Inducible expression of tryptophan hydroxylase without serotonin synthesis in hypothalamic dopaminergic neurons.
In the present study we have further studied the previous findings that rat hypothalamic dopaminergic neuronal cell groups may express tryptophan hydroxylase (TpH), the serotonin synthesizing enzyme, without a detectable serotonin synthesis. Chemical and mechanical neuronal injuries, namely colchicine treatment and axonal transection, respectively, were performed, and distributions of neurons exhibiting immunoreactivity for TpH and/or tyrosine hydroxylase (TH), the dopamine synthesizing enzyme, were analyzed throughout the hypothalamic periventricular and arcuate nuclei. After colchicine treatment there was a statistically significant 87% (P = 0,01) increase in the number of TpH expressing neurons, while TH expression remained essentially similar. Axonal transection resulted also in a statistically significant 131% (P < 0,01) increase in the number of TpH expressing neurons, while TH expression was not significantly altered. All TpH expression coexisted with TH expression, and the induction of TpH expression by neuronal injuries occurred evenly throughout the rostrocaudal length of the territory studied. A possible serotonin synthesis by TpH was examined by giving drugs that increase brain serotonin synthesis, but no immunohistochemically detectable serotonin synthesis could be found in any of the TpH expressing neurons. Finally the possibility was studied that the relative shortage of the cofactor tetrahydrobiopterin would limit serotonin synthesis. However, an administration of tetrahydrobiopterin did not result in detectable serotonin synthesis in these neurons. Taken together these results suggest that dopaminergic neurons in the hypothalamic periventricular and arcuate nuclei are able to express TpH, this expression is induced after neuronal injury, and this induction occurs similarly throughout the territories studied. TpH expression occurs independently of TH expression, and the newly expressed TpH appears not to synthesize serotonin, regardless of pharmacological pretreatments. Thus, our findings (i) support the idea that neurons may possess inducible expression of nonfunctional transmitter-synthesizing enzymes, in this case TpH, and (ii) suggest that expression of an enzyme synthesizing a certain transmitter may not necessarily imply the corresponding transmitter phenotype.
Vanhatalo
S
S
Department of Anatomy, Institute of Biomedicine, University of Helsinki, Finland.
Soinila
S
S
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000201:enzymology; D001708:Biopterins / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D003078:Colchicine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D004790:Enzyme Induction; D007031:Hypothalamus / Q000187:drug effects / Q000201:enzymology*; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D010286:Paraventricular Hypothalamic Nucleus / Q000201:enzymology; D010904:Pituitary Gland, Posterior / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D014365:Tryptophan Hydroxylase / Q000032:analysis / Q000096:biosynthesis*
D001708:Biopterins; D012701:Serotonin; D014365:Tryptophan Hydroxylase; C003402:sapropterin; D003078:Colchicine; D004298:Dopamine