トロホブラストからのhPLの分泌に関する基礎的研究
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概要
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In order to study the secretory mechanism of human placental lactogen (hPL : hCS) from trophoblastic tissues, tissue culture and new placental perifusion systems were developed and used to clarify the effect of various substances on the secretion of hPL. These substances were (1), metal ions ([Ca<SUP>2+</SUP>], [K<SUP>+</SUP>], [Mg<SUP>2+</SUP>], [Na<SUP>+</SUP>]); (2) growth hormone and prolactin releasing or inhibiting factors (arginine, TRH, somatostatin, dopamine); (3) LHRH, dibutyryl cyclic-AMP which stimulates hCG secretion; (4) prostaglandins F<SUB>2α</SUB>, and E<SUB>2</SUB>, bradykinin; (5) EGF and insulin which have the receptors in the placenta; (6) glucose. It was found that most of the substances examined had no effect on the secretion of hPL, except dopamine and glucose. The effect of dopamine in the tissue culture system is dosedependent. At high concentrations dopamine slightly inhibited hPL secretion (5mM; 38.6 ± 15.0 and 10mM; 35.7 ± 19.0μg/g wet tissue) compared with the control (63.2 ± 29.8μg/g wet tissue).However, these effects may be due to the deviation of pH in the medium from the direct addition of dopamine hydrochloride. At a low concentration (1mM) it was observed to have a rather stimulatory effect (125.7 ± 18.0ggig wet tissue, p<0.05), but in the perifusion system, this effect could not be observed. The addition of glucose in the perifusion system gave a slightly higher hPL secretion than that of the control. Perhaps this resulted from increased cell activity rather than a stimulatory effect.<BR>An incorporation experiment of [<SUP>3</SUP>H] leucine was also carried out to study the biosynthesis of hPL. Newly synthesized ([<SUP>3</SUP>H] -labelled) hPL was secreted into the medium within two hours. Furthermore, a labelled larger molecular weight substance together with the tritiated hPL was also observed on a Sephadex G-100 gel chromatography. These labelled substances were immunoprecipitatable using an anti-hPL serum, indicating that the substances contain the same immunological determinants. This result indicates that the larger molecular substance may represent the biosynthetic precursor or the aggregate of hPL.<BR>These data indicate that the secretion of hPL has a unique mechanism, different from GH and PRL, and may be self regulated.
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