Sensitivity to corticosterone-induced cleft palate is not associated with H-2.
The frequency of cleft palate (CP) and corticosterone levels in maternal plasma and amniotic fluid were determined in pregnant C57BL/10 (H-2b) and congenic B10.A (H-2a) mice after the ip injection of repository ACTH, corticosterone acetate, or desoxycorticosterone acetate (DOCA) on the 11th through 14th day of gestation. It was found that ACTH (a) induces CP in B10.A but not C57BL/10 mice, (b) induces CP in B10.A mice at about the same frequency noted when diluent alone is injected, and (c) produces an elevation in maternal plasma corticosterone levels 1.5- to 2.0-fold lower and amniotic fluid levels 3- to 5-fold lower than those found after the injection of 5 mg corticosterone acetate, a dose which induces a comparable frequency of CP in B10.A mice. The injection of 5 mg corticosterone acetate produced CP frequencies in C57BL/10 and B10.A mice of 4.9 and 3.3%, respectively, and increasing the dose to 9.2 mg resulted in significant increases in CP to 23.8 and 24.7%, respectively. DOCA at two dose levels induced CP in B10.A fetuses at about the frequency noted when diluent alone has been given. These findings show that susceptibility to corticosterone induced CP is not associated with the major histocompatibility complex of the mouse, H-2, as is the case with glucocorticoids (e.g., cortisone, dexamethasone), and they raise the possibility that factors other than or in addition to corticosterone may be involved in spontaneous or ACTH- or stress-induced CP.