Glucocorticoids impair fetal b-cell development in rats

Blondeau, B., J. Lesage, P. Czernichow, J. P. Dupouy, and B. Bréant. Glucocorticoids impair fetal b-cell development in rats. Am J Physiol Endocrinol Metab 281: E592–E599, 2001.—In rats, poor fetal growth due to maternal food restriction during pregnancy is associated with decreased b-cell mass at birth and glucose intolerance in adulthood. Overexposure to glucocorticoids in utero can induce intrauterine growth retardation in humans and animals and subsequent glucose intolerance in rodents. The aims of this study were to investigate whether glucocorticoid overexposure mediates the effect of undernutrition on b-cell mass and to study their potential role in normally nourished rats. Undernutrition significantly increased maternal and fetal corticosterone levels. Twenty-one-day-old fetuses with undernutrition showed growth retardation and decreased pancreatic insulin content; adrenalectomy and subcutaneous corticosterone implants in their dams prevented the maternal corticosterone increase and restored fetal b-cell mass. In fetuses with normal nutrition, fetal corticosterone levels were negatively correlated to fetal weight and insulin content; fetal b-cell mass increased from 355 6 48 mg in sham to 516 6 160 mg after maternal adrenalectomy; inhibition of steroid production by metyrapone induced a further increase to 757 6 125 mg. Our data support the new concept of a negative role of glucocorticoids in fetal b-cell development.