Species-related differences in steroid-binding specificity of glucocorticoid receptors in lung

The steroid-binding affinities and specificities of pulmonary glucocorticoid receptors have been examined in different mammalian species. The receptors of all species examined are highly specific for binding glucocorticoids, the order of binding affinity being similar to the order of their biological potency. Progesterone also binds significantly to the receptors with an affinity varying between 16% and 41% of the corresponding affinity of corticosterone in different species. The affinity of triamcinolone acetonide for the receptor is highest in the rabbit, lowest in the guinea pig, and intermediate in the rat, mouse, and man, suggesting an inverse relationship between the affinity of glucocorticoids for the receptors and the level of glucocorticoids in blood. Glucocorticoid receptors of cortisol-secreting species (man, guinea pig, rabbit) bind cortisol with a much higher affinity than corticosterone, whereas glucocorticoid receptors of corticosterone-secreting species (rat, mouse) bind corticosterone with a much higher affinity than cortisol. In addition to cortisol, other 17 alpha-hydroxylated steroids also bind receptors of cortisol-secreting species with a relatively higher affinity than receptors of corticosterone-secreting species. Thus, in a given species glucocorticoid receptors seem to bind steroids better that are normally secreted by that species than steroids that are not secreted. A change in the pattern of glucocorticoids secreted during development (e.g. the rabbit fetus secretes primarily cortisol whereas the adult rabbit secretes predominantly corticosterone) is not accompanied by a corresponding change in the binding specificity of glucocorticoid receptors.