Hostname: page-component-78c5997874-j824f Total loading time: 0 Render date: 2024-11-10T16:08:46.192Z Has data issue: false hasContentIssue false
  • English
  • Français

Energy balance and cancer: the role of insulin and insulin-like growth factor-I

Published online by Cambridge University Press:  28 February 2007

R. Kaaks  and
A. Lukanova
R. Kaaks*
Affiliation:
International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon Cedex 08, France
A. Lukanova
Affiliation:
International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon Cedex 08, France
*
*Corresponding author: Dr R. Kaaks, fax +33 4 72 73 83 61, email kaaks@iarc.fr
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Recent theories propose that a Western lifestyle may increase cancer risk through alterations in the metabolism of insulin and insulin-like growth factors (IGF; McKeown-Eyssen, 1994; Giovannucci, 1995; Kaaks, 1996; Werner & LeRoith, 1996). Insulin regulates energy metabolism, and increases the bioactivity of IGF-I, by enhancing its synthesis, and by decreasing several of its binding proteins (IGFBP; IGFBP-1 and -2). Insulin and IGF-I both stimulate anabolic processes as a function of available energy and elementary substrates (e.g. amino acids). The anabolic signals by insulin or IGF-I can promote tumour development by inhibiting apoptosis, and by stimulating cell proliferation. Furthermore, both insulin and IGF-I stimulate the synthesis of sex steroids, and inhibit the synthesis of sex hormone-binding globulin (SHBG), a binding protein that regulates the bioavailability of circulating sex steroids to tissues. The present paper reviews epidemiological findings relating the risk of cancers of the colo-rectum, pancreas, breast, endometrium and prostate to body size (obesity, height) and physical activity, and discusses the relationships between obesity and physical activity and plasma levels of insulin, IGF-I and IGFBP. Subsequent sections review epidemiological findings relating cancer risk to indices of chronic hyperinsulinaemia, and to plasma levels of IGF-I and IGFBP. Conclusions are that chronic hyperinsulinaemia may be a cause of cancers of the colon, pancreas and endometrium, and also possibly of the breast. On the other hand, elevated plasma IGF-I, as total concentrations or relative to levels of IGFBP-3, appears to be related to an increased risk of prostate cancer, breast cancer in young women, and possibly colo-rectal cancer. For cancers of the endometrium, breast and prostate, these findings are discussed in the context of relationships between insulin and IGF-I and levels of bioavailable sex steroids.

Keywords

CancerInsulinInsulin-like growth factorsEnergy balance
Type
Macronutrient Metabolism Group Symposium on ‘Energy flux and cancer’
Information
Proceedings of the Nutrition Society , Volume 60 , Issue 1 , February 2001 , pp. 91 - 106
Copyright
Copyright © The Nutrition Society 2001

References

Abate, N (1996) Insulin resistance and obesity. The role of fat distribution pattern. Diabetes Care 19, 292–294.CrossRefGoogle ScholarPubMed
Adami, HO, Dami, HO, McLaughlin, J, Ekbom, A, Berne, C, Silverman, D, Hacker, D & Persson, I (1991) Cancer risk in patients with diabetes mellitus. Cancer Causes Control 2, 307–314.CrossRefGoogle ScholarPubMed
Argente, J, Caballo, N, Barrios, V, Munoz, MT, Pozo, J, Chowen, JA, Morande, G & Hernandez, M (1997) Multiple endocrine abnormalities of the growth hormone and insulin-like growth factor axis in patients with anorexia nervosa: effect of short- and long-term weight recuperation. Journal of Clinical Endocrinology and Metabolism 82, 2084–2092.Google Scholar
Ayabe, T, Tsutsumi, O, Sakai, H, Yoshikawa, H, Yano, T, Kurimoto, F & Taketani, Y (1997) Increased circulating levels of insulin-like growth factor-I and decreased circulating levels of insulin-like growth factor binding protein-1 in postmenopausal women with endometrial cancer. Endocrine Journal 44, 419–424.CrossRefGoogle ScholarPubMed
Ballard-Barbash, R (1994) Anthropometry and breast cancer. Body size – a moving target. Cancer 74, 1090–1100.3.0.CO;2-X>CrossRefGoogle ScholarPubMed
Bang, P, Brandt, J, Degerblad, M, Enberg, G, Kaijser, L, Thoren, M & Hall, K (1990) Exercise-induced changes in insulin-like growth factors and their low molecular weight binding protein in healthy subjects and patients with growth hormone deficiency. European Journal of Clinical Investigation 20, 285–292.CrossRefGoogle ScholarPubMed
Bang, P, Brismar, K, Rosenfeld, RG & Hall, K (1994) Fasting affects serum insulin-like growth factors (IGFs) and IGF-binding proteins differently in patients with noninsulin-dependent diabetes mellitus versus healthy nonobese and obese subjects. Journal of Clinical Endocrinology and Metabolism 78, 960–967.Google ScholarPubMed
Barbieri, RL, Smith, S & Ryan, KJ (1988) The role of hyperinsulinemia in the pathogenesis of ovarian hyperandrogenism. Fertility and Sterility 50, 197–212.Google ScholarPubMed
Bates, GW & Whitworth, NS (1982) Effect of body weight reduction on plasma androgens in obese, infertile women. Fertility and Sterility 38, 406–409.CrossRefGoogle ScholarPubMed
Baumann, G & Mercado, M (1993) Growth hormone-binding proteins in plasma. Nutrition 9, 546–553.Google ScholarPubMed
Baxter, RC, Bryson, JM & Turtle, JR (1981) The effect of fasting on liver receptors for prolactin and growth hormone. Metabolism 30, 1086–1090.CrossRefGoogle ScholarPubMed
Baxter, RC & Turtle, JR (1978) Regulation of hepatic growth hormone receptors by insulin. Biochemical and Biophysical Research Communications 84, 350–357.CrossRefGoogle ScholarPubMed
Bebakar, WM, Honour, JW, Foster, D, Liu, YL & Jacobs, HS (1990) Regulation of testicular function by insulin and transforming growth factor-beta. Steroids 55, 266–270.CrossRefGoogle ScholarPubMed
Belfiore, F & Iannello, S (1998) Insulin resistance in obesity: metabolic mechanisms and measurement methods. Molecular and Genetic Metabolism 65, 121–128.CrossRefGoogle ScholarPubMed
Bereket, A, Lang, CH, Blethen, SL, Fan, J, Frost, RA & Wilson, TA (1995 a) Insulin-like growth factor binding protein-3 proteolysis in children with insulin-dependent diabetes mellitus: a possible role for insulin in the regulation of IGFBP-3 protease activity. Journal of Clinical Endocrinology and Metabolism 80, 2282–2288.Google ScholarPubMed
Bereket, A, Lang, CH, Blethen, SL, Gelato, MC, Fan, J, Frost, RA & Wilson, TA (1995 b) Effect of insulin on the insulin-like growth factor system in children with new-onset insulin-dependent diabetes mellitus. Journal of Clinical Endocrinology and Metabolism 80, 1312–1317.Google ScholarPubMed
Bereket, A, Lang, CH & Wilson, TA (1999) Alterations in the growth hormone-insulin-like growth factor axis in insulin dependent diabetes mellitus. Hormone and Metabolism Research 31, 172–181.CrossRefGoogle ScholarPubMed
Bermon, S, Ferrari, P, Bernard, P, Altare, S & Dolisi, C (1999) Responses of total and free insulin-like growth factor-I and insulin-like growth factor binding protein-3 after resistance exercise and training in elderly subjects. Acta Physiologia Scandinavica 165, 51–56.CrossRefGoogle ScholarPubMed
