Skip to main content
Genes & Nutrition logoLink to Genes & Nutrition
. 2006 Sep;1(3-4):177–188. doi: 10.1007/BF02829967

Is there an estrogenic component in the metabolic syndrome?

S Starcke 1,, G Vollmer 1
PMCID: PMC3454834  PMID: 18850213

Abstract

One of the major upcoming concerns leading to health related problems in the industrialized societies is the metabolic syndrome which is characterized by central obesity, hypertension, raised fasting glucose and triglyceride levels. The focus of this review is on a potential estrogenic linkage between the metabolic mechanisms involved into the development of this disease cluster and specific estrogen related regulatory pattern. The candidate molecules for this link are insulin and insulin-like growthfactor, C-reactive protein, peroxisome-proliferation-activatingreceptorγ, and leptin which all seem to interact with each other and show a responsiveness to changing estrogen levels. From this perspective they might also represent target molecules for a phytochemical intervention with phytoestrogens.

Key words: Estrogen, Metabolic syndrome, Obesity, Phytoestrogen

Full Text

The Full Text of this article is available as a PDF (160.0 KB).

References

  1. Anonymous (2001) Executive summary of the third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel iii).Journal of the American Medical Association285, 2486–2497. [DOI] [PubMed]
  2. Aguirre V., Uchida T., Yenush L., Davis R., White M. F. The c-jun nh2-terminal kinase promotes insulin resistance during association with insulin receptor substrate-1 and phosphorylation of ser307. Journal of Biological Chemistry. 2000;275:9047–9054. doi: 10.1074/jbc.275.12.9047. [DOI] [PubMed] [Google Scholar]
  3. Alberti K. G., Zimmet P. Z. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: Diagnosis and classification of diabetes mellitus provisional report of a who consultation. Diabetic Medicine. 1998;15:539–553. doi: 10.1002/(SICI)1096-9136(199807)15:7<539::AID-DIA668>3.0.CO;2-S. [DOI] [PubMed] [Google Scholar]
  4. Andrade P. M., Silva I. D., Borra R. C., Lima G. R., Baracat E. C. Estrogen and selective estrogen receptor modulator regulation of insulin-like growth factor binding protein 5 in the rat uterus. Gynecological endocrinology. 2002;16:265–270. [PubMed] [Google Scholar]
  5. Barbier O., Villeneuve L., Bocher V., Fontaine C., Torra I. P., Duhem C., Kosykh V., Fruchart J.-C., Guillemette C., Staels B. The udp-glucuronosyltransferase 1a9 enzyme is a peroxisome proliferator-activated receptor alpha and gamma target gene. Journal of Biological Chemistry. 2003;278:13975–13983. doi: 10.1074/jbc.M300749200. [DOI] [PubMed] [Google Scholar]
  6. Belgorosky A., Pepe C., Marino R., Guercio G., Saraco N., Vaiani E., Rivarola M. A. Hypothalamic-pituitaryovarian axis during infancy, early and late prepuberty in an aromatase-deficient girl who is a compound heterocygote for two new point mutations of the cyp19 gene. Journal of clinical endocrinology and metabolism. 2003;88:5127–5131. doi: 10.1210/jc.2003-030433. [DOI] [PubMed] [Google Scholar]
  7. Bilezikian J. P., Morishima A., Bell J., Grumbach M. M. Increased bone mass as a result of estrogen therapy in a man with aromatase deficiency. New England Journal of Medicine. 1998;339:599–603. doi: 10.1056/NEJM199808273390905. [DOI] [PubMed] [Google Scholar]
  8. Bonanni B., Johansson H., Gandini S., Guerrieri-Gonzaga A., Sandri M. T., Mariette F., Lien E. A., Decensi A. Effect of tamoxifen at low doses on ultrasensitive creactive protein in healthy women. Journal of thrombosis and haemostasis. 2003;1:2149–2152. doi: 10.1046/j.1538-7836.2003.00392.x. [DOI] [PubMed] [Google Scholar]
