Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
권호 표지
DOI QR코드

DOI QR Code

Effects of Chungkookjang Extract on Growth Hormone Secretion from GH3 Mouse Pituitary Cell and Growth Hormone Receptor Signaling Pathway

GH3 뇌하수체 세포주로부터 성장호르몬의 분비와 성장호르몬 수용체 신호전달에 미치는 청국장 추출물의 효능

  • Choi, Sun-Il (Department of Biomaterial Science, College of Natural Resources & Life Science, Pusan National University) ;
  • Kim, Ji-Eun (Department of Biomaterial Science, College of Natural Resources & Life Science, Pusan National University) ;
  • Hwang, In-Sik (Department of Biomaterial Science, College of Natural Resources & Life Science, Pusan National University) ;
  • Lee, Hye-Ryun (Department of Biomaterial Science, College of Natural Resources & Life Science, Pusan National University) ;
  • Lee, Young-Ju (Department of Biomaterial Science, College of Natural Resources & Life Science, Pusan National University) ;
  • Son, Hong-Joo (Department of Life Science and Environmental Biochemistry, College of Natural Resources & Life Science, Pusan National University) ;
  • Kim, Dong-Seob (Department of Food Science and Technology, College of Natural Resources & Life Science, Pusan National University) ;
  • Park, Kyu-Min (Jangmaeul Co.) ;
  • Hwang, Dae-Youn (Department of Biomaterial Science, College of Natural Resources & Life Science, Pusan National University)
  • 최선일 (부산대학교 생명자원과학대학 바이오소재과학과) ;
  • 김지은 (부산대학교 생명자원과학대학 바이오소재과학과) ;
  • 황인식 (부산대학교 생명자원과학대학 바이오소재과학과) ;
  • 이혜련 (부산대학교 생명자원과학대학 바이오소재과학과) ;
  • 이영주 (부산대학교 생명자원과학대학 바이오소재과학과) ;
  • 손홍주 (부산대학교 생명자원과학대학 생명환경화학과) ;
  • 김동섭 (부산대학교 생명자원과학대학 식품공학과) ;
  • 박규민 (장마을) ;
  • 황대연 (부산대학교 생명자원과학대학 바이오소재과학과)
  • Received : 2012.08.07
  • Accepted : 2012.09.20
  • Published : 2012.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

The production and secretion of growth hormone (GH) in the anterior pituitary gland can be induced by several natural products to control cell proliferation, differentiation, and migration. To investigate whether Chungkookjang (CKJ) produced by the fermentation process affects GH-related metabolism, the secretion and the response of GH were observed in pituitary cells and GH target cells. Among six CKJs manufactured by different strains of glycine max, only three CKJs, including Daewon (DW), Daepung (DP), and Taegwang (TG), induced GH secretion from GH3 cells at 5.0 mg/ml concentration. There were no significant changes detected in the viability of any of the cells treated with these CKJs. In addition, the increase in GH secretion from the GH3 cells was dependent on the concentration of the three types of CKJs. The proliferation of cell lines, including MG63 and HepG2 cells, that originated from those derived from the GH target organs was significantly activated by treatment with the GH-containing conditional medium (GCM) harvested from the three CKJ-treated GH3 cells, although their induction rate was different from each other. In these cells, p-STAT5 was maximally translocated into the nucleus of MG63 cells 30 min after DW treatment, while it was translocated in HepG2 cells at 60 min. These results suggest that these three types of CKJ could enhance the secretion of GH, as well as the GCM-derived response, in the two target organs.

뇌하수체 전엽에서 성장호르몬의 생산과 분비는 세포의 분열과 분화 그리고 이동을 조절하는 몇 가지 천연물질에 의해 유도된다. 따라서 발효과정을 통해 제조된 청국장이 성장호르몬의 대사에 미치는 영향을 평가하기 위하여 성장호르몬 분비능과 반응성을 뇌하수체 세포와 성장호르몬 표적세포에서 관찰하였다. 6가지 종류의 콩 품종으로 제조된 청국장 추출물 중에서, 대원, 대풍, 태광의 3종류 청국장 추출물은 5 mg/ml 농도에서 GH3 세포로부터 성장호르몬의 분비를 촉진하였다. 비록 세포 생존능은 이러한 추출물에 의해 유의적인 변화가 유도되지 않았으나, 성장호르몬의 분비량은 청국장 추출물의 농도에 의존적으로 증가하였다. 또한 성장호르몬의 표적 기관으로부터 유래된 MG63과 HepG2 세포는 GH3로부터 수집된 조건적 배양액에 의해 유의적으로 활성화되었다. 또한 이러한 세포에서 STAT5 발현은 대원 청국장 추출물을 처리 후, 15분 혹은 30분부터 세포질에서 유의적으로 증가하였으며, p-STAT5는 핵에서 30분 혹은 60분부터 증가하였다. 따라서 이러한 결과는 3가지 종류의 청국장 추출물은 성장호르몬의 분비를 촉진시키며, 청국장의 조건적 배양액은 성장호르몬 표적세포에서 신호전달을 유도함을 제시하고 있다.