Bernardi, F, Petraglia, F, Seppala, M, Spinetti, A, Bertolini, S, Ferdeghini, M & Genazzani, AR (1998) Somatotropic axis and body weight in pre-menopausal and post-menopausal women: evidence for a neuroendocrine derangement, in absence of changes of insulin-like growth factor binding protein concentrations. Human Reproduction 13, 279–284.CrossRefGoogle ScholarPubMed
Bernstein, L & Ross, RK (1993) Endogenous hormones and breast cancer risk. Epidemiologic Reviews 15, 48–65.CrossRefGoogle ScholarPubMed
Bjorntorp, P (1992) Abdominal obesity and the metabolic syndrome. Annal of Medicine 24, 465–468.CrossRefGoogle ScholarPubMed
Bjorntorp, P (1994) Fatty acids, hyperinsulinemia, and insulin resistance: which comes first? Current Opinion in Lipidology 5, 166–174.CrossRefGoogle ScholarPubMed
Bohlke, K, Cramer, DW, Trichopoulos, D & Mantzoros, CS (1998) Insulin-like growth factor-I in relation to premenopausal ductal carcinoma in situ of the breast. Epidemiology 9, 570–573.CrossRefGoogle ScholarPubMed
Bol, DK, Kiguchi, K, Gimenez-Conti, I, Rupp, T & Digiovanni, J (1997) Overexpression of insulin-like growth factor-1 induces hyperplasia, dermal abnormalities, and spontaneous tumor formation in transgenic mice. Oncogene 14, 1725–1734.Google Scholar
Boni-Schnetzler, M, Schmid, C, Mary, JL, Zimmerli, B, Meier, PJ, Zapf, J, Schwander, J & Froesch, ER (1990) Insulin regulates the expression of the insulin-like growth factor binding protein 2 mRNA in rat hepatocytes. Molecular Endocrinology 4, 1320–1326.CrossRefGoogle ScholarPubMed
Bonnefoy, M, Kostka, T, Patricot, MC, Berthouze, SE, Mathian, B & Lacour, JR (1999) Influence of acute and chronic exercise on insulin-like growth factor-I in healthy active elderly men and women. Aging (Milano) 11, 373–379.Google ScholarPubMed
Bruning, PF, Bonfrer, JM, Van Noord, PA, Hart, AA, Jong-Bakker, M & Nooijen, WJ (1992) Insulin resistance and breast-cancer risk. International Journal of Cancer 52, 511–516.CrossRefGoogle ScholarPubMed
Bruning, PF, Van Doorn, J, Bonfrer, JM, Van Noord, PA, Korse, CM, Linders, TC & Hart, AA (1995) Insulin-like growth-factor-binding protein 3 is decreased in early-stage operable pre-menopausal breast cancer. International Journal of Cancer 62, 266–270.CrossRefGoogle ScholarPubMed
Calle, EE, Murphy, TK, Rodriguez, C, Thun, MJ & Heath, CW Jr (1998) Diabetes mellitus and pancreatic cancer mortality in a prospective cohort of United States adults. Cancer Causes Control 9, 403–410.CrossRefGoogle Scholar
Cappon, J, Brasel, JA, Mohan, S & Cooper, DM (1994) Effect of brief exercise on circulating insulin-like growth factor I. Journal of Applied Physiology 76, 2490–2496.CrossRefGoogle ScholarPubMed
Cara, JF (1994) Insulin-like growth factors, insulin-like growth factor binding proteins and ovarian androgen production. Hormone Research 42, 49–54.CrossRefGoogle ScholarPubMed
Casanueva, FF (1992) Physiology of growth hormone secretion and action. Endocrinology and Metabolism Clinics of North America 21, 483–517.CrossRefGoogle ScholarPubMed
Caufriez, A, Golstein, J, Lebrun, P, Herchuelz, A, Furlanetto, R & Copinschi, G (1984) Relations between immunoreactive somatomedin C, insulin and T3 patterns during fasting in obese subjects. Clinical Endocrinology 20, 65–70.CrossRefGoogle ScholarPubMed
Chadan, SG, Dill, RP, Vanderhoek, K & Parkhouse, WS (1999) Influence of physical activity on plasma insulin-like growth factor-1 and insulin-like growth factor binding proteins in healthy older women. Mechanisms of Ageing and Development 109, 21–34.CrossRefGoogle ScholarPubMed
Chan, JM, Stampfer, MJ, Giovannucci, E, Gann, PH, Ma, J, Wilkinson, P, Hennekens, CH & Pollak, M (1998) Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study. Science 279, 563–566.CrossRefGoogle ScholarPubMed
Chang, TC, Tung, CC & Hsiao, YL (1994) Hormonal changes in elderly men with non-insulin-dependent diabetes mellitus and the hormonal relationships to abdominal adiposity. Gerontology 40, 260–267.CrossRefGoogle ScholarPubMed
Chapman, IM, Hartman, ML, Pieper, KS, Skiles, EH, Pezzoli, SS, Hintz, RL & Thorner, MO (1998) Recovery of growth hormone release from suppression by exogenous insulin-like growth factor I (IGF-I): evidence for a suppressive action of free rather than bound IGF-I. Journal of Clinical Endocrinology and Metabolism 83, 2836–2842.Google ScholarPubMed
Chuzel, F, Clark, AM, Avallet, O & Saez, JM (1996) Transcriptional regulation of the lutropin/human choriogonadotropin receptor and three enzymes of steroidogenesis by growth factors in cultured pig Leydig cells. European Journal of Biochemistry 239, 8–16.CrossRefGoogle ScholarPubMed
Clemmons, DR, Klibanski, A, Underwood, LE, Mcarthur, JW, Ridgway, EC, Beitins, IZ & Van Wyk, JJ (1981) Reduction of plasma immunoreactive somatomedin C during fasting in humans. Journal of Clinical Endocrinology and Metabolism 53, 1247–1250.CrossRefGoogle ScholarPubMed
Clemmons, DR & Underwood, LE (1991) Nutritional regulation of IGF-I and IGF binding proteins. Annual Review of Nutrition 11, 393–412.CrossRefGoogle ScholarPubMed
Colditz, GA, Cannuscio, CC & Frazier, AL (1997) Physical activity and reduced risk of colon cancer: implications for prevention. Cancer Causes Control 8, 649–667.CrossRefGoogle ScholarPubMed
Conover, CA & Lee, PD (1990) Insulin regulation of insulin-like growth factor-binding protein production in cultured HepG2 cells. Journal of Clinical Endocrinology and Metabolism 70, 1062–1067.CrossRefGoogle ScholarPubMed
Copeland, KC, Colletti, RB, Devlin, JT & McAuliffe, TL (1990) The relationship between insulin-like growth factor-I, adiposity, and aging. Metabolism 39, 584–587.CrossRefGoogle ScholarPubMed
Cordido, F, Casanueva, FF, Vidal, JI & Dieguez, C (1991) Study of insulin-like growth factor I in human obesity. Hormone Research 36, 187–191.CrossRefGoogle ScholarPubMed
Coulam, CB, Annegers, JF & Kranz, JS (1983) Chronic anovulation syndrome and associated neoplasia. Obstetrics and Gynecology 61, 403–407.Google Scholar
Counts, DR, Gwirtsman, H, Carlsson, LM, Lesem, M & Cutler, GB Jr (1992) The effect of anorexia nervosa and refeeding on growth hormone-binding protein, the insulin-like growth factors (IGFs), and the IGF-binding proteins. Journal of Clinical Endocrinology and Metabolism 75, 762–767.Google ScholarPubMed
Crave, JC, Lejeune, H, Brebant, C, Baret, C & Pugeat, M (1995) Differential effects of insulin and insulin-like growth factor I on the production of plasma steroid-binding globulins by human hepatoblastoma-derived (Hep G2) cells. Journal of Clinical Endocrinology and Metabolism 80, 1283–1289.Google Scholar
Culig, Z, Hobisch, A, Cronauer, MV, Radmayr, C, Hittmair, A, Zhang, J, Thurnher, M, Bartsch, G & Klocker, H (1996) Regulation of prostatic growth and function by peptide growth factors. Prostate 28, 392–405.3.0.CO;2-C>CrossRefGoogle ScholarPubMed
