Glucocorticoid receptor-mediated teratogenesis and cell proliferation in the limbs and face of the chick embryo.
The susceptibility of the face region of the chick embryo to the teratogenic action of intraamniotically injected hydrocortisone contrasts with the resistance of the limbs to its action while at the same time their dysmorphogenesis may be induced by other agents. Since glucocorticoid receptors were shown to mediate face teratogenesis, their development was investigated in freshly dissected limb buds of 3-, 3.5-, and 4-day-old chick embryos in comparison with the face region. The specific binding of 3H-dexamethasone to molybdate-stabilized glucocorticoid receptors was estimated by the dextran-coated charcoal method and complemented by cytologic analysis of mitotic activity in control and hydrocortisone-treated embryos. The glucocorticoid receptors were found in both organ anlagen already on day 3 when their concentration in femtomoles per microgram DNA was significantly higher in the face region. Accordingly, on day 3 intraamniotic hydrocortisone inhibited the mitotic activity in the face without affecting the developing limbs. On days 3.5 and 4 the concentration of glucocorticoid receptors was similar in both organ anlagen. Administration of hydrocortisone on day 4 induced mitotic depression in the face as well as in the limbs. However, the degree of inhibition appeared to be dependent upon the actual mitotic rate. In the face region where the mitotic activity culminated at that time, the inhibition was much deeper and longer-lasting than in the developing limbs characterized by continuous decrease of proliferation rate in controls. These findings are consistent with a view that glucocorticoid receptors are a prerequisite, but not the only factor in receptor-mediated teratogenesis.
D000014:Abnormalities, Drug-Induced / Q000196:embryology* / Q000378:metabolism; D000818:Animals; D002642:Chick Embryo; D005121:Extremities / Q000196:embryology / Q000378:metabolism; D005145:Face / Q000002:abnormalities* / Q000196:embryology / Q000378:metabolism; D006854:Hydrocortisone / Q000633:toxicity*; D017880:Limb Deformities, Congenital; D008938:Mitosis / Q000187:drug effects; D011965:Receptors, Glucocorticoid / Q000378:metabolism*
D011965:Receptors, Glucocorticoid; D006854:Hydrocortisone