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. 1986 Jan;77(1):176–180. doi: 10.1172/JCI112273

Exogenous growth hormone inhibits growth hormone-releasing factor-induced growth hormone secretion in normal men.

S M Rosenthal, J A Hulse, S L Kaplan, M M Grumbach
PMCID: PMC423324  PMID: 3080472

Abstract

Previous studies from this laboratory and by others in rats, monkeys, and humans support the concept that growth hormone (GH) can regulate its own secretion through an autofeedback mechanism. With the availability of human growth hormone-releasing factor (GRF), the possible existence of such a mechanism was reexplored by examining the effect of exogenous GH on the GH response induced by GRF-44-NH2 in six normal men (mean age, 32.4 yr). In all subjects the plasma GH response evoked by GRF-44-NH2 (1 microgram/kg i.v. bolus) was studied before and after 5 d of placebo (1 ml normal saline i.m. every 12 h), and then before and 12 h after 5 d of biosynthetic methionyl human GH (5 U i.m. every 12 h). The GH response to GRF (maximal increment over time 0 value) was significantly inhibited after GH treatment (0-1.3 vs. 2.3-11.2 ng/ml before treatment, P = 0.05), but was not significantly affected by placebo. This impaired pituitary response to GRF persisted for at least 24 h following exogenous GH treatment in two subjects who underwent further study. Serum somatomedin-C concentrations were significantly increased after 5 d of GH treatment (2.66-5.00 vs. 0.92-1.91 U/ml before treatment, P = less than 0.01). The impaired pituitary response to GRF may be mediated indirectly through somatomedin, somatostatin, by a direct effect of GH on the pituitary somatotropes, or by all of these mechanisms. These data suggest that after GH treatment, the blunted GH response to synthetic GRF is not solely a consequence of the inhibition of hypothalamic GRF secretion.