  9. Bonofiglio D., Gabriele S., Aquila S., Catalano S., Gentile M., Middea E., Giordano F., Ando S. Estrogen receptor {alpha} binds to peroxisome proliferator-activated receptor response element and negatively interferes with peroxisome proliferator-activated receptor {gamma{ signaling in breast cancer cells. Clinical Cancer Research. 2005;11:6139–6147. doi: 10.1158/1078-0432.CCR-04-2453. [DOI] [PubMed] [Google Scholar]
  10. Bonora E., Kiechl S., Willeit J., Oberhollenzer F., Egger G., Bonadonna R. C., Muggeo M. Metabolic syndrome: Epidemiology and more extensive phenotypic description. Crosssectional data from the bruneck study. International journal of obesity and related metabolic disorders. 2003;27:1283–1289. doi: 10.1038/sj.ijo.0802381. [DOI] [PubMed] [Google Scholar]
  11. Branca F. Dietary phyto-oestrogens and bone health. Proceedings of the Nutrition Society. 2003;62:877–887. doi: 10.1079/PNS2003309. [DOI] [PubMed] [Google Scholar]
  12. Britt K. L., Simpson E. R., Findlay J. K. Effects of phytoestrogens on the ovarian and pituitary phenotypes of estrogen-deficient female aromatase knockout mice. Menopause. 2005;12:174–185. doi: 10.1097/00042192-200512020-00012. [DOI] [PubMed] [Google Scholar]
  13. Browning L. M., Jebb S. A., Mishra G. D., Cooke J. H., O’Connell M. A., Crook M. A., Krebs J. D. Elevated sialic acid, but not crp, predicts features of the metabolic syndrome independently of bmi in women. International journal of obesity and related metabolic disorders. 2004;28:1004–1010. doi: 10.1038/sj.ijo.0802711. [DOI] [PubMed] [Google Scholar]
  14. Cabrero Ã., Cubero M., Llaverias G., Alegret M., Sanchez R., Laguna J. C., Vazquez-Carrera M. Leptin downregulates peroxisome proliferator-activated receptor gamma (ppargamma) mrna levels in primary human monocyte-derived macrophages. Molecular and Cellular Biochemistry. 2005;275:173–179. doi: 10.1007/s11010-005-1353-8. [DOI] [PubMed] [Google Scholar]
  15. Carani C., Qin K., Simoni M., Faustini-Fustini M., Serpente S., Boyd J., Korach K. S., Simpson E. R. Effect of testosterone and estradiol in a man with aromatase deficiency. New England Journal of Medicine. 1997;337:91–95. doi: 10.1056/NEJM199707103370204. [DOI] [PubMed] [Google Scholar]
  16. Cassidy A., Albertazzi P., Lise Nielsen I., Hall W., Williamson G., Tetens I., Atkins S., Cross H., Manios Y., Wolk A., Steiner C., Branca F. Critical review of health effects of soyabean phyto-oestrogens in post-menopausal women. Proceedings of the Nutrition Society. 2006;65:76–92. doi: 10.1079/pns2005476. [DOI] [PubMed] [Google Scholar]
  17. Castillo G., Brun R. P., Rosenfield J. K., Hauser S., Park C. W., Troy A. E., Wright M. E., Spiegelman B. M. An adipogenic cofactor bound by the differentiation domain of ppargamma. EMBO Journal. 1999;18:3676–3687. doi: 10.1093/emboj/18.13.3676. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Catalano S., Marsico S., Giordano C., Mauro L., Rizza P., Panno M. L., Ando S. Leptin enhances, via ap-1, expression of aromatase in the mcf-7 cell line. Journal of Biological Chemistry. 2003;278:28668–28676. doi: 10.1074/jbc.M301695200. [DOI] [PubMed] [Google Scholar]
  19. Catalano S., Mauro L., Marsico S., Giordano C., Rizza P., Rago V., Montanaro D., Maggiolini M., Panno M. L., Ando S. Leptin induces, via erk1/erk2 signal, functional activation ofestrogen receptor {alpha{ in mcf-7 cells. Journal of Biological Chemistry. 2004;279:19908–19915. doi: 10.1074/jbc.M313191200. [DOI] [PubMed] [Google Scholar]
  20. Cella F., Giordano G., Cordera R. Serum leptin concentrations during the menstrual cycle in normal-weight women: Effects of an oral triphasic estrogen-progestin medication. European journal of endocrinology. 2000;142:174–178. doi: 10.1530/eje.0.1420174. [DOI] [PubMed] [Google Scholar]
  21. Chawla A., Boisvert W. A., Lee C.-H., Laffitte B. A., Barak Y., Joseph S. B., Liao D., Nagy L., Edwards P. A., Curtiss L. K. A ppar[gamma]-lxr-abca1 pathway in macrophages is involvedin cholesterol efflux and atherogenesis. Molecular Cell. 2001;7:161–171. doi: 10.1016/s1097-2765(01)00164-2. [DOI] [PubMed] [Google Scholar]
