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-releasing factor (GRF) synthesis, we measured hypothalamic prepro-GRF mRNA by solution hybridization/nuclease protection analysis in food-deprived rats refed protein-free diets (PF) supplemented with individual amino 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 with a normal (NF) diet, a protein-free (PF) diet, or PF diets containing tyrosine, tryptophan (Trp), glutamic acid, or histidine (His). Food-deprived rats displayed the expected 80% reduction in hypothalamic prepro-GRF mRNA. Upon refeeding, levels were normalized in rats refed a normal diet, but not in those refed a PF diet alone or with tyrosine, Trp, 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 reduced 25% by feeding animals a PF diet with His. Groups of rats allowed free access to food were treated for 72 h with two daily injections of 100 mg/kg alpha-fluoremethylhistidine, a specific irreversible inhibitor of histidine decarboxylase, to determine if the effect of His on prepro-GRF mRNA depended on neural conversion to histamine. alpha-Fluoremethylhistidine-treated rats showed a 40% reduction in hypothalamic 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 in the regulation of hypothalamic GRF expression.