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Selected References

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  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. 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]
  4. Borges J. L., Blizzard R. M., Gelato M. C., Furlanetto R., Rogol A. D., Evans W. S., Vance M. L., Kaiser D. L., MacLeod R. M., Merriam G. R. Effects of human pancreatic tumour growth hormone releasing factor on growth hormone and somatomedin C levels in patients with idiopathic growth hormone deficiency. Lancet. 1983 Jul 16;2(8342):119–124. doi: 10.1016/s0140-6736(83)90113-7. [DOI] [PubMed] [Google Scholar]
  5. Brazeau P., Guillemin R., Ling N., van Wyk J., Humbel R. Inhibition par les somatomédines de la sécrétion de l'hormone de croissance stimulée par le facteur hypothalamique somatocrinine (GRF) ou le peptide de synthèse hpGRF. C R Seances Acad Sci III. 1982 Nov 29;295(11):651–654. [PubMed] [Google Scholar]
  6. Brazeau P., Ling N., Böhlen P., Esch F., Ying S. Y., Guillemin R. Growth hormone releasing factor, somatocrinin, releases pituitary growth hormone in vitro. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7909–7913. doi: 10.1073/pnas.79.24.7909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Brazeau P., Vale W., Burgus R., Ling N., Butcher M., Rivier J., Guillemin R. Hypothalamic polypeptide that inhibits the secretion of immunoreactive pituitary growth hormone. Science. 1973 Jan 5;179(4068):77–79. doi: 10.1126/science.179.4068.77. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Chihara K., Minamitani N., Kaji H., Kodama H., Kita T., Fujita T. Human pancreatic growth hormone-releasing factor stimulates release of growth hormone in conscious unrestrained male rabbits. Endocrinology. 1983 Dec;113(6):2081–2085. doi: 10.1210/endo-113-6-2081. [DOI] [PubMed] [Google Scholar]
  10. Gelato M. C., Merriam G. R., Vance M. L., Goldman J. A., Webb C., Evans W. S., Rock J., Oldfield E. H., Molitch M. E., Rivier J. Effects of growth hormone-releasing factor on growth hormone secretion in acromegaly. J Clin Endocrinol Metab. 1985 Feb;60(2):251–257. doi: 10.1210/jcem-60-2-251. [DOI] [PubMed] [Google Scholar]
  11. Grossman A., Savage M. O., Wass J. A., Lytras N., Sueiras-Diaz J., Coy D. H., Besser G. M. Growth-hormone-releasing factor in growth hormone deficiency: demonstration of a hypothalamic defect in growth hormone release. Lancet. 1983 Jul 16;2(8342):137–138. doi: 10.1016/s0140-6736(83)90118-6. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. 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]
  14. Jacobs L. S., Sneid D. S., Garland J. T., Laron Z., Daughaday W. H. Receptor-active growth hormone in Laron dwarfism. J Clin Endocrinol Metab. 1976 Feb;42(2):403–406. doi: 10.1210/jcem-42-2-403. [DOI] [PubMed] [Google Scholar]
  15. Katz S. H., Molitch M., McCann S. M. Effects of hypothalmic implants of GH on anterior pituitary weight and GH concentration. Endocrinology. 1969 Oct;85(4):725–734. doi: 10.1210/endo-85-4-725. [DOI] [PubMed] [Google Scholar]
  16. Krulich L., McCann S. M. Influence of growth hormone (GH) on content of GH in the pituitaries of normal rats. Proc Soc Exp Biol Med. 1966 Apr;121(4):1114–1117. doi: 10.3181/00379727-121-30980. [DOI] [PubMed] [Google Scholar]
  17. MacLeod R. M., DeWitt G. W., Smith M. C. Suppression of pituitary gland hormone content by pituitary tumor hormones. Endocrinology. 1968 May;82(5):889–894. doi: 10.1210/endo-82-5-889. [DOI] [PubMed] [Google Scholar]
  18. MacLeod R. M., Smith M. C., DeWitt G. W. Hormonal properties of transplanted pituitary tumors and their relation to the pituitary gland. Endocrinology. 1966 Dec;79(6):1149–1156. doi: 10.1210/endo-79-6-1149. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Müller E., Pecile A. Influence of exogenous growth hormone on endogenous growth hormone release. Proc Soc Exp Biol Med. 1966 Aug-Sep;122(4):1289–1291. doi: 10.3181/00379727-122-31384. [DOI] [PubMed] [Google Scholar]
  21. Patel Y. C. Growth hormone stimulates hypothalamic somatostatin. Life Sci. 1979 Apr 23;24(17):1589–1593. doi: 10.1016/0024-3205(79)90020-1. [DOI] [PubMed] [Google Scholar]
  22. Peake G. T., Mariz I. K., Daughaday W. H. Radioimmunoassay of growth hormone in rats bearing somatotropin producing tumors. Endocrinology. 1968 Oct;83(4):714–720. doi: 10.1210/endo-83-4-714. [DOI] [PubMed] [Google Scholar]