Keywords

References

  1. Andreassen, T. T., Jorgensen, P. H., Flyvvbjerg, A., Orskov, H. and Oxlund, H. 1995. Growth hormone stimulates bone formation and strength of cortical bone in aged rats. J. Bone Miner. Res. 10, 1057-1067.
  2. Anthony, M. S., Clarkson, T. B., Hughes, J. R., Morgan, T. M. and Burke, G. L. 1996. Soybean isoflavones improve cardiovascular risk factors without affecting the reproductive system of peripubertal rhesus monkey. J. Nutr. 126, 43-50.
  3. Atti, K. M. 2000. The importance of growth hormone replacement therapy for bone mass in young adults with growth hormone deficiency. J. Pediatr. Endocrinol. Metab. 13, 1011-1021.
  4. Campbell, G. S.1997. Growth hormone signal transduction. J. Pediatr. 131 (Suppl), S42. https://doi.org/10.1016/S0022-3476(97)70010-6
  5. Carter-Su, C., King, A. P., Argetsinger, L. S., Smit, L. S., Vanderkuur, J. and Campbell, G. S. 1996. Signalling pathway of GH. Endocr. J. 43(Suppl), S65-S70. https://doi.org/10.1507/endocrj.43.Suppl_S65
  6. Cassidy, A., Bing ham, S. and Setchell, K. 1995. Biological effects of isoflavones in young women: importance of the chemical composition of soybean products. Br. J. Nutr. 74, 587-601. https://doi.org/10.1079/BJN19950160
  7. Darnell, J. E. Jr, Kerr, I. M. and Stark, G. R. 1994. Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science 264, 1415-1421. https://doi.org/10.1126/science.8197455
  8. Gerlier, D. and Thomasset, N. 1986. Use of MTT colorimetric assay to measure cell activation. J. Immunol. Methods 94, 57-63. https://doi.org/10.1016/0022-1759(86)90215-2
  9. Herrington, J., Smit, L. S., Schwartz, J. and Carter-Su, C. 2000. The role of STAT proteins in growth hormone signaling. Oncogene 19, 2585-2597. https://doi.org/10.1038/sj.onc.1203526
  10. Hong, S. W., Kim, Y. J., Lee, B. K. and Chung, K. S. 2006. The bacterial biological response modifier enriched Cheonggukjang fermentation. Korea J. Food Sci. Technol. 38, 548-553.
  11. Ihle, J. N. 1996. STATs: signal transducers and activators of transcription. Cell 84, 331-334. https://doi.org/10.1016/S0092-8674(00)81277-5
  12. Ishida, H., Uesugi, T., Hirai, K., Toda, T., Nukaya, H., Yokotsuka, K. and Tsuji, K. 1998. Preventive effects of the plant isoflavones, daidzin, and genistin, on bone loss in ovariectomized rats fed a calcium-deficient diet. Biol. Pharm. Bull. 21, 62-66. https://doi.org/10.1248/bpb.21.62
  13. Kajiya, H., Takekoshi, S., Miyai, S., Ikeda, T., Kimura, S. and Osamura, R. Y. 2005. Dietary soybean enhances Pit-1 dependent pituitary hormone production in iodine deficient rats. J. Mol. Histol. 36, 265-274. https://doi.org/10.1007/s10735-005-4710-8
  14. Kassem, M., Blum, W. and Risteli, J. 1993. Growth hormone stimulates proliferation and differentiation of normal human osteoblast-like cells in vitro. Calcif. Tissue Int. 52, 222-226. https://doi.org/10.1007/BF00298723
  15. Kim, J. S. 1996. Current research trends on bioactive function of soybean. Korea Soybean Digest 13, 17-24.
  16. Kim, S. H., Yang, J. L. and Song, Y. S. 1999. Physiological functions of Chungkukjang. Food Indus. Nutr. 4, 40-46.
  17. Kim, W. K., Choi, K. H., Kim, Y. T., Park, H. H., Choi, J. Y., Lee, Y. S., Oh, H. I., Kwon, I. B. and Lee, S. Y. 1996. Purification and characterization of a fibrinolytic enzyme produced for Bacillus sp. Strain CK 11-4 screened from Cheonggukjang. Appl. Environ. Microbiol. 62, 2482-2488.
  18. Kim, Y. T., Kim, W. K. and Oh, H. I. 1995. General microbiology, physiology and metabolism Screening and identification of the fibrinolytic bacterial strain from Cheonggukjang. Korean J. Microbiol. Biotechnol. 23, 1-5.
