An Autocrine/Paracrine Role forInsulin-Like Growth Factors inthe Regulation ofHuman Placental Growth*

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Abstract
Tissue derived from preterm (9¬19 weeks gestation) and term (38 ¬ 41 weeks gestation) human placentae were examined fortheir ability to synthesize and secrete insulin¬like growth factors (IGFs) in organ culture. IGF¬I was measuredby a specific RIA, and IGF¬II bya rat placental membrane radiore¬ceptor assay. First, explants ofplacental tissue were maintained i n organ culture. These explants secreted immunoreactiveIGF¬I(IR¬IGF¬I). There were nodifferences inthe IR¬IGF¬I content of media conditioned byterm andpreterm placentae under these conditions. The similarity of this material to authentic human IGF¬I was supported byparallel displacement in a specific RIA and coelution during Sephadex G¬50gel filtration. Second, monolayer cultures of fibroblasts from normal human preterm placentae (15¬19 weeks gestation) were established. Confluent monolayers of these fibroblasts secreted IR¬IGF¬I (3¬10pg/105cells ¬40 h).IR¬9GF¬I secretion was reversibly inhibited by 5.3 MM cycloheximide, suggesting that theIR¬IGF¬I wasthe resultof de novo protein synthesis. IR¬IGF¬ I secretion was stimulated 5¬fold byplatelet¬derived growth factor (0.6 U/ml). Theresponse of monolayers of placental fibroblasts to IGF¬I also was tested. IGF¬I stimulated a¬[3H]aminoisobutyric acid transport in these fibroblasts, with half¬ maximal stimulation occurring at 2¬3 ng/ ml. Stimulation of a¬[3H]aminoisobutyric acid uptake byIGF¬I correlated with specific binding of [125I]iodo¬IGF¬I. Half-maximal inhibition of [125I]iodo¬IGF¬I binding occurred at 2¬3 ng/ml IGF¬I. Placental tissue also secreted IGF¬II¬like activity, as measured by radioreceptor assay. Media conditioned by placental explants contained 15¬20 ng/mg protein¬48 h, and media conditioned by placental fibroblasts contained 3¬7 ng/105 cells¬40 h IGF¬II determined by radioreceptor assay. These data support the hypothesis that the human placenta produces IGFs (IGF¬II and/or IGF¬I) that act locally to regulate placental growth.

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