Gupta C, Katsumata M, Goldman A S
J Craniofac Genet Dev Biol. 1985;5(3):277-85.
We have reported that susceptibility to glucocorticoid- and phenytoin-induced cleft palate and glucocorticoid receptor levels in mice are influenced by the H-2 histocompatibility complex on chromosome 17. Phenytoin competes with glucocorticoids for the glucocorticoid receptor and inhibits production of prostaglandins and thromboxanes. In this paper, we have investigated whether glucocorticoids and phenytoin inhibit arachidonic acid release and prostaglandin biosynthesis directly in the embryonic palates and whether the H-2 gene complex influences the degree of inhibition. Using congenic strains varying only in the H-2 region, we demonstrate here that both glucocorticoids and phenytoin inhibit the release of 3H-arachidonic acid and prostaglandin biosynthesis from embryonic palatal tissue, prelabeled with 3H-arachidonic acid. The degree of inhibition of arachidonic acid release and of prostaglandin biosynthesis is greater in the strain with H-2a (A/Wy) than in its corresponding congenic partner H-2b (A.BY). Thus, these results provide further evidence for a similar genetic and biochemical pathway for the teratogenic action of both phenytoin and glucocorticoids.
我们曾报道，小鼠对糖皮质激素和苯妥英钠诱导腭裂的易感性以及糖皮质激素受体水平受17号染色体上的H-2组织相容性复合体影响。苯妥英钠与糖皮质激素竞争糖皮质激素受体，并抑制前列腺素和血栓素的产生。在本文中，我们研究了糖皮质激素和苯妥英钠是否直接抑制胚胎腭中花生四烯酸的释放和前列腺素的生物合成，以及H-2基因复合体是否影响抑制程度。利用仅在H-2区域不同的同源近交系，我们在此证明，糖皮质激素和苯妥英钠均抑制预先用3H-花生四烯酸标记的胚胎腭组织中3H-花生四烯酸的释放和前列腺素的生物合成。与相应的同源近交系H-2b（A.BY）相比，携带H-2a（A/Wy）的品系中花生四烯酸释放和前列腺素生物合成的抑制程度更大。因此，这些结果为苯妥英钠和糖皮质激素致畸作用的相似遗传和生化途径提供了进一步的证据。