Dahlgren, E, Friberg, LG, Johansson, S, Lindstrom, B, Oden, A, Samsioe, G & Janson, PO (1991) Endometrial carcinoma; ovarian dysfunction – a risk factor in young women. European Journal of Obstetrics, Gynecology and Reproductive Biology 41, 143–150.CrossRefGoogle ScholarPubMed
DeFronzo, RA (1988) Lilly lecture 1987. The triumvirate: beta-cell, muscle, liver. A collusion responsible for NIDDM. Diabetes 37, 667–687.CrossRefGoogle ScholarPubMed
Del Giudice, ME, Fantus, IG, Ezzat, S, McKeown-Eyssen, G, Page, D & Goodwin, PJ (1998) Insulin and related factors in premenopausal breast cancer risk. Breast Cancer Research and Treatment 47, 111–120.Google Scholar
De Mellow, JS, Handelsman, DJ & Baxter, RC (1987) Short-term exposure to insulin-like growth factors stimulates testosterone production by testicular interstitial cells. Acta Endocrinologica 115, 483–489.Google ScholarPubMed
DeMoura, MD, Choi, D, Adashi, EY & Payne, DW (1997) Insulin-like growth factor-I-mediated amplification of follicle-stimulating hormone-supported progesterone accumulation by cultured rat granulosa cells: enhancement of steroidogenic enzyme activity and expression. Biology of Reproduction 56, 946–953.CrossRefGoogle ScholarPubMed
Dickson, RB & Lippman, ME (1995) Growth factors in breast cancer. Endocrinology Review 16, 559–589.Google Scholar
DiGiovanni, J, Bol, DK, Wilker, E, Beltran, L, Carbajal, S, Moats, S, Ramirez, A, Jorcano, J & Kiguchi, K (2000 a) Constitutive expression of insulin-like growth factor-1 in epidermal basal cells of transgenic mice leads to spontaneous tumor promotion. Cancer Research 60, 1561–1570.Google ScholarPubMed
DiGiovanni, J, Kiguchi, K, Frijhoff, A, Wilker, E, Bol, DK, Beltran, L, Moats, S, Ramirez, A, Jorcano, J & Conti, C (2000 b) Deregulated expression of insulin-like growth factor 1 in prostate epithelium leads to neoplasia in transgenic mice. Proceedings of the National Academy of Sciences USA 97, 3455–3460.CrossRefGoogle ScholarPubMed
Di Luigi, L, Conti, FG, Casini, A, Guidetti, L, Zezze, G, Pigozzi, F, Spera, G, Fortunio, G & Romanelli, F (1997) Growth hormone and insulin-like growth factor I responses to moderate submaximal acute physical exercise in man: effects of octreotide, a somatostatin analogue, administration. International Journal of Sports Medicine 18, 257–263.Google Scholar
Dunaif, A (1999) Insulin action in the polycystic ovary syndrome. Endocrinology and Metabolism Clinics of North America 28, 341–359.CrossRefGoogle ScholarPubMed
Dunger, DB & Cheetham, TD (1996) Growth hormone insulin-like growth factor I axis in insulin-dependent diabetes mellitus. Hormone Research 46, 2–6.Google Scholar
Eaton, NE, Reeves, GK, Appleby, PN & Key, TJ (1999) Endogenous sex hormones and prostate cancer: a quantitative review of prospective studies. British Journal of Cancer 80, 930–934.Google Scholar
Ehrmann, DA (1999) Insulin-lowering therapeutic modalities for polycystic ovary syndrome. Endocrinology and Metabolism Clinics of North America 28, 423–438.Google Scholar
Eliakim, A, Brasel, JA, Mohan, S, Wong, WLT & Cooper, DM (1998) Increased physical activity and the growth hormone-IGF-I axis in adolescent males. American Journal of Physiology 275, R308–R314.Google Scholar
Elias, AN, Pandian, MR, Wang, L, Suarez, E, James, N & Wilson, AF (2000) Leptin and IGF-I levels in unconditioned male volunteers after short-term exercise. Psychoneuroendocrinology 25, 453–461.CrossRefGoogle ScholarPubMed
Erfurth, EM, Hagmar, LE, Saaf, M & Hall, K (1996) Serum levels of insulin-like growth factor I and insulin-like growth factor-binding protein 1 correlate with serum free testosterone and sex hormone binding globulin levels in healthy young and middle-aged men. Clinical Endocrinology 44, 659–664.Google Scholar
Everhart, J & Wright, D (1995) Diabetes mellitus as a risk factor for pancreatic cancer. A meta-analysis. Journal of the American Medical Association 273, 1605–1609.CrossRefGoogle ScholarPubMed
Falkner, B, Sherif, K, Sumner, A & Kushner, H (1999) Hyperinsulinism and sex hormones in young adult African Americans. Metabolism 48, 107–112.CrossRefGoogle ScholarPubMed
Ferrini, RL & Barrett-Connor, E (1998) Sex hormones and age: a cross-sectional study of testosterone and estradiol and their bioavailable fractions in community-dwelling men. American Journal of Epidemiology 147, 750–754.Google Scholar
Fishbein, L (1991) Biological Effects of Dietary Restriction, ILSI Monographs, pp. 1–354. Berlin and Heidelberg: Springer–Verlag.Google Scholar
Frame, LT, Hart, RW & Leakey, JE (1998) Caloric restriction as a mechanism mediating resistance to environmental disease. Environmental Health Perspective 106, Suppl. 1, 313–324.Google ScholarPubMed
Friedman, GD & Van Den Eeden, SK (1993) Risk factors for pancreatic cancer: an exploratory study. International Journal of Epidemiology 22, 30–37.Google Scholar
Frystyk, J, Vestbo, E, Skjaerbaek, C, Mogensen, CE & Orskov, H (1995) Free insulin-like growth factors in human obesity. Metabolism 44, 37–44.CrossRefGoogle ScholarPubMed
Gama, R, Teale, JD & Marks, V (1990) The effect of synthetic very low calorie diets on the GH-IGF-1 axis in obese subjects. Clinical Chimica Acta 188, 31–38.Google Scholar
Gammon, MD, John, EM & Britton, JA (1998) Recreational and occupational physical activities and risk of breast cancer. Journal of the National Cancer Institute 90, 100–117.Google Scholar
Gapstur, SM, Gann, PH, Lowe, W, Liu, K, Colangelo, L & Dyer, A (2000) Abnormal glucose metabolism and pancreatic cancer mortality. Journal of the American Medical Association 283, 2552–2558.Google Scholar
Giacosa, A, Franceschi, S, La Vecchia, C, Favero, A & Andreatta, R (1999) Energy intake, overweight, physical exercise and colorectal cancer risk. European Journal of Cancer Prevention 8, Suppl. 1, S53–S60.Google Scholar
Gill, ZP, Perks, CM, Newcomb, PV & Holly, JM (1997) Insulin-like growth factor-binding protein (IGFBP-3) predisposes breast cancer cells to programmed cell death in a non-IGF-dependent manner. Journal of Biological Chemistry 272, 25602–25607.CrossRefGoogle Scholar
Giovannucci, E (1995) Insulin and colon cancer. Cancer Causes Control 6, 164–179.Google Scholar
Giovannucci, E, Pollak, MN, Platz, EA, Willett, WC, Stampfer, MJ, Majeed, N, Colditz, GA, Speizer, FE & Hankinson, SE (2000) A prospective study of plasma insulin-like growth factor-1 and binding protein-3 and risk of colorectal neoplasia in women. Cancer Epidemiology Biomarkers and Prevention 9, 345–349.Google Scholar
Giovannucci, E, Rimm, EB, Stampfer, MJ, Colditz, GA & Willett, WC (1998) Diabetes mellitus and risk of prostate cancer. Cancer Causes Control 9, 3–9.CrossRefGoogle ScholarPubMed
Giustina, A & Wehrenberg, WB (1995) Influence of thyroid hormones on the regulation of growth hormone secretion. European Journal of Endocrinology 133, 646–653.CrossRefGoogle ScholarPubMed
Golden, NH, Kreitzer, P, Jacobson, MS, Chasalow, FI, Schebendach, J, Freedman, SM & Shenker, IR (1994) Disturbances in growth hormone secretion and action in adolescents with anorexia nervosa. Journal of Pediatrics 125, 655–660.Google Scholar