  19. Koh, J. B. 2006. Effects of Cheonggukjang on lipid metabolism in hyperlipidemic female rats. Korean J. Nutr. 39, 331-337.
  20. Kwak, C. S., Kim, M. Y., Kim, S. A. and Lee, M. S. 2006. Cytotoxicity on human cancer cells and antitumorigenesis of Cheonggukjang, a fermented soybean product, im DMBA-treated rats. Korean J. Nutr. 39, 347-356.
  21. Kwon, D. Y., Jang, J. S., Lee, J. E., Kim, Y. S., Shin, D. H. and Park, S. 2006. The isoflavonoid aglycone-rich fraction of chungkookjang, fermented unsalted soybeans, enhance insulin signaling and peroxisome proliferator-activated receptor-gamma activity in vitro. Biofactors 26, 245-258. https://doi.org/10.1002/biof.5520260403
  22. Lee, E. H. and Chyun, J. H. 2007. Effects of Chongkukjang intake on lipid metabolism and liver function in ethanol consumed rats. Korean J. Nutr. 40, 684-692.
  23. Leung, K. C., Howe, C., Gui, L. Y., Trout, G., Veldhuis, J. D. and Ho, K. K. 2002. Physiological and pharmacological regulation of 20-kDa growth hormone. Am. J. Physiol. Endocrinol. Metab. 283, 836-843.
  24. Li, L., He, D., Wilborn, T. W., Falany, J. L. and Falany, C. N. 2009. Increased SULT1E1 activity in HepG2 hepatocytes decreases growth hormone stimulation of STAT5b phosphorylation. Steroids 74, 20-29. https://doi.org/10.1016/j.steroids.2008.09.002
  25. Merz-Demlow, B. E., Duncan, A. M., Wangen, K. E., Xu, X., Carr, T. P., Phipps, W. R. and Kurzer, M. S. 2000. Soy isoflavones improve plasma lipids in normocholesterolmic, premenopausal women. Am. J. Clin. Nutr. 71, 1462-1469.
  26. Miquet, J. G., Muñoz, M. C., Giani, J. F., González, L., Dominici, F. P., Bartke, A., Turyn, D. and Sotelo, A. I. 2010. Ames dwarf (Prop1(df)/Prop1(df)) mice display increased sensitivity of the major GH-signaling pathways in liver and skeletal muscle. Growth Horm. IGF Res. 20, 118-126. https://doi.org/10.1016/j.ghir.2009.11.003
  27. Perez, F. R., Casabiell, X., Camina, J. P., Zugaza, J. L. and Casanueva, F. F. 1997. cis-unsaturated free fatty acids block growth hormone and prolactin secretion in thyrotropin-releasing hormone-stimulated GH3 cells by perturbing the function of plasma membrane integral proteins. Endocrinology 138, 264-272. https://doi.org/10.1210/en.138.1.264
  28. Potter, S. M., Baum, J. A., Teng, H., Stillman, R. J., Shay, N. F. and Erdman, J. W. Jr. 1998. Soy protein and isoflavones; Their effects on blood lipids and bone density n postemenopausal women. Am. J. Clin. Nutr. 68, 1375-1379.
  29. Shim, S. H., Lee, E. J., Kim, J. S., Kang, S. S., Ha, H., Lee, H. Y., Kim, C., Lee, J. H. and Son, K. H. 2008. Rat growth-hormone release stimulators from fenugreek seeds. Chem. Biodivers 5, 1753-1761. https://doi.org/10.1002/cbdv.200890164
  30. Slootweg, M. C., Swolin, D., Netelenbos, J. C., Isaksson, O. G. and Ohlsson, C. 1997. Estrogen enhances growth hormone receptor expression and growth hormone action in rat osteosarcoma cells and human osteoblast-like cells. J. Endocrinol. 155, 159-164. https://doi.org/10.1677/joe.0.1550159
  31. Yang, J. L., Lee, S. H. and Song, Y. S. 2003. Improving effect of powders of cooked soybean and Cheonggukjang on blood pressure and lipid metabolism in spontaneously hypertentive rats. J. Korean Soc. Food Sci. Nutr. 32, 899-905. https://doi.org/10.3746/jkfn.2003.32.6.899
  32. Yoshizato, H., Fujikawa, T., Shibata, M., Tanaka, M. and Nakashima, K. 1999. Stimulation of growth hormone gene expression in the pituitary and brain by Panax ginseng C. A. MEYER. Endocr. J. 46, 85-88. https://doi.org/10.1507/endocrj.46.Suppl_S85

Cited by

  1. Fermented soybean product (Cheonggukjang) improved some attributes of protein and growth hormone measurements in Sprague-Dawley rats vol.34, pp.4, 2014, https://doi.org/10.1016/j.nutres.2014.02.004