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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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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DOI: https://doi.org/10.1038/sj.tpj.6500166
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