Goodman, MT, Hankin, JH, Wilkens, LR, Lyu, LC, McDuffie, K, Liu, LQ & Kolonel, LN (1997) Diet, body size, physical activity, and the risk of endometrial cancer. Cancer Research 57, 5077–5085.Google Scholar
Grady, D & Ernster, VL (1996) Endometrial Cancer. In Cancer Epidemiology and Prevention, pp. 1058–1089 [Schottenfeld, D and Fraumeni, FJ, editors]. Oxford: Oxford University Press.Google Scholar
Grimm, JJ (1999) Interaction of physical activity and diet: implications for insulin-glucose dynamics. Public Health Nutrition 2, 363–368.CrossRefGoogle ScholarPubMed
Grino, PB, Griffin, JE & Wilson, JD (1990) Testosterone at high concentrations interacts with the human androgen receptor similarly to dihydrotestosterone. Endocrinology 126, 1165–1172.Google Scholar
Haffner, SM, Karhapaa, P, Mykkanen, L & Laakso, M (1994) Insulin resistance, body fat distribution, and sex hormones in men. Diabetes 43, 212–219.CrossRefGoogle ScholarPubMed
Haffner, SM, Mykkanen, L, Valdez, RA & Katz, MS (1993 a) Relationship of sex hormones to lipids and lipoproteins in nondiabetic men. Journal of Clinical Endocrinology and Metabolism 77, 1610–1615.Google Scholar
Haffner, SM, Valdez, RA, Stern, MP & Katz, MS (1993 b) Obesity, body fat distribution and sex hormones in men. International Journal of Obesity Related Metabolism Disorder 17, 643–649.Google Scholar
Hankinson, SE, Willett, WC, Colditz, GA, Hunter, DJ, Michaud, DS, Deroo, B, Rosner, B, Speizer, FE & Pollak, M (1998) Circulating concentrations of insulin-like growth factor-I and risk of breast cancer. Lancet 351, 1393–1396.Google Scholar
Hill, HA & Austin, H (1996) Nutrition and endometrial cancer. Cancer Causes Control 7, 19–32.CrossRefGoogle ScholarPubMed
Ho, KK, O'Sullivan, AJ, Weissberger, AJ & Kelly, JJ (1996) Sex steroid regulation of growth hormone secretion and action. Hormone Research 45, 67–73.Google Scholar
Hochberg, Z, Hertz, P, Colin, V, Ish-Shalom, S, Yeshurun, D, Youdim, MB & Amit, T (1992) The distal axis of growth hormone (GH) in nutritional disorders: GH-binding protein, insulin-like growth factor-I (IGF-I), and IGF-I receptors in obesity and anorexia nervosa. Metabolism 41, 106–112.Google Scholar
Hopkins, NJ, Jakeman, PM, Hughes, SC & Holly, JM (1994) Changes in circulating insulin-like growth factor-binding protein-1 (IGFBP-1) during prolonged exercise: effect of carbohydrate feeding. Journal of Clinical Endocrinology and Metabolism 79, 1887–1890.Google ScholarPubMed
Hornum, M, Cooper, DM, Brasel, JA, Bueno, A & Sietsema, KE (1997) Exercise-induced changes in circulating growth factors with cyclic variation in plasma estradiol in women. Journal of Applied Psychology 82, 1946–1951.Google Scholar
Hu, FB, Manson, JE, Liu, S, Hunter, D, Colditz, GA, Michels, KB, Speizer, FE & Giovannucci, E (1999) Prospective study of adult onset diabetes mellitus (type 2) and risk of colorectal cancer in women. Journal of The National Cancer Institute 91, 542–547.Google Scholar
Hu, HY, Yamamoto, H, Sohmiya, M, Abe, T, Murakami, Y & Kato, Y (1994) Body composition assessed by bioelectrical impedance analysis (BIA) and the correlation with plasma insulin-like growth factor I (IGF-I) in normal Japanese subjects and patients with acromegaly and GH deficiency. Endocrinology Journal 41, 63–69.Google ScholarPubMed
Hunter, DJ & Willett, WC (1993) Diet, body size, and breast cancer. Epidemiologic Reviews 15, 110–132.Google Scholar
International Agency for Research on Cancer (1997) Cancer Incidence in Five Continents, vol. 8. IARC Scientific Publication i-1240. Lyon, France: IARC.Google Scholar
Jahreis, G, Kauf, E, Frohner, G & Schmidt, HE (1991) Influence of intensive exercise on insulin-like growth factor I, thyroid and steroid hormones in female gymnasts. Growth Regulation 1, 95–99.Google Scholar
Jasper, H, Pennis, P, Vitale, M, Mella, A, Ropelato, G & Chervin, A (1999) Evaluation of disease activity by IGF-I and IGF binding protein-3 (IGFBP3) in acromegaly patients distributed according to a clinical score. Journal of Endocrinological Investigation 22, 29–34.Google Scholar
Ji, BT, Hatch, MC, Chow, WH, McLaughlin, JK, Dai, Q, Howe, GR, Gao, YT & Fraumeni, JF Jr (1996) Anthropometric and reproductive factors and the risk of pancreatic cancer: a case-control study in Shanghai, China. International Journal of Cancer 66, 432–437.3.0.CO;2-X>CrossRefGoogle ScholarPubMed
Jones, JI & Clemmons, DR (1995) Insulin-like growth factors and their binding proteins: biological actions. Endocrine Reviews 16, 3–34.Google Scholar
Juul, A, Flyvbjerg, A, Frystyk, J, Muller, J & Skakkebaek, NE (1996) Serum concentrations of free and total insulin-like growth factor-I, IGF binding proteins -1 and -3 and IGFBP-3 protease activity in boys with normal or precocious puberty. Clinical Endocrinology 44, 515–523.CrossRefGoogle ScholarPubMed
Juul, A, Main, K, Blum, WF, Lindholm, J, Ranke, MB & Skakkebaek, NE (1994) 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. Clinical Endocrinology 41, 85–93.Google Scholar
Kaaks, R (1996) Nutrition, hormones, and breast cancer: is insulin the missing link? Cancer Causes Control 7, 605–625.Google Scholar
Kaaks, R, Toniolo, P, Akhmedkhanov, A, Lukanova, A, Biessy, C, Dechaud, H, Rinaldi, S, Zeleniuch-Jacquotte, A, Shore, RE & Riboli, E (2000) Serum C-peptide, insulin-like growth factor (IGF)-I, IGF-binding proteins and colorectal cancer risk in women. Journal of the National Cancer Institute 92, 1592–1600.CrossRefGoogle ScholarPubMed
Karas, M, Danilenko, M, Fishman, D, LeRoith, D, Levy, J & Sharon, Y (1997) Membrane-associated insulin-like growth factor-binding protein-3 inhibits insulin-like growth factor-I-induced insulin-like growth factor-I receptor signaling in ishikawa endometrial cancer cells. Journal of Biological Chemistry 272, 16514–16520.Google Scholar
Key, TJ, Allen, NE, Verkasalo, PK & Banks, E (2001) Energy balance and cancer: the role of sex hormones. Proceedings of the Nutrition Society 60, 81–89.Google Scholar
Key, TJ & Pike, MC (1988 a) The dose-effect relationship between 'unopposed' oestrogens and endometrial mitotic rate: its central role in explaining and predicting endometrial cancer risk. British Journal of Cancer 57, 205–212.CrossRefGoogle ScholarPubMed
Key, TJ & Pike, MC (1988 b) The role of oestrogens and progestagens in the epidemiology and prevention of breast cancer. European Journal of Cancer and Clinical Oncology 24, 29–43.Google Scholar
Kiddy, DS, Hamilton-Fairley, D, Seppälä, M, Koistinen, R, James, VH, Reed, MJ & Franks, S (1989) Diet-induced changes in sex hormone binding globulin and free testosterone in women with normal or polycystic ovaries: correlation with serum insulin and insulin-like growth factor-I. Clinical Endocrinology 31, 757–763.Google Scholar
Koistinen, H, Koistinen, R, Selenius, L, Ylikorkala, Q & Seppälä, M (1996) Effect of marathon run on serum IGF-I and IGF-binding protein 1 and 3 levels. Journal of Applied Psychology 80, 760–764.Google Scholar
