Ontogeny of growth factor receptors in the human placenta

The present study was undertaken to further elucidate the role during gestation of insulin, epidermal growth factor-urogastrone (EGF-URO), and a slightly acidic insulin-like growth factor we have referred to as insulin-like activity (ILAs). We examined the ontogeny of the placental receptors for these peptides utilizing membrane fractions (600 x g, 15,000 x g, 100,000 x g) and cytosol (200,000 x g supernatant) prepared by differential centrifugation of early gestation (11-19 wk) and term gestation (38-42 week) human placentae. Aliquots of each membrane fraction were also assayed for 5' nucleotidase activity. The ontogeny of the insulin and EGF receptors closely resembled the pattern of 5' nucleotidase activity, with greater levels seen in term tissue for all membrane fractions assayed. Highest levels of specific binding per mg protein and enzyme specific activity were seen in the 100,000 x g fraction within either gestational age group. The pattern of [125I]-ILAs specific binding was quite different: binding per mg protein was higher in membranes from early gestation placentae regardless of the fraction, with the biggest differential occurring in the 600 X g pellet. As observed with [125I]-insulin and [125I]-EGF, the 100,000 x g pellets from either age group were also enriched in [125I]-ILAs binding. Although neither early gestation nor term cytosol bound [125I]-insulin or [125I]-EGF, binding of [125I]-ILAs to both gestational age groups was clearly demonstrable with significantly higher levels observed in cytosol from early gestation placentae. A knowledge of the mechanisms involved in placental growth may well be a prerequisite to a full understanding of fetal growth control. The demonstration of specific human placental receptors for insulin, EGF-URO, and ILAs as early as 11-19 wk of gestation suggests that these peptides should continue to receive attention as possible modulators of placental growth and function. Furthermore, the high levels of [125I]-ILAs specific binding to membrane and cytosols from early gestation placentae may indicate a more important role for the insulin-like growth factors compared to insulin or EGF-URO during early placental development.