Skip to main content
SpringerLink
Log in

Growth responses to patterned GH delivery

  • Papers
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

We have investigated the effects of different patterns of administration of recombinant human growth hormone (rhGH) on weight gain, organ growth, serum GH binding protein (GHBP) and insulin-like growth factor-l (IGF-1) levels in a series of studies using hypophysectomized (Hx) or GH-deficient dwarf (dw/dw) rats. Animals were given rhGH either by subcutaneous (s.c.) injections (1 or 2 per day) or s.c. infusions and rhlGF-1 (2 mg/kg/day) by s.c. infusion. In Hx rats, all rhGH regimes increased body weight, tibial epiphyseal plate width, and organ weights in a dose-related manner. Dwarf rats showed a smaller growth response to rhGH than Hx rats, whereas rhGH induced greater elevations in serum GHBP in drarf rats. Growth responses depended on the pattern of rhGH administration (twice daily injections > continuous infusions > daily injections). The shape of the body growth curves also differed; rhGH injections increased weight gain linearly, whereas infusions gave an initial rapid weight gain which slowed with time (a curvilinear response). For both regimens, tibial epiphyseal plate width increased linearly with rhGH dose but infusions were 5-fold more potent than daily injections. Spleen and thymus weights were markedly increased by rhGH and were also affected by the pattern of GH exposure. At 5 mg rhGH/kg/day, thymus weights were 390±35 mg for injectionsvs. 613 ± 34 mg for infusions (P<0.001) compared with 248 ± 16 mg in vehicle-treated Hx controls. Infusions of rhlGF-1 also stimulated specific organ growth but caused less weight gain. RhlGF-1 additively increased the weight gain caused by rhGH injections but not by rhGH infusions. Circulating IGF-1 and GHBP levels were increased in a dose-dependent manner by rhGH infusion, whereas daily injections were ineffective. Thus, differential organ growth could be related to the higher serum IGF-1 concentrations induced by continuous rhGH administration. These studies show that whole body growth is best maintained by intermittent rhGH exposure, whereas, paradoxically, differential organ growth is most pronounced with continuous rhGH administration.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Baumann, G., Shaw, M.A. & Amburn, K. (1989).Metabolism,38, 683–689.

    Article  PubMed  CAS  Google Scholar 

  • Baumbach, W.R., Horner, D.L. & Logan J.S. (1989).Genes Dev.,3, 1199–1205.

    Article  PubMed  CAS  Google Scholar 

  • Baxter, R.C. (1993).Trends Endocrinol. Metab.,4, 91–96.

    Article  PubMed  CAS  Google Scholar 

  • Carmignac, D., Wells, T., Carlsson, L.M.S., Clark, R.G. & Robinson, I.C.A.F. (1992).J. Endocr.,135, 447–457.

    PubMed  CAS  Google Scholar 

  • Charlton, H.M., Clark, R.G., Robinson, I.C.A.F., Porter-Goff, A.E., Cox, B.S., Bugnon, C. & Bloch, B.S. (1988).J. Endocr.,119, 51–58.

    PubMed  CAS  Google Scholar 

  • Clark, R.G., Carlsson, L.M.S., Mortensen, D. & Cronin, M.J. (1994).Endocrinology and Metabolism,1, 49–54.

    CAS  Google Scholar 

  • Clark, R.G., Jansson, J.O., Isaksson, O.G.P. & Robinson, I.C.A.F. (1985).J. Endocr.,104, 53–61.

    PubMed  CAS  Google Scholar 

  • Clark, R., Strasser, J., McCabe, S., Robbins, K. & Jardieu, P. (1993).J. Clin. Invest.,92, 540–548.

    Article  PubMed  CAS  Google Scholar 

  • Cotes, P.M., Bartlett, W.A., Gaines Das, R.E., Flechnell, P. & Termeer, R. (1980).J. Endocr.,87, 303–312.

    PubMed  CAS  Google Scholar 

  • Daughaday, W.H. (1989).Persp. Biol. Med.,32, 194–211.

    CAS  Google Scholar 

  • Fontoura, M., Mugnier, E., Brauner, R., Rappaport, R. & Postel-Vinay, M.C. (1992).Clin. Endocrinol.,37, 249–253.

    Article  CAS  Google Scholar 

  • Gargosky, S.E., Tapanainen, P. & Rosenfeld, R.G. (1994).Endocrinology,134, 2267–2276.

    Article  PubMed  CAS  Google Scholar 

  • Gevers, E.F., Wit, J.M. & Robinson, I.C.A.F. (1995).J. Endocr.,145, 69–79.

    PubMed  CAS  Google Scholar 

  • Groesbeck, M.D. & Parlow, A.F. (1987).Endocrinology,120, 2582–2590.

    Article  PubMed  CAS  Google Scholar 

  • Groesbeck, M.D., Parlow, A.F. & Daughaday, W.H. (1987).Endocrinology,120, 1963–1975.

    PubMed  CAS  Google Scholar 

  • Guler, H.P., Zapf, J., Scheiwiller, E. & Froesch, E.R. (1988).Proc. Natl. Acad. Sci. USA.,85, 4889–4893.

    Article  PubMed  CAS  Google Scholar 

  • Hazel, S.J., Gillespie, CM., Moore, R.J., Clark, R.G., Jureidini, K.F. & Martin, A.A. (1994).Kidney Int.,46, 58–68.