Koivisto, VA, Yki-Jarvinen, H & DeFronzo, RA (1986) Physical training and insulin sensitivity. Diabetes and Metabolism Reviews 1, 445–481.CrossRefGoogle ScholarPubMed
Kolonel, LN (1996) Nutrition and prostate cancer. Cancer Causes Control 7, 83–44.Google Scholar
Kopelman, PG, White, N, Pilkington, TR & Jeffcoates, SL (1981) The effect of weight loss on sex steroid secretion and binding in massively obese women. Clinical Endocrinology 15, 113–116.Google Scholar
Koziris, LP, Hickson, RC, Chatterton, RT Jr, Groseth, RT, Christie, JM, Goldflies, DG & Unterman, TG (1999) Serum levels of total and free IGF-I and IGFBP-3 are increased and maintained in long-term training. Journal of Applied Psychology 86, 1436–1442.Google ScholarPubMed
Kraemer, WJ, Auiler, BA, Terada, M, Newton, RU, Lynch, JM, Rosendaal, G, McBride, JM, Gordon, SE & Hakkinen, K (1995) Responses of IGF-I to endogenous increases in growth hormone after heavy-resistance exercise. Journal of Applied Psychology 79, 1310–1315.Google ScholarPubMed
Kristiansen, SB, Endoh, A, Casson, PR, Buster, JE & Hornsby, PJ (1997) Induction of steroidogenic enzyme genes by insulin and IGF-I in cultured adult human adrenocortical cells. Steroids 62, 258–265.Google Scholar
Kritchevsky, D (1999) Caloric restriction and experimental carcinogenesis. Toxicological Sciences 52, 13–16.CrossRefGoogle ScholarPubMed
La Vecchia, C, Negri, E, Decarli, A & Franceschi, S (1997) Diabetes mellitus and colorectal cancer risk. Cancer Epidemiology Biomarkers and Prevention 6, 1007–1010.Google Scholar
La Vecchia, C, Negri, E, Franceschi, S, D'Avanzo, B & Boyle, P (1994) A case-control study of diabetes mellitus and cancer risk. British Journal of Cancer 70, 950–953.Google Scholar
Lee, AV, Hilsenbeck, SG & Yee, D (1998) IGF system components as prognostic markers in breast cancer. Breast Cancer Research and Treatment 47, 295–302.Google Scholar
Lee, PD, Giudice, LC, Conover, CA & Powell, DR (1997) Insulin-like growth factor binding protein-1: recent findings and new directions. Proceedings of the Society for Experimental Biology and Medicine 216, 319–357.Google Scholar
Le Marchand, L, Wilkens, LR, Kolonel, LN, Hankin, JH & Lyu, LC (1997) Associations of sedentary lifestyle, obesity, smoking, alcohol use, and diabetes with the risk of colorectal cancer. Cancer Research 57, 4787–4794.Google Scholar
Lin, T, Haskell, J, Vinson, N & Terraccio, L (1986) Direct stimulatory effects of insulin-like growth factor-I on Leydig cell steroidogenesis in primary culture. Biochemical and Biophysical Research Communications 137, 950–956.Google Scholar
Lonning, PE, Johannessen, DC, Lien, EA, Ekse, D, Fotsis, T & Adlercreutz, H (1995) Influence of tamoxifen on sex hormones, gonadotrophins and sex hormone binding globulin in postmenopausal breast cancer patients. Journal of Steroid Biochemistry and Molecular Biology 52, 491–496.CrossRefGoogle ScholarPubMed
McKeown-Eyssen, G (1994) Epidemiology of colorectal cancer revisited: are serum triglycerides and/or plasma glucose associated with risk? Cancer Epidemiology Biomarkers and Prevention 3, 687–695.Google Scholar
McTiernan, A, Ulrich, C, Slates, S & Potter, J (1998) Physical activity and cancer etiology: associations and mechanisms. Cancer Causes Control 9, 487–509.Google Scholar
Ma, J, Pollak, MN, Giovannucci, E, Chan, JM, Tao, Y, Hennekens, CH & Stampfer, MJ (1999) Prospective study of colorectal cancer risk in men and plasma levels of insulin-like growth factor (IGF)-I and IGF-binding protein-3. Journal of the National Cancer Institute 91, 620–625.Google Scholar
Maes, M, Ketelslegers, JM & Underwood, LE (1983) Low plasma somatomedin-C in streptozotocin-induced diabetes mellitus. Correlation with changes in somatogenic and lactogenic liver binding sites. Diabetes 32, 1060–1069.Google Scholar
Magoffin, DA, Kurtz, KM & Erickson, GF (1990) Insulin-like growth factor-I selectively stimulates cholesterol side-chain cleavage expression in ovarian theca-interstitial cells. Molecular Endocrinology 4, 489–496.Google Scholar
Magoffin, DA & Weitsman, SR (1993 a) Differentiation of ovarian theca-interstitial cells in vitro: regulation of 17 alpha-hydroxylase messenger ribonucleic acid expression by luteinizing hormone and insulin-like growth factor-I. Endocrinology 132, 1945–1951.Google Scholar
Magoffin, DA & Weitsman, SR (1993 b) Insulin-like growth factor-I stimulates the expression of 3 beta-hydroxysteroid dehydrogenase messenger ribonucleic acid in ovarian theca-interstitial cells. Biology of Reproduction 48, 1166–1173.Google Scholar
Manousos, O, Souglakos, J, Bosetti, C, Tzonou, A, Chatzidakis, V, Trichopoulos, D, Adami, HO & Mantzoros, C (1999) IGF-I and IGF-II in relation to colorectal cancer. International Journal of Cancer 83, 15–17.Google Scholar
Mantzoros, CS, Tzonou, A, Signorello, LB, Stampfer, M, Trichopoulos, D & Adami, HO (1997) Insulin-like growth factor 1 in relation to prostate cancer and benign prostatic hyperplasia. British Journal of Cancer 76, 1115–1118.Google Scholar
Marin, P, Kvist, H, Lindstedt, G, Sjoström, L & Björntorp, P (1993) Low concentrations of insulin-like growth factor-I in abdominal obesity. International Journal of Obesity Related Metabolism Disorder 17, 83–89.Google Scholar
Mercado, M & Baumann, G (1995) Characteristics of the somatotropic axis in insulin dependent diabetes mellitus. Archives of Medical Research 26, 101–109.Google ScholarPubMed
Merimee, TJ, Zapf, J & Froesch, ER (1982) Insulin-like growth factors in the fed and fasted states. Journal of Clinical Endocrinology and Metabolism 55, 999–1002.Google Scholar
Mesiano, S, Katz, SL, Lee, JY & Jaffe, RB (1997) Insulin-like growth factors augment steroid production and expression of steroidogenic enzymes in human fetal adrenal cortical cells: implications for adrenal androgen regulation. Journal of Clinical Endocrinology and Metabolism 82, 1390–1396.Google Scholar
Møller, H, Mellemgaard, A, Lindvig, K & Olsen, JH (1994) Obesity and cancer risk: a Danish record-linkage study. European Journal of Cancer 30A, 344–350.Google Scholar
Moore, MA, Park, CB & Tsuda, H (1998) Physical exercise: a pillar for cancer prevention? European Journal of Cancer Prevention 7, 177–193.CrossRefGoogle ScholarPubMed
Morales, AJ, Laughlin, GA, Butzow, T, Maheshwari, H, Baumann, G & Yen, SS (1996) Insulin, somatotropic, and luteinizing hormone axes in lean and obese women with polycystic ovary syndrome: common and distinct features. Journal of Clinical Endocrinology and Metabolism 81, 2854–2864.Google Scholar
Moseson, M, Koenig, KL, Shore, RE & Pasternack, BS (1993) The influence of medical conditions associated with hormones on the risk of breast cancer. International Journal of Epidemiology 22, 1000–1009.Google Scholar
Nam, SY, Lee, EJ, Kim, KR, Cha, BS, Song, YD, Lim, SK, Lee, HC & Huh, KB (1997) Effect of obesity on total and free insulin-like growth factor (IGF)-1, and their relationship to IGF-binding protein (BP)-1, IGFBP-2, IGFBP-3, insulin, and growth hormone. International Journal of Obesity Related Metabolism Disorder 21, 355–359.Google Scholar
