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Soy and social stress affect serotonin neurotransmission in primates

The Pharmacogenomics Journal volume 3, pages 114–121 (2003)Cite this article

ABSTRACT

Stress and sex steroidal milieu can each influence mood in women. The purpose of this study was to compare the effect of long-term conjugated equine estrogen (CEE), soy phytoestrogen (SPE), and social subordination stress on dorsal raphe serotonin neurotransmission of ovariectomized cynomolgus monkeys. Tryptophan hydroxylase (TPH) and serotonin reuptake transporter (SERT) protein content were determined, and the in vitro degradation of macaque SERT protein was examined in the presence and absence of protease inhibitors, serotonin (5-HT), and citalopram. Like CEE, SPE increased TPH protein levels. Social subordinates had markedly lower TPH protein levels than dominants regardless of hormone replacement. Therefore, these two variables had independent and additive effects. CEE and SPE increased SERT, and social status had no effect. Thus, the hormone-induced increase in SERT was accompanied by increased 5-HT synthesis and neuronal firing, which appears biologically reasonable as 5-HT prevented SERT degradation in vitro.

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Abbreviations

5-HT:

serotonin

8-OH-DPAT:

8-hydroxy-2-(di-n-propylamine) tetralin

ANOVA:

analysis of variance

BW:

body weight

CEE:

conjugated equine estrogen

ERβ:

estrogen receptor beta

GTPγS:

glutamate triphosphate gamma subunit

HRT:

hormone replacement therapy

MDMA:

3,4-methylenedioxy-methamphetamine

OVX:

ovariectomized

PET scans:

positron emission tomography scans

SERMs:

selective estrogen receptor modulators

SERT:

serotonin reuptake transporter

SPE:

soy phytoestrogen

SSRIs:

selective 5-HT reuptake inhibitors

TPH:

tryptophan hydroxylase

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Acknowledgements

This work was supported by the John D & Catherine T MacArthur Foundation to CAS; the NIH-NHLBI, HL 45666 to TBC; Training Grant NS07422 to Wake Forest University; NIH-NIMH, MH 62677 to CLB; NIH-NICHD, U54 Contraceptive Center Grant HD 18185 and NIH-NCRR, RR 000163 for the operation of Oregon National Primate Research Center. We also thank Jay R Kaplan for sharing social status data and critical commentary, Dewayne Cairnes for brain collection, and Dewayne Cairnes and Melissa Ayers for social status determinations.

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Authors and Affiliations

  1. Department of Pathology, Section of Comparative Medicine, Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, NC, USA

    C A Shively & J A Henderson

  2. Department of Psychology, Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, NC, USA

    C A Shively

  3. Divisions of Reproductive Sciences and Neuroscience, Oregon National Primate Research Center, Beaverton, OR, USA

    S J Mirkes, N Z Lu & C L Bethea

  4. Department of Physiology & Pharmacology, Oregon Health and Science University, Portland, OR, USA

    N Z Lu & C L Bethea

  5. Interdiscipliniary Program in Neuroscience, Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, NC, USA

    J A Henderson

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  1. C A Shively
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Correspondence to C A Shively.

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Shively, C., Mirkes, S., Lu, N. et al. Soy and social stress affect serotonin neurotransmission in primates. Pharmacogenomics J 3, 114–121 (2003). https://doi.org/10.1038/sj.tpj.6500166

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