Human growth hormone-variant is a biologically active somatogen and lactogen.
The human GH-variant (hGH-V) gene, a member of the GH-PRL gene family, is expressed by the placenta during the second and third trimesters of gestation. The secreted hGH-V protein differs from pituitary GH (hGH-N) by only 13 amino acids. We have previously demonstrated that hGH-V can bind to both somatogen and lactogen cell surface receptors in vitro, but that the ratio of its somatogen to lactogen receptor-binding affinities is substantially higher than that of hGH-N. We now characterize the somatogen and lactogen bioactivities of hGH-V and contrast them to the bioactivity of hGH-N. Somatogen bioactivity was assayed by stimulation of weight gain in hypophysectomized rats, and lactogen bioactivity was assayed by the mitogenic response of the Nb2 lymphoma cell line. While the average increase in rat body weight in response to a fixed concentration of hormone was comparable using either hGH-V or hGH-N, the mitotic response of the lactogen-inducible Nb2 cells was significantly less for hGH-V. The comparable somatogen, but lower lactogen, bioactivity of hGH-V relative to hGH-N parallels the previously reported receptor binding profiles of the two hormones and suggests that hGH-V has the potential to perform a unique role during human gestation.
MacLeod
J N
JN
Department of Human Genetics, University of Pennsylvania, Philadelphia 19104-6144.
Worsley
I
I
Ray
J
J
Friesen
H G
HG
Liebhaber
S A
SA
Cooke
N E
NE
D000818:Animals; D001681:Biological Assay; D001835:Body Weight / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D014644:Genetic Variation; D013006:Growth Hormone / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D007016:Hypophysectomy; D007774:Lactation / Q000502:physiology*; D008223:Lymphoma / Q000473:pathology; D008297:Male; D008934:Mitogens / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014407:Tumor Cells, Cultured / Q000473:pathology
D008934:Mitogens; D013006:Growth Hormone