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Inhibition of Lactogenic Activities of Ovine Prolactin and Human Growth Hormone (hGH) by a Novel Form of a Modified Recombinant hGH^*

Department of Agricultural Biochemistry, Faculty of Agriculture, The Hebrew University of Jerusalem Rehovot 76100
Bio-technology General (Israel) Ltd. Rehovot 76326, Israel
The Department of Physiology, Faculty of Medicine, University of Manitoba Winnipeg, Manitoba, Canada R3E 0W3

Address requests for reprints to: Dr. Arieh Gertler, Department of Agricultural Biochemistry, Hebrew University of Jerusalem, Rehovot, 76100 Israel.

Abstract

A recombinant analog of human GH (hGH) lacking 13 amino acids at the amino-terminus (Met¹⁴hGH) inhibited the hGH- or ovine PRL (oPRL)-stimulated proliferation of Nb2 lymphoma cells and bovine PRL-stimulated fat synthesis and -lactalbumin secretion in explants from bovine lactating mammary gland. The inhibition was competitive in nature, and in Nb2 cells could be abolished by an excess of hGH or oPRL. Inhibition of oPRL-stimulated proliferation of Nb2 cells by Met¹⁴hGH could also be specifically abolished by anti-hGH monoclonal antibodies. Met¹⁴hGH had no growth-stimulating activity in Nb2 cells and was not cytotoxic. It also did not affect glucose uptake by the mammary gland explants. Met¹⁴hGH competed with [¹²⁵I]hGH for binding to intact Nb2 cells, IM-9 lymphocytes, solubilized microsomal fraction from lactating bovine mammary gland, and microsomal fraction from the liver of female virgin rats, but its affinity for those receptors was 2 orders of magnitude lower than the affinity of hGH. Since Met¹⁴hGH used in most experiments contained about 25% impurities and degradation products, a small amount of it was further purified by immunoaffinity chromatography. Two purified fractions, one consisting of a single 20K protein and the other accompanied by a small amount of 25K protein, were obtained. Both fractions exhibited increased inhibition of hGH-or oPRL-stimulated proliferation of Nb2 cells, thus indicating that the inhibitory activity results from the intact Met¹⁴hGH molecule. To the best of our knowledge, this is the first report describing the inhibition of lactogenic hormone activities by a modified hGH. (Endocrinology 118: 720–726, 1986)

Footnotes

^* This work was supported in part by a grant from the National Research and Development Israel Council (to A.G.), and grants from MRC Canada and USPHS Grant MDO 7843-12 (to H.G.F.)

Received June 27, 1985.

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