DOI QR코드

DOI QR Code

Responses of Plasma IGF-1, IGFBPs and Hepatic GH Receptor to Growth Hormone Releasing Peptides (GHRP)-2 Administration and Energy Level in Wethers

거세면양에 있어서 에너지수준에 GHRP-2의 투여가 혈장 IGF-1, IGFBPs 및 hepatic GH 수용체에 미치는 반응

  • Lee, Hong-Gu (Department of Bio-Resources and Applied Life Science, Pusan National University) ;
  • Jin, Young-Cheng (Department of Agricultural Biotechnology, Seoul National University) ;
  • Hidari, Hisashi (Obihiro University of Agriculture and Veterinary Medicine) ;
  • Choi, Yun-Jaie (Department of Agricultural Biotechnology, Seoul National University) ;
  • Kim, Seon-Ku (Department of Bio-Resources and Applied Life Science, Pusan National University) ;
  • Shin, Teak-Soon (Department of Bio-Resources and Applied Life Science, Pusan National University) ;
  • Cho, Byung-Uuk (Department of Bio-Resources and Applied Life Science, Pusan National University) ;
  • Kim, Yong-Gyun (Department of Bio-Resources and Applied Life Science, Pusan National University) ;
  • Kim, Keun-Ki (Department of Bio-Resources and Applied Life Science, Pusan National University) ;
  • Son, Hong-Joo (Department of Bio-Resources and Applied Life Science, Pusan National University) ;
  • Lee, Sang-Mong (Department of Bio-Resources and Applied Life Science, Pusan National University) ;
  • Park, Hyun-Chul (Department of Bio-Resources and Applied Life Science, Pusan National University) ;
  • Kang, Han-Seok (Department of Bio-Resources and Applied Life Science, Pusan National University)
  • 이홍구 (부산대학교 생명자원과학대학 생명자원과학부 및 응용생명과학부) ;
  • 김영성 (서울대학교 농업생명과학대학 농생명공학부) ;
  • ;
  • 최윤재 (서울대학교 농업생명과학대학 농생명공학부) ;
  • 김선구 (부산대학교 생명자원과학대학 생명자원과학부 및 응용생명과학부) ;
  • 신택순 (부산대학교 생명자원과학대학 생명자원과학부 및 응용생명과학부) ;
  • 조병욱 (부산대학교 생명자원과학대학 생명자원과학부 및 응용생명과학부) ;
  • 김용균 (부산대학교 생명자원과학대학 생명자원과학부 및 응용생명과학부) ;
  • 김근기 (부산대학교 생명자원과학대학 생명자원과학부 및 응용생명과학부) ;
  • 손홍주 (부산대학교 생명자원과학대학 생명자원과학부 및 응용생명과학부) ;
  • 이상몽 (부산대학교 생명자원과학대학 생명자원과학부 및 응용생명과학부) ;
  • 박현철 (부산대학교 생명자원과학대학 생명자원과학부 및 응용생명과학부) ;
  • 강한석 (부산대학교 생명자원과학대학 생명자원과학부 및 응용생명과학부)
  • Published : 2008.07.30

Abstract

The purpose of this study was to determine the effect of energy supplement on responses of plasma insulin-like growth factor (IGF)-1 and IGF binding proteins (IGFBPs) to growth hormone-releasing peptide-2 (GHRP-2) administration in normal protein-fed wethers, and to observe the effect of GHRP-2 treatment on hepatic growth hormone (GH) receptor in well-fed wethers. Plasma IGF-1 and 39-42 kDa IGFBP-3 during the HENP (CP, crude protein 0.34 and TDN, total digestible nutrients 1.83 kg/day DM, dry matter intake) treatment period were higher than in the LENP (CP 0.32 kg and TDN 0.87 kg/day DM intake) period (P<0.05). The response of GH was stimulated by GHRP-2 ($12.5\;{\mu}g/kg$ body weight/day) administration during both of the feed treatment periods (P<0.05). The area under curve (AUC) increment and average concentration of GH (0-180 min) with GHRP-2 administration was higher during HENP treatment than LENP treatment (P<0.01). During the HENP treatment period from day 1 to day 7 of twice daily GHRP-2 treatment, the plasma IGF-1 increment was increased on days 2, 6 and 7 of GHRP-2 administration (P<0.05). On the basis of ligand blotting, the proportions of plasma 39-43 kDa IGFBP-3 during the HENP treatment period only showed a significant difference on days 6 and 7 with GHRP-2 administration. No significant difference in the specific binding of $^{125}I-labeled$ oGH to hepatic membranes was detected between the saline and GHRP-2 treatments of the HENP-fed wethers. These results suggest that the nutritional balance between energy and protein may affect the endogenous GH / IGF-1 axis as well as plasma IGFBP-3 levels.