Nguyen, UN, Mougin, F, Simon-Rigaud, ML, Rouillon, JD, Marguet, P & Regnard, J (1998) Influence of exercise duration on serum insulin-like growth factor and its binding proteins in athletes. European Journal of Applied Psychology 78, 533–537.Google Scholar
Nicklas, BJ, Ryan, AJ, Treuth, MM, Harman, SM, Blackman, MR, Hurley, BF & Rogers, MA (1995) Testosterone, growth hormone and IGF-I responses to acute and chronic resistive exercise in men aged 55–70 years. International Journal of Sports and Medicine 16, 445–450.Google Scholar
Niwa, K, Imai, A, Hashimoto, M, Yokoyama, Y, Mori, H, Matsuda, Y & Tamaya, T (2000) A case-control study of uterine endometrial cancer of pre- and post-menopausal women. Oncology Reports 7, 89–93.Google Scholar
Nyomba, BL, Berard, L & Murphy, LJ (1997) Free insulin-like growth factor I (IGF-I) in healthy subjects: relationship with IGF-binding proteins and insulin sensitivity. Journal of Clinical Endocrinology and Metabolism 82, 2177–2181.CrossRefGoogle ScholarPubMed
O'Mara, BA, Byers, T & Schoenfeld, E (1985) Diabetes mellitus and cancer risk: a multisite case-control study. Journal of Chronic Disease 38, 435–441.Google Scholar
Parazzini, F, LaVecchia, C, Negri, E, Riboldi, GL, Surace, M, Benzi, G, Main, A & Chiaffarino, F (1999) Diabetes and endometrial cancer: an Italian case-control study. International Journal of Cancer 81, 539–542.Google Scholar
Pasquali, R, Casimirri, F, Cantobelli, S, Melchionda, N, Morselli Labate, AM, Fabbri, R, Capelli, M & Bortoluzzi, L (1991) Effect of obesity and body fat distribution on sex hormones and insulin in men. Metabolism 40, 101–104.CrossRefGoogle ScholarPubMed
Pasquali, R, Casimirri, F & Vicennati, V (1997) Weight control and its beneficial effect on fertility in women with obesity and polycystic ovary syndrome. Human Reproduction 12, Suppl. 1, 82–87.Google Scholar
Penhoat, A, Ouali, R, Viard, I, Langlois, D & Saez, JM (1996) Regulation of primary response and specific genes in adrenal cells by peptide hormones and growth factors. Steroids 61, 176–183.Google Scholar
Petridou, E, Papadiamantis, Y, Markopoulos, C, Spanos, E, Dessypris, N & Trichopoulos, D (2000) Leptin and insulin growth factor I in relation to breast cancer (Greece). Cancer Causes Control 11, 383–388.Google Scholar
Peyrat, JP, Bonneterre, J, Hecquet, B, Vennin, P, Louchez, MM, Fournier, C, Lefebvre, J & Demaille, A (1993) Plasma insulin-like growth factor-1 (IGF-1) concentrations in human breast cancer. European Journal of Cancer 29A, 492–497.Google Scholar
Pfeilschifter, J, Scheidt-Nave, C, Leidig-Bruckner, G, Woitge, HW, Blum, WF, Wuster, C, Haack, D & Ziegler, R (1996) Relationship between circulating insulin-like growth factor components and sex hormones in a population-based sample of 50- to 80-year-old men and women. Journal of Clinical Endocrinology and Metabolism 81, 2534–2540.Google Scholar
Plymate, SR, Jones, RE, Matej, LA & Friedl, KE (1988) Regulation of sex hormone binding globulin (SHBG) production in Hep G2 cells by insulin. Steroids 52, 339–340.Google Scholar
Poretsky, L, Cataldo, NA, Rosenwaks, Z & Giudice, LC (1999) The insulin-related ovarian regulatory system in health and disease. Endocrine Reviews 20, 535–582.Google Scholar
Postel-Vinay, MC, Cohen-Tanugi, E & Charrier, J (1982) Growth hormone receptors in rat liver membranes: effects of fasting and refeeding, and correlation with plasma somatomedin activity. Molecular and Cellular Endocrinology 28, 657–669.Google Scholar
Prager, D, Li, HL, Asa, S & Melmed, S (1994) Dominant negative inhibition of tumorigenesis in vivo by human insulin-like growth factor I receptor mutant. Proceedings of the National Academy of Sciences USA 91, 2181–2185.Google Scholar
Prelevic, GM, Wurzburger, MI, Balint-Peric, L & Ginsburg, J (1992) Twenty-four-hour serum growth hormone, insulin, C-peptide and blood glucose profiles and serum insulin-like growth factor-I concentrations in women with polycystic ovaries. Hormone Research 37, 125–131.Google Scholar
Pugeat, M, Crave, JC, Elmidani, M, Nicolas, MH, Garoscio-Cholet, M, Lejeune, H, Dechaud, H & Tourniaire, J (1991) Pathophysiology of sex hormone binding globulin (SHBG): relation to insulin. Journal of Steroid Biochemistry and Molecular Biology 40, 841–849.Google Scholar
Pugeat, M & Ducluzeau, PH (1999) Insulin resistance, polycystic ovary syndrome and metformin. Drugs 58, Suppl. 1, 41–46.Google Scholar
Ragozzino, M, Melton, LJ III, Chu, CP & Palumbo, PJ (1982) Subsequent cancer risk in the incidence cohort of Rochester, Minnesota, residents with diabetes mellitus. Journal of Chronic Disease 35, 13–19.Google Scholar
Rajah, R, Valentinis, B & Cohen, P (1997) Insulin-like growth factor (IGF)-binding protein-3 induces apoptosis and mediates the effects of transforming growth factor-beta 1 on programmed cell death through a p53- and IGF-independent mechanism. Journal of Biological Chemistry 272, 12181–12188.Google Scholar
Randle, PJ (1998) Regulatory interactions between lipids and carbohydrates: the glucose fatty acid cycle after 35 years. Diabetes and Metabolism Reviews 14, 263–283.Google Scholar
Rasmussen, MH, Frystyk, J, Andersen, T, Breum, L, Christiansen, JS & Hilsted, J (1994) The impact of obesity, fat distribution, and energy restriction on insulin-like growth factor-1 (IGF-1), IGF-binding protein-3, insulin, and growth hormone. Metabolism 43, 315–319.Google Scholar
Rasmussen, MH, Hvidberg, A, Juul, A, Main, KM, Gotfredsen, A, Skakkebaek, NE, Hilsted, J & Skakkebaek, NE (1995 a) Massive weight loss restores 24-hour growth hormone release profiles and serum insulin-like growth factor-I levels in obese subjects. Journal of Clinical Endocrinology and Metabolism 80, 1407–1415.Google Scholar
Rasmussen, MH, Juul, A, Kjems, LL, Skakkebaek, NE & Hilsted, J (1995 b) Lack of stimulation of 24-hour growth hormone release by hypocaloric diet in obesity. Journal of Clinical Endocrinology and Metabolism 80, 796–801.Google Scholar
Rechler, MM (1997) Growth inhibition by insulin-like growth factor (IGF) binding protein-3 – what's IGF got to do with it? Endocrinology 138, 2645–2647.Google Scholar
Roelen, CA, DeVries, WR, Koppeschaar, HP, Vervoorn, C, Thijssen, JH & Blankenstein, MA (1997) Plasma insulin-like growth factor-I and high affinity growth hormone-binding protein levels increase after two weeks of strenuous physical training. International Journal of Sports and Medicine 18, 238–241.Google Scholar
Ross, RK, Paganini-Hill, A, Wan, PC & Pike, MC (2000) Effect of hormone replacement therapy on breast cancer risk: estrogen versus estrogen plus progestin. Journal of the National Cancer Institute 92, 328–332.Google Scholar
Rutanen, EM (1998) Insulin-like growth factors in endometrial function. Gynecological Endocrinology 12, 399–406.Google Scholar
Rutanen, EM, Nyman, T, Lehtovirta, P, Ammala, M & Pekonen, F (1994) Suppressed expression of insulin-like growth factor binding protein-1 mRNA in the endometrium: a molecular mechanism associating endometrial cancer with its risk factors. International Journal of Cancer 59, 307–312.Google Scholar
