Androstenedione synergizes with stress or prenatal drug exposure to retard fetal growth: Role of IGF

Pregnant Sprague-Dawley dams were implanted with a Silastic capsule (3 or 10 mm) containing androstenedione (AN) or cholesterol prior to being administered one of several treatments that create an endocrine profile of stress: maternal exposure to alcohol, pair feeding (PF), cocaine (COC), or restraint stress (RS). Controls (chow fed, CF) were left undisturbed during pregnancy. Treatments were administered from day 14 to day 22 of gestation. Fetuses were delivered by cesarean section on day 22. Results revealed that administration of AN to pregnant dams at a dose that does not influence fetal growth by itself can retard fetal growth in the presence of alcohol, PF, COC or RS. Data indicate that these effects are not directly attributable to changes in adrenocorticotropin (ACTH) or corticosterone levels. Preliminary results suggest a role for insulinlike growth factor (IGF) binding proteins (IGFBPs). Overall, these data demonstrate that AN can synergize with drugs and/or stress to enhance intrauterine growth retardation (IUGR). One underlying cause of this synergism between stress-related environmental events and androgenic actions on fetal growth may be increased expression of IGFBPs, which can sequester IGFs, thereby inhibiting their trophic actions on fetal and/or placental tissue.