Effects of insulin, glucose and ACTH on corticosterone production by fetal adrenal cells from diabetic rats

Abstract

Experiments were carried out on Sprague-Dawley rats to determine whether changes in fetal corticosterone levels during maternal diabetes were caused by the accompanying fetal hyperinsulinaemia or fetal hyperglycaemia. Diabetes was induced by injecting streptozotocin (30-45 mg/kg, i.v.) on day 2 of gestation. Fetal adrenals were removed on day 20 of gestation and cultured. Streptozotocin caused moderate (blood glucose 14-22.5 mmol/l) to severe (blood glucose greater than 25 mmol/l) diabetes. Both moderate and severe diabetes caused a decrease in fetal body weights. Relative to non-diabetic controls, maternal and fetal plasma concentrations of corticosterone were higher in the severely and lower in the moderately diabetic rats. Corticosterone production by fetal adrenal cells from control and moderately diabetic rats was comparable, but cells from the severely diabetic animals produced significantly greater amounts of corticosterone than did control cells. Neither glucose (28 mmol/l) nor insulin (1 nmol/l) exerted significant effects on [3H]thymidine uptake or corticosterone production by fetal adrenal cells from non-diabetic, moderately diabetic or severely diabetic rats. Human ACTH (0.02-20 nmol/l) caused a concentration-dependent increase in corticosterone output of comparable magnitude by cells from all three groups of animals. These data suggest that fetal growth abnormalities during diabetic pregnancy are not directly related to changes in glucocorticoid levels and that changes in glucocorticoid levels are not caused by any direct action of fetal hyperinsulinaemia or hyperglycaemia on adrenal cells.

Expression of glucocorticoid receptor and glucose transporter-1 during placental development in the diabetic rat

“…Glucocorticoid dynamics during diabetic pregnancy is a controversial issue. Plasma corticosterone levels at term are dependent on the severity of maternal diabetes [24]. Maternal and fetal plasma corticosterone levels of diabetic rats were significantly lower than the corresponding control values between GD19 and GD22 [25].…”

Adrenocortical Imprint in the Fetus of a Diabetic Gestation

“…Conliffe and Mulay [12] observed that fetal rat plasma corticosterone appeared to be related to the degree of hyperglycemia. Cugini et al [27] have reported elevated aldosterone levels in the newborns of human diabetics.…”

“…Mulay and Solomon [10] reported decreased corticosterone levels in late gestation fetuses of moderately diabetic, untreated dams, whereas Gewolb and Warshaw [11] observed no difference in unbound corticosterone. Conliffe and Mulay [12] have shown that plasma corticosterone levels were lower in fetuses of moderately (which they defined as a maternal glucose of 21.4 mM/l) diabetic untreated gestations compared with control. However, DNA synthesis and basal in vitro production of corticosterone by dispersed fetal adrenal cells from these diabetic dams were unchanged upon addition of insulin or glucose to the media, leading the authors to conclude that neither insulin nor glucose exerted a direct effect in vitro upon fetal adrenal cells.…”

“…Briefly, 5 Ìg of total RNA was hybridized with oligo (dT) [12][13][14][15][16][17][18] and the reaction was carried out using SuperScriptII RNaseH reverse transcriptase for 50 min at 42°C. The reaction was terminated by heating for 15 min at 70°C.…”

“…Corticosteroid dynamics are poorly understood in the diabetic, with reports of circulating glucocorticoids as increased, decreased and unchanged [10][11][12]. Even less is known regarding coricosteroids at the level of gene expression.…”