Dexamethasone receptor levels in palatal and lung fibroblasts of adult A/J and C57BL/6J mice: relationship to glucocorticoid-induced cleft palate.

Abstract

Glucocorticoid-induced cleft palate (CP) has been used as an animal model for hormonal teratogenesis. In mice, the susceptibility to glucocorticoid-induced CP varies with the strain, A/J being very sensitive and C57/BL6J relatively resistant. Studies in adult and embryonic murine tissues have attempted to correlate the number of glucocorticoid receptors and CP susceptibility, with conflicting results. The relative quantities of dexamethasone receptors were now studied in established palatal and lung fibroblast cell cultures obtained from adult C57 and A/J mice. A rapidly saturable, stable binding system was demonstrated. Scatchard plots were linear indicating a single class of high affinity receptors. The glucocorticoid receptor number ranged from 6.2 x 10(-16) mole/microgram prot to 8.6 x 10(-16) mole/microgram prot, while the KD varied from 1.0 x 10(-8) M to 2.8 x 10(-8) M. The differences in receptor characteristics between murine strains were not significant (p greater than 0.05). The absence of a difference in receptor number between the two strains may reflect the limitation of fibroblast cell culture in assessing glucocorticoid binding in vivo. Alternatively, if a difference in palatal dexamethasone receptor levels between mice strains exists, it may occur only in the embryo.