본연구는 정상으로 단백질을 급여한 거세면양에 있어서 에너지 첨가가 GHRP-2투여에 대한 IGF-1 및 IGFBPs에 대한 반응과, 고에너지 급여에 따른 GHRP-2투여가 hepatic GH 수용체에 미치는 영향을 검증하기 위하여 실시하였다. 시험 결과 HENP (CP 0.34 kg, TDN 1.83 kg/day DM intake)처리기간 동안 혈장 IGF-1 과 39-42kDa IGFBP-3수준은 LENP (CP 0.32 kg, TDN 0.87 kg/day DM intake)기간에 비하여 높게 나타났으나 (P<0.05), 혈장 34 kDa IGFBP-2와 24 kDa IGFBP-4는 영양처리에 의해 영향을 받지 않았다. 각 영양처리 기간동안 GHRP-2 ($12.5\;{\mu}g/kg$ body weight/day)투여는 혈장 GH 반응이 촉진되었으며(P<0.05), 혈장 GH 평균 함량과 AUC증가에 있어서는 LENP처리 기간에 비하여 HENP처리기간에서 유의적으로 높게 나타났다(P<0.01). 특히 HENP에서 7일간 GHRP-2투여에 의한 일중 혈장 IGF-1 변화양상을 조사한 결과 투여 2, 6 및 7일에서 뚜렷한 증가양상이 보였다(P<0.05). 이에 반하여 LENP에서는 오직 투여 3일째에서 Saline구에 비하여 유의적인 증가를 확인하였다(P<0.05). IGFBPs의 ligand blotting 결과 HENP구에서 혈장 39-43 kDa IGFBP-3의 수준의 증가가 투여 6일과 7일에서 관찰되었으나 혈장 IGFBP-2수준은 두 영양처리시기에서 유의적인 차이를 관찰하지 못했다. 아울러 HENP구에 있어서 간세포막에 $^{125}I-oGH$의 결합력을 측정한 결과 GHRP-2투여에 의한 영향은 관찰되지 않았다. 이와 같은 결과는 거세면양에 있어서 단백질과 에너지 사이에 영양적 균형은 내인성 GH/IGF-1 axis는 물론 혈장 IGFBP-3수준의 변화에 영향을 미치고 있음을 시사한다.

