title: 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.
abstract: 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.
authors.affiliation: Institute of Experimental Endocrinology Slovak Academy of Sciences, Bratislava. KVET@UEE.SAVBA.SK
authors.forename: M
authors.initials: M
authors.lastname: Rusnák
authors.forename: J
authors.initials: J
authors.lastname: Jeloková
authors.forename: I
authors.initials: I
authors.lastname: Vietor
authors.forename: E L
authors.initials: EL
authors.lastname: Sabban
authors.forename: R
authors.initials: R
authors.lastname: Kvetnanský
mesh_terms: D000313:Adrenal Medulla / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology*; D015152:Blotting, Northern; D003847:Deoxyglucose / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics / Q000502:physiology; D005947:Glucose / Q000502:physiology; D007003:Hypoglycemia / Q000139:chemically induced / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007103:Immobilization; D017403:In Situ Hybridization; D007328:Insulin / Q000494:pharmacology*; D008125:Locus Coeruleus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis* / Q000235:genetics*
chemical_list: D000963:Antimetabolites; D007004:Hypoglycemic Agents; D007328:Insulin; D012333:RNA, Messenger; D003847:Deoxyglucose; D014446:Tyrosine 3-Monooxygenase; D005947:Glucose