Introduction

Growth in utero consists of a series of integrated biological processes. It is most commonly considered as a time of rapid cellular hyperplasia, yet this is not uniform in all tissues throughout gestation. In the early embryo considerable cell migration and spatial orientation occurs as organogenesis and somite development proceed. As gestation progresses ordered tissue differentiation must occur to prepare the infant for extra-uterine survival, while in the final trimester cell hypertrophy and, in the human, progressive adiposity contribute relatively more to increasing fetal size than does cellular hyperplasia. Peptide growth factors have the potential to drive and coordinate each of these developmental aspects since this class of molecules can variously promote cell hyperplasia, hypertrophy and differentiation; act as chemoattractants to influence cell migration; and, in some circumstances, slow or arrest cell proliferation.

Our conception of peptide growth factors has arisen from studies of postnatal growth, and is ambiguous. The somatomedins/insulin-like growth factors have been traditionally thought to act as liver-derived endocrine hormones which drive longitudinal skeletal growth and whose synthesis is under growth hormone control. Conversely, platelet-derived growth factor has been considered as a peptide whose role is largely limited to wound healing. Such rigid concepts have come increasingly under attack largely due to novel evaluations of growth factor presence and function in the embryo and fetus. These peptides are now considered to be ubiquitously distributed among tissues and to act at or near to their sites of synthesis as paracrine or autocrine messengers. Both peptide synthesis and tissue receptivity vary with ontogeny. This may create a dynamic balance of growth enhancing and inhibiting molecules within the extracellular fluid of each organ and tissue.