Yonsei Med J.  2009 Jun;50(3):407-413. 10.3349/ymj.2009.50.3.407.

Influence of Gender on Serum Growth Hormone, Insulin-Like Growth Factor-I and Its Binding Protein-3 during Aging

• Lin CM
• Huang YL
• Lin ZY

• KMID: 1758570
• DOI: http://doi.org/10.3349/ymj.2009.50.3.407

Abstract

PURPOSE: The serum concentrations of insulin-like growth factors-I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3) and growth hormone (GH) are related to body composition, function and metabolism, and are influenced by the aging process. This study was to investigate the influence of gender on serum concentrations of IGF-I, IGFBP-3 and GH in middle and old age subjects.
MATERIALS AND METHODS
Sixty healthy volunteers (male 35, female 25, 36-70 years) were divided into < or = 50 and > 50 years groups, based on gender. Women > 50 years were post-menopause. IGF-I, IGFBP-3, and GH were determined by immunoradiometric assay.
RESULTS
IGF-I was shown to be negatively correlated with age (women r = -0.62, p < 0.001; men r = -0.38, p < 0.05), whereas there was no correlation between IGF-I and GH values. Women > 50 years showed a significant reduction in IGF-I values than women < or = 50 years (p < 0.01). Women > 50 years showed smaller IGF-I/IGFBP-3 molar ratios (0.177998 +/- 0.039404) than men of same age group (0.228326 +/- 0.050979, p < 0.01) and women < or = 50 years (0.247667 +/- 0.069411, p < 0.01). Age was shown to positively correlate with GH/IGF-I (r = 0.49, p < 0.05) and GH/IGFBP-3 ratios (r = 0.40, p < 0.05) in women.
CONCLUSIONS
The influence of aging on serum concentrations of IGF-I is more remarkable in women than in men. Menopause causes reduction of IGF-I/IGFBP-3 molar ratio. Women have the trend of progressive hypoactivity of GH to stimulate IGF-I and IGFBP-3 secretions with age.

Keyword

Growth hormone; insulin-like growth factors-I; insulin-like growth factor binding protein-3; menopause; middle age; aging

MeSH Terms

Adult
Age Factors
Aged
Aging/*physiology
Female
Gene Expression Regulation, Developmental
Human Growth Hormone/*blood
Humans
Immunoradiometric Assay
Insulin-Like Growth Factor Binding Protein 3/*blood
Insulin-Like Growth Factor I/*metabolism
Male
Middle Aged
Sex Factors

Reference

1. Zapf J, Schmid C, Froesch ER. Biological and immunological properties of insulin-like growth factors (IGF) I and II. Clin Endocrinol Metab. 1984. 13:3–30.

2. Jones JI, Clemmons DR. Insulin-like growth factors and their binding proteins: biological actions. Endocr Rev. 1995. 16:3–34.

3. Rosen CJ. Serum insulin-like growth factors and insulin-like growth factor-binding proteins: clinical implications. Clin Chem. 1999. 45:1384–1390.

4. van Dam PS, Aleman A. Insulin-like growth factor-I, cognition and brain aging. Eur J Pharmacol. 2004. 490:87–95.

5. Sonntag WE, Ramsey M, Carter CS. Growth hormone and insulin-like growth factor-1 (IGF-1) and their influence on cognitive aging. Ageing Res Rev. 2005. 4:195–212.

6. Aberg ND, Brywe KG, Isgaard J. Aspects of growth hormone and insulin-like growth factor-I related to neuroprotection, regeneration, and functional plasticity in the adult brain. ScientificWorldJournal. 2006. 6:53–80.

7. Fernandez S, Fernandez AM, Lopez-Lopez C, Torres-Aleman I. Emerging roles of insulin-like growth factor-I in the adult brain. Growth Horm IGF Res. 2007. 17:89–95.

8. Trejo JL, Piriz J, Llorens-Martin MV, Fernandez AM, Bolós M, LeRoith D, et al. Central actions of liver-derived insulin-like growth factor I underlying its pro-cognitive effects. Mol Psychiatry. 2007. 12:1118–1128.

9. Chan JM, Stampfer MJ, Giovannucci E, Gann PH, Ma J, Wilkinson P, et al. Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study. Science. 1998. 279:563–566.

