From animal to molecule: aspects of the biology of insulin-like growth factors.
The synthesis of IGF-II mRNA in sheep foetal tissues is considerably higher than IGF-I. IGF-II probably has a paracrine role in the foetus; however it is likely that IGF-I originates mainly from the foetal liver and has an endocrine function. Although in the adult system IGF-I is tightly bound to serum carrier proteins it is potentially biologically active. Galactopoiesis in the goat mammary gland provides a useful model for demonstrating the importance of circulating IGF-I as a mediator of GH action. Ligand-receptor interactions involved in the stimulation of Swiss 3T3 fibroblasts by IGF-I, II and insulin were examined. It was found that the potency of binding to type I receptors was IGF-I greater than IGF-II much greater than insulin by competitive binding assays and chemical cross-linking studies, and that some cell lines secrete an IGF binding protein which is specific for IGF-I and II and which acts as an inhibitor in cellular binding assays. Maximal stimulation of DNA synthesis induced by IGF-I, II and insulin in the presence of synergising mitogens were similar. While the actions of the IGFs were consistent with type I receptor binding insulin appeared to act through its own receptor. The reduction of EGF receptor affinity following the addition of IGF-I and insulin to 3T3 cells may involve a protein kinase that is not sensitive to phorbol esters. 3T3 cell nuclei contain endogenous inositol phospholipids and their corresponding kinases and monoesterases.(ABSTRACT TRUNCATED AT 250 WORDS)
Gilmour
R S
RS
AFRC Institute of Animal Physiology and Genetics Research, Babraham Hall, Cambridge UK.
Prosser
C G
CG
Fleet
I R
IR
Cocco
L
L
Saunders
J C
JC
Brown
K D
KD
Corps
A N
AN
D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D007328:Insulin / Q000502:physiology; D007774:Lactation / Q000187:drug effects / Q000502:physiology; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000502:physiology; D010716:Phosphatidylinositols / Q000502:physiology; D011247:Pregnancy; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology; D017451:Receptors, Somatomedin; D013002:Somatomedins / Q000032:analysis / Q000502:physiology*
D007328:Insulin; D010716:Phosphatidylinositols; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D013002:Somatomedins