DIFFERENTIAL REGULATION OF MELANIN-CONCENTRATING HORMONE GENE-EXPRESSION IN DISTINCT HYPOTHALAMIC AREAS UNDER OSMOTIC STIMULATION IN RAT

Melanin-concentrating hormone and associated peptides represent a nove l peptide neuronal system that may be involved in the control of water homeostasis in mammals. We have examined the effect of 24 h dehydrati on or salt-loading over a period of six days, on melanin-concentrating hormone messenger RNA levels in rat brains by using complementary met hods of Northern blotting and in situ hybridization histochemistry. In response to one to six day salt-loading regimen, hypothalamic melanin -concentrating hormone messenger RNA content in male or female rats de creased by two to three-fold. Levels of melanin-concentrating hormone messenger RNA in the hypothalamus were also dramatically decreased fol lowing dehydration in female rats whereas contrasting responses were n oted in male rats. In addition, no significant variation in the low le vels of melanin-concentrating hormone gene transcripts in medulla pons and cortex was found after osmotic stimulus. In agreement with Northe rn blot data, in situ hybridization studies revealed that the majority of the melanin-concentrating hormone-expressing neurons in the anteri or part of the lateral hypothalamus of dehydrated or salt-loaded rats expressed lower amounts of melanin-concentrating hormone messenger RNA s than those found in control rats. Interestingly, less variation was found in the posterior part of the lateral hypothalamus. Furthermore f ew clusters of cells, located in zona incerta and near the internal ca psula and fornix, increased their contents in melanin-concentrating ho rmone messenger RNA in salt-loaded but not in dehydrated rats suggesti ng that melanin-concentrating hormone gene expression may be regulated differently by various osmotic stimuli. Finally, diurnal variations i n melanin-concentrating hormone messenger RNA contents were observed i n normal and dehydrated rats with highest levels around 22.00 h and lo west levels during daylight hours. However, the up-regulation of melan in-concentrating hormone gene activity at night was found lower in deh ydrated rats than in control animals suggesting that osmotic stress ma y interfere with the generation of the diurnal pattern of melanin-conc entrating hormone messenger RNA expression. Altogether, our results in dicate that osmotic stimulations lead to a selective and conspicuous i nhibition of melanin-concentrating hormone gene activity in the whole hypothalamus of rat. We suggest that the melanin-concentrating hormone neuronal system plays an important role in integration processes rela tive to nocturnal regulation of water homeostasis and drinking behavio r.