Predominant expression of tryptophan hydroxylase 1 mRNA in the pituitary: a postmortem study in human brain

Although the predominant role of tryptophan hydroxylase 2 (TPH2) in the CNS and its influence on the vulnerability to psychiatric disorders have clearly been demonstrated in several studies, the role of TPH1 on neuronal mechanisms, respectively on behavioral traits is still poorly understood. In a previous study of tryptophan hydroxylase 1 (TPH1) and TPH2 mRNA expression in different human brain regions we observed significantly higher TPH1 than TPH2 mRNA concentrations in the pituitary (unpublished observations). Considering the importance of the pituitary in the functional circuits between brain and body, we investigated the TPH1 and TPH2 mRNA expression in more detail, using human postmortem samples of the posterior and anterior pituitary compared to cortex, hippocampus and raphe nuclei. Specimens were available from different psychiatric patients (drug abusers, n=12; suicide victims, n=11; schizophrenics, n=9) and controls (n=15). Additionally we performed immunohistochemical analysis applying monospecific antibodies for both TPH isoforms to verify that the mRNA is of cellular and not just vascular or other origin. Highest TPH2 mRNA levels were observed in the raphe nuclei in patients and controls. By contrast, in the anterior and posterior pituitary TPH1 was found to be the predominantly expressed isoform in all subgroups. TPH1 and TPH2 mRNA expression in the further brain regions was only marginal and nearly identical except in the hypothalamus where higher TPH1 than TPH2 mRNA levels could be measured. Interindividual differences between the subgroups were not detectable. The results of the present study extended our previous findings by the additional immunohistochemical determination of the neuronal TPH1 and TPH2 protein expression in the anterior pituitary and provide evidence against a strictly separated duality of the serotonergic system. It seems that TPH1 might also have an impact on neuronal mechanisms via hypothalamic-pituitary-adrenal axis regulation by its predominant localization in the pituitary. These observations may open up new research strategies not only for several psychiatric disorders, but also for the relationship between psychiatric and somatic diseases.