title: The effects of triacetyloleandomycin and oleandomycin phosphate on the glucocorticoid receptor in cultured skin fibroblasts.
abstract: Triacetyloleandomycin (TAO) has been described as a "steroid-sparing" drug in that poorly controlled asthmatic patients can be stabilized or improved with the addition of TAO despite decreasing dosages of steroids, specifically methylprednisolone (MP). It is not clear whether the beneficial effects of TAO are due to decreased MP clearance or are due to enhanced glucocorticoid effect peripherally. We tested the latter possibility by studying the interaction of TAO and oleandomycin phosphate (OLEO), the active metabolite of TAO in vivo, with glucocorticoid receptors in dispersed, intact cultured human skin fibroblasts. With the use of cells incubated with [3H]dexamethasone at 22 degrees C, we examined the competitive binding properties of TAO and OLEO (at varying concentrations) with and without MP as compared with several other steroids and MP alone. We also studied the effects on cellular glucocorticoid receptor number and affinity when TAO at a concentration of 4 X 10(-5) alone, at 10(-5) M in combination with a receptor saturating concentration of MP (5 X 10(-8) M), with MP alone, or with OLEO (10(-5) M) combined with MP was added to fibroblasts in the growth phase 1 wk before assay. TAO and OLEO did not compete for the binding of [3H]dexamethasone to the fibroblast glucocorticoid receptor, nor did they alter the binding properties of MP. With prolonged cellular exposure, TAO alone did not alter the number of glucocorticoid receptors (per cell) or their affinity for [3H]dexamethasone. Interestingly, prolonged exposure to saturating concentrations of MP alone decreased glucocorticoid receptor density; this effect was not altered by the presence of TAO or OLEO.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D002452:Cell Count; D002478:Cells, Cultured; D005347:Fibroblasts / Q000648:ultrastructure*; D006801:Humans; D008775:Methylprednisolone / Q000494:pharmacology; D009827:Oleandomycin / Q000494:pharmacology*; D011965:Receptors, Glucocorticoid / Q000187:drug effects*; D011987:Receptors, Steroid / Q000187:drug effects*; D012867:Skin / Q000166:cytology; D014217:Troleandomycin / Q000494:pharmacology*
chemical_list: D011965:Receptors, Glucocorticoid; D011987:Receptors, Steroid; D014217:Troleandomycin; D009827:Oleandomycin; D008775:Methylprednisolone