Inositol phosphoglycans and signal transduction systems in pregnancy in preeclampsia and diabetes: Evidence for a significant regulatory role in preeclampsia at placental and systemic levels

Measurements have been made of the urinary content of inositol phosphoglyca ns IPG P-type and IPG A-type, putative insulin second messengers, in preecl ampsia, in type I insulin-treated diabetic pregnant women and their matched control subjects, and nonpregnant women of child-bearing age. The content of IPG P-type and IPG A-type was also measured in the placenta from preecla mptic patients and from normal pregnancies. Pregnancy was associated with a n increase, approximately twofold, in urinary output of IPG-P-type relative to nonpregnant controls (P < 0.01). The 24-h output of IPG P-type in urine in preeclamptic women was significantly higher (2- to 3-fold) than in preg nant control subjects matched for age, parity, and stage of gestation (P < 0.02). In contrast, insulin-dependent diabetic pregnant women did not show any significant change in urinary output of IPG P-type or IPG A-type relati ve to pregnant control subjects. Evidence for a possible relationship and c orrelation between the urinary excretion of IPG P-type and markers of preec lampsia, including proteinuria (r = 0.720, P < 0.01), plasma aspartate tran saminase (r = 0.658, P < 0.05), and platelet counts (r = 0.613, P < 0.05) i s presented. A high yield of IPG P-type was extracted from human placenta, in preeclampsia some 3-fold higher (P = 0.03) than the normal value, wherea s no IPG A-type ( with lipogenic-stimulating activity) was found. Low conce ntrations of placental IPG A-type were detected relative to IPG P-type usin g assay systems dependent upon the effect of this mediator on cAMP-dependen t protein kinase or on a proliferation assay using thymidine incorporation into DNA of EGFR T17 fibroblasts. It is postulated that the high urinary ex cretion IPG P-type in preeclampsia reflects high placental levels and relat es to the accumulation of glycogen in the placenta. The paracrine effects o f placental IPG P-type (stimulation off other endocrine glands and/or endot helial cells) could contribute to the pathogenesis of the maternal syndrome . A possible theoretical Link between elevated placental IPG P-type and apo ptosis is proposed. (C) 2000 Academic Press.