  23. Phillips L. S., Vassilopoulou-Sellin R. Somatomedins (second of two parts). N Engl J Med. 1980 Feb 21;302(8):438–446. doi: 10.1056/NEJM198002213020805. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Rosenthal S. M., Schriock E. A., Kaplan S. L., Guillemin R., Grumbach M. M. Synthetic human pancreas growth hormone-releasing factor (hpGRF1-44-NH2) stimulates growth hormone secretion in normal men. J Clin Endocrinol Metab. 1983 Sep;57(3):677–679. doi: 10.1210/jcem-57-3-677. [DOI] [PubMed] [Google Scholar]
  26. Sakuma M., Knobil E. Inhibition of endogenous growth hormone secretion by exogenous growth hormone infusion in the rhesus monkey. Endocrinology. 1970 Apr;86(4):890–894. doi: 10.1210/endo-86-4-890. [DOI] [PubMed] [Google Scholar]
  27. Sassolas G., Rousset H., Cohen R., Chatelain P., Claustrat B., Laporte S., Laferrère B., El Charfi A., Ferry S. La somatocrinine provoque la libération de somathormone dans un cas de déficit en somathormone d'origine hypothalamique chez l'enfant. C R Seances Acad Sci III. 1983;296(11):527–530. [PubMed] [Google Scholar]
  28. Schriock E. A., Lustig R. H., Rosenthal S. M., Kaplan S. L., Grumbach M. M. 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 or multiple pituitary hormone deficiencies: evidence for hypothalamic GRH deficiency. J Clin Endocrinol Metab. 1984 Jun;58(6):1043–1049. doi: 10.1210/jcem-58-6-1043. [DOI] [PubMed] [Google Scholar]
  29. Sheppard M. C., Kronheim S., Pimstone B. L. Stimulation by growth hormone of somatostatin release from the rat hypothalamus in vitro. Clin Endocrinol (Oxf) 1978 Dec;9(6):583–586. doi: 10.1111/j.1365-2265.1978.tb01518.x. [DOI] [PubMed] [Google Scholar]
  30. Shibasaki T., Shizume K., Masuda A., Nakahara M., Hizuka N., Miyakawa M., Takano K., Demura H., Wakabayashi I., Ling N. Plasma growth hormone response to growth hormone-releasing factor in acromegalic patients. J Clin Endocrinol Metab. 1984 Jan;58(1):215–217. doi: 10.1210/jcem-58-1-215. [DOI] [PubMed] [Google Scholar]
  31. Takano K., Hizuka N., Shizume K., Asakawa K., Miyakawa M., Hirose N., Shibasaki T., Ling N. C. Plasma growth hormone (GH) response to GH-releasing factor in normal children with short stature and patients with pituitary dwarfism. J Clin Endocrinol Metab. 1984 Feb;58(2):236–241. doi: 10.1210/jcem-58-2-236. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. Tannenbaum G. S., Guyda H. J., Posner B. I. Insulin-like growth factors: a role in growth hormone negative feedback and body weight regulation via brain. Science. 1983 Apr 1;220(4592):77–79. doi: 10.1126/science.6338593. [DOI] [PubMed] [Google Scholar]
  34. 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]
  35. Vale W., Vaughan J., Yamamoto G., Spiess J., Rivier J. Effects of synthetic human pancreatic (tumor) GH releasing factor and somatostatin, triiodothyronine and dexamethasone on GH secretion in vitro. Endocrinology. 1983 Apr;112(4):1553–1555. doi: 10.1210/endo-112-4-1553. [DOI] [PubMed] [Google Scholar]
  36. Van Vliet G., Styne D. M., Kaplan S. L., Grumbach M. M. Growth hormone treatment for short stature. N Engl J Med. 1983 Oct 27;309(17):1016–1022. doi: 10.1056/NEJM198310273091703. [DOI] [PubMed] [Google Scholar]
  37. Voogt J. L., Clemens J. A., Negro-Vilar A., Welsch C., Meites J. Pituitary GH and hypothalamic GHRF after median eminence implantation of ovine or human GH. Endocrinology. 1971 Jun;88(6):1363–1367. doi: 10.1210/endo-88-6-1363. [DOI] [PubMed] [Google Scholar]
  38. Webb C. B., Vance M. L., Thorner M. O., Perisutti G., Thominet J., Rivier J., Vale W., Frohman L. A. Plasma growth hormone responses to constant infusions of human pancreatic growth hormone releasing factor. Intermittent secretion or response attenuation. J Clin Invest. 1984 Jul;74(1):96–103. doi: 10.1172/JCI111424. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Wehrenberg W. B., Ling N., Böhlen P., Esch F., Brazeau P., Guillemin R. Physiological roles of somatocrinin and somatostatin in the regulation of growth hormone secretion. Biochem Biophys Res Commun. 1982 Nov 30;109(2):562–567. doi: 10.1016/0006-291x(82)91758-2. [DOI] [PubMed] [Google Scholar]
  40. Youlton R., Kaplan S. L., Grumbach M. M. Growth and growth hormone. IV. Limitations of the growth hormone response to insulin and arginine and of the immunoreactive insulin response to arginine in the assessment of growth hormone deficiency in children. Pediatrics. 1969 Jun;43(6):989–1004. [PubMed] [Google Scholar]

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