10. Hankinson SE, Willett WC, Colditz GA, Hunter DJ, Michaud DS, Deroo B, et al. Circulating concentrations of insulin-like growth factor-I and risk of breast cancer. Lancet. 1998. 351:1393–1396.

11. Cohen P. Serum insulin-like growth factor-I levels and prostate cancer risk--interpreting the evidence. J Natl Cancer Inst. 1998. 90:876–879.

12. Ma J, Pollak MN, Giovannucci E, Chan JM, Tao Y, Hennekens CH, et al. Prospective study of colorectal cancer risk in men and plasma levels of insulin-like growth factor (IGF)-I and IGF-binding protein-3. J Natl Cancer Inst. 1999. 91:620–625.

13. Stuver SO, Kuper H, Tzonou A, Lagiou P, Spanos E, Hsieh CC, et al. Insulin-like growth factor 1 in hepatocellular carcinoma and metastatic liver cancer in men. Int J Cancer. 2000. 87:118–121.

14. Yu H, Rohan T. Role of the insulin-like growth factor family in cancer development and progression. J Natl Cancer Inst. 2000. 92:1472–1489.

15. Moschos SJ, Mantzoros CS. The role of the IGF system in cancer: from basic to clinical studies and clinical applications. Oncology. 2002. 63:317–332.

16. Mazziotti G, Sorvillo F, Morisco F, Carbone A, Rotondi M, Stornaiuolo G, et al. Serum insulin-like growth factor I evaluation as a useful tool for predicting the risk of developing hepatocellular carcinoma in patients with hepatitis C virus-related cirrhosis: a prospective study. Cancer. 2002. 95:2539–2545.

17. Mattera D, Capuano G, Colao A, Pivonello R, Manguso F, Puzziello A, et al. Increased IGF-I: IGFBP-3 ratio in patients with hepatocellular carcinoma. Clin Endocrinol (Oxf). 2003. 59:699–706.

18. Ibrahim YH, Yee D. Insulin-like growth factor-I and cancer risk. Growth Horm IGF Res. 2004. 14:261–269.

19. Jenkins PJ, Bustin SA. Evidence for a link between IGF-I and cancer. Eur J Endocrinol. 2004. 151:Suppl 1. S17–S22.

20. Elsammak MY, Amin GM, Khalil GM, Ragab WS, Abaza MM. Possible contribution of serum activin A and IGF-1 in the development of hepatocellular carcinoma in Egyptian patients suffering from combined hepatitis C virus infection and hepatic schistosomiasis. Clin Biochem. 2006. 39:623–629.

21. Peeters PH, Lukanova A, Allen N, Berrino F, Key T, Dossus L, et al. Serum IGF-I, its major binding protein (IGFBP-3) and epithelial ovarian cancer risk: the European Prospective Investigation into Cancer and Nutrition (EPIC). Endocr Relat Cancer. 2007. 14:81–90.

22. Baglietto L, English DR, Hopper JL, Morris HA, Tilley WD, Giles GG. Circulating insulin-like growth factor-I and binding protein-3 and the risk of breast cancer. Cancer Epidemiol Biomarkers Prev. 2007. 16:763–768.

23. Serin IS, Tanriverdi F, Yilmaz MO, Ozcelik B, Unluhizarci K. Serum insulin-like growth factor (IGF)-I, IGF binding protein (IGFBP)-3, leptin concentrations and insulin resistance in benign and malignant epithelial ovarian tumors in postmenopausal women. Gynecol Endocrinol. 2008. 24:117–121.

24. Holman SR, Baxter RC. Insulin-like growth factor binding protein-3: factors affecting binary and ternary complex formation. Growth Regul. 1996. 6:42–47.

25. Daughaday WH, Rotwein P. Insulin-like growth factors I and II. Peptide, messenger ribonucleic acid and gene structures, serum, and tissue concentrations. Endocr Rev. 1989. 10:68–91.

26. Arany E, Afford S, Strain AJ, Winwood PJ, Arthur MJ, Hill DJ. Differential cellular synthesis of insulin-like growth factor binding protein-1 (IGFBP-1) and IGFBP-3 within human liver. J Clin Endocrinol Metab. 1994. 79:1871–1876.

