Some aspects of corticosteroid-induced cleft palate: a review.
Since the discovery 25 years ago that cortisone can produce cleft palate in mouse embryos investigations into possible mechanisms of this corticosteroid-induced defect have been many and varied. However, the teratogenic mode of action remains not fully clarified. It is with this thought in mind that we have reflected upon what is known concerning corticosteroids and cleft palate. The major metabolic pathways upon which glucocorticoids act as well as their intracellular mode of action are well known. Differential sensitivity of various mouse strains to cortisone treatment as well as recent results from interstrain blastocyst transfer experiments demonstrate that corticosteroid action is influenced by both the fetal and maternal genomes. Labeling experiments indicate that corticosteroid-induced cleft palate is the result of direct action of the steroid molecule on the fetus, whose own sensitivity to insult, perhaps owing to differences in binding of corticosteroids to tissue proteins, determines the final effect. Possible mechanisms that have been proposed by which corticoids may produce cleft palate include: disruption of glycosaminoglycan or collagen synthesis or both, intracellular lysosomal membrane stabilization, myopathy, weakened midline fusion, and loss of amniotic fluid. Also discussed is the role of stress and stress-induced corticosteroids and their possible role in the production of cleft palate.
D000305:Adrenal Cortex Hormones / Q000009:adverse effects* / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000009:adverse effects; D000818:Animals; D002972:Cleft Palate / Q000139:chemically induced*; D003094:Collagen / Q000096:biosynthesis; D003348:Cortisone / Q000009:adverse effects; D003433:Crosses, Genetic; D004624:Embryo Transfer; D004622:Embryo, Mammalian / Q000187:drug effects; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D005260:Female; D005838:Genotype; D005938:Glucocorticoids / Q000009:adverse effects / Q000378:metabolism; D006025:Glycosaminoglycans / Q000009:adverse effects; D006801:Humans; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D013315:Stress, Psychological; D014184:Transplantation, Homologous; D014222:Triamcinolone Acetonide / Q000009:adverse effects
D000305:Adrenal Cortex Hormones; D005938:Glucocorticoids; D006025:Glycosaminoglycans; D000324:Adrenocorticotropic Hormone; D003094:Collagen; D014222:Triamcinolone Acetonide; D003348:Cortisone