Keywords

References

  1. Bass, J. J., J. M. Oldham, S. C. Hodgkinson, P. J. Fowke, H. Sauerwein, P. Molan, B. H. Breier and P. D. Gluckman. 1991. Influence of nutrition and bovine growth hormone (GH) on hepatic GH binding, insulin-like growth factor-1 and growth of lambs. J. Endocrinol. 128, 181-186. https://doi.org/10.1677/joe.0.1280181
  2. Baxter, R. C. 1991. Insulin-like growth factor (IGF) binding proteins; the role of serum IGFBPs in regulating IGF availability. Acta Paediatr. Scand. (Supply) 372, 107-114.
  3. Bradford, M. M. 1976. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72, 248-254. https://doi.org/10.1016/0003-2697(76)90527-3
  4. Breier, B. H., P. D. Gluckman and J. J. Bass. 1988b. The somatotrophic axis in young steers: influence of nutritional status and oestradiol-17$\beta$ on hepatic high- and low-affinity somatotrophic biding sites. J. Endodrinol. 116, 169-177. https://doi.org/10.1677/joe.0.1160169
  5. Breier, B. H., P. D. Gluckman and J. J. Bass. 1988a. Influence of nutritional status and oestradiol-17$\beta$ on plasma growth hormone, insulin-like growth factors -I and -II and the response to exogenous growth hormone in young steers. J. Endocrinol. 118, 243-250. https://doi.org/10.1677/joe.0.1180243
  6. Campbell, R. G., R. J. Johnson, R. H. King, M. R. Taverner and D. J. Meisinger. 1990. Interaction of dietary protein content and exogenous porcine growth hormone administration on protein and lipid accretion rates in growing pigs. J. Anim. Sci. 68, 3217-3225. https://doi.org/10.2527/1990.68103217x
  7. Clarke, I. J., T. P. Fletcher, C. C. Pomares, J. H. G. Holmes, F. Dunshea, G. B. Thomas, A. J. Tilbrook, P. E. Walton and D. B. Galloway. 1993. Effect of high-protein feed supplements on concentrations of growth hormnone (GH), insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 in plasma and on the amounts of GH and messenger RNA for GH in the pituitary glands of adult rams. J. Endocrinol. 138, 421-427. https://doi.org/10.1677/joe.0.1380421
  8. Dardevet, D., M. Manin, M. Balage, C. Sornet and J. Grizard. 1991. Influence of low- and high-protein diets on insulin and insulin-like growth factor-1 binding to skeletal muscle and liver in the growing rat. Br. J. Nutr. 65, 47-60. https://doi.org/10.1079/BJN19910065
  9. Daughaday, W. H., I. K. Mariz and S. L. Blethen. 1980. Inhibition of assess of bound somatomedin to membrane receptor and immunobinding sites: A comparision of radioreceptor and radioimmunoassay of somatomedin in native and acid-ethanol extraction serum. J. Clin. Endocrinol. Metab. 51, 781-788. https://doi.org/10.1210/jcem-51-4-781
  10. Donovan, S. M., L. C. Atilano, R. L. Hintz, D. M. Wilson and R. G. 1991. Rosenfeld. Differential regulation of the insulin-like growth factor (IGF-I and -II) and IGF binding proteins during malnutrition in the neonatal rat. Endocrinology 129, 149-157. https://doi.org/10.1210/endo-129-1-149
  11. Elsasser, T. H., T. S. Rumsey and A. C. Hammond. 1989. Influence of diet on basal and growth hormone-stimulated plasma concentrations of IGF-1 in beef cattle. J. Anim. Sci. 67, 128-141. https://doi.org/10.2527/jas1989.671128x
  12. Gallaher, B. W., B. H. Breier, M. H. Oliver, J. E. Harding and P. D. Gluckman. 1992. Ontogenic differences in the nutritional regulation of circulating IGF binding proteins in sheep plasma. Acta Endocrinol. 126, 49-54.
  13. Gucev, Z. S., Y. Oh, K. M. Kelley, J. I. Labarta, P. Vorwerk and R. G. Rosenfeld. 1997. Evidence for insuli-like grwoth factor (IGF)-independent transcriptional regulation of IGF binding protein-3 by growth hormone in SKHEP-1 human hepatocarcinoma cells. Endocrinology 138, 1464-1470. https://doi.org/10.1210/en.138.4.1464
