The structure-activity relationship of steroid hormones were studied with respect to the carbohydrate synthesis in liver slices and the chemical reactivities ofΔ4-3-ketone and C-20, 21-ketol groups of their molecules with isonicotinic acid hydrazide and blue tetrazolium, respectively. At the dose level of 10-4M, glucocorticoids such as cortisol, prednisolone, triamcinolone, and triamcinolone acetonide enhanced14C incorporation from 2-14C pyruvate and LU-14C alanine into glucose in rat liver slices. Triamcinolone acetonide was most potent of the steroids examined followed by triamcinolone. Prednisolone was less active than triamcinolone, but more potent than cortisol. This suggests that the double bond between C-l and C-2, and the C-16, 17-acetonide play important roles in increased glucocorticoid activity. TheΔ4-3-ketone group ofΔ2,4-3-ketosteroids such as prednisolone, triamcinolone, and triamcinolone acetonide reacted more slowly with isonicotinic acid hydrazide than the correspondingΔ4-3-ketosteroids. The rate of reaction of the C-20, 21-ketol with blue tetrazolium to form formazan was increased by the 16a-hydroxylation and decreased by the introduction of C-16, 17-acetonide. 16α-Hydroxycortisol, 16α-hydroxypredniso-lone, and triamcinolone showed greater formazan formation than the corresponding non-16α-hydroxylated parent steroids. However, cortisol acetonide, triamcinolone acetonide, and 6α-fluoro-17α-hydroxy-11-desoxycorticosterone acetonide showed less formazan formation than the corresponding parent steroids. These findings indicate that the enhanced glucocorticoid activity of adrenal cortical hormones is associated with the reduced chemical reactivity of theΔ4-3-ketone or the C-20, 21-ketol of their
展开▼