    Article  PubMed  CAS  Google Scholar 

  • Ho, K.Y., Jorgensen, J., Valiontis, E., Waters, M.J., Rajkovic, I.A. & Christiansen, J.S. (1993).Clin. Endocrinol.,38, 143–148.

    Article  CAS  Google Scholar 

  • Ho, K.Y. & Kelly, J.J. (1991).Horm. Res.,36, 44–48.

    Article  PubMed  Google Scholar 

  • Isaksson, O.G.P., Lindahl, A., Nilsson, A. & Isgaard, J. (1987).Endocr. Rev.,8, 426–438.

    PubMed  CAS  Google Scholar 

  • Isgaard, J., Carlsson, L.M.S., Isaksson, O.G.P. & Jansson, J-O. (1988).Endocrinology,123, 2605–2610.

    PubMed  CAS  Google Scholar 

  • Jansson, J-O., Albertsson-Wikland, K., Eden, S., Thorngren, K.G. & Isaksson, O.G.P. (1982a).Acta. Endocrinol.,99, 24–30.

    PubMed  CAS  Google Scholar 

  • Jansson, J-O., Albertsson-Wikland, K., Eden, S., Thorngren, K.G. & Isaksson, O.G.P. (1982b).Acta Physiol. Scand.,114, 261–265.

    PubMed  CAS  Google Scholar 

  • Jeffery, S., Wilson, C.A., Mode, A., Gustafsson, J-A. & Carter, N.D. (1986).J. Encocr.,110, 123–126.

    CAS  Google Scholar 

  • Klindt, J., Buonomo, F.C. & Yen, J.T. (1992).J. Anim. Sci.,70, 3721–3733.

    PubMed  CAS  Google Scholar 

  • Maiter, D., Underwood, L.E., Maes, M., Davenport, M.L. & Ketelslegers, J.M. (1988).Endocrinology,123, 1053–1059.

    PubMed  CAS  Google Scholar 

  • Martha, P.M., Reiter, E.O., Davila, N., Shaw, M.A., Holcombe, J.H. & Baumann G. (1992).J. Clin. Endocrinol. Metab.,75, 1464–1469.

    Article  PubMed  Google Scholar 

  • Massa, G., Mulumba, N., Ketelslegers, J.M. & Maes, M. (1990).Endocrinology,126, 1976–1980.

    PubMed  CAS  Google Scholar 

  • Mode, A. (1993).J. Reprod. Fertil.,46, 77–86.

    CAS  Google Scholar 

  • Oscarsson, J., Carlsson, L.M., Bick, T., Lidell, A., Olofsson. S.O. & Eden, S. (1991).J. Endocr.,128, 433–438.

    Article  PubMed  CAS  Google Scholar 

  • Robbins, K., McCabe, S., Scheiner, T., Strasser, J., Clark, R. & Jardieu, P. (1994).Clin. Exp. Immunol.,95, 337–342.

    PubMed  CAS  Google Scholar 

  • Robinson, I.C.A.F., Carmignac, D.F. & Fairhall, K.M. (1993).Acta Ped.,82, 22–28.

    Article  Google Scholar 

  • Robinson, I.C.A.F. & Clark R.G. (1987). In:Growth hormone: Basic and Clinical Aspects. Isaksson, O., Binder, C, Hall, K., Hokfelt, B. (eds). Elsevier: Amsterdam, pp. 109–127.

    Google Scholar 

  • Schoenle, E., Zapf, J., Humbel, R.E. & Froesch E.R. (1982).Nature,296, 252–253.

    Article  PubMed  CAS  Google Scholar 

  • Skottner, A., Clark, R.G., Fryklund, L. & Robinson, I.C.A.F. (1989).Endocrinology,124, 2519–2526.

    PubMed  CAS  Google Scholar 

  • Skottner, A., Clark, R.G., Robinson, I.C.A.F. & Fryklund, L. (1987).J. Endocr.,112, 123–132.

    PubMed  CAS  Google Scholar 

  • Smith, P.J., Hindmarsh, P.C. & Brook, C.G.D. (1988).Arch. Dis. Child.,63, 491–494.

    Article  PubMed  CAS  Google Scholar 

  • Tauber, M., De Bouet Du Portal, H., Sallerin-Caute, B., Rochiccioloi, P. & Bastide, R. (1993).J. Clin. Endocrinol. Metab.,76, 1135–1139.

    Article  PubMed  CAS  Google Scholar 

  • Wise, T., KJindt, J., Buonomo, F.C. & Yen J.T. (1994). In:Growth hormone II: Basic and Clinical Aspects. Bercu, B., Walker, F. (eds). Springer-Verlag: New York. pp. 317–327.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Endocrine Research Department, Genentech, Inc, 390 Pt. San Bruno Blvd., 94080, South San Francisco, California, USA

    R. G. Clark & D. Mortensen

  2. Research Centre for Endocrinology and Metabolism, Sahlgren’s Hospital, Goteborg, Sweden

    L. M. S. Carlsson

  3. National Institute for Medical Research, Mill Hill, London, UK

    D. Carmignac & ICAF Robinson

Authors
  1. R. G. Clark
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D. Mortensen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L. M. S. Carlsson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D. Carmignac
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. ICAF Robinson
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Clark, R.G., Mortensen, D., Carlsson, L.M.S. et al. Growth responses to patterned GH delivery. Endocr 3, 717–723 (1995). https://doi.org/10.1007/BF03000203

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03000203

Keywords

Search

Navigation