Effects of ovarian steroids and raloxifene on proteins that synthesize, transport, and degrade serotonin in the raphe region of macaques

Lisa J. Smith, Jessica A. Henderson, Creed W. Abell, Cynthia L. Bethea

Research output: Contribution to journalArticlepeer-review

127 Scopus citations


In the monkey dorsal raphe, we reported that 1-month (mo) of estrogen replacement, with or without progesterone supplementation for 14 days, significantly increased tryptophan hydroxylase-1 (TPH-1) mRNA; decreased serotonin reuptake transporter (SERT) mRNA and decreased monoamine oxidase (MAO)-A mRNA, but had no effect on MAO-B mRNA. Here, we questioned what effect would 1 or 5 mo of ovarian hormones or the selective estrogen receptor modulator (SERM), raloxifene, have on TPH protein and phosphorylation and on protein expression of SERT, MAO-A or MAO-B? Raloxifene antagonizes estrogen in breast or uterus, but estrogen-like activities in the brain have been reported. Cytoplasmic and membrane extracts of the dorsal raphe region were processed for Western blotting. TPH, phosphoserine, SERT, MAO-A, and MAO-B were detected with specific antibodies. The optical densities of the signals were measured with NIH image and analyzed by ANOVA Both 1 and 5 mo of estrogen, with or without progesterone, and 5 mo of raloxifene significantly increased TPH protein. Administration for 5 mo of estrogen plus progesterone and raloxifene also increased TPH phosphorylation. Estrogen, with or without progesterone, for 1 mo had no effect on SERT protein. However, 5 mo of estrogen and 5 mo of raloxifene increased SERT protein. Estrogen alone or combined with progesterone for 1 mo caused a significant reduction in MAO-A. Yet, after 5 mo of the same treatments, MAO-A was not different from spayed controls. Estrogen alone had no effect on MAO-B. However, the addition of progesterone significantly increased MAO-B. Raloxifene for 5 mo had no effect on MAO-A or MAO-B. Thus, to various extents, estrogen, progesterone, and raloxifene may increase serotonin production and transport. The expression of the degradative enzymes suggests a complex combination of gene transcription, post-transcriptional processing, and substrate feedback mechanisms.

Original languageEnglish (US)
Pages (from-to)2035-2045
Number of pages11
Issue number11
StatePublished - Nov 2004
Externally publishedYes


  • Estrogen
  • Macaques
  • Monoamine oxidases
  • Phosphorylation
  • Progesterone
  • Raloxifene
  • Reuptake transporter
  • SERM
  • Selective estrogen receptor modulator
  • Serotonin
  • Tryptophan hydroxylase
  • Western blots

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health


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