  22. Chen W.-F., Lau W.-S., Cheung P.-Y., Guo D.-A., Wong M.-S. Activation of insulin-like growth factor i receptormediated pathway by ginsenoside rg1. Br J PharmacolCheung, C. C., Thornton, J. E., Kuijper, J. L., Weigle, D. S., Clifton, D. K. and Steiner, R. A., ( 1997) Leptin is a metabolic gate for the onset of puberty in the female rat. Endocrinology. 2006;138:855–858. doi: 10.1210/endo.138.2.5054. [DOI] [PubMed] [Google Scholar]
  23. Chu N. V., Kong A. P., Kim D. D., Armstrong D., Baxi S., Deutsch R., Caulfield M., Mudaliar S. R., Reitz R., Henry R. R., Reaven P. D. Differential effects of metformin and troglitazone on cardiovascular risk factors in patients with type 2 diabetes. Diabetes Care. 2002;25:542–549. doi: 10.2337/diacare.25.3.542. [DOI] [PubMed] [Google Scholar]
  24. Clement K., Vaisse C., Lahlou N., Cabrol S., Pelloux V., Cassuto D., Gourmelen M., Dina C., Chambaz J., Lacorte J. M., Basdevant A., Bougneres P., Lebouc Y., Froguel P., Guy-Grand B. A mutation in the human leptin receptorgene causes obesity and pituitary function. Nature. 1998;392:398–401. doi: 10.1038/32911. [DOI] [PubMed] [Google Scholar]
  25. Considine R. V., Sinha M. K., Heiman M. L., Kriauciunas A., Stephens T. W., Nyce M. R., Ohannesian J. P., Marco C. C., McKee L. J., Bauer T. L., et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. New England Journal of Medicine. 1996;334:292–295. doi: 10.1056/NEJM199602013340503. [DOI] [PubMed] [Google Scholar]
  26. Dang Z. C., Audinot V., Papapoulos S. E., Boutin J. A., Lowik C. W. Peroxisomeproliferator-activated receptor gamma (ppargamma ) as a molecular target for the soy phytoestrogen genistein. Journal of Biological Chemistry. 2003;278:962–967. doi: 10.1074/jbc.M209483200. [DOI] [PubMed] [Google Scholar]
  27. Danilovich N., Babu P. S., Xing W., Gerdes M., Krishnamurthy H., Sairam M. R. Estrogen deficiency, obesity, and skeletal abnormalities in follicle-stimulating hormone receptor knockout (forko) female mice. Endocrinology. 2000;141:4295–4308. doi: 10.1210/endo.141.11.7765. [DOI] [PubMed] [Google Scholar]
  28. Deladoey J., Fluck C., Bex M., Yoshimura N., Harada N., Mullis P. E. Aromatase deficiency caused by a novel p450arom gene mutation: Impact of absent estrogen production on serum gonadotropin concentration in a boy. Journal of clinical endocrinology and metabolism. 1999;84:4050–4054. doi: 10.1210/jcem.84.11.6135. [DOI] [PubMed] [Google Scholar]
  29. Emilsson V., Liu Y. L., Cawthorne M. A., Morton N. M., Davenport M. Expression of the functional leptin receptor mrna in pancreatic islets and direct inhibitory action of leptin on insulin secretion. Diabetes. 1997;46:313–316. doi: 10.2337/diab.46.2.313. [DOI] [PubMed] [Google Scholar]
  30. Etchegoyen G. S., Borelli M. I., Rossi J. P., Gagliardino J. J. Effect of 2-hydroxyoestradiol on insulin secretion in normal rat pancreatic islets. Diabetes & Metabolism. 1998;24:428–433. [PubMed] [Google Scholar]
  31. Faddy H. M., Robinson J. A., Lee W. J., Holman N. A., Monteith G. R., Roberts-Thomson S. J. Peroxisome proliferator-activated receptor [alpha] expression is regulated by estrogen receptor [alpha] and modulates the response of mcf-7 cells to sodium butyrate. The International Journal of Biochemistry & Cell Biology. 2006;38:255–266. doi: 10.1016/j.biocel.2005.09.002. [DOI] [PubMed] [Google Scholar]
  32. Fisher C. R., Graves K. H., Parlow A. F., Simpson E. R. Characterization of mice deficient in aromatase (arko) because of targeted disruption of the cyp19 gene. Proceedings of the National Academy of Sciences of the United States of America. 1998;95:6965–6970. doi: 10.1073/pnas.95.12.6965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Ford E. S., Giles W. H., Dietz W. H. Prevalence of the metabolic syndrome among us adults: Findings from the third national health and nutrition examination survey. Journal of the American Medical Association. 2002;287:356–359. doi: 10.1001/jama.287.3.356. [DOI] [PubMed] [Google Scholar]
