Glucocorticoid receptors in palatal mesenchymal cells from the human embryo: relevance to human cleft palate formation.
Glucocorticoids are potent inducers of cleft palate (CP) in experimental animals. The present study was performed in order to examine whether human embryonic palatal mesenchymal (HEPM) cells contain glucocorticoid receptors and are responsive to the growth inhibitory effects of glucocorticoids. We have found that there is a single population of specific, high affinity, saturable glucocorticoid receptors in HEPM cells. Scatchard analysis of the binding data revealed that the apparent dissociation constant (Kd) was 26 nM and the number of receptors was 1.4 x 10(5) per cell. Dexamethasone (DEX), a potent synthetic glucocorticoid analog, inhibited growth of HEPM cells cultured in serum-free chemically defined medium by 20-40%. Dose-response experiments showed that DEX inhibition of HEPM cell growth was closely correlated with specific binding of [3H]DEX to the cells, suggesting that the suppression of HEPM cell growth may be receptor-mediated. DEX also inhibited collagen synthesis in HEPM cells. These results indicate that HEPM cells are capable of responding to both physiological and pharmacological levels of glucocorticoids and suggest that either endogenous or exogenous glucocorticoids may have the potential to interfere with human palate formation by perturbing the growth and differentiation of palatal mesenchymal cells.
D002460:Cell Line; D002478:Cells, Cultured; D002972:Cleft Palate / Q000209:etiology*; D003094:Collagen / Q000096:biosynthesis; D003470:Culture Media; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D006801:Humans; D066298:In Vitro Techniques; D010159:Palate / Q000166:cytology* / Q000187:drug effects; D011965:Receptors, Glucocorticoid / Q000032:analysis*; D011987:Receptors, Steroid / Q000032:analysis*
D003470:Culture Media; D011965:Receptors, Glucocorticoid; D011987:Receptors, Steroid; D003907:Dexamethasone; D003094:Collagen