BINDING OF PLACENTAL-LACTOGEN AND GROWTH-HORMONE TO FETAL SHEEP FIBROBLASTS

被引:13
|
作者
FOWLKES, J [1 ]
FREEMARK, M [1 ]
机构
[1] DUKE UNIV, MED CTR, DEPT CELL BIOL, DURHAM, NC 27710 USA
关键词
D O I
10.1203/00006450-199208000-00015
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
Growth hormone (GH) regulates growth an development in the postnatal period but lacks somatotropic activity in the fetus. In contrast, the placental hormone placental lactogen (PL) stimulates amino acid transport, DNA synthesis, and somatomedin production in isolated fetal tissues, suggesting that PL may function as a "fetal GH." To elucidate the mechanisms by which PL exerts GH-like effects in fetal tissues, we examined the binding of PL, GH, and prolactin to cultured skin fibroblasts obtained from midgestational fetal lambs. Ovine fetal fibroblasts bound radiolabeled ovine PL (oPL) specifically and with high affinity (EC50 0.20 nM). In competitive displacement assays using I-125-oPL as the radioligand, the potency of unlabeled oPL was eight to 12 times greater than that of ovine GH and congruent-to 1000 times greater than that of ovine prolactin. Covalent cross-linking of I-125-oPL (22 kD) to ovine fetal fibroblasts revealed a specific hormone-receptor complex with an apparent Mr of 130 000, suggesting that the high affinity oPL binding site has a molecular mass of approximately 108 kD. The specific bindings of radiolabeled ovine GH (0.6% per 250-mu-g protein) and ovine prolactin (0.04% per 250 ug protein) were only 1/15 and 1/230 that of radiolabeled oPL (9.1% per 250-mu-g protein), and no specific cross-linking of I-125-ovine GH or I-125-ovine prolactin to ovine fetal fibroblasts was detected. These findings demonstrate preferential binding of PL by isolated fetal sheep fibroblasts in culture, providing a cellular mechanism whereby PL may exert growth-promoting effects in the fetus.
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页码:200 / 203
页数:4
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