Glucocorticoid induction of cleft palate in mice, no correlation with inhibition of mucopolysaccharide synthesis.

Glucocorticoids were administered once intramuscularly on day 11.5 of gestation to pregnant C3H/An mice. Triamcinolone acetonide (10 mg/ kg) produced 80% fetal cleft palates and reduced 35S-sulfate incorporation into palate mucopolysaccharides to 74% of control values. Cortisol acetate (320 mg/ kg) administration under the same conditions resulted in 70% cleft palate and 35% of control incorporation. A nonteratogenic dose of cortisol (64 mg/kg) in-hibited mucopolysaccharide synthesis to 68% of control values, i.e., this effect was similar to that obtained with the teratogenic dose of triamcinolone. Maximal palatal mucopolysaccharide synthesis occurs during day 14.5 of gestation, the time at which fetal palate shelves normally move horizontally and grow toward each other prior to fusion. Marked inhibition of mucopolysaccharide synthesis by glucocorticoids at this time has been considered to be the basis of their induction of cleft palates, analogous to their antiinflammatory effects on other connective tissue. However, our results suggest that the induction of cleft palate by gluco-corticoids is not related to inhibition of mucopolysaccharide synthesis by them but rather to growth inhibition.