Poster Presentation The International Congress of Neuroendocrinology 2014

The effect of Oestrogen on Human Brain Tryptophan metabolism  (#199)

Josien de Bie 1 , Edwin Lim 1 , Gilles J Guillemin 1
  1. Macquarie University, NSW, Australia

Introduction: Serotonin precursor tryptophan is metabolized in the kynurenine pathway. Kynurenine metabolism is altered in many psychiatric disorders with a neuroinflammatory background such as depression and schizophrenia. Interestingly, many of these diseases show sexual dimorphism in disease onset and progression indicating sex hormone involvement. The kynurenine pathway starts at the conversion of tryptophan into kynurenine by either tryptophan 2,3-dioxygenase (TDO)  or indoleamine 2,3-dioxygenase (IDO).  Originally thought to be a passive NAD+ producing pathway, discovery of the role of IDO /TDO driven tryptophan depletion in immune activation revealed that kynurenine metabolism is an active process which can be triggered by both immune and endocrine factors. The exact role of hormones in regulation of the kynurenine pathway during inflammation is not yet well understood. Method:  We treated human primary brain cells with 17B-Oestradiol (55nm-10um) in vitro and characterised kynurenine metabolism activity using HPLC and PCR. Both physiological and super‑physiological concentrations of oestradiol were used to mimic both the natural and hormone treatment situation. Treatment with oestradiol led to a slight increase in IDO/TDO activity in neurons. However, when cells were challenged with cytokines to emulate the inflammatory milieu oestradiol decreased IDO/TDO activity. Conclusion: Taken together our results offer a new perspective on gender differences in neurochemistry as well as an important clue in the uncovering of the mechanisms behind sexual dimorphism in psychiatric and neuroinflammatory disorders.

  1. Chen, Y., & Guillemin, G. J. (2009). Kynurenine pathway metabolites in humans: disease and healthy States. International Journal of Tryptophan Research : IJTR, 2, 1–19.
  2. Wolf, H., Walter, S., Brown, R. R., & Arend, R. a. (1980). Effect of natural oestrogens on tryptophan metabolism: evidence for interference of oestrogens with kynureninase. Scandinavian Journal of Clinical and Laboratory Investigation, 40(1), 15–22.