Characteristics of binding of a new anti-inflammatory glucocorticoid, hydrocortisone 17-butyrate 21-propionate (HBP), to glucocorticoid receptors of rat liver.

Characteristics of the specific binding of hydrocortisone 17-butyrate 21-propionate (HBP) to the cytoplasmic fraction from rat liver were investigated. The inhibition constant (Ki) of HBP for the site of 3H-dexamethasone (3H-DM) binding was approximately equal to the value of DM and significantly smaller than that of hydrocortisone (HC). The maximum number of binding sites (Bmax) and dissociation constant (Kd) for 3H-HBP were also approximately equal to those for 3H-DM. The Scatchard and Hofstee plots analyses of 3H-HC binding indicated that the HC binding sites consisted of three components with different affinity, while that of 3H-DM had only one site with an intermediate affinity. HBP and hydrocortisone 17-butyrate (HB) bound to other binding sites of HC in addition to the site for DM. The IC50 value for synthetic glucocorticoids determined from the inhibition curves of 3H-HC binding in the first phase agreed with the values determined by the displacement study of 3H-DM binding. Furthermore, the first phase of HBP in the inhibition curve of 3H-HC binding disappeared from the curve, and only the second phase remained following the addition of DM. These results indicate that the esterification of C-17 and C-21 OH increases the affinity of the binding site for synthetic glucocorticoid and attenuates the affinity for the other binding sites of HC.