Adrenalectomy decreases lipocortin-I messenger ribonucleic acid and tissue protein content in rats.
Clinical and experimental observations revealed that glucocorticoid-deficient states are associated with an enhanced inflammatory response. The antiinflammatory response of pharmacological doses of glucocorticoids has been tentatively attributed to the induction of lipocortin-I. To determine whether glucocorticoid deficiency causes lipocortin-I down-regulation, the expression of lipocortin-I mRNA and protein was quantified in rats with and without adrenalectomy (ADX). The mRNA of lipocortin-I was quantified by polymerase chain reaction, using a constant amount of modified lipocortin-I cDNA transcript as an internal standard. The lipocortin-I mRNA was decreased by 56 +/- 14% in lung tissue of ADX rats. This down-regulation of lipocortin-I mRNA was not due to a nonspecific effect of ADX, since the mRNA levels of other proteins (c-fos, c-myc, c-erbA beta, and metallothionein-II) remained unchanged. The decrease in lipocortin-I mRNA in ADX rats was reflected by a corresponding decrease in tissue (lung, spleen, liver, and kidney) lipocortin-I protein content, as assessed by quantitative Western blot analysis. Thus, ADX causes a decline in lipocortin-I message and protein, an observation compatible with the increased susceptibility to inflammatory reactions in glucocorticoid deficiency.
Vishwanath
B S
BS
Medizinische Poliklinik, University of Bern, Switzerland.
Frey
F J
FJ
Bradbury
M
M
Dallman
M F
MF
Frey
B M
BM
D000315:Adrenalectomy; D000818:Animals; D017302:Annexins; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D003345:Corticosterone / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D003845:Deoxycytosine Nucleotides / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000502:physiology*; D008168:Lung / Q000187:drug effects / Q000502:physiology*; D008297:Male; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013154:Spleen / Q000187:drug effects / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects
D017302:Annexins; D002135:Calcium-Binding Proteins; D003845:Deoxycytosine Nucleotides; D006023:Glycoproteins; D012333:RNA, Messenger; C024107:2'-deoxycytidine 5'-triphosphate; D004247:DNA; D003345:Corticosterone