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The presence of cation‐dependent proteases for insulin‐like growth factor binding proteins does not alter the size distribution of insulin‐like growth factors in pregnancy
Author(s) -
Davies S. C.,
Holly J. M. P.,
Coulson V. J.,
Cotterill A. M.,
Abdulla A. F.,
Whlttakert P. G.,
Chard T.,
Wass J. A. H.
Publication year - 1991
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.1991.tb00331.x
Subject(s) - proteases , endocrinology , blot , medicine , insulin like growth factor binding protein , insulin like growth factor , insulin , pregnancy , growth factor , enzyme , distribution (mathematics) , pregnancy associated plasma protein a , third trimester , biology , chemistry , fetus , receptor , first trimester , biochemistry , mathematical analysis , genetics , mathematics , gene
SUMMARY objective The aim was to Investigate the sera of pregnant women for the presence of specific proteases for insulin‐like growth factor binding proteins (IGFBPs) and to determine the effect of these on the distribution of IGFs in the circulation design The method used was the chromatographic and electrophoretic analysis of patients’ serumpatients Sera were examined from normal women during pregnancy: first trimester ( n =4), second trimester ( n = 4) and third trimester ( n = 10). Eight women with Type I diabetes in the third trimester were also studied along with sera from ten normal adult volunteers . measurements Circulating IGF‐I and IGF‐II levels were measured by RIA and their distribution examined by gel filtration. The pattern and stability of the IGFBPs was Investigated by Western Iigand blotting results A marked reduction in the serum levels of IGFBP‐2, IGFBP‐3 and IGFBP‐4 on Western Iigand blotting, which was associated with the presence of three Independent, cation‐dependent proteases that were specific for different IGFBPs, was found in late pregnancy. Gel filtration of third trimester serum revealed most of the IGF‐I to be present in a complex larger than 130 kDa, with a similar distribution to that found in serum of non‐pregnant women. The enzymatic modification of the binding proteins made apparent by the decrease in binding protein bands on Western Iigand blotting of preincubated samples had no effect on the distribution of IGF‐I following size ractionation conclusions There appear to be at least three Independent enzymes that are Induced or activated during pregnancy to modify IGFBP‐2, IGFBP‐3 and IGFBP‐4 sufficiently to prevent their detection by Iigand blotting. However, this enzymatic processing does not alter the distribution of IGFs, suggesting that the altered binding proteins are still able to carry IGFs but with reduced affinity. Such an alteration in the carrying mechanism of IGFs may have profound effects upon the bioavailability of the IGFs to the maternal tissues and contribute to the altered metabolic demands of pregnancy