In vivo evidence for a greater brain tryptophan hydroxylase capacity in female than in male rats

Naunyn Schmiedebergs Arch Pharmacol. 1988 Oct;338(4):345-9. doi: 10.1007/BF00172108.


Previous studies have revealed that brain levels of tryptophan, 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) are moderately higher in female than in male rats. Since tryptophan hydroxylase is only about half saturated with substrate, the greater availability of precursor in female rats might contribute to their higher 5-hydroxyindole levels. The present investigation was aimed at clarifying whether there is a sex difference in central tryptophan hydroxylase capacity. Hence, both sexes received a high dose of L-tryptophan (400 mg/kg), which resulted in a tenfold increase in brain tryptophan concentrations and presumably a virtual saturation of tryptophan hydroxylase. Following such treatment, 5-hydroxytryptophan (5-HTP) levels, measured after L-amino acid decarboxylase inhibition, were compared in males and females. Both in saline- and L-tryptophan-treated rats, 5-HTP levels were generally higher in females. In another group of animals, receiving 400 mg/kg of L-tryptophan as sole treatment, 5-HT and 5-HIAA concentrations were measured. As in the case of 5-HTP, the higher 5-HT and 5-HIAA levels observed in females persisted after L-tryptophan treatment. The present data suggest that brain tryptophan hydroxylase activity is greater in females; this sex difference probably contributes to the higher 5-HT and 5-HIAA levels in females.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5-Hydroxytryptophan / metabolism
  • Animals
  • Brain / enzymology*
  • Corpus Striatum / metabolism
  • Dihydroxyphenylalanine / metabolism
  • Female
  • Hydroxyindoleacetic Acid / metabolism
  • Hypothalamus / metabolism
  • Limbic System / metabolism
  • Male
  • Rats
  • Rats, Inbred Strains
  • Serotonin / metabolism
  • Sex Factors
  • Tryptophan Hydroxylase / metabolism*


  • Serotonin
  • Hydroxyindoleacetic Acid
  • Dihydroxyphenylalanine
  • 5-Hydroxytryptophan
  • Tryptophan Hydroxylase