Membrane modification differentially affects the binding of the lactogenic hormones human growth hormone and ovine prolactin.
Human growth hormone (hGH) and ovine prolactin (oPRL) are both lactogenic as defined by their ability to induce milk-protein synthesis in vitro in the presence of insulin and hydrocortisone. At physiological concentrations, both hGH and oPRL have similar dose-response curves in a mouse mammary gland organ culture system. Binding of 125I-labeled hGH (125I-hGH) to lactogenic receptors is competed by both hGH and oPRL, and the competition curves are nearly superimposable. Moreover, solubilized membrane proteins bound with either 125I-hGH or 125I-labeled oPRL (125I-oPRL) show the same sedimentation pattern on sucrose gradients. However, methylation of membrane phospholipids in the presence of the methyl donor S-adenosyl-L-methionine only increases the binding of 125I-hGH. Binding of either 125I-oPRL or 125I-labeled bovine growth hormone (125I-bGH) was unaffected. Addition of concanavalin A (Con A) to the membranes decreased binding of 125I-oPRL to the lactogenic site by 80%, whereas 125I-hGH binding was decreased by only 40%, with the binding of 125I-bGH unaffected. However, both hGH-and oPRL-bound proteins bind to Con A-Sepharose columns to the same extent. These results suggest that although hGH and oPRL bind to the same lactogenic site with similar affinities and elicit similar biological responses, modification of membranes either by phospholipid methylation or by Con A differentially affects the binding of these two hormones.
D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D013006:Growth Hormone / Q000378:metabolism*; D006801:Humans; D007774:Lactation / Q000187:drug effects; D008321:Mammary Glands, Animal / Q000378:metabolism*; D008563:Membrane Lipids / Q000378:metabolism; D008745:Methylation; D051379:Mice; D010713:Phosphatidylcholines / Q000096:biosynthesis; D011247:Pregnancy; D011388:Prolactin / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012436:S-Adenosylmethionine / Q000494:pharmacology
D008563:Membrane Lipids; D010713:Phosphatidylcholines; D011956:Receptors, Cell Surface; D012436:S-Adenosylmethionine; D011388:Prolactin; D013006:Growth Hormone