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. 1986 Sep;83(18):6854–6857. doi: 10.1073/pnas.83.18.6854

Growth hormone-releasing factor stimulates proliferation of somatotrophs in vitro.

N Billestrup, L W Swanson, W Vale
PMCID: PMC386608  PMID: 3018748

Abstract

The mitogenic effect of the hypothalamic peptides growth hormone-releasing factor (GRF) and somatostatin on cultured growth hormone (GH)-producing cells (somatotrophs) was studied. Using autoradiographic detection of [3H]thymidine uptake and immunocytochemical identification of GH-producing cells, we show that 5 nM GRF causes a 20-fold increase in the percentage of somatotrophs labeled with [3H]thymidine. The total number of somatotrophs in GRF-treated cultures was increased by 60%. Somatostatin had no measurable effect on the labeling index by itself, but it partly inhibited the GRF-induced increase in both the labeling index and the total number of cells. Forskolin caused an increase in both the percentage of somatotrophs with a [3H]thymidine-labeled nucleus and the somatotroph number similar to that caused by GRF. GH secretion as well as cellular GH content in the GRF- or forskolin-treated cells increased with culture time over the entire period, whereas secretion and content of GH gradually decreased in control or somatostatin-treated cultures during the entire culture period. These data suggest that GRF and somatostatin regulate the mitotic activity of GH-producing cells and that the effect of GRF is possibly mediated by cyclic AMP.

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Selected References

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  1. Asa S. L., Scheithauer B. W., Bilbao J. M., Horvath E., Ryan N., Kovacs K., Randall R. V., Laws E. R., Jr, Singer W., Linfoot J. A. A case for hypothalamic acromegaly: a clinicopathological study of six patients with hypothalamic gangliocytomas producing growth hormone-releasing factor. J Clin Endocrinol Metab. 1984 May;58(5):796–803. doi: 10.1210/jcem-58-5-796. [DOI] [PubMed] [Google Scholar]
  2. Barinaga M., Bilezikjian L. M., Vale W. W., Rosenfeld M. G., Evans R. M. Independent effects of growth hormone releasing factor on growth hormone release and gene transcription. Nature. 1985 Mar 21;314(6008):279–281. doi: 10.1038/314279a0. [DOI] [PubMed] [Google Scholar]
  3. Barinaga M., Yamonoto G., Rivier C., Vale W., Evans R., Rosenfeld M. G. Transcriptional regulation of growth hormone gene expression by growth hormone-releasing factor. Nature. 1983 Nov 3;306(5938):84–85. doi: 10.1038/306084a0. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. 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]
  6. 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]
  7. 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]
  8. Fukata J., Diamond D. J., Martin J. B. Effects of rat growth hormone (rGH)-releasing factor and somatostatin on the release and synthesis of rGH in dispersed pituitary cells. Endocrinology. 1985 Aug;117(2):457–467. doi: 10.1210/endo-117-2-457. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Hammer R. E., Brinster R. L., Rosenfeld M. G., Evans R. M., Mayo K. E. Expression of human growth hormone-releasing factor in transgenic mice results in increased somatic growth. 1985 May 30-Jun 5Nature. 315(6018):413–416. doi: 10.1038/315413a0. [DOI] [PubMed] [Google Scholar]
  11. Leveston S. A., McKeel D. W., Jr, Buckley P. J., Deschryver K., Greider M. H., Jaffe B. M., Daughaday W. H. Acromegaly and Cushing's syndrome associated with a foregut carcinoid tumor. J Clin Endocrinol Metab. 1981 Oct;53(4):682–689. doi: 10.1210/jcem-53-4-682. [DOI] [PubMed] [Google Scholar]
  12. Lowry P. J., Silas L., McLean C., Linton E. A., Estivariz F. E. Pro-gamma-melanocyte-stimulating hormone cleavage in adrenal gland undergoing compensatory growth. Nature. 1983 Nov 3;306(5938):70–73. doi: 10.1038/306070a0. [DOI] [PubMed] [Google Scholar]
  13. Pastan I. H., Johnson G. S., Anderson W. B. Role of cyclic nucleotides in growth control. Annu Rev Biochem. 1975;44:491–522. doi: 10.1146/annurev.bi.44.070175.002423. [DOI] [PubMed] [Google Scholar]
  14. Raff M. C., Hornby-Smith A., Brockes J. P. Cyclic AMP as a mitogenic signal for cultured rat Schwann cells. Nature. 1978 Jun 22;273(5664):672–673. doi: 10.1038/273672a0. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Saeed uz Zafar M., Mellinger R. C., Fine G., Szabo M., Frohman L. A. Acromegaly associated with a bronchial carcinoid tumor: evidence for ectopic production of growth hormone-releasing activity. J Clin Endocrinol Metab. 1979 Jan;48(1):66–71. doi: 10.1210/jcem-48-1-66. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Spira O., Vlodavsky I., Ulmansky R., Atzmon R., Fuks Z., Gordon A., Gross J. Thyrotrophin and growth hormone secretion and cell morphology in hypothyroid pituitary cells cultured on a natural extracellular matrix. Acta Endocrinol (Copenh) 1983 Nov;104(3):279–286. doi: 10.1530/acta.0.1040279. [DOI] [PubMed] [Google Scholar]
  19. Thorner M. O., Perryman R. L., Cronin M. J., Rogol A. D., Draznin M., Johanson A., Vale W., Horvath E., Kovacs K. Somatotroph hyperplasia. Successful treatment of acromegaly by removal of a pancreatic islet tumor secreting a growth hormone-releasing factor. J Clin Invest. 1982 Nov;70(5):965–977. doi: 10.1172/JCI110708. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Vale W., Vaughan J., Yamamoto G., Bruhn T., Douglas C., Dalton D., Rivier C., Rivier J. Assay of corticotropin releasing factor. Methods Enzymol. 1983;103:565–577. doi: 10.1016/s0076-6879(83)03040-2. [DOI] [PubMed] [Google Scholar]
  21. Vlodavsky I., Lui G. M., Gospodarowicz D. Morphological appearance, growth behavior and migratory activity of human tumor cells maintained on extracellular matrix versus plastic. Cell. 1980 Mar;19(3):607–616. doi: 10.1016/s0092-8674(80)80037-7. [DOI] [PubMed] [Google Scholar]

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