  34. Frühbeck G., Gomez-Ambrosi J., Muruzabal F. J., Burrell M. A. The adipocyte: A model for integration of endocrine and metabolic signaling in energy metabolism regulation. American journal of physiology. Endocrinology and metabolism. 2001;280:E827–847. doi: 10.1152/ajpendo.2001.280.6.E827. [DOI] [PubMed] [Google Scholar]
  35. Gambacciani M., Ciaponi M., Cappagli B., Benussi C., Simone L., Genazzani A. R. Climacteric modifications in body weight and fat tissue distribution. Climacteric. 1999;2:37–44. doi: 10.3109/13697139909025561. [DOI] [PubMed] [Google Scholar]
  36. Gambacciani M., Ciaponi M., Cappagli B., Simone L., Orlandi R., Genazzani A. R. Prospective evaluation of body weight and body fat distribution in early postmenopausal women with and without hormonal replacement therapy. Maturitas. 2001;39:125–132. doi: 10.1016/s0378-5122(01)00194-3. [DOI] [PubMed] [Google Scholar]
  37. Gambacciani M., Ciaponi M., Cappagli B., Piaggesi L., Simone L., Orlandi R., Genazzani A. R. Body weight, body fat distribution, and hormonal replacement therapy in early postmenopausal women. Journal of clinical endocrinology and metabolism. 1997;82:414–417. doi: 10.1210/jcem.82.2.3735. [DOI] [PubMed] [Google Scholar]
  38. Geis R.-B., Diel P., Degen G. H., Vollmer G. Effects of genistein on the expression of hepatic genes in two rat strains (sprague-dawleyandwistar) Toxicology Letters. 2005;157:21–29. doi: 10.1016/j.toxlet.2005.01.001. [DOI] [PubMed] [Google Scholar]
  39. Ghanim H., Aljada A., Hofmeyer D., Syed T., Mohanty P., Dandona P. Circulating mononuclear cells in the obese are in a proinflammatory state. Circulation. 2004;110:1564–1571. doi: 10.1161/01.CIR.0000142055.53122.FA. [DOI] [PubMed] [Google Scholar]
  40. Ghanim H., Garg R., Aljada A., Mohanty P., Kumbkarni Y., Assian E., Hamouda W., Dandona P. Suppression of nuclear factor-{kappa}}b and stimulation of inhibitor {kappa}}b by troglitazone: Evidence for an anti-inflammatory effect and a potential antiatherosclerotic effect in the obese. Journal of clinical endocrinology and metabolism. 2001;86:1306–1312. doi: 10.1210/jcem.86.3.7309. [DOI] [PubMed] [Google Scholar]
  41. Gonzalez R. R., Caballero-Campo P., Jasper M., Mercader A., Devoto L., Pellicer A., Simon C. Leptin and leptin receptor are expressed in the human endometrium and endometrial leptin secretion is regulated by the human blastocyst. Journal of clinical endocrinology and metabolism. 2000;85:4883–4888. doi: 10.1210/jcem.85.12.7060. [DOI] [PubMed] [Google Scholar]
  42. Greenfield J. R., Samaras K., Jenkins A. B., Kelly P. J., Spector T. D., Campbell L. V. Moderate alcohol consumption, estrogen replacement therapy, and physical activity are associated with increased insulin sensitivity: Is abdominal adiposity the mediator. Diabetes Care. 2003;26:2734–2740. doi: 10.2337/diacare.26.10.2734. [DOI] [PubMed] [Google Scholar]
  43. Gunin A. G., Bitter A. D., Demakov A. B., Vasilieva E. N., Suslonova N. V. Effects of peroxisome proliferator activated receptors-alpha and -gamma agonists on estradiol-induced proliferation and hyperplasia formation in the mouse uterus. Journal of Endocrinology. 2004;182:229–239. doi: 10.1677/joe.0.1820229. [DOI] [PubMed] [Google Scholar]
  44. Halaas J. L., Gajiwala K. S., Maffei M., Cohen S. L., Chait B. T., Rabinowitz D., Lallone R. L., Burley S. K., Friedman J. M. Weight-reducing effects of the plasma protein encoded by the obese gene. Science. 1995;269:543–546. doi: 10.1126/science.7624777. [DOI] [PubMed] [Google Scholar]
