Glucocorticoid inhibition of RNA synthesis and the critical period for cleft palate induction in inbred mice

A comparison was made of the teratogenic effects of triamcinolone (induction of cleft palate) and its ability to inhibit RNA synthesis in the C3H and A/J strains of mice. The “critical period” for induction of cleft palate in C3H mice was at day 11.5 of gestation, 3 days before palate shelf elevation. The extent of inhibition of RNA synthesis decreased when the drug was administered at later times of development and was correlated with a lower concentration of drug in fetuses. However when a higher dose (15 mg/kg) was administered at a later time (day 13.5), although the fetal drug concentration and inhibition of RNA synthesis were approximately equal to that produced by 10 mg/kg triamcinolone administered at day 11.5 (which produces 80% cleft palate), the frequency of cleft palate was much lower (33%). Thus the critical period for teratogenesis is not related to maximal absorption of drug. In A/J mice the critical period was at day 12.5. When one‐fifth as much triamcinolone (2 mg/kg) was administered to A/J mice the inhibition of RNA synthesis in palate and total fetus was similar to that seen after 10 mg/kg in the C3H strain. The concentration of drug in fetuses of each strain was approximately proportional to the dose administered. Thus A/J may be more sensitive to the effect of triamcinolone on RNA synthesis than C3H. The mechanism of action of the glucocorticoid with respect to the “critical period,” inhibition of RNA synthesis, and strain differences is discussed.