This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ishikawa, M. Articles by Tanaka, T. Search for Related Content PubMed PubMed Citation Articles by Ishikawa, M. Articles by Tanaka, T.

A Novel Specific Bioassay for Serum Human Growth Hormone

Department of Endocrinology and Metabolism, National Children’s Medical Research Center, (M.I., A.N., R.H., N.K., T.T.) Setagaya-ku, Tokyo 154-8509; The 1st Department of Internal Medicine, Toho University of School Medicine (M.I.), Ota-Ku, Tokyo 143-8541; Department of Pediatrics, Dokyo University School of Medicine (O.Y.), Shimotuka-gun, Ibaragi 321-0267; and Life Science Laboratories Mitsui Chemicals, Inc., (M.W., M.H.), Mobara, Chiba 297-0017, Japan

Address correspondence and requests for reprints to: Mayumi Ishikawa, Department of Endocrinology and Metabolism, National Children’s Medical Research Center, 3-35-31, Taishido, Setagaya-ku, Tokyo 154-8509, Japan.

Human GH receptor (hGHR) was recently expressed on a Ba/F3 cell line, which is a mouse pro-B cell lymphoma that has been induced to become a cloned cell line (Ba/F3-hGHR). Using a Ba/F3-hGHR cell line, we have established a bioassay for serum hGH.

hGH stimulated cell proliferation in a dose-dependent manner in concentrations ranging from 1 ng to 100 ng/mL. Cell proliferation was not influenced by other hormones or growth factors in the bioassay, with the exception of insulin-like growth factor I (IGF-I) and GH binding protein. Free IGF-I significantly stimulated the proliferation of Ba/F3-hGHR cells at concentrations over 25.85 ng/mL in this bioassay system, but serum IGF-I did not stimulate cell proliferation because the sensitivity of cell proliferation was insufficient for free IGF-I in serum. GH binding protein, however, did suppress cell proliferation at the highest concentration (100 ng/mL), but did not at the average concentration (20 ng/mL). Human serum stimulated cell proliferation, which was completely suppressed by anti-GH antibody. The GH bioactivity of serum samples from normal children and patients with non-GH deficient short stature correlated strongly with the serum hGH concentration determined by immunoradiometric assay (IRMA) (r = 0.967, r = 0.924, P < 0.0001, respectively). The ratio of bioactivity/IRMA was 1.01 ± 0.26 in sera from normal children and 1.18 ± 0.24 and 1.00 ± 0.29 at basal values and peak values in GH stimulation tests, respectively, in sera from patients with non-GH deficient short stature. The bioactivity/IRMA ratio for the serum GH bioactivity of a patient who had biologically inactive GH caused by an amino acid substitution was 0.333 ± 0.056 (mean ± SD).

In conclusion, we established a new sensitive bioassay for hGH that is specific for hGH somatogenic action and is useful for screening of patients with short stature caused by biologically inactive hGH.