  45. Hall W. L., Vafeiadou K., Hallund J., Bugel S., Koebnick C., Reimann M., Ferrari M., Branca F., Talbot D., Dadd T., Nilsson M., Dahlman-Wright K., Gustafsson J.-A., Minihane A.-M., Williams C. M. Soy-isoflavone-enriched foods and inflammatory biomarkers of cardiovascular disease risk in postmenopausal women: Interactions with genotype and equol production. American Journal of Clinical Nutrition. 2005;82:1260–1268. doi: 10.1093/ajcn/82.6.1260. [DOI] [PubMed] [Google Scholar]
  46. Haller H. [epidermiology and associated risk factors of hyperlipoproteinemia] Zeitschrift für die gesamte innere Medizin und ihre Grenzgebiete. 1977;32:124–128. [PubMed] [Google Scholar]
  47. Harmon A. W., Harp J. B. Differential effects of flavonoids on 3t3-l1 adipogenesis and lipolysis. American journal of physiology. Cell physiology. 2001;280:C807–813. doi: 10.1152/ajpcell.2001.280.4.C807. [DOI] [PubMed] [Google Scholar]
  48. Haynes W. G., Sivitz W. I., Morgan D. A., Walsh S. A., Mark A. L. Sympathetic and cardiorenal actions of leptin. Hypertension. 1997;30:619–623. doi: 10.1161/01.hyp.30.3.619. [DOI] [PubMed] [Google Scholar]
  49. Heine P. A., Taylor J. A., Iwamoto G. A., Lubahn D. B., Cooke P. S. Increased adipose tissue in male and female estrogen receptor-alpha knockout mice. Proceedings of the National Academy of Sciences of the United States of America. 2000;97:12729–12734. doi: 10.1073/pnas.97.23.12729. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Hewitt K. N., Boon W. C., Murata Y., Jones M. E., Simpson E. R. The aromatase knockout mouse presents with a sexually dimorphic disruption to cholesterol homeostasis. Endocrinology. 2003;144:3895–3903. doi: 10.1210/en.2003-0244. [DOI] [PubMed] [Google Scholar]
  51. Hu E B., Manson J. E., Liu S., Hunter D., Colditz G. A., Michels K. B., Speizer E E., Giovannucci E. Prospective study of adult onset diabetes mellitus (type 2) and risk of colorectal cancer in women. Journal of the National Cancer Institute. 1999;91:542–547. doi: 10.1093/jnci/91.6.542. [DOI] [PubMed] [Google Scholar]
  52. Jones M. E., Thorburn A. W., Britt K. L., Hewitt K. N., Wreford N. G., Proietto J., Oz O. K., Leury B. J., Robertson K. M., Yao S., Simpson E. R. Aromatase-deficient (arko) mice have a phenotype of increased adiposity. Proceedings of the National Academy of Sciences of the United States of America. 2000;97:12735–12740. doi: 10.1073/pnas.97.23.12735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Kahlert S., Nuedling S., Eickels M., Vetter H., Meyer R., Grohe C. Estrogen receptor alpha rapidly activates the igf-1 receptor pathway. Journal of Biological Chemistry. 2000;275:18447–18453. doi: 10.1074/jbc.M910345199. [DOI] [PubMed] [Google Scholar]
  54. Kamei Y., Suzuki M., Miyazaki H., Tsuboyama-Kasaoka N., Wu J., Ishimi Y., Ezaki O. Ovariectomy in mice decreases lipid metabolism-related gene expression in adipose tissue and skeletal muscle with increased body fat. Journal of nutritional science and vitaminology. 2005;51:110–117. doi: 10.3177/jnsv.51.110. [DOI] [PubMed] [Google Scholar]
  55. Kamohara S., Burcelin R., Halaas J. L., Friedman J. M., Charron M. J. Acute stimulation of glucose metabolism in mice by leptin treatment. Nature. 1997;389:374–377. doi: 10.1038/38717. [DOI] [PubMed] [Google Scholar]
  56. Keith J. C., Albert L. M., Leathurby Y., Follettie M., Wang L., Borges-Marcucci L., Chadwick C. C., Steffan R. J., Harnish D. C. The utility of pathway selective estrogen receptor ligands that inhibit nuclear factor-kappab transcriptional activity in models of rheumatoid arthritis. Arthritis research & therapy. 2005;7:R427–438. doi: 10.1186/ar1692. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Keller H., Givel F., Perroud M., Wahli W. Signaling cross-talk between peroxisome proliferator-activated receptor/ retinoid x receptor and estrogen receptor through estrogen response elements. Molecular Endocrinology. 1995;9:794–804. doi: 10.1210/mend.9.7.7476963. [DOI] [PubMed] [Google Scholar]