  14. Hart, I. C, P. M. E. Chadwick, A. Coert, S. James and A. D. Simmonds. 1985. Effect of different growth hormone- releasing factors on the concentrations of growth hormone, insulin and metabolites in the plasma of sheep maintained in positive and negative energy balance. J. Endocrinol. 105, 113-119. https://doi.org/10.1677/joe.0.1050113
  15. Hodgkinson, S. C., J. J. Bass and P. D.Gluckman. 1991. Plasma IGF-1 binding proteins in sheep: effect of recombinant growth hormone treatment and nutritional status. Domest. Anim. Endocrinol. 8, 343-351. https://doi.org/10.1016/0739-7240(91)90002-2
  16. Hossenlopp, P., D. Seurin, B. Segovia-Quinson, S. Hardouin and M. Binoux. 1986. Analysis of serum insulin- like growth factor binding proteins using western blotting: use of the method for titration of the binding proteins and competitive binding studies. Anal. Biochem. 154, 138-143. https://doi.org/10.1016/0003-2697(86)90507-5
  17. Howard, A. D., S. D. Feighner, D. F. Cully, J. P. Arena, P. A. Liberator, C. I. Rosenblum, M. Hamelin, D. L. Hreniuk, O. C. Palyha, J. Anderson, P. S. Paress, C. Diaz, M. Chou, K. K. Liu, K. K. McKee, S. S. Pong, L. Y. Chaung, A. Elbrecht, M. Dashkevicz. R. Heavens, M. Rigby, D. J. S Sirinathsinghii, D. C. Dean, D. G. Melillo, A. A. Patchett, R. Nargund, P. R. Griffin, J. A. DeMartino, S. K. Gupta, J. M. Schaeffer, R. G. Smith and L. H. T. Van der Ploeg. 1996. A receptor in pituitary and hypothalamus that functions in growth hormone release. Science (Wash DC) 273, 974-977.哖吖則⠻᎗⨀Ԁ攀?ଢ଼堙則䠻᎗⨀ 昀顜顜多則栻᎗⨀ 最崚ᯚ多則蠻᎗⨀ 栀妚ᯈ?則꠻᎗⨀ 椀ớ鬜夞則젻᎗⨀ 樀哑톓酓則᎗⨀ 欀崚鵛ᥙ則࠼᎗⨀ 氀?孝孛則⠼᎗⨀ 洀飝鬜屛則䠼᎗⨀ 渀Ὕ騝衛則格᎗⨀ 漀埘堚饛則蠼᎗⨀ 瀀屙ᶛ饛則꠼᎗⨀ 焀岛?饛則젼᎗⨀ᴀ爀慘ᩝ驛則᎗⨀ 猀嚘尙鵛則࠽᎗⨀ 琀ᦜ尙鵛則⠽᎗⨀ 甀ᷙ鬜鵛則䠽᎗⨀ 瘀陔픐졜則栽᎗⨀ 眀쩜姝?則蠽᎗⨀ 砀圚嶙寚則꠽᎗⨀ 礀婛髜堘升젽᎗⨀Ḁ稀釋ᐈ䬙升᎗⨀ᨀ笀ᷚ多升࠾᎗⨀ 簀᠈寘?升⠾᎗⨀ 紀唙ᗈ?升䠾᎗⨀ 縀᪈츔呒升栾᎗⨀ 缀雛多存升蠾᎗⨀ 耀ᱝ?屘升꠾᎗⨀ऀ脀顜?塙升젾᎗⨀ 舀齛ᣚ塙升᎗⨀ 茀怋嬘嵙升࠿᎗⨀ 萀默鯜塚升⠿᎗⨀ᬀ蔀彘定孚升䠿᎗⨀ 蘀圚嬙?升栿᎗⨀ 蜀廝堙?升蠿᎗⨀ 蠀騜ࣙ?升꠿᎗⨀  https://doi.org/10.1126/science.273.5277.974
  18. Laemmli, U. K. 1970. Cleavage of structural proteins during the assembly of the head of bacteiophage T4. Nature (London) 227, 680-685. https://doi.org/10.1038/227680a0
  19. Lee, H. G., R. A. Vega, L. T. Phung, N. Matsunaga, H. Kuwayama and H. Hidari. 2000. The effect of growth hormone releasing peptide-2 (KP102) administration on plasma insulin-like growth factor (IGF)-I and IGF-binding proteins in Holstein steers on different planes of nutrition. Dome. Anim. Endocrinol. 18, 293-308. https://doi.org/10.1016/S0739-7240(00)00051-5
  20. Lee, H. G., Y. J. Choi, S. R. Lee, H. Kuwayama, H. Hidari and S. K. You. 2005. Effects of dietary protein and growth hormone-releasing peptide (GHRP-2) on plasma IGF-1 and IGFBPs in Hostein steers. Dome. Anim. Endocrinol. 28, 134-146. https://doi.org/10.1016/j.domaniend.2004.07.001
  21. Lemozy, S., J. B. Pucilowska and L. E. Underwood. 1994. Reduction of insulin-like growth factor-I (IGF-I) in protein- restricted rats is associated with differential regulation of IGF-binding protein messenger ribonucleic acids in liver and kidney, and peptides in liver and serum. Endocrinology 135, 617-623. https://doi.org/10.1210/en.135.2.617
  22. Ellenberger, M. A., D. E. Johnson, G. E. Carstens, K. L. Hossner, M. D. Holland, T. M. Nett and C. F. Nockels. 1989. Endocrine and metabolic changes during altered growth rates in beef cattle. J. Anim. Sci. 67, 1446-1454. https://doi.org/10.2527/jas1989.6761446x
  23. Maes, M., Y. Amand, L. E. Underwood, D. Maiter and J. M. Ketelslegers. 1988. Decreased serum insulin-like growth factor I response to growth hormone in hypophysectomized rats fed a low protein diet: evidence for a postreceptor defect. Acta Endocrinol. (Copenh) 117, 320-326.
