Pediatric Nephrology

, Volume 4, Issue 4, pp 387–391 | Cite as

Regulation of renal phosphate reabsorption during development: implications from a new model of growth hormone deficiency

  • Aviad Haramati
  • Susan E. Mulroney
  • Michael D. Lumpkin
Proceedings of the Fourth International Workshop on Developmental Renal Physiology August 24–26, 1989 Montreal, Canada Review Article


It has been hypothesized that the high rate of renal phosphate (Pi) reabsorption in the immature animal is a consequence of the increased demand for Pi associated with the rapid rate of growth. Although growth hormone (GH) has been proposed to play a role in this process, investigations of the relationship between GH, growth and the renal Pi transport have been hampered by the lack of methods available to specifically alter circulating GH levels. This review summarizes the findings from recent studies using a newly developed peptidic antagonist to GH-releasing factor (GRF-AN) as a method of specifically inhibiting GH release. Systemic injection of GRF-AN was effective in suppressing the pulsatile release of GH, and in significantly attenuating the rate of growth, in both immature and adult rats. However, the inhibition of growth was associated with a reduction in net Pi retention only in immature rats, resulting in a doubling in the urinary excretion of Pi. GRF-AN treatment of immature rats lead to a decrease in the maximum tubular capacity to transport Pi-down to the level seen in adult rats. However, GRF-AN treatment did not alter renal Pi reabsorption in adult rats. We conclude that chronic administration of an antagonist to GRF in rats provides a new model of GH deficiency with which to study the interrelationships between growth, GH and other physiological systems. Furthermore, the findings suggest that the pulsatile release of GH, directly or indirectly, contributes to the high rate of renal Pi reabsorption in young, growing animals and may play a critical role in regulating Pi homeostasis during development.

Key words

Renal phosphate reabsorption Growth hormone deficiency Growth hormone releasing factor antagonist Renal development Rat 


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  1. 1.
    Haramati A (1989) Phosphate handling by the kidney during development: immaturity or unique adaptations for growth? News Physiol Sci 4:234–238Google Scholar
  2. 2.
    Spitzer A, Kaskel FJ, Feld LG, Trachtman H, Johnson V, Choi Y, Kumar AM (1983) Renal regulation of phosphate homeostasis during growth. Semin Nephrol 3:87–93Google Scholar
  3. 3.
    Spitzer A (1985) The developing kidney and the process of growth. In: Seldin DW, Giebisch G (eds) The kidney: physiology and pathophysiology, Raven Press, New York, pp 1979–2015Google Scholar
  4. 4.
    Caverzasio J, Bonjour J-P, Fleisch H (1982) Tubular handling of Pi in young growing and adult rats. Am J Physiol 242 11:F705-F710PubMedGoogle Scholar
  5. 5.
    Haramati A, Mulroney SE, and Webster SK (1988) Developmental changes in the tubular capacity for phosphate reabsorption in the rat. Am J Physiol 255 24:F287-F291PubMedGoogle Scholar
  6. 6.
    Johnson V, Spitzer A (1986) Renal reabsorption of phosphate during development: whole kidney events. Am J Physiol 251 20:F251l-lF256Google Scholar
  7. 7.
    Corvilain J, Abramow M (1964) Effect of growth hormone on tubular transport of phosphate in normal and parathyroidectomized dogs. J Clin Invest 43:1608–1612PubMedGoogle Scholar
  8. 8.
    Henneman PH, Forbes AP, Moldawer M, Dempsey EF, Carroll EL (1960) Effects of human growth hormone in man. J Clin Invest 39: 1223–1228PubMedGoogle Scholar
  9. 9.
    Corvilain J, Abramow M (1962) Some effects of human growth hormone on renal hemodynamics and on tubular phosphate transport in man. J Clin Invest 41:1230–1235PubMedGoogle Scholar
  10. 10.
    Camanni F (1968) Increased renal tubular reabsorption of phosphorus in acromegaly. J Clin Endocrinol Metab 28:999–1003PubMedGoogle Scholar
  11. 11.
    Hammerman MR, Karl IE, Hruska KA (1980) Regulation of canine renal vesicle phosphate transport by growth hormone and parathyroid hormone. Biochem Biophys Acta 603:322–334PubMedGoogle Scholar
  12. 12.
    Caverzasio J, Faundez R, Fleisch H, Bonjour J-P (1981) Tubular adaptation to Pi restriction in hypophysectomized rats. Pflügers Arch, 392:17–21Google Scholar
  13. 13.
    Wehrenberg WB, Brazeau P, Luben R, Bohlen P, Guillemin R (1982) Inhibition of the pulsatile secretion of growth hormone by monoclonal antibodies to the hypothalamic growth hormone releasing factor (GRF). Endocrinology 111:2147–2148PubMedGoogle Scholar
  14. 14.
    Tannenbaum GS, Ling N (1984) The interrelationship of growth hormone (GH))-releasing factor and somatostatin in generation of the ultradian rhythm of GH secretion. Endocrinology 115:1952PubMedGoogle Scholar
  15. 15.
    Plotsky PM, Vale W (1985) Patterns of growth hormone-releasing factor and somatostatin secretion into the hypophysial-portal circulation of the rat. Science 230:461–463PubMedGoogle Scholar
  16. 16.
    Clark RG, Robinson ICAF (1985) Growth induced by pulsatile infusion of an amidated fragment of human growth hormone releasing factor in normal and GHRF-deficient rats. Nature 314:281–283PubMedGoogle Scholar
  17. 17.
    Wehrenberg W (1986) The role of growth hormone-releasing factor and somatostatin on somatic growth in rats. Endocrinology 118: 489–494PubMedGoogle Scholar
  18. 18.
    Coy DH, Murphy WA, Sueiras-Diaz J, Coy EJ, Vance VA (1985) Structure-activity studies on the N-terminal region of growth hormone-releasing factor. J Med Chem 28:181PubMedGoogle Scholar
  19. 19.
    Robberecht P, Coy DH, Waelbroech M, Heiman ML, DeNeef P, Camus J.-C, Christophe J (1985) Structural requirements for the activation of rat anterior pituitary adenylate cyclase by growth hormone-releasing factor (GRF): discovery of (N−Ac−Tyr1, D−Arg2)-GRF(1-29)-NH2 as a GRF antagonist on membranes. Endocrinology 117:1759–1764PubMedGoogle Scholar
  20. 20.
    Lumpkin MD, McDonald JK (1989) Blockade of growth hormone-releasing factor (GRF) activity in the pituitary and hypothalamus of the conscious rat with a peptidic GRF antagonist. Endocrinology 124:1522–1531PubMedGoogle Scholar
  21. 21.
    Lumpkin MD, Mulroney SE, Haramati A (1989) Inhibition of pulsatile growth hormone secretion and somatic growth in immature rats with a synthetic growth hormone-releasing factor antagonist. Endocrinology 124:1154–1159PubMedGoogle Scholar
  22. 22.
    Mulroney SE, Lumpkin MD, Haramati A (1989) Antagonist to growth hormone-releasing factor inhibits growth and renal phosphate reabsorption in immature rats. Ann J Physiol 257 26:F29-F34Google Scholar

Copyright information

© IPNA 1990

Authors and Affiliations

  • Aviad Haramati
    • 1
  • Susan E. Mulroney
    • 1
  • Michael D. Lumpkin
    • 1
  1. 1.Department of Physiology and BiophysicsGeorgetwon University School of MedicineWashington, DCUSA

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