Differential mRNA expression of the tryptophan hydroxylases 1 and 2 in the human brain: A post mortem study

The tryptophan hydroxylase (TPH), the rate limiting enzyme in the synthesis of the neurotransmitter serotonin (5-HT), is widely discussed as a candidate gene in many psychiatric disorders. Two TPH isoforms are currently known: TPH1 and the neuronal TPH2. We could recently demonstrate that TPH2 is expressed in the human brain (frontal cortex, thalamus, hippocampus, amygdala, cerebellum, hypothalamus) with a predominant expression in the raphe nuclei, but not in peripheral tissues (heart, lung, kidney, duodenum, liver, adrenal gland). The present study compares the expression levels of the TPH1 and TPH2 genes in the human brain regions cortex, hippocampus, hypothalamus, pituitary and raphe nuclei. Postmortem probes were obtained from 8 controls, 9 individuals who died on drug abuse (n=9), on suicide (n=4) and from 7 schizophrenics. The results of our study show that the mRNA expression of TPH1 and TPH2 is nearly identical except in the raphe nuclei and the pituitary. In raphe nuclei, the major locus of the serotonin synthesis, TPH2 was the predominant gene (p<0.001), whereas in the adeno- and neuron-pituitary TPH1 mRNA was expressed at significant higher levels (p<0.02). Although the tissues were obtained from individuals who died on different causes of death, respectively suffered from different disorders there were no interindividual differences. Our findings suggest a priority role of the TPH2 in neuronal 5-HT synthesis, whereas TPH1 could play a major role in HPA-a