Development of Hormone Receptors Within the Fetus

Many factors affect the rate of fetal growth and development in addition to overall fetal well-being. In eutherian mammals, the placenta serves as the primary mediator and modulator of those factors that ultimately determine development rate. The placenta accomplishes this task in the following ways: (a) by serving as the site of nutrient and waste transfer between the mother and fetus; (b) by serving as a barrier against the maternal immune system and pathogens; and (c) by functioning as an endocrine organ. Regarding this latter function, the placenta is capable of synthesizing and secreting a plethora of protein and steroid hormones, growth factors, cytokines, and other bioactive molecules (1-3), many of which are produced at extraplacental sites as well. However, some are synthesized only by the placenta and are "true" placental hormones, such as the placental lactogens (1-3). Assigning specific biologic roles to any placental hormone is difficult, because classic ablation-replacement experiments are not feasible. Emphasis has therefore been placed on identifying the receptor for each placental hormone—its location and mechanism of action. Considerable effort has been expended on determining whether or not the placental lactogens act through structurally distinct receptors, or if they act through the growth hormone or prolactin receptor. As yet, firm conclusions cannot be drawn about the existence of distinct placental lactogen receptors, which has hampered our understanding of the function of this placental hormone. In some species (human and sheep), it has been suggested (4) that placental lactogen serves to modulate maternal and fetal metabolism, possibly by stimulating the expression of the insulin-like growth factors (IGFs). If this hypothesis is correct, it provides a direct link between placental hormone production and fetal growth regulation, because evidence now in hand clearly shows the importance and developmental pattern of the IGF system within the fetus (2). This chapter focuses on our current knowledge of the development of fetal growth hormone/placental lactogen receptors and their mechanism of action, with emphasis on humans and sheep.