LITHIUM INCREASES MELANIN-CONCENTRATING HORMONE MESSENGER-RNA STABILITY AND INHIBITS TYROSINE-HYDROXYLASE GENE-EXPRESSION IN PC12 CELLS

Melanin-concentrating hormone (MCH) is a cyclic peptide involved in th e regulation of food-intake behaviour and stress response in mammals. Expression of tile MCH gene predominates in hypothalamic neurons. Mech anisms governing the regulation of expression of MCH gene in establish ed Sell lines were not explored yet. Here, we analysed the actions of nerve growth factor (NGF), dexamethasone forskolin and lithium on MCH mRNA levels in the PC12 pheochromocytoma fell line. We compared them w ith those observed on tyrosine hydroxylase (TH) mRNA, constitutively e xpressed in PC12 cells, and neurotensin (NT) mRNA, taken as a control. in untreated cells. MCH RNA species of high molecular weight were fou nd. Exposure cf cells at a combination of NGF and lithium resulted in decreased expression of these RICH RNAs and in the transient productio n of mature MCH mRNA, Strikingly, after short exposure of PC12 cells t o NGF, lithium per se elicited a marked increase in MCH mRNA levels wh ilst it exerted a potent inhibitory action on TH mRNA expression. Deta iled investigations revealed that lithium enhanced MCH mRNA expression through post-transcriptional mechanisms whereas it regulated TW gene expression mainly at the level of transcription. These results demonst rate that lithium, an agent widely used for treatment of manic depress ive illness. can exert an opposite effect on MCH and TH mRNA productio n in PC12 cells. The MCH gene system in NGF-treated PC12 cells provide s a good opportunity for studying the effect of lithium on gene expres sion at post-transcriptional levels in a neuron-like cellular model. ( C) 1997 Elsevier Science B.V.