24703-00-2

The effects of metabolites of betamethasone 17,21-dipropionate (BMDP) on the hypothalamo-pituitary-adrenocortical axis were assessed by measurements of adrenal weights, after studying the metabolism of BMDP in vivo and in vitro in pregnant rats and mice.After BMDP was injected intravenously at a dose of 5mg/kg into rats and mice in late stages of pregnancy, it disappeared rapidly from the plasma and brain in both mothers and fetuses while betamethasone 17-propionate (BMP) was detected as the main metabolite followed by betamethasone (BM).In vitro studies demonstrated that BMDP was metabolized to BMP in maternal and fetal tissues (plasma, liver, brain and placenta) of both species.The subcutaneous administration of BMP to rats in the late stages of pregnancy induced adrenal hypertrophy in fetuses, though the adrenals of the mothers became atrophic.In the case of mice, both maternal and fetal adrenals became atrophic.Administration of BM produced adrenal atrophy in mothers and fetuses of both species.The subcutaneous administration of 6β-hydroxybetamethasone 17-propionate (6β-OH-BMP) to rat fetuses in utero produced adrenal hypertrophy and 6β-hydroxybetamethasone (6β-OH-BM) showed no effect.These data suggest that BMP is transferred across the placental barrier to produce marked adrenal hypertrophy in rat fetuses.