Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1984 Jul;74(1):96–103. doi: 10.1172/JCI111424

Plasma growth hormone responses to constant infusions of human pancreatic growth hormone releasing factor. Intermittent secretion or response attenuation.

C B Webb, M L Vance, M O Thorner, G Perisutti, J Thominet, J Rivier, W Vale, L A Frohman
PMCID: PMC425189  PMID: 6429198

Abstract

Administration of human pancreatic tumor growth hormone (GH) releasing factor (hpGRF[1-40]) as a single injection to normal human subjects stimulates the secretion of GH in a dose-responsive manner. In the present studies, hpGRF(1-40) was infused in a graded stepwise manner over a 6-h period in order to determine whether the GH secretory response would be sustained. Normal adult males received four consecutive 90-min infusions of hpGRF(1-40) at doses of 1, 3.3, 10, and 33 ng/kg per min, preceded and followed by a 90-min saline infusion; and the plasma GH responses were compared with those during a separate control infusion. Plasma GH levels were significantly elevated by each hpGRF(1-40) infusion; and dose responsiveness was evident for the lowest three doses. Mean integrated GH secretory rates for the four doses were 1.95, 3.29, 4.29, and 3.65 times those of the respective control study. Plasma GH responses exhibited considerable variability, frequently decreasing during the latter part of each infusion; and at the highest dose, they decreased continuously beginning shortly after the onset of infusion. Episodic GH secretion occurred in individual subjects during each of the infusion periods. The possible contribution of hypothalamic somatostatin secretion to the diminished GH responsiveness was evaluated by determining plasma thyroid stimulating hormone (TSH) levels during the infusions and the TSH responses to thyrotropin-releasing hormone (500 micrograms i.v.) during a separate hpGRF(1-40) infusion of 2 ng/kg per min. Neither basal nor stimulated TSH levels differed between GRF-infused and control groups. The results indicate that GH secretion is dose responsive to hpGRF(1-40) infusions, though the response to hpGRF(1-40) infusions, though the response is complex. The absence of impaired TSH secretion provides evidence against a mediating role of somatostatin. The explanation for the loss of GH responsiveness remains undetermined but could include GRF-induced receptor down-regulation, a postreceptor effect, or, in spite of our negative results, a somatostatin-mediated inhibition.

