Studies of the composition and radioreceptor activity of "big" and "little" human growth hormone.
Immunoreactive growth hormone (GH) from human pituitary and plasma contains "big" (BGH) and "little" (LGH) components. BGH itself consists of a "urea-labile" form and a "urea-stable" form (usBGH). In the present study we determined the amino acid composition of a BGH preparation containing both the urea-labile and urea-stable components and bound it to be indistinguishable from that of LGH. This finding, coupled with observations of others, suggests that urea-labile BGH is a simple LGH dimer and that usBGH is a disulfide dimer. We have prepared LGH, BGH, and usBGH from human pituitary GH, and studied their radioreceptor activity, in relation to their immunoreactivity, in plasma membrane systems from rabbit, rat and human liver and rabbit mammary gland. When 125I-LGH was used as the radioligand, LGH and usBGH caused parallel displacement, usBGH was 60-74% as active as LGH in the animal preparations, while in human liver the two forms were equally active. Three different BGH preparations studied in the animal systems were 26-33% as active as LGH. The receptor activity of these BGH preparations was greater than expected from their usBGH content, suggesting that urea-labile BGH also binds to the LGH receptor. When 125I-usBGH was employed as radioligand, we found that in the presence of 2,000 ng/ml of LGH, which caused maximal displacement of 125I-usBGH, the addition of 2 ng/ml of usBGH produced additional displacement. This suggested the presence of a receptor specific for usBGH. However, the phenomenon proved to be due to a contaminant in the usBGH preparations which decreased binding of 125I-usBGH. BGH containing a substantial fraction of usBGH, and "freeze-stable" BGH which is probably identical with usBGH, both failed to displace 125I-usBGH in the presence of 2,000 ng/ml LGH. These observations rule against the existence of a specific receptor for usBGH.
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D002462:Cell Membrane / Q000648:ultrastructure; D013006:Growth Hormone / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D011817:Rabbits; D011869:Radioligand Assay; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D014508:Urea
D000596:Amino Acids; D011956:Receptors, Cell Surface; D014508:Urea; D013006:Growth Hormone