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. 1995 Mar 14;92(6):1856–1860. doi: 10.1073/pnas.92.6.1856

Growth hormone-releasing hormone stimulates cAMP release in superfused rat pituitary cells.

J E Horváth 1, K Groot 1, A V Schally 1
PMCID: PMC42381  PMID: 7892191

Abstract

The release of growth hormone (GH) and cAMP was studied in superfused rat pituitary cells by infusing growth hormone-releasing hormone (GHRH) at different doses or a combination of GHRH and somatostatin 14 (SS-14). Three-minute pulses of GHRH caused a dose-dependent GH and cAMP release (effective concentration of 50% of the maximal biological effect is 0.21 nM and 52.5 nM, respectively). The lowest effective doses of GHRH in the superfusion system were 0.03 nM for GH release and 0.3 nM for cAMP discharge when 3-min pulses were applied. The amount of cAMP liberated from the cells was not proportional to GH release: cAMP responses to low doses of GHRH were disproportionally small, and the gradual increase in the release of cAMP after high doses of GHRH was not followed by a parallel rise in GH release. The desensitization induced by repeated pulses or prolonged infusion of GHRH resulted in a greater reduction in GH release than in cAMP liberation. A simultaneous infusion of SS-14 completely blocked GH release stimulated by GHRH but did not inhibit the immediate release of cAMP caused by GHRH. An abrupt decrease in GHRH-stimulated GH release induced by SS-14 was followed by only a minimal reduction in cAMP liberation 9 min later. Our findings indicate that a discharge of cAMP is stimulated after a GHRH pulse, but this effect alone cannot maintain the release of GH. Other steps of the signal transduction mechanisms that are independent of the cAMP route may participate in the process of GH release. The nature of the mechanisms involved in the mediation of GH release may vary with the doses of GHRH used.