  58. Kenchaiah S., Evans J. C., Levy D., Wilson P. W., Benjamin E. J., Larson M. G., Kannel W. B., Vasan R. S. Obesity and the risk of heart failure. New England Journal of Medicine. 2002;347:305–313. doi: 10.1056/NEJMoa020245. [DOI] [PubMed] [Google Scholar]
  59. Khan A., Safdar M., Ali Khan M. M., Khattak K. N., Anderson R. A. Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes Care. 2003;26:3215–3218. doi: 10.2337/diacare.26.12.3215. [DOI] [PubMed] [Google Scholar]
  60. Khera A., McGuire D. K., Murphy S. A., Stanek H. G., Das S. R., Vongpatanasin W., Wians J. F. H., Grundy S. M., Lemos J. A. Race and gender differences in c-reactive protein levels. Journal of the American College of Cardiology. 2005;46:464–469. doi: 10.1016/j.jacc.2005.04.051. [DOI] [PubMed] [Google Scholar]
  61. Khovidhunkit W., Memon R. A., Feingold K. R., Grunfeld C. Infection and inflammation-induced proatherogenic changes of lipoproteins. Journal of infectious diseases. 2000;181(3):S462–472. doi: 10.1086/315611. [DOI] [PubMed] [Google Scholar]
  62. Klotz D.M., Hewitt S. C., Ciana P., Raviscioni M., Lindzey J. K., Foley J., Maggi A., DiAugustine R. P., Korach K. S. Requirement of estrogen receptor-alpha in insulin-like growth factor-1 (igf-1)-induced uterine responses and in vivo evidence for igf-1/estrogen receptor cross-talk. Journal of Biological Chemistry. 2002;277:8531–8537. doi: 10.1074/jbc.M109592200. [DOI] [PubMed] [Google Scholar]
  63. Koenuma M., Yamori T., Tsuruo T. Insulin and insulin-like growth factor 1 stimulate proliferation of metastatic variants of colon carcinoma 26. Japanese journal of cancer research. 1989;80:51–58. doi: 10.1111/j.1349-7006.1989.tb02244.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Kok L., Kreijkamp-Kaspers S., Grobbee D. E., Lampe J. W., Schouw Y. T. A randomized, placebo-controlled trial on the effects of soy protein containing isoflavones on quality of life in postmenopausal women. Menopause. 2005;12:56–62. doi: 10.1097/00042192-200512010-00011. [DOI] [PubMed] [Google Scholar]
  65. Kolaczynski J. W., Nyce M. R., Considine R. V., Boden G., Nolan J. J., Henry R., Mudaliar S. R., Olefsky J., Caro J. F. Acute and chronic effects of insulin on leptin production in humans: Studies in vivo and in vitro. Diabetes. 1996;45:699–701. doi: 10.2337/diab.45.5.699. [DOI] [PubMed] [Google Scholar]
  66. Koohestani N., Chia M. C., Pham N.A., Tran T. T., Minkin S., Wolever T. M., Bruce W. R. Aberrant crypt focus promotion and glucose intolerance: Correlation in the rat across diets differing in fat, n-3 fatty acids and energy. Carcinogenesis. 1998;19:1679–1684. doi: 10.1093/carcin/19.9.1679. [DOI] [PubMed] [Google Scholar]
  67. Korbonits M., Trainer P. J., Little J. A., Edwards R., Kopelman P. G., Besser G. M., Svec F., Grossman A. B. Leptin levels do not change acutely with food administration in normal or obese subjects, but are negatively correlated with pituitaryadrenal activity. Clinical endocrinology. 1997;46:751–757. doi: 10.1046/j.1365-2265.1997.1820979.x. [DOI] [PubMed] [Google Scholar]
  68. Krajcik R. A., Borofsky N. D., Massardo S., Orentreich N. Insulin-like growth factor i (igf-i), igf-binding proteins, and breast cancer. Cancer epidemiology, biomarkers & prevention. 2002;11:1566–1573. [PubMed] [Google Scholar]
  69. Krattenmacher R., Knauthe R., Parczyk K., Walker A., Hilgenfeldt U., Fritzemeier K. H. Estrogen action on hepatic synthesis of angiotensinogen and igf-i: Direct and indirect estrogen effects. Journal of steroid biochemistry and molecular biology. 1994;48:207–214. doi: 10.1016/0960-0760(94)90146-5. [DOI] [PubMed] [Google Scholar]
