Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1988 Apr;81(4):968–975. doi: 10.1172/JCI113450

Fasting enhances growth hormone secretion and amplifies the complex rhythms of growth hormone secretion in man.

K Y Ho 1, J D Veldhuis 1, M L Johnson 1, R Furlanetto 1, W S Evans 1, K G Alberti 1, M O Thorner 1
PMCID: PMC329619  PMID: 3127426

Abstract

Studies in man have shown that the episodic release of growth hormone (GH) is infrequent and erratic, and unlike that in the rat does not appear to have discernible ultradian periodicities. However, these observations in nonfasted subjects may be invalid since mixed nutrients have unpredictable effects on GH release. Moreover, in the fed state basal GH levels are frequently undetectable, thus rendering the identification of low amplitude pulses unreliable. Accordingly, the 24-h pulsatile pattern of GH secretion obtained from repetitive venous sampling in six normal adult male subjects was examined during a control fed day and during the first and fifth days of a 5-d fast. The GH data were analyzed using two distinct methods: a discrete pulse detection algorithm (Cluster analysis) and Fourier expansion time-series, which allows fixed periodicities of secretory activity to be resolved. The 5-d fast resulted in a significant increase in discrete GH pulse frequency (5.8 +/- 0.7 vs. 9.9 +/- 0.7 pulses/24 h, P = 0.028), 24 h integrated GH concentration (2.82 +/- 0.50 vs. 8.75 +/- 0.82 micrograms.min/ml; P = 0.0002), and maximal pulse amplitude (5.9 +/- 1.1 vs. 12.3 +/- 1.6 ng/ml, P less than 0.005). While multiple low-amplitude sinusoidal periodicities were present on the control fed day, time-series analysis revealed enhancement of circadian and ultradian cycles on the first and fifth days of fasting. Concomitantly, fasting resulted in a decline (day 1 vs. day 5) in serum concentrations of somatomedin C (1.31 +/- 0.22 vs. 0.77 +/- 0.18 U/ml) and glucose (4.9 +/- 0.2 vs. 3.2 +/- 0.2 mmol/liter), and a marked rise in free fatty acid (0.43 +/- 0.12 vs. 1.55 +/- 0.35 mmol/liter) and acetoacetate (35 +/- 6 vs. 507 +/- 80 nmol/liter). We conclude that the acute nutritional status is an important determinant of spontaneous pulsatile GH secretion in man. Fast-induced enhancement of GH release is achieved through combined frequency (discrete pulses) and amplitude (sinusoidal periodicities) modulation. Such alterations in somatotropic hormone release may play an important role in substrate homeostasis during starvation.

