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Growth hormone response to hpGRF-40 in different forms of growth retardation and endocrine-metabolic diseases

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Abstract

The effect of one of the new human pancreatic growth hormone releasing factors (hpGRFs) was assessed in children or young adults with different forms of growth retardation or endocrine-metabolic diseases. Intravenously administered synthetic hpGRF-40 (1 μg/kg) induced a clear-cut and prompt rise in plasma growth hormone (GH) levels in 8 normal prepubertal children and a definite GH rise in 11 out of 14 children with isolated GH deficiency (IGHD) and one child with the Silver-Russel syndrome. In two out of three subjects with craniopharyngioma hpGRF-40 did not induce any plasma GH increase.

In seven out of ten children with constitutional growth delay (CGD), hpGRF-40 induced a biphasic GH response, with a prompt small GH increment followed by a second, more consistent rise. Both in children with IGHD and with CGD the rise in plasma GH following hpGRF-40 was markedly lower than in controls. In children with CGD the GH response to hpGRF-40 was defective, despite the fact that in most of them the GH response to standard pharmacological stimuli was normal according to generally accepted criteria.

hpGRF induced a small but sustained plasma GH rise in four hypothyroid subjects, while in three out of four children with idiopathic obesity the GH response to hpGRF was strikingly reduced. These data demonstrate that hpGRF is a potent stimulus of GH release in normal prepubertal children and a physiological means of investigating GH function in diseases associated with growth impairment.

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Abbreviations

hpGRF:

human pancreatic growth hormone releasing factor

IGHD:

isolated growth hormone deficiency

CGD:

costitutional growth delay

GH:

growth hormone

GRF:

growth hormone releasing factor

YR:

years

LHRH:

luteinizing hormone releasing hormone

ACTH:

adreno-corticotropic hormone

TRH:

thyrotropin releasing hormone

IU:

international units

SDS:

standard deviation score

LH:

lutcinizing hormone

FSH:

follicle stimulating hormone

TSH:

thyrotropin hormone

T3 :

thriiodotyronine

T4 :

Tyroxine

RIA:

radioimmunoassay

SE:

standard error

A:

adult

IBW:

ideal body weight

RT:

replacement therapy

PH:

primary hypothyroidism

CT:

computed tomography

References

  1. Berelowitz M, Szabo M, Frohman LA, Firestone S, Chu L, Hintz RL (1981) Somatomedin-C mediates growth hormone negative feedback by effects on both the hypothalamus and the pituitary. Science 212:1279–1281

    Google Scholar 

  2. Bierich JR, Potthod K (1979) Spontaneous secretion of growth hormone in children with constitutional delay of growth and adolescence and with early hormonal puberty. Monatsschr Kinderheilkd 127:561–565

    Google Scholar 

  3. Bogardus C, La Grange BM, Horton ES, Sims EAH (1981) Comparison of carbohydrate-containing and carbohydrate restricted hypocaloric diets in the treatment of obesity: endurance and metabolic fuel homeostasis during strenous exercise. J Clin Invest 68:399–404

    Google Scholar 

  4. Borges JLC, Blizzard RM, Gelato M, Furlanetto R, Rogol AD, Evans WS, Vance ML, Kaiser DN, MacLeod RM, Merriam GR, Loriaux DL, Spiess J, Rivier J, Vale W, Thorner MD (1983) Effects of human pancreatic growth hormone releasing factor on growth hormone and somatomedin C levels in patients with idiopathic growth hormone deficiency. Lancet ii:119–123

    Google Scholar 

  5. Brauman H, Corvilain J (1968) Growth hormone response to hypoglycemia in mixedema. J Clin Endocrinol Metab 28:301–304

    Google Scholar 

  6. Carlson HE, Drenick EJ, Chopra IJ, Hershman JN (1977) Alterations in basal and TRH stimulated serum levels of thyrotropin, prolactin and thyroid hormones in starved obese men. J Clin Endocrinol Metab 45:707–713

    Google Scholar 

  7. Chihara K, Kashio Y, Abe H, Minamitani N, Kaji H, Kita T, Fujita T (1985) Idiopathic growth hormone (GH) deficiency, and GH deficiency secondary to hypothalamic germinoma: effect of single and repeated administration of human GH-releasing factor (hpGRF) on plasma GH level and endogenous hpGRF-like immunoreactive level in cerebrospinal fluid. J Clin Endocrinol Metab 60:269–278

    Google Scholar 

  8. Collu R, Leboeuf G, Letarte J, Ducharme JR (1977) Increase in plasma growth hormone levels following-thyrotropin releasing hormone injection in children with primary hypothyroidism. J Clin Endocrinol Metab 44:743–747

    Google Scholar 

  9. Daughday WH (1980) The adenohypophysis. In: Williams RH (ed) Textbook of endocrinology. W. B. Saunders Co, Philadelphia, pp 73–116

    Google Scholar 

  10. Daughaday WH, Peake GT, Birge CA, Mariz IK (1968) The influence of endocrine factors on the concentration of growth hormone in rat pituitary. In: Pecile A, Müller EE (eds) Growth hormone. Excerpta Medica, Amsterdam, pp 238–252

    Google Scholar 

  11. Frasier SD (1981) Abnormalities of growth. In: Collu R, Ducharme JR, Guyda H (eds) Pediatric endocrinology. Raven Press, New York, pp 167–204

    Google Scholar 

  12. Glass AR, Burman KD, Dahmas WT, Boehm TM (1981) Endocrine function in human obesity. Metabolism 30:89–104

    Google Scholar 

  13. Grossman A, Wass JAH, Sueiras-Diaz J, Savage MO, Lytras N, Coy DH, Besser GM (1983) Growth-hormone-releasing factor in growth hormone deficiency: demonstration of a hypothalamic defect in growth hormone release. Lancet ii:137–138

    Google Scholar 

  14. Guillemin R, Brazeau P, Böhlen P, Esch F, Ling N, Weherenberg W (1982) Growth hormone releasing factor from a human pancreatic tumor that caused acromegaly. Science 585–587

  15. Kato N, Sundmark VC, Van Middlesworth L, Havlicek V, Friesen HG (1982) Immunoreactive somatostatin and β-endorphin content in the brain of mature rats after neonatal exposure to propyltiouracil. Endocrinology 110:1851–1855

    Google Scholar 

  16. Katz HP, Youlton R, Kaplan SL, Grumbach MM (1969) Growth and growth hormone. III. Growth hormone release in children with primary hypothyroidism and thyrotoxicosis. J Clin Endocrinol Metab 29:346–351

    Google Scholar 

  17. Meistas MT, Foster GV, Margolis S, Kowarski AA (1982) Integrated concentrations of growth hormone, insulin, C-peptide and prolactin in human obesity. Metabolism 31:1224–1228

    Google Scholar 

  18. Pintor C, Fanni V, Loche S, Locatelli V, Cella SG, Villa F, Minuto F, Corda R, Müller EE (1983) Synthetic hpGRF1-40 stimulates growth hormone and inhibits prolactin secretion in normal children and children with isolated growth hormone deficiency. Peptides 4:929–933

    Google Scholar 

  19. Rastogi RB, Singhal RL (1974) Alterations in brain norepinephrine and serotonin metabolism following experimental hypothyroidism induced by methimazole. Endocr Res Commun 1:26–31

    Google Scholar 

  20. Rivier J, Spiess J, Thorner MO, Vale W (1982) Characterization of a growth-hormone releasing factor from a human pancreatic islet tumor. Nature 300:276–278

    Google Scholar 

  21. Rogol AD, Blizzard RM, Johanson AJ, Furlanetto RW, Evans WS, Rivier J, Vale W, Thorner MO (1984) Growth hormone release in response to human pancreatic tumor growth hormone-releasing hormone-40 in children with short stature. J Clin Endocrinol Metab 59:580–586

    Google Scholar 

  22. Schriock EA, Lustig RH, Rosenthal SM, Kaplan SL, Grumbach MM (1984). Effect of growth hormone (GH)-releasing hormone (GRH) on plasma GH in relation to magnitude and duration of GH deficiency in 26 children and adults with isolated GH deficiency of multiple pituitary hormone deficiencies: evidence for hypothalamic GRH deficiency. J Clin Endocrinol Metab 58: 1043–1049

    Google Scholar 

  23. Spiliotis BE, August GP, Hung W, Sonis W, Mendelson W, Bercu BB (1984) Growth hormone neurosecretory dysfunction. A treatable cause of short stature. JAMA 251:2223–2230

    Google Scholar 

  24. Takano K, Izuka N, Shizume K, Asakawa K, Niyakawa M, Hirose N, Shibasaki T, Ling NC (1984) Plasma growth hormone (GH) response to GH-releasing factor in normal children with short stature and patients with pituitary dwarfism. J Clin Endocrinol Metab 58:236–241

    Google Scholar 

  25. Thorner MO, Reschke J, Chitwood J, Rogol AD, Furlanetto R, Rivier J, Vale W, Blizzard RM (1985) Acceleration of growth in two children treated with human growth hormone-relasing factor. N Engl J Med 312:4–9

    Google Scholar 

  26. Underwood LE, Van Wyk J (1980) Hormones in normal and aberrant growth. In: Williams RH (ed) Textbook of endocrinology. W. B. Saunders Co, Philadelphia, pp 1149–1191

    Google Scholar 

  27. Vance ML, Borges JLC, Kaiser DL, Evans WS, Furlanetto R, Thominet J, Frohman LA, Rogol AD, MacLeod RM, Bloom S, Rivier J, Vale W, Thorner MO (1984) Human pancreatic tumor growth hormone-releasing factor: dose-response relationships in normal man. J Clin Endocrinol Metab 58:808–844

    Google Scholar 

  28. Vimpani GV, Vimpani AF, Pocock SJ, Farquhar JW (1981) Differences in physical characteristics, perinatal histories, and social backgrounds between children with growth hormone deficiency and constitutional short stature. Arch Dis Child 56:922–930

    Google Scholar 

  29. Williams T, Berelowitz M, Joffe SN, Thorner MO, Rivier MBJ, Vale W, Frohman LA (1984) Impaired growth hormone responses to growth hormone-releasing factor in obesity. N Engl J Med 311:1403–1407

    Google Scholar 

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Authors and Affiliations

  1. First Department of Pediatrics, University of Cagliari, Cagliari, Italy

    C. Pintor, S. Loche, R. Puggioni & R. Corda

  2. Department of Pharmacology, Chemotherapy and Toxicology, University of Milan, Milan, Italy

    S. G. Cella, V. Locatelli & E. E. Müller

  3. Maggioni Farmaceutici S.p.A., Milan, Italy

    F. Villa

Authors
  1. C. Pintor
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  2. S. Loche
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  3. R. Puggioni
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  4. S. G. Cella
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  5. V. Locatelli
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  6. F. Villa
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  7. R. Corda
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  8. E. E. Müller
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Pintor, C., Loche, S., Puggioni, R. et al. Growth hormone response to hpGRF-40 in different forms of growth retardation and endocrine-metabolic diseases. Eur J Pediatr 144, 475–481 (1986). https://doi.org/10.1007/BF00441742

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  • DOI: https://doi.org/10.1007/BF00441742

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