  70. Kristensen K., Pedersen S. B., Richelsen B. Regulation of leptin by steroid hormones in rat adipose tissue. Biochemical and biophysical research communications. 1999;259:624–630. doi: 10.1006/bbrc.1999.0842. [DOI] [PubMed] [Google Scholar]
  71. Kuhl H. Breast cancer risk in the whi study: The problem of obesity. Maturitas. 2005;51:83–97. doi: 10.1016/j.maturitas.2005.02.018. [DOI] [PubMed] [Google Scholar]
  72. Lakoski SG, Brosnihan B, DM H. Hormone therapy, c-reactive protein, and progression of atherosclerosis: Data from the estrogen replacement on progression of coronary artery atherosclerosis (era) trial. American Heart Journal. 2005;150:907–911. doi: 10.1016/j.ahj.2004.11.025. [DOI] [PubMed] [Google Scholar]
  73. Landsberg L. Hyperinsulinemia: Possible role in obesityinduced hypertension. Hypertension. 1992;19:I61–66. doi: 10.1161/01.hyp.19.1_suppl.i61. [DOI] [PubMed] [Google Scholar]
  74. Landsberg L. Insulin and the sympathetic nervous system in the pathophysiology of hypertension. Blood Pressure Suppl. 1996;1:25–29. [PubMed] [Google Scholar]
  75. Lemieux C., Phaneuf D., Labrie F., Giguere V., Richard D., Deshaies Y. Estrogen receptor alpha-mediated adiposity-lowering and hypocholesterolemic actions of the selective estrogen receptor modulator acolbifene. International Journal of Obesity. 2005;29:1236–1244. doi: 10.1038/sj.ijo.0803014. [DOI] [PubMed] [Google Scholar]
  76. Liang Y. Q., Akishita M., Kim S., Ako J., Hashimoto M., Iijima K., Ohike Y., Watanabe T., Sudoh N., Toba K., Yoshizumi M., Ouchi Y. Estrogen receptor beta is involved in the anorectic action of estrogen. International journal of obesity and related metabolic disorders. 2002;26:1103–1109. doi: 10.1038/sj.ijo.0802054. [DOI] [PubMed] [Google Scholar]
  77. Licinio J., Negrao A. B., Mantzoros C., Kaklamani V., Wong M. L., Bongiorno P. B., Mulla A., Cearnal L., Veldhuis J. D., Flier J. S., McCann S. M., Gold P. W. Synchronicity of frequently sampled, 24-h concentrations of circulating leptin, luteinizing hormone, and estradiol in healthy women. Proceedings of the National Academy of Sciences of the United States of America. 1998;95:2541–2546. doi: 10.1073/pnas.95.5.2541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  78. Lundholm L., Moverare S., Steffensen K. R., Nilsson M., Otsuki M., Ohlsson C., Gustafsson J. A., Dahlman-Wright K. Gene expression profiling identifies liver x receptor alpha as an estrogen-regulated gene in mouse adipose tissue. Journal of Molecular Endocrinology. 2004;32:879–892. doi: 10.1677/jme.0.0320879. [DOI] [PubMed] [Google Scholar]
  79. Maffei L., Murata Y., Rochira V., Tubert G., Aranda C., Vazquez M., Clyne C. D., Davis S., Simpson E. R., Carani C. Dysmetabolic syndrome in a man with a novel mutation of the aromatase gene: Effects of testosterone, alendronate, and estradiol treatment. Journal of clinical endocrinology and metabolism. 2004;89:61–70. doi: 10.1210/jc.2003-030313. [DOI] [PubMed] [Google Scholar]
  80. Mannucci E., Ognibene A., Becorpi A., Cremasco F., Pellegrini S., Ottanelli S., Rizzello S. M., Massi G., Messeri G., Rotella C. M. Relationship between leptin and oestrogens in healthy women. European journal of endocrinology. 1998;139:198–201. doi: 10.1530/eje.0.1390198. [DOI] [PubMed] [Google Scholar]
  81. McCarty M. F. Up-regulation of igf binding protein-1 as an anticarcinogenic strategy: Relevance to caloric restriction, exercise, and insulin sensitivity. Medical hypotheses. 1997;48:297–308. doi: 10.1016/s0306-9877(97)90098-0. [DOI] [PubMed] [Google Scholar]
  82. McKenna N. J., O’Malley B. W. Combinatorial control of gene expression by nuclear receptors and coregulators. Cell. 2002;108:465–474. doi: 10.1016/s0092-8674(02)00641-4. [DOI] [PubMed] [Google Scholar]
