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 muscle cells (VSMCs), which express AM specific receptors. In the survey for substances regulating AM production, we found that dexamethasone, hydrocortisone and aldosterone stimulate AM production in cultured rat VSMC with ED50 values of 2.4 nM, 16 nM and 270 nM, while progesterone, estradiol and testosterone induced weak or no effect. Maximal stimulation levels of dexamethasone, hydrocortisone and aldosterone were comparable and a little lower than those of the most potent stimulants, interleukin-1 and tumor necrosis factor. Hydrocortisone dose-dependently activated AM gene transcription, and AM mRNA level was highest at 12 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% after 14 h incubation. These results demonstrate a complex regulation system of AM production in VSMC by hormones and related substances. Furthermore, effects of actinomycin D and cycloheximide suggest that biosynthesis of AM is designed for quick response to physiological stimulation.
Minamino
N
N
National Cardiovascular Center Research Institute, Osaka, Japan.
Shoji
H
H
Sugo
S
S
Kangawa
K
K
Matsuo
H
H
D053607:Adrenomedullin; D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D006854:Hydrocortisone / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D010452:Peptide Biosynthesis; D010455:Peptides; D011374:Progesterone / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000494:pharmacology; D013963:Thyroid Hormones / Q000494:pharmacology*; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000959:Antihypertensive Agents; D007375:Interleukin-1; D008070:Lipopolysaccharides; D010455:Peptides; D013963:Thyroid Hormones; D014409:Tumor Necrosis Factor-alpha; D053607:Adrenomedullin; D003609:Dactinomycin; D013739:Testosterone; D000450:Aldosterone; D011374:Progesterone; D004958:Estradiol; D014212:Tretinoin; D003907:Dexamethasone; D003513:Cycloheximide; D006854:Hydrocortisone