The mechanism of action of glucocorticoids is reviewed from the standpoint of seeing how far current concepts of the molecular action of steroids go towards explaining the varied physiologic and metabolic effects induced. The role of plasma binding to transport proteins in modifying steroid action is considered. The interactions between glucocorticoids and other hormones, particularly those mediated by cAMP are considered along with a discussion of the mechanism of “permissive” effects. Various proposals concerning the way in which glucocorticoids induce their effects including direct interactions with enzymes, nucleic acids, lysosomes, and receptor proteins are considered in detail, and an attempt is made to consider how far each of these mechanisms can go in explaining steroid action. Those biologic effects that cannot be accounted for by currently available mechansims are mentioned. Effects of glucocorticoids on growth, differentiation, and the inflammatory response are discussed from a mechanistic point of view. Catabolic or inhibitory effects of glucocorticoids as well as enzyme induction are examined using several exemplary systems. Finally an attempt is made to summarize the current state of knowledge concerning glucocorticoid and genome interaction.

Mechanism of action of glucocorticoids.

Glucocorticoid hormone action.

Thirty-two infants, aged 1 to 12 months, hospitalized with acute wheezing, were studied. They were randomly divided into four treatment groups of eight patients each. The treatments were intramuscular dexamethasone or placebo (double-blind), and salbutamol (oral and inhaled), or none (open), in all four possible combinations. The study was carried out as a randomized block design with eight blocks of four infants each, matched by age and clinical score. Average daily improvements, as reflected by changes in the clinical score and length of hospital stay, was essentially the same for infants treated with placebo, salbutamol alone, and dexamethasone alone. However, combined salbutamol-dexamethasone treatment resulted in more than twice the rate of improvement of the other treatments. The difference was statistically highly significant (P less than .01). Furthermore, the response of this combined treatment was observed within 24 hours; none of the ten infants in whom there was no significant improvement within 48 hours and neither of the two patients who developed respiratory failure received the combined salbutamol-dexamethasone treatment. A potentiating effect of corticosteroids on the beta-adrenergic responsiveness is a possible explanation for the advantage of this combined treatment in the management of acute wheezing in infancy.

Dexamethasone and Salbutamol in the Treatment of Acute Wheezing in Infants

Agonist-induced destabilization of beta-adrenergic receptor mRNA. Attenuation of glucocorticoid-induced up-regulation of beta-adrenergic receptors.

Atopic dermatitis is a disease of fascination and frustration to medical practitioners and researchers. This very common disorder is confusing from several standpoints. The confusion begins with nomenclature; in discussions with American nondermatologic physicians, we might hear atopic dermatitis referred to as "eczema," allergic dermatitis, allergic eczema, or even neurodermatitis. Many Europeans continue to use the term prurigo Besnier. Diagnostic features of atopic dermatitis are another source of confusion. The skin lesions a pediatrician sees on a child's skin may be vastly different from the lesions the general practitioner sees on that same individual 15 years later. There may be no single distinguishing characteristic; diagnosis may depend on a combination of morphologic, distributional, and historical features. Histological findings provide very little aid in diagnosis, though a recent preliminary report by Mihm et al 1 raises the hope that new histologic techniques may reveal distinct histopathologic features in atopic dermatitis. With

Newer concepts of atopic dermatitis.

To evaluate the theory of beta-adrenergic blockade in asthma, we measured the effects of hydrocortisone and isoproterenol on adenyl cyclase in peripheral blood leukocytes from asthmatic and nonasthmatic children and nonasthmatio adults. An intact cell method was used, allowing cells to incorporate 3 H-adenine and convert it to 3 H-adenosine triphosphate (ATP) during a 2 hour incubation. Experimental compounds were then added for a pulse exposure of 5 minutes. AdenyZ cyclase catalyzes the transformation of 3 H-ATP to 3 H-cyclic adenosine monophosphate (AMP), which was measured after chromatographic separation. To rule out effects on rate of cyclic AMP destruction, aminophylline was routinely added at 25 mM., a concentration which completely inhibited cyclic AMP phosphodiesterase. Hydrocortisone at 10 −6 M stimulated adenyl cyclase in leukocytes from all subjects by 24 to 85 per cent. Isoproterenol at 10 −6 M stimulated adenyl cyclase by 16 to 19 per cent in control subjects, but not in cells from asthmatic subjects, a finding which supports the beta-adrenergic blockade hypothesis. Children receiving glucocorticosteroid therapy showed a restoration of leukocyte adenyl cyclase responsiveness to Isoproterenol. No synergistic effects between the steroid and catecholamine were observed in vitro. The data suggest at least 2 mechanisms by which gluoocorticosteroids benefit asthmatic patients: (1) Increased activity of adenyl cyclase, and (2) Restoration of adenyl cyclase responsiveness to catecholamines.

https://www.jacionline.org/article/0091-6749(72)90078-4/pdf

Patricia J. Logsdon

Papers

Stimulation of leukocyte adenyl cyclase by hydrocortisone and isoproterenol in asthmatic and nonasthmatic subjects