27. Blum WF, Albertsson-Wikland K, Rosberg S, Ranke MB. Serum levels of insulin-like growth factor I (IGF-I) and IGF binding protein 3 reflect spontaneous growth hormone secretion. J Clin Endocrinol Metab. 1993. 76:1610–1616.

28. Ghigo E, Arvat E, Gianotti L, Ramunni J, DiVito L, Maccagno B, et al. Human aging and the GH-IGF-I axis. J Pediatr Endocrinol Metab. 1996. 9:Suppl 3. 271–278.

29. Arvat E, Broglio F, Ghigo E. Insulin-Like growth factor I: implications in aging. Drugs Aging. 2000. 16:29–40.

30. Lombardi G, Di Somma C, Rota F, Colao A. Associated hormonal decline in aging: is there a role for GH therapy in aging men? J Endocrinol Invest. 2005. 28(3):Suppl. 99–108.

31. Sherlock M, Toogood AA. Aging and the growth hormone/insulin like growth factor-I axis. Pituitary. 2007. 10:189–203.

32. Lunenfeld B. Androgen therapy in the aging male. World J Urol. 2003. 21:292–305.

33. Cuzin B, Giuliano F, Jamin C, Legros JJ, Lejeune H, Rigot JM, et al. [Investigation, treatment and surveillance of late-onset hypogonadism in males: the official guidelines of the International Society for the Study of the Aging Male (ISSAM) with comments]. Prog Urol. 2004. 14:1–14.

34. Castro-Acuna V, Martínez-Martínez L, Larrea F. [Partial androgen deficiency in the aging male]. Rev Invest Clin. 2004. 56:507–512.

35. Lenk VS. [Diagnosis of the "aging male"--what is recommended?]. Urologe A. 2005. 44:1167–1172.

36. Guay AT. Testosterone and erectile physiology. Aging Male. 2006. 9:201–206.

37. Jung BH, Jeon MJ, Bai SW. Hormone-dependent aging problems in women. Yonsei Med J. 2008. 49:345–351.

38. Granada ML, Ulied A, Casanueva FF, Pico A, Lucas T, Torres E, et al. Serum IGF-I measured by four different immunoassays in patients with adult GH deficiency or acromegaly and in a control population. Clin Endocrinol (Oxf). 2008. 68:942–950.

39. Kiel DP, Puhl J, Rosen CJ, Berg K, Murphy JB, MacLean DB. Lack of an association between insulin-like growth factor-I and body composition, muscle strength, physical performance or self-reported mobility among older persons with functional limitations. J Am Geriatr Soc. 1998. 46:822–828.

40. Vahl N, Jørgensen JO, Skjaerbaek C, Veldhuis JD, Orskov H, Christiansen JS. Abdominal adiposity rather than age and sex predicts mass and regularity of GH secretion in healthy adults. Am J Physiol. 1997. 272:E1108–E1116.

41. Ghigo E, Arvat E, Gianotti L, Lanfranco F, Broglio F, Aimaretti G, et al. Hypothalamic growth hormone-insulin-like growth factor-I axis across the human life span. J Pediatr Endocrinol Metab. 2000. 13:Suppl 6. 1493–1502.

42. Leung KC, Johannsson G, Leong GM, Ho KK. Estrogen regulation of growth hormone action. Endocr Rev. 2004. 25:693–721.

43. Gleeson HK, Shalet SM. GH responsiveness varies during the menstrual cycle. Eur J Endocrinol. 2005. 153:775–779.

44. Binoux M. GH, IGFs, IGF-binding protein-3 and acid-labile subunit: what is the pecking order? Eur J Endocrinol. 1997. 137:605–609.

45. Juul A, Main K, Blum WF, Lindholm J, Ranke MB, Skakkebaek NE. The ratio between serum levels of insulin-like growth factor (IGF)-I and the IGF binding proteins (IGFBP-1, 2 and 3) decreases with age in healthy adults and is increased in acromegalic patients. Clin Endocrinol (Oxf). 1994. 41:85–93.

46. Benbassat CA, Maki KC, Unterman TG. Circulating levels of insulin-like growth factor (IGF) binding protein-1 and -3 in aging men: relationships to insulin, glucose, IGF, and dehydroepiandrosterone sulfate levels and anthropometric measures. J Clin Endocrinol Metab. 1997. 82:1484–1491.