Full text

PDF
975

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Berelowitz M., Szabo M., Frohman L. A., Firestone S., Chu L., Hintz R. L. Somatomedin-C mediates growth hormone negative feedback by effects on both the hypothalamus and the pituitary. Science. 1981 Jun 12;212(4500):1279–1281. doi: 10.1126/science.6262917. [DOI] [PubMed] [Google Scholar]
  2. Bougneres P. F., Artavia-Loria E., Ferre P., Chaussain J. L., Job J. C. Effects of hypopituitarism and growth hormone replacement therapy on the production and utilization of glucose in childhood. J Clin Endocrinol Metab. 1985 Dec;61(6):1152–1157. doi: 10.1210/jcem-61-6-1152. [DOI] [PubMed] [Google Scholar]
  3. Bratusch-Marrain P. R., Smith D., DeFronzo R. A. The effect of growth hormone on glucose metabolism and insulin secretion in man. J Clin Endocrinol Metab. 1982 Nov;55(5):973–982. doi: 10.1210/jcem-55-5-973. [DOI] [PubMed] [Google Scholar]
  4. Cahill G. F., Jr, Herrera M. G., Morgan A. P., Soeldner J. S., Steinke J., Levy P. L., Reichard G. A., Jr, Kipnis D. M. Hormone-fuel interrelationships during fasting. J Clin Invest. 1966 Nov;45(11):1751–1769. doi: 10.1172/JCI105481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Clemmons D. R., Klibanski A., Underwood L. E., McArthur J. W., Ridgway E. C., Beitins I. Z., Van Wyk J. J. Reduction of plasma immunoreactive somatomedin C during fasting in humans. J Clin Endocrinol Metab. 1981 Dec;53(6):1247–1250. doi: 10.1210/jcem-53-6-1247. [DOI] [PubMed] [Google Scholar]
  6. Coccagna G., Mantovani M., Brignani F., Manzini A., Lugaresi E. Laboratory note. Arterial pressure changes during spontaneous sleep in man. Electroencephalogr Clin Neurophysiol. 1971 Sep;31(3):277–281. doi: 10.1016/0013-4694(71)90098-8. [DOI] [PubMed] [Google Scholar]
  7. DEMENT W., KLEITMAN N. Cyclic variations in EEG during sleep and their relation to eye movements, body motility, and dreaming. Electroencephalogr Clin Neurophysiol. 1957 Nov;9(4):673–690. doi: 10.1016/0013-4694(57)90088-3. [DOI] [PubMed] [Google Scholar]
  8. Evans W. S., Faria A. C., Christiansen E., Ho K. Y., Weiss J., Rogol A. D., Johnson M. L., Blizzard R. M., Veldhuis J. D., Thorner M. O. Impact of intensive venous sampling on characterization of pulsatile GH release. Am J Physiol. 1987 Apr;252(4 Pt 1):E549–E556. doi: 10.1152/ajpendo.1987.252.4.E549. [DOI] [PubMed] [Google Scholar]
  9. FISHER C., GORSS J., ZUCH J. CYCLE OF PENILE ERECTION SYNCHRONOUS WITH DREAMING (REM) SLEEP. PRELIMINARY REPORT. Arch Gen Psychiatry. 1965 Jan;12:29–45. doi: 10.1001/archpsyc.1965.01720310031005. [DOI] [PubMed] [Google Scholar]
  10. Fain J. N., Kovacev V. P., Scow R. O. Effect of growth hormone and dexamethasone on lipolysis and metabolism in isolated fat cells of the rat. J Biol Chem. 1965 Sep;240(9):3522–3529. [PubMed] [Google Scholar]
  11. Felig P., Marliss E. B., Cahill G. F., Jr Metabolic response to human growth hormone during prolonged starvation. J Clin Invest. 1971 Feb;50(2):411–421. doi: 10.1172/JCI106508. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Finkelstein J. W., Roffwarg H. P., Boyar R. M., Kream J., Hellman L. Age-related change in the twenty-four-hour spontaneous secretion of growth hormone. J Clin Endocrinol Metab. 1972 Nov;35(5):665–670. doi: 10.1210/jcem-35-5-665. [DOI] [PubMed] [Google Scholar]
  13. Furlanetto R. W., Underwood L. E., Van Wyk J. J., D'Ercole A. J. Estimation of somatomedin-C levels in normals and patients with pituitary disease by radioimmunoassay. J Clin Invest. 1977 Sep;60(3):648–657. doi: 10.1172/JCI108816. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Goldsmith S. J., Glick S. M. Rhythmicity of human growth hormone secretion. Mt Sinai J Med. 1970 Jul-Aug;37(4):501–509. [PubMed] [Google Scholar]
  15. Haymond M. W., Karl I., Weldon V. V., Pagliara A. S. The role of growth hormone and cortisone on glucose and gluconeogenic substrate regulation in fasted hypopituitary children. J Clin Endocrinol Metab. 1976 May;42(5):846–856. doi: 10.1210/jcem-42-5-846. [DOI] [PubMed] [Google Scholar]
  16. Ho K. Y., Evans W. S., Blizzard R. M., Veldhuis J. D., Merriam G. R., Samojlik E., Furlanetto R., Rogol A. D., Kaiser D. L., Thorner M. O. Effects of sex and age on the 24-hour profile of growth hormone secretion in man: importance of endogenous estradiol concentrations. J Clin Endocrinol Metab. 1987 Jan;64(1):51–58. doi: 10.1210/jcem-64-1-51. [DOI] [PubMed] [Google Scholar]
  17. Imaki T., Shibasaki T., Shizume K., Masuda A., Hotta M., Kiyosawa Y., Jibiki K., Demura H., Tsushima T., Ling N. The effect of free fatty acids on growth hormone (GH)-releasing hormone-mediated GH secretion in man. J Clin Endocrinol Metab. 1985 Feb;60(2):290–293. doi: 10.1210/jcem-60-2-290. [DOI] [PubMed] [Google Scholar]
