh, Magee-Women’s Research Institute, Pittsburgh, Pennsylvania, USA (ELM, WCD, GS, MAB, SLB)
    Search for articles by this author
  • Mark P. Leondires
    Affiliations
    NICHD/NIH/ERRB, National Institutes of Health, Bethesda, MarylandUSA (MPL)
    Search for articles by this author
  • Phil J. Greer
    Affiliations
    Department of Radiology, University of Pittsburgh, Magee-Women’s Research Institute, Pittsburgh, Pennsylvania, USA (WCD, CAM, PJG, BL)
    Search for articles by this author
  • Brian Lopresti
    Affiliations
    Department of Radiology, University of Pittsburgh, Magee-Women’s Research Institute, Pittsburgh, Pennsylvania, USA (WCD, CAM, PJG, BL)
    Search for articles by this author
  • Tammy L. Loucks
    Affiliations
    Department of Ob/Gyn/ReproSci, University of Pittsburgh, Magee-Women’s Research Institute, Pittsburgh, Pennsylvania, USA (BNK, TLL, SLB)
    Search for articles by this author
  • Sarah L. Berga
    Affiliations
    Department of Ob/Gyn/ReproSci, University of Pittsburgh, Magee-Women’s Research Institute, Pittsburgh, Pennsylvania, USA (BNK, TLL, SLB)

    Department of Psychiatry, University of Pittsburgh, Magee-Women’s Research Institute, Pittsburgh, Pennsylvania, USA (ELM, WCD, GS, MAB, SLB)
    Search for articles by this author