Full text

PDF
96

Selected References

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

  1. Abrams R. L., Grumbach M. M., Kaplan S. L. The effect of administration of human growth hormone on the plasma growth hormone, cortisol, glucose, and free fatty acid response to insulin: evidence for growth hormone autoregulation in man. J Clin Invest. 1971 Apr;50(4):940–950. doi: 10.1172/JCI106566. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Berelowitz M., Firestone S. L., Frohman L. A. Effects of growth hormone excess and deficiency on hypothalamic somatostatin content and release and on tissue somatostatin distribution. Endocrinology. 1981 Sep;109(3):714–719. doi: 10.1210/endo-109-3-714. [DOI] [PubMed] [Google Scholar]
  3. Bloch B., Brazeau P., Ling N., Bohlen P., Esch F., Wehrenberg W. B., Benoit R., Bloom F., Guillemin R. Immunohistochemical detection of growth hormone-releasing factor in brain. Nature. 1983 Feb 17;301(5901):607–608. doi: 10.1038/301607a0. [DOI] [PubMed] [Google Scholar]
  4. Chihara K., Minamitani N., Kaji H., Arimura A., Fujita T. Intraventricularly injected growth hormone stimulates somatostatin release into rat hypophysial portal blood. Endocrinology. 1981 Dec;109(6):2279–2281. doi: 10.1210/endo-109-6-2279. [DOI] [PubMed] [Google Scholar]
  5. Clayton R. N. Gonadotropin-releasing hormone modulation of its own pituitary receptors: evidence for biphasic regulation. Endocrinology. 1982 Jul;111(1):152–161. doi: 10.1210/endo-111-1-152. [DOI] [PubMed] [Google Scholar]
  6. Ferland L., Labrie F., Jobin M., Arimura A., Schally A. V. Physiological role of somatostatin in the control of growth hormone and thyrotropin secretion. Biochem Biophys Res Commun. 1976 Jan 12;68(1):149–156. doi: 10.1016/0006-291x(76)90022-x. [DOI] [PubMed] [Google Scholar]
  7. Frohman L. A., Bernardis L. L. Growth hormone and insulin levels in weanling rats with ventromedial hypothalamic lesions. Endocrinology. 1968 Jun;82(6):1125–1132. doi: 10.1210/endo-82-6-1125. [DOI] [PubMed] [Google Scholar]
  8. Frohman L. A., Horton E. S., Lebovitz H. E. Growth hormone releasing action of a Pseudomonas endotoxin (piromen). Metabolism. 1967 Jan;16(1):57–67. doi: 10.1016/0026-0495(67)90159-x. [DOI] [PubMed] [Google Scholar]
  9. Frohman L. A., Szabo M., Berelowitz M., Stachura M. E. Partial purification and characterization of a peptide with growth hormone-releasing activity from extrapituitary tumors in patients with acromegaly. J Clin Invest. 1980 Jan;65(1):43–54. doi: 10.1172/JCI109658. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Frohman L. A., Thominet J. L., Webb C. B., Vance M. L., Uderman H., Rivier J., Vale W., Thorner M. O. Metabolic clearance and plasma disappearance rates of human pancreatic tumor growth hormone releasing factor in man. J Clin Invest. 1984 May;73(5):1304–1311. doi: 10.1172/JCI111333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Guillemin R., Brazeau P., Böhlen P., Esch F., Ling N., Wehrenberg W. B. Growth hormone-releasing factor from a human pancreatic tumor that caused acromegaly. Science. 1982 Nov 5;218(4572):585–587. doi: 10.1126/science.6812220. [DOI] [PubMed] [Google Scholar]
  12. Hagen T. C., Lawrence A. M., Kirsteins L. Autoregulation of growth hormone secretion in normal subjects. Metabolism. 1972 Jul;21(7):603–610. doi: 10.1016/0026-0495(72)90084-4. [DOI] [PubMed] [Google Scholar]
  13. Heiman M. L., Ben-Jonathan N. Dopaminergic receptors in the rat anterior pituitary change during the estrous cycle. Endocrinology. 1982 Jul;111(1):37–41. doi: 10.1210/endo-111-1-37. [DOI] [PubMed] [Google Scholar]
  14. MacGillivray M. H., Frohman L. A., Doe J. Metabolic clearance and production rates of human growth hormone in subjects with normal and abnormal growth. J Clin Endocrinol Metab. 1970 May;30(5):632–638. doi: 10.1210/jcem-30-5-632. [DOI] [PubMed] [Google Scholar]
  15. Mendelson W. B., Jacobs L. S., Gillin J. C. Negative feedback suppression of sleep-related growth hormone secretion. J Clin Endocrinol Metab. 1983 Mar;56(3):486–488. doi: 10.1210/jcem-56-3-486. [DOI] [PubMed] [Google Scholar]
  16. Neill J. D., Patton J. M., Dailey R. A., Tsou R. C., Tindall G. T. Luteinizing hormone releasing hormone (LHRH) in pituitary stalk blood of rhesus monkeys: relationship to level of LH release. Endocrinology. 1977 Aug;101(2):430–434. doi: 10.1210/endo-101-2-430. [DOI] [PubMed] [Google Scholar]
  17. Parker K. M., Eddy R. L. Growth hormone refractory interval to levodopa stimulation. J Clin Endocrinol Metab. 1976 Jun;42(6):1188–1191. doi: 10.1210/jcem-42-6-1188. [DOI] [PubMed] [Google Scholar]
  18. Rick J., Szabo M., Payne P., Kovathana N., Cannon J. G., Frohman L. A. Prolactin-suppressive effects of two aminotetralin analogs of dopamine: their use in the characterization of the pituitary dopamine receptor. Endocrinology. 1979 May;104(5):1234–1242. doi: 10.1210/endo-104-5-1234. [DOI] [PubMed] [Google Scholar]
  19. Rivier J., Spiess J., Thorner M., Vale W. Characterization of a growth hormone-releasing factor from a human pancreatic islet tumour. Nature. 1982 Nov 18;300(5889):276–278. doi: 10.1038/300276a0. [DOI] [PubMed] [Google Scholar]
  20. Schneider A. B., Favus M. J., Stachura M. E., Arnold J. E., Ryo U. Y., Pinsky S., Colman M., Arnold M. J., Frohman L. A. Plasma thyroglobulin in detecting thyroid carcinoma after childhood head and neck irradiation. Ann Intern Med. 1977 Jan;86(1):29–34. doi: 10.7326/0003-4819-86-1-29. [DOI] [PubMed] [Google Scholar]
  21. Spiess J., Rivier J., Vale W. Characterization of rat hypothalamic growth hormone-releasing factor. Nature. 1983 Jun 9;303(5917):532–535. doi: 10.1038/303532a0. [DOI] [PubMed] [Google Scholar]
  22. Stachura M. E. Basal and dibutyryl cyclic AMP-stimulated release of newly synthesized and stored growth hormone from perifused rat pituitaries. Endocrinology. 1976 Mar;98(3):580–589. doi: 10.1210/endo-98-3-580. [DOI] [PubMed] [Google Scholar]
  23. Szabo M., Chu L., Frohman L. A. Biological effects of an ectopic growth hormone-releasing peptide in cultured adenohypophyseal cells: comparison with growth hormone-releasing activity of porcine hypothalamus. Endocrinology. 1982 Oct;111(4):1235–1240. doi: 10.1210/endo-111-4-1235. [DOI] [PubMed] [Google Scholar]
  24. Tannenbaum G. S. Evidence for autoregulation of growth hormone secretion via the central nervous system. Endocrinology. 1980 Dec;107(6):2117–2120. doi: 10.1210/endo-107-6-2117. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Vance M. L., Borges J. L., Kaiser D. L., Evans W. S., Furlanetto R., Thominet J. L., Frohman L. A., Rogol A. D., MacLeod R. M., Bloom S. Human pancreatic tumor growth hormone-releasing factor: dose-response relationships in normal man. J Clin Endocrinol Metab. 1984 May;58(5):838–844. doi: 10.1210/jcem-58-5-838. [DOI] [PubMed] [Google Scholar]
  27. Wehrenberg W. B., Ling N., Brazeau P., Esch F., Böhlen P., Baird A., Ying S., Guillemin R. Somatocrinin, growth hormone releasing factor, stimulates secretion of growth hormone in anesthetized rats. Biochem Biophys Res Commun. 1982 Nov 30;109(2):382–387. doi: 10.1016/0006-291x(82)91732-6. [DOI] [PubMed] [Google Scholar]
  28. Wynn P. C., Aguilera G., Morell J., Catt K. J. Properties and regulation of high-affinity pituitary receptors for corticotropin-releasing factor. Biochem Biophys Res Commun. 1983 Jan 27;110(2):602–608. doi: 10.1016/0006-291x(83)91192-0. [DOI] [PubMed] [Google Scholar]

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

RESOURCES