  18. Levin B. E., Rappaport M., Natelson B. H. Ultradian variations of plasma noradrenaline in humans. Life Sci. 1979 Aug 13;25(7):621–627. doi: 10.1016/0024-3205(79)90557-5. [DOI] [PubMed] [Google Scholar]
  19. Lloyd B., Burrin J., Smythe P., Alberti K. G. Enzymic fluorometric continuous-flow assays for blood glucose, lactate, pyruvate, alanine, glycerol, and 3-hydroxybutyrate. Clin Chem. 1978 Oct;24(10):1724–1729. [PubMed] [Google Scholar]
  20. Manson J. M., Wilmore D. W. Positive nitrogen balance with human growth hormone and hypocaloric intravenous feeding. Surgery. 1986 Aug;100(2):188–197. [PubMed] [Google Scholar]
  21. Mauras N., Blizzard R. M., Link K., Johnson M. L., Rogol A. D., Veldhuis J. D. Augmentation of growth hormone secretion during puberty: evidence for a pulse amplitude-modulated phenomenon. J Clin Endocrinol Metab. 1987 Mar;64(3):596–601. doi: 10.1210/jcem-64-3-596. [DOI] [PubMed] [Google Scholar]
  22. Merimee T. J., Felig P., Marliss E., Fineberg S. E., Cahill G. G., Jr Glucose and lipid homeostasis in the absence of human growth hormone. J Clin Invest. 1971 Mar;50(3):574–582. doi: 10.1172/JCI106527. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Orr W. C., Hoffman H. J., Hegge F. W. Ultradian rhythms in extended performance. Aerosp Med. 1974 Sep;45(9):995–1000. [PubMed] [Google Scholar]
  24. Oswald I., Merrington J., Lewis H. Cyclical "on demand" oral intake by adults. Nature. 1970 Mar 7;225(5236):959–960. doi: 10.1038/225959a0. [DOI] [PubMed] [Google Scholar]
  25. Owen O. E., Felig P., Morgan A. P., Wahren J., Cahill G. F., Jr Liver and kidney metabolism during prolonged starvation. J Clin Invest. 1969 Mar;48(3):574–583. doi: 10.1172/JCI106016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Quabbe H. J. Chronobiology of growth hormone secretion. Chronobiologia. 1977 Jul-Sep;4(3):217–246. [PubMed] [Google Scholar]
  27. Quabbe H. J., Schilling E., Helge H. Pattern of growth hormone secretion during a 24-hour fast in normal adults. J Clin Endocrinol Metab. 1966 Oct;26(10):1173–1177. doi: 10.1210/jcem-26-10-1173. [DOI] [PubMed] [Google Scholar]
  28. ROTH J., GLICK S. M., YALOW R. S., BERSON S. A. Secretion of human growth hormone: physiologic and experimental modification. Metabolism. 1963 Jul;12:577–579. [PubMed] [Google Scholar]
  29. Steiner R. A., Stewart J. K., Barber J., Koerker D., Goodner C. J., Brown A., Illner P., Gale C. C. Somatostatin: a physiological role in the regulation of growth hormone secretion in the adolescent male baboon. Endocrinology. 1978 May;102(5):1587–1594. doi: 10.1210/endo-102-5-1587. [DOI] [PubMed] [Google Scholar]
  30. Takahashi Y., Kipnis D. M., Daughaday W. H. Growth hormone secretion during sleep. J Clin Invest. 1968 Sep;47(9):2079–2090. doi: 10.1172/JCI105893. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Tannenbaum G. S. Growth hormone secretory dynamics in streptozotocin diabetes: evidence of a role for endogenous circulating somatostatin. Endocrinology. 1981 Jan;108(1):76–82. doi: 10.1210/endo-108-1-76. [DOI] [PubMed] [Google Scholar]
  32. Tannenbaum G. S., Martin J. B., Colle E. Ultradian growth hormone rhythm in the rat: effects of feeding, hyperglycemia, and insulin-induced hypoglycemia. Endocrinology. 1976 Sep;99(3):720–727. doi: 10.1210/endo-99-3-720. [DOI] [PubMed] [Google Scholar]
  33. Tannenbaum G. S., Martin J. B. Evidence for an endogenous ultradian rhythm governing growth hormone secretion in the rat. Endocrinology. 1976 Mar;98(3):562–570. doi: 10.1210/endo-98-3-562. [DOI] [PubMed] [Google Scholar]
  34. Tannenbaum G. S., Rorstad O., Brazeau P. Effects of prolonged food deprivation on the ultradian growth hormone rhythm and immunoreactive somatostatin tissue levels in the rat. Endocrinology. 1979 Jun;104(6):1733–1738. doi: 10.1210/endo-104-6-1733. [DOI] [PubMed] [Google Scholar]
  35. Thorner M. O., Rivier J., Spiess J., Borges J. L., Vance M. L., Bloom S. R., Rogol A. D., Cronin M. J., Kaiser D. L., Evans W. S. Human pancreatic growth-hormone-releasing factor selectively stimulates growth-hormone secretion in man. Lancet. 1983 Jan 1;1(8314-5):24–28. doi: 10.1016/s0140-6736(83)91563-5. [DOI] [PubMed] [Google Scholar]
  36. Veldhuis J. D., Johnson M. L. Cluster analysis: a simple, versatile, and robust algorithm for endocrine pulse detection. Am J Physiol. 1986 Apr;250(4 Pt 1):E486–E493. doi: 10.1152/ajpendo.1986.250.4.E486. [DOI] [PubMed] [Google Scholar]
  37. Wehrenberg W. B., Brazeau P., Luben R., Böhlen P., Guillemin R. Inhibition of the pulsatile secretion of growth hormone by monoclonal antibodies to the hypothalamic growth hormone releasing factor (GRF). Endocrinology. 1982 Dec;111(6):2147–2148. doi: 10.1210/endo-111-6-2147. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES