Elevated glucocorticoid receptor levels in lymphocytes of children with the fetal hydantoin syndrome (FHS).
Our recent studies of the teratogenic mechanisms of phenytoin (DPH) and glucocorticoids in mice have indicated that DPH utilizes the anti-inflammatory pathway of glucocorticoids in producing congenital defects, such as cleft palate. This pathway is influenced by H-2 and H-3 histocompatibility-linked genes in the mouse, such that congenic strains have H-2 or H-3 alleles that confer susceptibility to DPH-induced congenital defects, and susceptible H-2 congenic strains have high glucocorticoid receptor levels. However, other H-2 or H-3 alleles confer resistance to these defects in their otherwise genetically identical congenic partner strains, and "resistant" H-2 alleles are associated with low levels of these receptors. To determine whether this animal work is applicable to the human, we have sought to investigate whether the level of glucocorticoid receptors in circulating lymphocytes of children with the fetal hydantoin syndrome (FHS) is as it is in the animals. We found that children with FHS had glucocorticoid receptor levels significantly elevated above those of unaffected children with similar DPH exposure in control families. The receptor level of affected children was also significantly elevated above that of fathers of children with the FHS and of fathers and mothers of control children. These findings are consistent with those documented in the animal models and suggest that an elevated level of glucocorticoid receptors in lymphocytes may be a marker for susceptibility to the FHS syndrome.
Goldman
A S
AS
Center for Craniofacial Anomalies, University of Illinois, College of Medicine at Chicago 60612.
Van Dyke
D C
DC
Gupta
C
C
Katsumata
M
M
D000014:Abnormalities, Drug-Induced / Q000235:genetics*; D002648:Child; D005260:Female; D005315:Fetal Diseases / Q000139:chemically induced* / Q000235:genetics; D006801:Humans; D006827:Hydantoins / Q000009:adverse effects*; D008214:Lymphocytes / Q000032:analysis*; D010672:Phenytoin / Q000009:adverse effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011965:Receptors, Glucocorticoid / Q000032:analysis*; D013577:Syndrome
D006827:Hydantoins; D011965:Receptors, Glucocorticoid; D010672:Phenytoin