Schairer, C, Lubin, J, Troisi, R, Sturgeon, S, Brinton, L & Hoover, R (2000) Menopausal estrogen and estrogen-progestin replacement therapy and breast cancer risk. Journal of the American Medical Association 283, 485–491.Google Scholar
Scheett, TP, Mills, PJ, Ziegler, MG, Stoppani, J & Cooper, DM (1999) Effect of exercise on cytokines and growth mediators in prepubertal children. Pediatric Research 46, 429–434.Google Scholar
Schmidt, W, Dore, S, Hilgendorf, A, Strauch, S, Gareau, R & Brisson, GR (1995) Effects of exercise during normoxia and hypoxia on the growth hormone-insulin-like growth factor I axis. European Journal of Applied Psychology 71, 424–430.Google Scholar
Schoen, RE, Tangen, CM, Kuller, LH, Burke, GL, Cushman, M, Tracy, RP, Dobs, A & Savage, PJ (1999) Increased blood glucose and insulin, body size, and incident colorectal cancer. Journal of the National Cancer Institute 91, 1147–1154.Google Scholar
Schwarz, AJ, Brasel, JA, Hintz, RL, Mohan, S & Cooper, DM (1996) Acute effect of brief low- and high-intensity exercise on circulating insulin-like growth factor (IGF) I, II, and IGF-binding protein-3 and its proteolysis in young healthy men. Journal of Clinical Endocrinology and Metabolism 81, 3492–3497.Google Scholar
Seidell, JC, Björntorp, P, Sjoström, L, Kvist, H & Sannerstedt, R (1990) Visceral fat accumulation in men is positively associated with insulin, glucose, and C-peptide levels, but negatively with testosterone levels. Metabolism 39, 897–901.Google Scholar
Sellers, TA, Anderson, KE, Olson, JE & Folsom, AR (1998) Family histories of diabetes mellitus and breast cancer and incidence of postmenopausal breast cancer. Epidemiology 9, 102–105.Google Scholar
Shoff, SM & Newcomb, PA (1998) Diabetes, body size, and risk of endometrial cancer. American Journal of Epidemiology 148, 234–240.Google Scholar
Shu, XO, Brinton, LA, Zheng, W, Gao, YT, Fan, J & Fraumeni, JF Jr (1991) A population-based case-control study of endometrial cancer in Shanghai, China. International Journal of Cancer 49, 38–43.Google Scholar
Silverman, DT, Schiffman, M, Everhart, J, Goldstein, A, Lillemoe, KD, Swanson, GM, Schwartz, AG, Brown, LM, Greenberg, RS, Schoenberg, JB, Pottern, LM, Hoover, RN & Fraumeni, JF (1999) Diabetes mellitus, other medical conditions and familial history of cancer as risk factors for pancreatic cancer. British Journal of Cancer 80, 1830–1837.Google Scholar
Silverman, DT, Swanson, CA, Gridley, G, Wacholder, S, Greenberg, RS, Brown, LM, Hayes, RB, Swanson, GM, Schoenberg, JB, Pottern, LM, Schwartz, AG, Fraumeni, JF Jr & Hoover, RN (1998) Dietary and nutritional factors and pancreatic cancer: a case-control study based on direct interviews. Journal of the National Cancer Institute 90, 1710–1719.CrossRefGoogle ScholarPubMed
Singh, A, Hamilton-Fairley, D, Koistnen, R, Seppälä, M, James, VH, Franks, S & Reed, MJ (1990) Effect of insulin-like growth factor-type I (IGF-I) and insulin on the secretion of sex hormone binding globulin and IGF-I binding protein (IBP-I) by human hepatoma cells. Journal of Endocrinology 124, R1–R3.Google Scholar
Singh, P & Rubin, N (1993) Insulinlike growth factors and binding proteins in colon cancer. Gastroenterology 105, 1218–1237.Google Scholar
Smith, GD, Egger, M, Shipley, MJ & Marmot, MG (1992) Post-challenge glucose concentration, impaired glucose tolerance, diabetes, and cancer mortality in men. American Journal of Epidemiology 136, 1110–1114.Google Scholar
Stattin, P, Bylund, A, Rinaldi, S, Biessy, C, Dechaud, H, Stenman, U-H, Egevad, L, Riboli, E, Hallmans, G & Kaaks, R (2000) Plasma insulin-like growth factor-I, insulin-like growth factor-binding proteins, and prostate cancer risk: a prospective study. Journal of the National Cancer Institute 92 (In the Press).Google Scholar
Steenland, K, Nowlin, S & Palu, S (1995) Cancer incidence in the National Health and Nutrition Survey I. Follow-up data: diabetes, cholesterol, pulse and physical activity. Cancer Epidemiology Biomarkers and Prevention 4, 807–811.Google Scholar
Stein, P, Bussmann, LE & Tesone, M (1995) In vivo regulation of the steroidogenic activity of rat luteal cells by insulin. Journal of Steroid Biochemistry and Molecular Biology 52, 329–335.Google Scholar
Stewart, CE & Rotwein, P (1996) Growth, differentiation, and survival: multiple physiological functions for insulin-like growth factors. Physiological Reviews 76, 1005–1026.Google Scholar
Straus, DS (1994) Nutritional regulation of hormones and growth factors that control mammalian growth. FASEB Journal 8, 6–12.Google Scholar
Straus, DS & Takemoto, CD (1990) Effect of fasting on insulin-like growth factor-I (IGF-I) and growth hormone receptor mRNA levels and IGF-I gene transcription in rat liver. Molecular Endocrinology 4, 91–100.Google Scholar
Suikkari, AM, Koivisto, VA, Rutanen, EM, Yki-Jarvinen, H, Karonen, SI & Seppälä, M (1988) Insulin regulates the serum levels of low molecular weight insulin-like growth factor-binding protein. Journal of Clinical Endocrinology and Metabolism 66, 266–272.Google Scholar
Suwanichkul, A, Allander, SV, Morris, SL & Powell, DR (1994) Glucocorticoids and insulin regulate expression of the human gene for insulin-like growth factor-binding protein-1 through proximal promoter elements. Journal of Biological Chemistry 269, 30835–30841.Google Scholar
Tanaka, T, Maesaka, H & Suwa, S (1985) Changes in somatomedin activity in anorexia nervosa. Endocrinologica Japonica 32, 891–897.Google Scholar
Tannenbaum, GS, Guyda, HJ & Posner, BI (1983) Insulin-like growth factors: a role in growth hormone negative feedback and body weight regulation via brain. Science 220, 77–79.Google Scholar
Thissen, JP, Ketelslegers, JM & Underwood, IE (1994) Nutritional regulation of the insulin-like growth factors. Endocrine Reviews 15, 80–101.Google Scholar
Thomas, HV, Reeves, GK & Key, TJ (1997) Endogenous estrogen and postmenopausal breast cancer: a quantitative review. Cancer Causes Control 8, 922–928.Google Scholar
Tibblin, G, Adlerberth, A, Lindstedt, G & Bjorntorp, P (1996) The pituitary-gonadal axis and health in elderly men: a study of men born in 1913. Diabetes 45, 1605–1609.Google Scholar
Tollet, P, Enberg, B & Mode, A (1990) Growth hormone (GH) regulation of cytochrome P-450IIC12, insulin-like growth factor-I (IGF-I), and GH receptor messenger RNA expression in primary rat hepatocytes: a hormonal interplay with insulin, IGF-I, and thyroid hormone. Molecular Endocrinology 4, 1934–1942.Google Scholar
Toniolo, P, Bruning, PF, Akhmedkhanov, A, Bonfrer, JMG, Koenig, KL, Lukanova, A, Shore, RE & Jacquotte, AZ (2000) Serum insulin-like growth factor-I and breast cancer. International Journal of Cancer (In the Press).Google Scholar
Troisi, R, Potischman, N, Hoover, RN, Siiteri, P & Brinton, LA (1997) Insulin and endometrial cancer. American Journal of Epidemiology 146, 476–482.Google Scholar