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Selected References

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

  1. Bilezikjian L. M., Seifert H., Vale W. Desensitization to growth hormone-releasing factor (GRF) is associated with down-regulation of GRF-binding sites. Endocrinology. 1986 May;118(5):2045–2052. doi: 10.1210/endo-118-5-2045. [DOI] [PubMed] [Google Scholar]
  2. Bilezikjian L. M., Vale W. W. Chronic exposure of cultured rat anterior pituitary cells to GRF causes partial loss of responsiveness to GRF. Endocrinology. 1984 Nov;115(5):2032–2034. doi: 10.1210/endo-115-5-2032. [DOI] [PubMed] [Google Scholar]
  3. Bilezikjian L. M., Vale W. W. Stimulation of adenosine 3',5'-monophosphate production by growth hormone-releasing factor and its inhibition by somatostatin in anterior pituitary cells in vitro. Endocrinology. 1983 Nov;113(5):1726–1731. doi: 10.1210/endo-113-5-1726. [DOI] [PubMed] [Google Scholar]
  4. Borgeat P., Labrie F., Drouin J., Bélanger A., Immer H., Sestanj K., Nelson V., Götz M., Schally A. V., Coy D. H. Inhibition of adenosine 3',5'-monophosphate accumulation in anterior pituitary gland in vitro by growth hormone-release inhibiting hormone. Biochem Biophys Res Commun. 1974 Feb 27;56(4):1052–1059. doi: 10.1016/s0006-291x(74)80295-0. [DOI] [PubMed] [Google Scholar]
  5. Brazeau P., Ling N., Esch F., Böhlen P., Mougin C., Guillemin R. Somatocrinin (growth hormone releasing factor) in vitro bioactivity; Ca++ involvement, cAMP mediated action and additivity of effect with PGE2. Biochem Biophys Res Commun. 1982 Nov 30;109(2):588–594. doi: 10.1016/0006-291x(82)91762-4. [DOI] [PubMed] [Google Scholar]
  6. Ceda G. P., Hoffman A. R. Growth hormone-releasing factor desensitization in rat anterior pituitary cells in vitro. Endocrinology. 1985 Apr;116(4):1334–1340. doi: 10.1210/endo-116-4-1334. [DOI] [PubMed] [Google Scholar]
  7. French M. B., Moor B. C., Lussier B. T., Kraicer J. Protein kinase C is not essential for growth hormone (GH)-releasing factor-induced GH release from rat somatotrophs. Endocrinology. 1989 May;124(5):2235–2244. doi: 10.1210/endo-124-5-2235. [DOI] [PubMed] [Google Scholar]
  8. Frohman L. A., Downs T. R., Chomczynski P. Regulation of growth hormone secretion. Front Neuroendocrinol. 1992 Oct;13(4):344–405. [PubMed] [Google Scholar]
  9. Harwood J. P., Grewe C., Aguilera G. Actions of growth hormone-releasing factor and somatostatin on adenylate cyclase and growth hormone release in rat anterior pituitary. Mol Cell Endocrinol. 1984 Oct;37(3):277–284. doi: 10.1016/0303-7207(84)90097-2. [DOI] [PubMed] [Google Scholar]
  10. Holl R. W., Thorner M. O., Leong D. A. Cytosolic free calcium in normal somatotropes: effects of forskolin and phorbol ester. Am J Physiol. 1989 Mar;256(3 Pt 1):E375–E379. doi: 10.1152/ajpendo.1989.256.3.E375. [DOI] [PubMed] [Google Scholar]
  11. Horváth J. E., Schally A. V. Reciprocal changes in prolactin and growth hormone secretion in vitro after in vivo estrogen treatment. Acta Biol Hung. 1994;45(2-4):249–262. [PubMed] [Google Scholar]
  12. Kato M., Suzuki M. The time course and extracellular Ca2+ involvement of growth hormone (GH) releasing factor-induced GH secretion in perifused dispersed rat pituitary cells. Jpn J Physiol. 1986;36(6):1225–1239. doi: 10.2170/jjphysiol.36.1225. [DOI] [PubMed] [Google Scholar]
  13. Labrie F., Gagné B., Lefèvre G. Growth hormone-releasing factor stimulates adenylate cyclase activity in the anterior pituitary gland. Life Sci. 1983 Nov 28;33(22):2229–2233. doi: 10.1016/0024-3205(83)90295-3. [DOI] [PubMed] [Google Scholar]
  14. Limor R., Ayalon D., Capponi A. M., Childs G. V., Naor Z. Cytosolic free calcium levels in cultured pituitary cells separated by centrifugal elutriation: effect of gonadotropin-releasing hormone. Endocrinology. 1987 Feb;120(2):497–503. doi: 10.1210/endo-120-2-497. [DOI] [PubMed] [Google Scholar]
  15. Login I. S., Judd A. M., MacLeod R. M. Association of 45Ca2+ mobilization with stimulation of growth hormone (GH) release by GH-releasing factor in dispersed normal male rat pituitary cells. Endocrinology. 1986 Jan;118(1):239–243. doi: 10.1210/endo-118-1-239. [DOI] [PubMed] [Google Scholar]
  16. Lussier B. T., French M. B., Moor B. C., Kraicer J. Free intracellular Ca2+ concentration and growth hormone (GH) release from purified rat somatotrophs. III. Mechanism of action of GH-releasing factor and somatostatin. Endocrinology. 1991 Jan;128(1):592–603. doi: 10.1210/endo-128-1-592. [DOI] [PubMed] [Google Scholar]
  17. Michel D., Lefèvre G., Labrie F. Interactions between growth hormone-releasing factor, prostaglandin E2 and somatostatin on cyclic AMP accumulation in rat adenohypophysial cells in culture. Mol Cell Endocrinol. 1983 Dec;33(2-3):255–264. doi: 10.1016/0303-7207(83)90171-5. [DOI] [PubMed] [Google Scholar]
  18. Narayanan N., Lussier B., French M., Moor B., Kraicer J. Growth hormone-releasing factor-sensitive adenylate cyclase system of purified somatotrophs: effects of guanine nucleotides, somatostatin, calcium, and magnesium. Endocrinology. 1989 Jan;124(1):484–495. doi: 10.1210/endo-124-1-484. [DOI] [PubMed] [Google Scholar]
  19. Schettini G., Cronin M. J., Hewlett E. L., Thorner M. O., MacLeod R. M. Human pancreatic tumor growth hormone-releasing factor stimulates anterior pituitary adenylate cyclase activity, adenosine 3',5'-monophosphate accumulation, and growth hormone release in a calmodulin-dependent manner. Endocrinology. 1984 Oct;115(4):1308–1314. doi: 10.1210/endo-115-4-1308. [DOI] [PubMed] [Google Scholar]
  20. Schöfl C., Sandow J., Knepel W. GRF elevates cytosolic free calcium concentration in rat anterior pituitary cells. Am J Physiol. 1987 Nov;253(5 Pt 1):E591–E594. doi: 10.1152/ajpendo.1987.253.5.E591. [DOI] [PubMed] [Google Scholar]
  21. Sheppard M. S., Moor B. C., Kraicer J. Release of growth hormone (GH) from purified somatotrophs: interaction of GH-releasing factor and somatostatin and role of adenosine 3',5'-monophosphate. Endocrinology. 1985 Dec;117(6):2364–2370. doi: 10.1210/endo-117-6-2364. [DOI] [PubMed] [Google Scholar]
  22. Simard J., Lefèvre G., Labrie F. Somatostatin prevents the desensitizing action of growth hormone-releasing factor on growth hormone release. Peptides. 1987 Mar-Apr;8(2):199–205. doi: 10.1016/0196-9781(87)90090-8. [DOI] [PubMed] [Google Scholar]
  23. Stachura M. E., Tyler J. M., Farmer P. K. Combined effects of human growth hormone (GH)-releasing factor-44 (GRF) and somatostatin (SRIF) on post-SRIF rebound release of GH and prolactin: a model for GRF-SRIF modulation of secretion. Endocrinology. 1988 Sep;123(3):1476–1482. doi: 10.1210/endo-123-3-1476. [DOI] [PubMed] [Google Scholar]

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