Growth hormone exerts hematopoietic growth-promoting effects in vivo and partially counteracts the myelosuppressive effects of azidothymidine.

Recombinant human growth hormone (rhGH) was administered to mice to determine its effect on hematopoiesis. BALB/c mice and mice with severe combined immune deficiency (SCID), which lack T cells and B cells, were administered intraperitoneal injections of rhGH for 7 days. Upon analysis, both strains of mice exhibited an increase in splenic and bone marrow hematopoietic progenitor cell content and cellularity, indicating that rhGH can act as a hematopoietic growth factor. C57BL/6 mice were then placed on azidothymidine (AZT). AZT is a reverse transcriptase inhibitor currently used as a treatment for acquired immune deficiency syndrome (AIDS), but which also produces significant myelotoxic effects. Treatment of mice with rhGH partially counteracted the myelosuppressive properties of AZT. Bone marrow cellularity, hematocrit values, white blood cell counts, and splenic hematopoietic progenitor cell content were all significantly increased if rhGH (20 micrograms injected intraperitoneally every other day) was concurrently administered with AZT. Administration of ovine GH (ovGH), which, unlike rhGH, has no effect on murine prolactin receptors, also prevented the erythroid-suppressive effects of AZT in mice, but had no significant effect on granulocyte counts. Thus, the effects of GH are mediated at least in part through GH receptors in vivo. Additionally, when mice were initially myelosuppressed by several weeks of AZT treatment, the subsequent administration of ovGH resulted in an increase in splenic hematopoietic progenitor cells. No significant pathologic effects were observed in mice receiving either repeated rhGH or ovGH injections. Thus, GH exerts significant direct hematopoietic growth-promoting effects in vivo and may be of potential clinical use to promote hematopoiesis in the face of myelotoxic therapy.

[1]  W. Urba,et al.  The toxic and hematologic effects of interleukin-1 alpha administered in a phase I trial to patients with advanced malignancies. , 1992, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  D. Longo,et al.  Immunologic and hematologic effects of neuroendocrine hormones. Studies on DW/J dwarf mice. , 1992, Journal of immunology.

[3]  J. Laurence,et al.  Effect of recombinant human growth hormone on acute and chronic human immunodeficiency virus infection in vitro. , 1992, Blood.

[4]  J. Groopman,et al.  Recombinant human granulocyte-macrophage colony-stimulating factor ameliorates zidovudine-induced neutropenia in patients with acquired immunodeficiency syndrome (AIDS)/AIDS-related complex. , 1991, Blood.

[5]  K. Clauser,et al.  Dimerization of the extracellular domain of the human growth hormone receptor by a single hormone molecule. , 1991, Science.

[6]  D. Aron,et al.  Secretion of insulinlike growth factor I and insulinlike growth factor-binding proteins by murine bone marrow stromal cells. , 1991, The Journal of clinical investigation.

[7]  S. Arkins,et al.  A novel role of growth hormone and insulin-like growth factor-I. Priming neutrophils for superoxide anion secretion. , 1991, Journal of immunology.

[8]  P. Sönksen,et al.  The effects of treatment with recombinant human growth hormone on body composition and metabolism in adults with growth hormone deficiency. , 1989, The New England journal of medicine.

[9]  Z. Hochberg,et al.  Enhancement of human granulopoiesis in vitro by biosynthetic insulin-like growth factor I/somatomedin C and human growth hormone. , 1988, The Journal of clinical investigation.

[10]  K. Kelley,et al.  A newly defined property of somatotropin: priming of macrophages for production of superoxide anion. , 1988, Science.

[11]  M A Fischl,et al.  The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. , 1987, The New England journal of medicine.

[12]  M A Fischl,et al.  The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. , 1987, The New England journal of medicine.

[13]  I. Weiler,et al.  Rearrangement of antigen receptor genes is defective in mice with severe combined immune deficiency , 1986, Cell.

[14]  A. Fauci,et al.  Monocyte function in the acquired immune deficiency syndrome. Defective chemotaxis. , 1984, The Journal of clinical investigation.

[15]  A. Stiles,et al.  Tissue concentrations of somatomedin C: further evidence for multiple sites of synthesis and paracrine or autocrine mechanisms of action. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[16]  R. Duquesnoy,et al.  Immunologic and Hematologic Deficiencies of the Hypopituitary Dwarf Mouse , 1981 .

[17]  N. Bersch,et al.  Growth hormone: species-specific stimulation of erythropoiesis in vitro. , 1977, Science.