Twigg, SM & Baxter, RC (1998) Insulin-like growth factor (IGF)-binding protein 5 forms an alternative ternary complex with IGFs and the acid-labile subunit. Journal of Biological Chemistry 273, 6074–6079.Google Scholar
Unterman, TG (1993) Insulin-like growth factor binding protein-1: identification, purification, and regulation in fetal and adult life. Advances in Experimental Medicine and Biology 343, 215–226.Google Scholar
Urban, RJ, Garmey, JC, Shupnik, MA & Veldhuis, JD (1990) Insulin-like growth factor type I increases concentrations of messenger ribonucleic acid encoding cytochrome P450 cholesterol side-chain cleavage enzyme in primary cultures of porcine granulosa cells. Endocrinology 127, 2481–2488.Google Scholar
Ursin, G, Longnecker, MP, Haile, RW & Greenland, S (1995) A meta-analysis of body mass index and risk of premenopausal breast cancer. Epidemiology 6, 137–141.Google Scholar
Vance, ML, Hartman, ML & Thorner, MO (1992) Growth hormone and nutrition. Hormone Research 38, Suppl. 1, 85–88.Google Scholar
Veldhuis, JD, Liem, AY, South, S, Weltman, A, Weltman, J, Clemmons, DA, Abbott, R, Mulligan, T, Johnson, ML & Pincus, S (1995) Differential impact of age, sex steroid hormones, and obesity on basal versus pulsatile growth hormone secretion in men as assessed in an ultrasensitive chemiluminescence assay. Journal of Clinical Endocrinology and Metabolism 80, 3209–3222.Google Scholar
Vermeulen, A (1996) Decreased androgen levels and obesity in men. Annals of Medicine 28, 13–15.Google Scholar
Vermeulen, A, Goemaere, S & Kaufman, JM (1999) Testosterone, body composition and aging. Journal of Endocrinological Investigation 22, 110–116.Google Scholar
Vermeulen, A, Kaufman, JM & Giagulli, VA (1996) Influence of some biological indexes on sex hormone-binding globulin and androgen levels in aging or obese males. Journal of Clinical Endocrinology and Metabolism 81, 1821–1826.Google Scholar
Vitiello, MV, Wilkinson, CW, Merriam, GR, Moe, KE, Prinz, PN, Ralph, DD, Colasurdo, EA & Schwartz, RS (1997) Successful 6-month endurance training does not alter insulin-like growth factor-I in healthy older men and women. Journal of Gerontology 52, M149–M154.Google Scholar
Wabitsch, M, Blum, WF, Muche, R, Heinze, E, Haug, C, Mayer, H & Teller, W (1996) Insulin-like growth factors and their binding proteins before and after weight loss and their associations with hormonal and metabolic parameters in obese adolescent girls. International Journal of Obesity Related Metabolism and Disorders 20, 1073–1080.Google Scholar
Wallace, JD, Cuneo, RC, Baxter, R, Orskov, H, Keay, N, Pentecost, C, Dall, R, Rosen, T, Jorgensen, JO, Cittadini, A, Longobardi, S, Sacca, L, Christiansen, JS, Bengtsson, BA, & Sonksen, PH (1999) Responses of the growth hormone (GH) and insulin-like growth factor axis to exercise, GH administration, and GH withdrawal in trained adult makes: a potential test for GH abuse in sport. Journal of Clinical Endocrinology and Metabolism 84, 3591–3601.Google Scholar
Wehrenberg, WB & Giustina, A (1992) Basic counterpoint: mechanisms and pathways of gonadal steroid modulation of growth hormone secretion. Endocrine Reviews 13, 299–308.Google Scholar
Weiderpass, E, Gridley, G, Persson, I, Nyren, O, Ekbom, A & Adam, HO (1997) Risk of endometrial and breast cancer in patients with diabetes mellitus. International Journal of Cancer 71, 360–363.Google Scholar
Weiderpass, E, Partanen, T, Kaaks, R, Vainio, H, Porta, M, Kauppinen, T, Ojajarvi, A, Boffetta, P & Malats, N (1998) Occurrence, trends and environment etiology of pancreatic cancer. Scandinavian Journal of Work and Environmental Health 24, 165–174.Google Scholar
Weiderpass, E, Persson, I, Adami, HO, Magnusson, C, Lindgren, A & Baron, JA (2000) Body size in different periods of life, diabetes mellitus, hypertension, and risk of postmenopausal endometrial cancer. Cancer Causes Control 11, 185–192.Google Scholar
Weindruch, R (1992) Effect of caloric restriction on age-associated cancers. Experimental Gerontology 27, 575–581.Google Scholar
Weiss, HA, Brinton, LA, Potischman, NA, Brogan, D, Coates, RJ, Gammon, MD, Malone, KE & Schoenberg, JB (1999) Breast cancer risk in young women and history of selected medical conditions. International Journal of Epidemiology 28, 816–823.Google Scholar
Werner, H & LeRoith, D (1996) The role of the insulin-like growth factor system in human cancer. Advances in Cancer Research 68, 183–223.Google Scholar
Wideman, L, Weltman, JY, Shah, N, Story, S, Veldhuis, JD & Weltman, A (1999) Effects of gender on exercise-induced growth hormone release. Journal of Applied Psychology 87, 1154–1162.Google Scholar
Wideroff, L, Gridley, G, Mellemkjaer, L, Chow, WH, Linet, M, Keehn, S, Borch-Johnsen, K & Olsen, JH (1997) Cancer incidence in a population-based cohort of patients hospitalized with diabetes mellitus in Denmark. Journal of the National Cancer Institute 89, 1360–1365.Google Scholar
Wilker, E, Bol, D, Kiguchi, K, Rupp, T, Beltran, L & DiGiovanni, J (1999) Enhancement of susceptibility to diverse skin tumor promoters by activation of the insulin-like growth factor-1 receptor in the epidermis of transgenic mice. Molecular Carcinogenesis 25, 122–131.Google Scholar
Will, JC, Galuska, DA, Vinicor, F & Calle, EE (1998) Colorectal cancer: another complication of diabetes mellitus? American Journal of Epidemiology 147, 816–825.Google Scholar
Will, JC, Vinicor, F & Calle, EE (1999) Is diabetes mellitus associated with prostate cancer incidence and survival? Epidemiology 10, 313–318.Google Scholar
Wilson, DM (1992) Clinical actions of growth hormone. Endocrinology and Metabolism Clinics of North America 21, 519–537.Google Scholar
Wilson, JD (1996) Role of dihydrotestosterone in androgen action. Prostate 6, Suppl., 88–92.Google Scholar
Wolk, A, Mantzoros, CS, Andersson, SO, Bergstrom, R, Signorello, LB, Lagiou, P, Adami, HO & Trichopoulos, D (1998) Insulin-like growth factor 1 and prostate cancer risk: a population-based, case-control study. Journal of the National Cancer Institute 90, 911–915.Google Scholar
World Cancer Research Fund/American Institute for Cancer Research (1997). Food, Nutrition and the Prevention of Cancer: a Global Perspective pp. 1–670. Washington, DC: World Cancer Research Fund/American Institute for Cancer Research.Google Scholar
Wu, AH, Whittemore, AS, Kolonel, LN, John, EM, Gallagher, RP, West, DW, Hankin, J, Teh, CZ, Dreon, DM & Paffenbarger, RS Jr (1995) Serum androgens and sex hormone-binding globulins in relation to lifestyle factors in older African-American, white, and Asian men in the United States and Canada. Cancer Epidemiology Biomarkers and Prevention 4, 735–741.Google Scholar
Wyshak, G & Frisch, RE (2000) Breast cancer among former college athletes compared to non-athletes: a 15-year follow-up. British Journal of Cancer 82, 726–730.Google Scholar
Yang, XF, Beamer, WG, Huynh, H & Pollak, M (1996) Reduced growth of human breast cancer xenografts in hosts homozygous for the lit mutation. Cancer Research 56, 1509–1511.Google Scholar