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Regulation of DNA synthesis in human fetal hepatocytes by placental lactogen, growth hormone, and insulin‐like growth factor I/somatomedin‐C
Author(s) -
Strain Alastair J.,
Hill David J.,
Swenne Ingemar,
Milner R. D. G.
Publication year - 1987
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041320105
Subject(s) - somatomedin , human placental lactogen , endocrinology , medicine , placental lactogen , growth factor , dna synthesis , biology , insulin like growth factor , incubation , collagenase , fetus , thymidine , monoclonal antibody , hormone , insulin , antibody , dna , biochemistry , growth hormone , receptor , placenta , pregnancy , genetics , immunology , enzyme
Hepatocytes were isolated by gentle collagenase digestion of liver fragments from human fetuses of 8–16 weeks gestation obtained following prostaglandin‐induced pregnancy terminations. They were maintained on collagencoated tissue culture dishes in selective arginine‐free medium for up to 72 hr, and the action of hormones and growth factors on DNA synthesis was studied by autoradiography following incubation with 3 H‐thymidine. The labeling index of hepatocytes was consistently enhanced by 25–250 ng/ml human placental lactogen (HPL), 25–250 ng/ml human growth hormone (HGH), 10–50 ng/ml insulin‐like growth factor l/somatomedin‐C (IGF l/Sm‐C), and 10% dialyzed fetal calf serum, reaching a maximum of three‐ to four‐fold greater than in basal medium alone. Under basal conditions, 30% of hepatocytes stained positively for the presence of IGF peptides using a monoclonal antibody raised against purified human IGF l/Sm‐C. Although this proportion did not change following treatment with HGH and HPL, IGF l/Sm‐C released by cells into culture medium was considerably increased in the presence of both hormones. Incubation with the SmC 1.2 monoclonal antibody abolished the increase in labeling index in response to IGF l/Sm‐C and partially blocked the response to both HPL and HGH. These results indicate that both HPL and HGH stimulate DNA synthesis in human fetal hepatocytes and suggest that this effect is at least partly indirect through the release and paracrine action of IGF l/Sm‐C.