REGULATION OF HYPOTHALAMIC PREPROGROWTH HORMONE-RELEASING FACTOR MESSENGER-RIBONUCLEIC-ACID EXPRESSION IN FOOD-DEPRIVED RATS - A ROLE FOR HISTAMINERGIC NEUROTRANSMISSION

To determine the component(s) of dietary protein that regulates GH-rel easing factor (GRF) synthesis, we measured hypothalamic prepro-GRF mRN A by solution hybridization/nuclease protection analysis in food-depri ved rats refed protein-free diets (PF) supplemented with individual am ino acids. Adult male Sprague-Dawley rats were allowed free access to food (Fed), food deprived for 72 h (FD), or FD then refed for 72 h wit h a normal (NF) diet, a protein-free (PF) diet, or PF diets containing tyrosine, tryptophan (Trp), glutamic acid, or histidine (His). Food-d eprived rats displayed the expected 80% reduction in hypothalamic prep ro-GRF mRNA. Upon refeeding, levels were normalized in rats refed a no rmal diet, but not in those refed a PF diet alone or with tyrosine, Tr p, or glutamic acid. In contrast, prepro-GRF mRNA was restored to 70% of Fed values by a PF diet with His. Supplementing a PF diet with His was sufficient to maintain hypothalamic prepro-GRF mRNA expression, as 3 days of feeding replete rats with PF diet or PF diet with added Trp resulted in a 50% reduction in prepro-GRF mRNA, whereas levels were r educed 25% by feeding animals a PF diet with His. Groups of rats allow ed free access to food were treated for 72 h with two daily injections of 100 mg/kg alpha-fluoremethylhistidine, a specific irreversible inh ibitor of histidine decarboxylase, to determine if the effect of His o n prepro-GRF mRNA depended on neural conversion to histamine. alpha-Fl uoremethylhistidine-treated rats showed a 40% reduction in hypothalami c prepro-GRF mRNA, with no concomitant change in preproneuropeptide-Y or preprosomatostatin. These data indicate that decreased hypothalamic prepro-GRF mRNA in FD rats is due in part to the lack of dietary and provide clear evidence for a role of the histaminergic neural system i n the regulation of hypothalamic GRF expression.