Adrenalectomy decreases lipocortin-I messenger ribonucleic acid and tissue protein content in rats.

ABSTRACT

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.