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

• Published in: Brain research bulletin Vol. 46; no. 5; pp. 447 - 452
• Main Authors: Rusnák, M., Jeloková, J., Vietor, I., Sabban, E.L., Kvetňanský, R.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 15.07.1998; Elsevier Science
• Subjects: Adrenal medulla; Adrenal Medulla - drug effects; Adrenal Medulla - metabolism; Animals; Antimetabolites - pharmacology; Biochemistry and metabolism; Biological and medical sciences; Blotting, Northern; Central nervous system; Deoxyglucose - pharmacology; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Enzymologic - genetics; Gene Expression Regulation, Enzymologic - physiology; Glucoprivation; Glucose - physiology; Hypoglycemia - chemically induced; Hypoglycemia - metabolism; Hypoglycemic Agents - pharmacology; Immobilization; In Situ Hybridization; Insulin - pharmacology; Locus coeruleus; Locus Coeruleus - drug effects; Locus Coeruleus - metabolism; Male; mRNA; Rats; Rats, Sprague-Dawley; RNA, Messenger - biosynthesis; RNA, Messenger - isolation & purification; Stress, Psychological - metabolism; Tyrosine 3-Monooxygenase - biosynthesis; Tyrosine 3-Monooxygenase - genetics; Tyrosine hydroxylase; Vertebrates: nervous system and sense organs; Immobilization; Tyrosine hydroxylase; mRNA; Glucoprivation; Adrenal medulla; Locus coeruleus; Pancreatic hormone; Deprivation; Rat; Enzyme; Rodentia; Central nervous system; Glucose; Gene expression; Tyrosine 3-monooxygenase; Insulin; Vertebrata; Mammalia; Oxidoreductases; Brain (vertebrata)
• ISSN: 0361-9230; 1873-2747
• DOI: 10.1016/S0361-9230(98)00033-1

The major brain norepinephrinergic nucleus, locus coeruleus, is an important integrating element of extero- and interoceptive stimuli in organisms facing different physiological challenges. We investigated the effects of single and repeated (seven times) exposure to immobilization stress (120 min daily), insulin (5 IU/kg, i.p. daily) or 2-deoxy- d-glucose (500 mg/kg, i.p. daily) administration on tyrosine hydroxylase (TH) mRNA levels, the rate-limiting enzyme in catecholamine biosynthesis, by in situ hybridization in locus coeruleus and by Northern blot analysis in the adrenal medulla of rats. Both the single and repeated immobilization caused a significant increase in TH mRNA levels in the locus coeruleus (1.5–2-fold; p < 0.05) and in the adrenal medulla (about 4-fold; p < 0.05) when compared with unstressed controls. Hypoglycemia induced by a single or repeated insulin administration led to about fourfold ( p < 0.01) elevation in adrenal medullary TH mRNA levels, whereas 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 coeruleus (twofold; p < 0.01). Our data suggest that in contrast to immobilization or cellular glucoprivation caused by 2-deoxy- d-glucose administration, insulin-induced hypoglycemia is not a specific or quantitatively sufficient stimulus for induction of TH gene expression in the locus coeruleus, although all these stressors strongly activate the process in the adrenal medulla.