Glucocorticoids impair fetal beta-cell development in rats

In rats, poor fetal growth due to maternal food restriction during pregnanc y is associated with decreased beta -cell mass at birth and glucose intoler ance in adulthood. Overexposure to glucocorticoids in utero can induce intr auterine growth retardation in humans and animals and subsequent glucose in tolerance in rodents. The aims of this study were to investigate whether gl ucocorticoid overexposure mediates the effect of undernutrition on beta -ce ll mass and to study their potential role in normally nourished rats. Under nutrition significantly increased maternal and fetal corticosterone levels. Twenty-one-day-old fetuses with undernutrition showed growth retardation a nd decreased pancreatic insulin content; adrenalectomy and subcutaneous cor ticosterone implants in their dams prevented the maternal corticosterone in crease and restored fetal beta -cell mass. In fetuses with normal nutrition , fetal corticosterone levels were negatively correlated to fetal weight an d insulin content; fetal beta -cell mass increased from 355 +/- 48 mug in s ham to 516 +/- 160 mug after maternal adrenalectomy; inhibition of steroid production by metyrapone induced a further increase to 757 +/- 125 mug. Our data support the new concept of a negative role of glucocorticoids in feta l beta -cell development.