DIFFERENT EFFECTS OF INSULIN AND 2-DEOXY-D-GLUCOSE ADMINISTRATION ON TYROSINE-HYDROXYLASE GENE-EXPRESSION IN THE LOCUS-COERULEUS AND THE ADRENAL-MEDULLA IN RATS

The major brain norepinephrinergic nucleus, locus coeruleus, is an imp ortant integrating element of extero- and interoceptive stimuli in org anisms facing different physiological challenges. We investigated the effects of single and repeated (seven times) exposure to immobilizatio n stress (120 min daily), insulin (5 IU/kg, i.p. daily) or 2-deoxy-D-g lucose (500 mg/kg, i.p, daily) administration on tyrosine hydroxylase (TH) mRNA levels, the rate-limiting enzyme in catecholamine biosynthes is, by in situ hybridization in locus coeruleus and by Northern blot a nalysis in the adrenal medulla of rats. Both the single and repeated i mmobilization caused a significant increase in TH mRNA levels in the l ocus coeruleus (1.5-2-fold; p < 0.05) and in the adrenal medulla (abou t 4-fold; p < 0.05) when compared with unstressed controls. Hypoglycem ia induced by a single or repeated insulin administration led to about fourfold (p < 0.01) elevation in adrenal medullary TH mRNA levels, wh ereas TH mRNA in locus coeruleus remained unchanged when compared with saline-treated controls. In contrast to the effect of insulin-induced hypoglycemia, cellular glucoprivation caused by a single or repeated 2-deoxy-D-glucose administration significantly elevated TH mRNA levels in both the adrenal medulla (fourfold; p < 0.01) and the locus coerul eus (twofold; p < 0.01). Our data suggest that in contrast to immobili zation or cellular glucoprivation caused by 2-deoxy-D-glucose administ ration, insulin-induced hypoglycemia is not a specific or quantitative ly sufficient stimulus for induction of TH gene expression in the locu s coeruleus, although all these stressors strongly activate the proces s in the adrenal medulla. (C) 1998 Elsevier Science Inc.