      Abstract

      Background: Preclinical studies demonstrate that 17β-estradiol (E2) increases serotonin-2A receptor (5-HT2AR) density in rat frontal cortex.
      Methods: We investigated the impact of hormone replacement therapy on 5-HT2AR binding potential (BP) using positron emission tomography and [18F]altanserin in five postmenopausal women. Subjects were imaged at baseline, following 8 to 14 weeks of transdermal E2, 0.1 mg/d, and following 2 to 6 weeks of E2 plus micronized progesterone (P) 100 mg per os twice daily. Regional BPs in the anterior cingulate cortex, dorsolateral prefrontal cortex, and lateral orbitofrontal cortex were calculated by Logan analysis.
      Results: There was a main effect of time (p = .017) for 5-HT2AR BP, which increased 21.2% ± 2.6% following combined E2 and P administration relative to baseline. This effect was evident in all cerebral cortex regions examined.
      Conclusions: 5-HT2AR BP increased in widespread areas of the cerebral cortex following combined E2 + P administration.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Anderson E.
        • Hamburger S.
        • Liu J.
        • Rebar R.
        Characteristics of menopausal women seeking assistance.
        Am J Obstet Gynecol. 1987; 156: 428-433
        • Arango V.
        • Underwood M.D.
        • Mann J.J.
        Postmortem findings in suicide victims. Implications for in vivo imaging studies.
        Ann N Y Acad Sci. 1997; 836: 269-287
        • Berga S.L.
        • Daniels T.L.
        • Giles D.E.
        Women with functional hypothalamic amenorrhea but not other forms of anovulation display amplified cortisol concentrations.
        Fertil Steril. 1997; 67: 1024-1030
        • Biegon A.
        • Reches A.
        • Snyder L.
        • McEwen B.S.
        Serotonergic and noradrenergic receptors in the rat brain.
        Life Sci. 1983; 32: 2015-2021
        • Brix G.
        • Zaers J.
        • Adam L.-E.
        • Belleman M.E.
        • Ostertag H.
        • Trojan H.
        Performance evaluation of a whole-body PET scanner using the NEMA protocol.
        J Nucl Med. 1997; 38: 1614-1623
        • Coble P.A.
        • Day N.L.
        The epidemiology of mental and emotional disorders during pregnancy and the postpartum period.
        in: Cohen R.L. Psychiatric Consultation in Childbirth Settings. Plenum Press, New York1988: 37-47
        • Crow T.
        • Ferrier I.
        • Johnson J.
        The selectivity of the reduction of serotonin S2 receptors in Alzheimer-type dementia.
        Neurobiol Aging. 1986; 7: 3-7
        • Cyr M.
        • Bosse R.
        • Di Paolo T.
        Gonadal hormones modulate 5-HT2A receptors.
        Neuroscience. 1998; 83: 829-836
        • Drevets W.C.
        • Raichle M.E.
        Reciprocal suppression of regional cerebral blood flow during emotional versus higher cognitive processes.
        Cogn Emotion. 1998; 12: 353-385
        • Gibbs R.B.
        Levels of trkA and BDNF mRNA, but not NGF mRNA, fluctuate across the estrous cycle and increase in response to acute hormone replacement.
        Brain Res. 1998; 787: 259-268
        • Hilditch J.R.
        • Lewis J.
        • Peter A.
        • van Maris B.
        • Ross A.
        • Franssen E.
        • et al.
        A menopause-specific quality of life questionnaire.
        Maturitas. 1996; 24: 161-175
        • Jakab R.L.
        • Goldman-Rakic P.S.
        5-Hydroxytryptamine2A serotonin receptors in the primate cerebral cortex.
        Proc Natl Acad Sci U S A. 1998; 95: 735-740
        • Lemaire C.
        • Cantineau Plenevaux A.
        • Christiaens L.
        Fluorine-18-Altanserin. A radioligand for the study of serotonin receptors with PET.
        J Nucl Med. 1991; 32: 2266-2272
        • Links J.M.
        • Zubieta J.K.
        • Meltzer C.C.
        • Stumpf M.J.
        • Frost J.J.
        Influence of spatially heterogeneous background activity on “hot object” quantification in brain emission computed tomography.
        J Comput Assist Tomogr. 1996; 20: 680-687
        • Logan J.
        • Volkow N.
        • Fowler J.
        • Wang G.-J.
        • Dewey S.L.
        • MacGregor R.
        • et al.
        Effects of blood flow on [11C]raclopride binding in the brain.
        J Cereb Blood Flow Metab. 1994; 14: 995-1010
        • McEwen B.S.
        • Alves S.E.
        Estrogen actions in the central nervous system.
        Endocr Rev. 1999; 20: 279-307
        • Mintun M.A.
        • Raichle M.E.
        • Kilbourn M.R.
        • Wooten G.F.
        • Welch M.J.
        A quantitative model for the in vivo assessment of drug binding sites with positron emission tomography.
        Ann Neurol. 1984; 15: 217-227
        • Osterlund M.K.
        • Hurd Y.L.
        Acute 17β-estradiol treatment down-regulates serotonin 5HT1A receptor mRNA expression in the limbic system of female rats.
        Mol Brain Res. 1998; 55: 169-172
        • Pazos A.
        • Probst A.
        • Palacios J.M.
        Serotonin receptors in the human brain. IV. Autographic mapping of serotonin-2 receptors.
        Neuroscience. 1987; 21: 123-139
        • Pecins-Thompson M.
        • Bethea C.L.
        Regulation of serotonin re-uptake transporter mRNA expression by ovarian steroids in rhesus macaques.
        Mol Brain Res. 1998; 53: 120-129
        • Phillips S.M.
        • Sherwin B.
        Effects of estrogen on memory function in surgically menopausal women.
        Psychoneuroendocrinology. 1992; 17: 485-495
        • Quarles R.P.
        • Mintun M.A.
        • Larson K.B.
        • Markham J.
        • MacLeod A.M.
        • Raichle M.E.
        Measurement of regional cerebral blood flow with positron emission tomography.
        J Cereb Blood Flow Metab. 1993; 13: 733-747
        • Rubinow D.R.
        • Schmidt P.J.
        • Roca C.A.
        Estrogen-serotonin interactions.
        Biol Psychiatry. 1998; 44: 839-850
        • Sadzot B.
        • Lemaire C.
        • Maquet P.
        • Salmon E.
        • Plenevaux A.
        • Degueldre C.
        • et al.
        Serotonin 5HT2 receptor imaging in the human brain using positron emission tomography and a new radioligand, [18F]altanserin.
        J Cerebr Blood Flow Metab. 1995; 15: 787-797
        • Sahakian B.J.
        • Owen A.M.
        Computerized assessment in neuropsychiatry using CANTAB.
        J R Soc Med. 1992; 85: 399-402
        • Smith G.S.
        • Price J.C.
        • Lopresti B.J.
        • Huang Y.
        • Simpson N.
        • Holt D.
        • et al.
        Test-retest variability of Serotonin 5-HT2A receptor binding measured with positron emission tomography and [18F]Altanserin in the human brain.
        Synapse. 1998; 30: 380-392
        • Sumner B.E.
        • Fink G.
        Estrogen increases the density of 5-HT2A receptors in cerebral cortex and nucleus accumbens in the female rat.
        J Steroid Biochem Mol Biol. 1995; 54: 15-20
        • Talairach J.
        • Tournoux P.
        Co-Planar Stereotaxic Atlas of the Human Brain 3-Dimensional Proportional System. Thieme, New York1988
        • Tang M.X.
        • Jaocbs D.
        • Stern Y.
        • Marder K.
        • Schofield Gurland B.
        Effect of oestrogen during menopause on risk and age at onset of Alzheimer’s disease.
        Lancet. 1996; 348: 429-432
        • Toran-Allerand C.D.
        Mechanisms of estrogen action during neural development.
        J Steroid Biochem Mol Biol. 1996; 56: 169-178
        • Woods R.P.
        • Mazziotta J.C.
        • Cherry S.R.
        MRI-PET registration with automated algorithm.
        J Comput Assist Tomogr. 1993; 17: 536-546
        • Yates M.
        • Leake A.
        • Candy J.M.
        • Fairbairn A.F.
        • McKeith I.G.
        • Ferrier I.N.
        5HT2 receptor changes in major depression.
        Biol Psychiatry. 1990; 27: 489-496