Insulin-like growth factor 2 and short-range stimulatory loops in control of human placental growth.

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Abstract
Substructures of the first‐trimester human placenta (within 3 months post‐conception) display ‘pseudo‐malignant’ properties. We show here, by in situ hybridization, that the insulin‐like growth factor 2 (IGF‐2) gene expression is particularly active in the cytotrophoblasts, which dominate these structures. Because the majority of placental IGF‐2 mRNA is polysomal in extracts of first‐trimester placenta, the spatial pattern of IGF‐2 transcripts generally also defines the pattern of IGF‐2 production. In primary trophoblast cultures, rendered quiescent by serum starvation. IGF‐2 performs as a human embryonic growth factor by activating cell cycle entry/progression. Although both type 1 and 2 IGF receptor mRNAs can be found co‐distributed with IGF‐2 mRNA during placental development (supporting an autocrine role for IGF‐2), these occasional patterns are confined to cytotrophoblasts with low proliferative potential. The reciprocity in ligand and receptor expression patterns are discussed in terms of rate‐limiting steps in the involvement of IGF‐2 in the proliferative phenotype of the early human placenta.