ADRENOCORTICAL STEROIDS, THYROID-HORMONES AND RETINOIC ACID AUGMENT THE PRODUCTION OF ADRENOMEDULLIN IN VASCULAR SMOOTH-MUSCLE CELLS

Adrenomedullin (AM) is produced and secreted from vascular smooth musc le cells (VSMCs), which express AM specific receptors. In the survey f or substances regulating AM production, we found that dexamethasone, h ydrocortisone and aldosterone stimulate AM production in cultured rat VSMC with ED(50) values of 2.4 nM, 16 nM and 270 nM, while progesteron e, estradiol and testosterone induced weak or no effect. Maximal stimu lation levels of dexamethasone, hydrocortisone and aldosterone were co mparable and a little lower than those of the most potent stimulants, interleukin-1 and tumor necrosis factor. Hydrocortisone dose-dependent ly activated AM gene transcription, and AM mRNA level was highest at 1 2 h after stimulation. A physiological concentration of hydrocortisone was deduced to be enough to regulate AM production in VSMC. Retinoic acid and thyroid hormones increased AM production to 400% and 150%, af ter 14 h incubation. These results demonstrate a complex regulation sy stem of AM production in VSMC by hormones and related substances. Furt hermore, effects of actinomycin D and cycloheximide suggest that biosy nthesis of AM. is designed for quick response to physiological stimula tion. (C) 1995 Academic Press, Inc.