The Binding of Rat Liver Cell Multiplication‐stimulating Activity (Msa) to Human Placenta and Serum Proteins

Abstract

Summary Multiplication‐stimulating activity (MSA) from the medium of BRL‐3A rat liver cells in culture binds to cell membrane and cytosol receptors from human placenta and to serum proteins. The binding of MSA to placental cell membranes is dependent on time, temperature, pH and divalent ion concentration. MSA bound to placental cytosol receptor and serum is not displaced by insulin, whereas that bound to placental cell membranes is displaced by insulin and insulin‐like peptides. The affinity of the three receptors for MSA is similar (≏ 108 M ‐1). An assay using 125I‐MSA and placental membrane receptor detects somatomedin‐like receptor activity (SmLRA) in unextracted sera from man and animals. A binding protein in serum that competes for 125I‐MSA with receptor could not be completely separated from SmLRA by‐heating, acidification, charcoal treatment and gel chromatography of the serum. The relative activities of SmLRA and serum binding protein remained constant in three disorders of human growth (acromegaly, growth hormone deficiency and Laron's dwarfism) in which values of SmLRA varied widely. However, the binding protein is only partly responsible for the apparent SmLRA of unextracted serum. It is concluded that MSA is a suitable radioligand for the investigation of somatomedin disorders in man either by receptor assays or by studies of tissue receptors.

Effect of Streptozotocin on Foetal Lambs in Mid-pregnancy

“…The inter-and intra-assay variation were 13•1 % and 11•1 % respectively. The binding of 125I_MSA to unextracted foetal serum was performed as previously described (Brinsmead and Liggins 1978b). The ligand was first purified by binding to and eluting from foetal liver receptor.…”

Receptors for insulin and insulin-like growth factor in cultured arterial smooth muscle cells depend on their growth state

“…Scatchard analysis of the 125I-labelled insulin binding and 125I-labelled IGF binding showed a curvilinear slope for 125I-labelled insulin binding indicating heterogeneity of the binding sites, and also a high-affinity, low-capacity and second low-affinity, high-capacity binding system for 125I-labelled IGF. Several classes of receptor with differing affinities have been described for IGF I (Daughaday, Mariz & Trivedi, 1981), multiplication stimulating activity (MSA) (Brinsmead & Liggins, 1978) and somatomedin C (D'Ercole, Underwood & Van Wyk, 1977). Therefore changes between the sub-classes of the IGF receptor with growth status may also explain the altered competitive binding by insulin.…”

THE AUSTRALIAN & NEW ZEALAND JOURNAL OF OBSTETRICS & GYNAECOLOGY

“…An alternative explanation arises from the work of Chochinov et al (1977) who reported that the major receptor assayable somatomedin in human amniotic fluid is a protein that binds labelled somatomedin Iigand and has no intrinsic growth-promoting properties. It is possible that such a binding protein may contribute to the activity measured by the receptor assay used in this study (Brinsmead and Liggins, 1978b). Heinrich et al (1978) recently reported substantial concentrations of a somatomedin-binding protein in human cord blood.…”

“…SmLRA and SFA concentrations differed significantly in the 24 sera for which both assays were performed. The receptor assay detects several insulin-like peptides in serum (Brinsmead and Liggins, 1978b) whose concentrations may vary independently (Van Wyk et al, 1977). The sulphation factor bioassay in turn is influenced by a number of inhibitors which are not active in receptor assays, but which may be important in the physiological regulation of serum somatomedin activity (Salmon, 1975).…”