Differential regulation of melanin-concentrating hormone gene expression in distinct hypothalamic areas under osmotic...

Melanin-concentrating hormone and associated peptides represent a novel peptide neuronal system that may be involved in the control of water homeostasis in mammals. We have examined the effect of 24 h dehydration or salt-loading over a period of six days, on melanin-concentrating hormone messenger RNA levels in rat brains by using complementary methods 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 decreased by two to three-fold. Levels of melanin-concentrating hormone messenger RNA in the hypothalamus were also dramatically decreased following dehydration in female rats whereas contrasting responses were noted in male rats. In addition, no significant variation in the low levels of melanin-concentrating hormone gene transcripts in medulla pons and cortex was found after osmotic stimulus. In agreement with Northern blot data, in situ hybridization studies revealed that the majority of the melanin-concentrating hormone-expressing neurons in the anterior part of the lateral hypothalamus of dehydrated or salt-loaded rats expressed lower amounts of melanin-concentrating hormone messenger RNAs than those found in control rats. Interestingly, less variation was found in the posterior part of the lateral hypothalamus. Furthermore few clusters of cells, located in zona incerta and near the internal capsula and fornix, increased their contents in melanin-concentrating hormone messenger RNA in salt-loaded but not in dehydrated rats suggesting that melanin-concentrating hormone gene expression may be regulated differently by various osmotic stimuli. Finally, diurnal variations in melanin-concentrating hormone messenger RNA contents were observed in normal and dehydrated rats with highest levels around 22.00 h and lowest levels during daylight hours. However, the up-regulation of melanin-concentrating hormone gene activity at night was found lower in dehydrated rats than in control animals suggesting that osmotic stress may interfere with the generation of the diurnal pattern of melanin-concentrating hormone messenger RNA expression. Altogether, our results indicate that osmotic stimulations lead to a selective and conspicuous inhibition 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 relative to nocturnal regulation of water homeostasis and drinking behavior.