  24. McFadden, T. B., T. E. Daniel and R. M. Akers. 1990. Effects of plane of nutrition, growth hormone and unsaturated fat on growth hormone, insulin and prolactin receptors in prepubertal lambs. J. Amin. Sci. 68, 3180-3189.
  25. McGuire, M. A., J. L. Vicini, D. E. Bauman and J. J. Veenhuizen. 1992. Insulin-like growth factors and binding proteins in ruminants and their nutritional regulation. J. Anim. Sci. 70, 2901-2910. https://doi.org/10.2527/1992.7092901x
  26. Min, S. H., D. D. Mackenzie, B. H. Breier, S. N. McCutcheon and P. D. Gluckman. 1999. Ontogeny of IGF-I responsiveness to bGH in young lambs. Domest. Anim. Endocrinol. 17, 409-419. https://doi.org/10.1016/S0739-7240(99)00052-1
  27. Mohan, S., C. Libanati, C. Dony, K. Lang, N. Srinivasan and D. J. Baylink. 1995. Development, validation, and application of a radioimmunoassay for insulin-like growth factor binding protein-5 in human serum and other biological fluids. J. Clin. Endocrinol. Metab. 80, 2638-2645. https://doi.org/10.1210/jc.80.9.2638
  28. NRC. 2001. Nutrient requirements of dairy cattle 7th revised edition. National academy press, Washington, DC.
  29. Pong, S. S., L. Y. P. Chaung, D. C. Dean, R. P. Nargund, A. A. Patchett and R. G. Smith. 1996. Identification of a new G-protein-linked receptor for growth hormone secretagogues. Mol. Endocrinol. 10, 57-61. https://doi.org/10.1210/me.10.1.57
  30. Roh, S. G., N. Matsunaga, S. Hidaka and H. Hidari. 1996. Characteristics of growth hormone secretion responsiveness to growth hormone-releasing peptide-2 (GHRP-2 or KP102) in calves. Endocr. J. 43, 291-298. https://doi.org/10.1507/endocrj.43.291
  31. Sauerwein, H., B. H. Breier, J. J. Bass and P. D. Gluckman. 1991. Chronic treatment with bovine growth hormone upregulates high-affinity hepatic somatotropic receptors in sheep. Acta Endocrinol. (Copenh) 124, 307-313.
  32. Scatchard, G. 1949. The attractions of proteins for small molecules and ions. Ann. NY Acad. Sci. 51, 660-675. https://doi.org/10.1111/j.1749-6632.1949.tb27297.x
  33. Seve, B., O. Ballevre, P. Ganier, J. Noblet, J. Prugnaud and C. Obled. 1993. Recombinant porcine somatotropin and dietary protein enhance protein synthesis in growing pigs. J. Nutr. 123, 529-540. https://doi.org/10.1093/jn/123.3.529
  34. Smith, W. J., L. E. Underwood and D. R. Clemmons. 1995. Effects of caloric or protein restriction on insulin-like growth factor-1(IGF-1) and IGF-binding proteins in children and adults. J. Clin. Endocrinol. Meta. 80, 443-449. https://doi.org/10.1210/jc.80.2.443
  35. Stanko, R. L., W. S. Cohick, D. W. Shaw, R. W. Harvey, D. R. Clemmons, M. D. Whitacre and J. D. Armstrong. 1994. Effect of somatotropin and/or equine chorionic gonadotropin on serum and follicular insulin-like growth factor I and insulin-like growth factor binding proteins in cattle. Biol. Reprod. 50, 290-300.
  36. Straus, D. S. and C. D. Takemoto. 1990. Effect of dietary protein deprivation on insulin-like growth factor (IGF)-I and -II, IGF binding protein-2, and serum albumin gene expression in rat. Endocrinology 127, 1849-1860. https://doi.org/10.1210/endo-127-4-1849
  37. Thissen, J. P., L. E. Underwood, D. Maiter, M. Maes, D. R. Clemmons and J. M. Ketelslegers. 1991. Failure of insulin- like growth factor-1 (IGF-1) infusion to promote growth in protein-restricted rats despite normalization of serum IGF-1 concentrations. Endocrinology 128, 885-890. https://doi.org/10.1210/endo-128-2-885
  38. Vanderkool, W. K., M. J. Vandehaar, B. K. Sharma, M. Binelli, H. A. Tucker, R. M. Akers and W. M. Moseley. 1995. Comparison of growth hormone-releasing factor and somatotropin: the somatotropic axis in lactating primiparous cows. J. Dairy Sci. 78, 2140-2149. https://doi.org/10.3168/jds.S0022-0302(95)76841-2