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VILA
,
MELISSA A. SHAW,
JHARNA RAY,
STEPHEN A. LIEBHABER
and
NANCY E. COOKE
Center for Endocrinology, Metabolism, and Nutrition, Department of Medicine, Northwestern University Medical School Chicago, Illinois 60611
The Howard Hughes Medical Institute, Departments of Human Genetics University of Pennsylvania Philadelphia, Pennsylvania 19104
The Howard Hughes Medical Institute, Department of Medicine University of Pennsylvania, Philadelphia Pennsylvania 19104
Address all correspondence and requests for reprints to: G. Baumann, M.D., 303 East Chicago Avenue, Chicago, Illinois 60611.
Human GH-variant (hGH-V) is a natural GH analog arising from the hGH-V gene. It is expressed in the placenta and secreted into the maternal circulation during the second half of pregnancy. To gain information about its bioactivity in man, we examined the interaction of hGH-V with the high affinity GH-binding protein/receptor (GH-BP) in human plasma. hGH-V was equipotent with pituitary hGH (hGH-N) as a ligand for the GH-BP. hGH-N/hGH-V chimeric proteins, where the sequences encoded by exon 3 (amino acid residues 32–71, thought to be exposed on the molecule's surface and involved in receptor binding) were exchanged, also bound with similarly high affinities. A corresponding hGH-N/rat PRL chimeric protein had 25-fold reduced affinity for the GH-BP. We conclude that hGH-V is a potent somatogen in man, and that some of the manifestations of late pregnancy, such as increased insulin-like growth factor-I levels and coarsening of features, are probably related to the high circulating levels of hGH-V. GH-BP measurements in pregnancy must take into account BP saturation by endogenous hGH-V.
* This work was supported by NIH Grant DK-38128 (to G.B.), a grant from the Northwestern Memorial Foundation (to G.B.), NIH Grant HD-25147 (to N.E.C. and S.E.L.), and March of Dimes Grant 1-1015 (to N.E.C).
Supported by the Fondo de Investigation de la Seguridad Social Española.
Associate Investigator of the Howard Hughes Medical Institute.
Received February 26, 1991.
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