  83. Merritt J. C. Metabolic syndrome: Soybean foods and serum lipids. Journal of the National Medical Association. 2004;96:1032–1041. [PMC free article] [PubMed] [Google Scholar]
  84. Miksicek R. J. Estrogenic flavonoids: Structural requirements for biological activity. Proceedings of the Society for Experimental Biology and Medicine. 1995;208:44–50. doi: 10.3181/00379727-208-43830. [DOI] [PubMed] [Google Scholar]
  85. Misso M. L., Hewitt K. N., Boon W. C., Murata Y., Jones M. E., Simpson E. R. Cholesterol feeding prevents adiposity in the obese female aromatase knockout (arko) mouse. Hormone and metabolic research. 2005;37:26–31. doi: 10.1055/s-2005-861028. [DOI] [PubMed] [Google Scholar]
  86. Misso M. L., Jang C., Adams J., Tran J., Murata Y., Bell R., Boon W. C., Simpson E. R., Davis S. R. Differential expression of factors involved in fat metabolism with age and the menopause transition. Maturitas. 2005;51:299–306. doi: 10.1016/j.maturitas.2004.08.013. [DOI] [PubMed] [Google Scholar]
  87. Misso M. L., Murata Y., Boon W. C., Jones M. E., Britt K. L., Simpson E. R. Cellular and molecular characterization of the adipose phenotype of the aromatasedeficient mouse. Endocrinology. 2003;144:1474–1480. doi: 10.1210/en.2002-221123. [DOI] [PubMed] [Google Scholar]
  88. Modan M., Halkin H., Almog S., Lusky A., Eshkol A., Shefi M., Shitrit A., Fuchs Z. Hyperinsulinemia. A link between hypertension obesity and glucose intolerance. Journal of clinical investigation. 1985;75:809–817. doi: 10.1172/JCI111776. [DOI] [PMC free article] [PubMed] [Google Scholar]
  89. Mohanty P., Aljada A., Ghanim H., Hofmeyer D., Tripathy D., Syed T., Al-Haddad W., Dhindsa S., Dandona P. Evidence for a potent antiinflammatory effect of rosiglitazone. Journal of clinical endocrinology and metabolism. 2004;89:2728–2735. doi: 10.1210/jc.2003-032103. [DOI] [PubMed] [Google Scholar]
  90. Molloy C. A., May F. E. B., Westley B. R. Insulin receptor substrate-1 expression is regulated by estrogen in the mcf-7 human breast cancer cell line. Journal of Biological Chemistry. 2000;275:12565–12571. doi: 10.1074/jbc.275.17.12565. [DOI] [PubMed] [Google Scholar]
  91. Molnar P., Murphy L.J. Effects of oestrogen on rat uterine expression of insulin-like growth factor-binding proteins. Journal of Molecular Endocrinology. 1994;13:59–67. doi: 10.1677/jme.0.0130059. [DOI] [PubMed] [Google Scholar]
  92. Morin-Papunen L., Rautio K., Ruokonen A., Hedberg P., Puukka M., Tapanainen J. S. Metformin reduces serum c-reactive protein levels in women with polycystic ovary syndrome. Journal of clinical endocrinology and metabolism. 2003;88:4649–4654. doi: 10.1210/jc.2002-021688. [DOI] [PubMed] [Google Scholar]
  93. Morishima A., Grumbach M., Simpson E., Fisher C., Qin K. Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of estrogens. Journal of clinical endocrinology and metabolism. 1995;80:3689–3698. doi: 10.1210/jcem.80.12.8530621. [DOI] [PubMed] [Google Scholar]
  94. Naaz A., Yellayi S., Zakroczymski M. A., Bunick D., Doerge D. R., Lubahn D. B., Helferich W. G., Cooke P. S. The soy isoflavone genistein decreases adipose deposition in mice. Endocrinology. 2003;144:3315–3320. doi: 10.1210/en.2003-0076. [DOI] [PubMed] [Google Scholar]
  95. Naaz A., Zakroczymski M., Heine P., Taylor J., Saunders P., Lubahn D., Cooke P. S. Effect of ovariectomy on adipose tissue of mice in the absence of estrogen receptor alpha (eralpha): A potential role for estrogen receptor beta (erbeta) Hormone and metabolic research. 2002;34:758–763. doi: 10.1055/s-2002-38259. [DOI] [PubMed] [Google Scholar]
  96. Nagira K., Sasaoka T., Wada T., Fukui K., Ikubo M., Hori S., Tsuneki H., Saito S., Kobayashi M. Altered subcellular distribution of estrogen receptor {alpha{ is implicated in estradiol-induced dual regulation of insulin signaling in 3t3-l1 adipocytes. Endocrinology. 2006;147:1020–1028. doi: 10.1210/en.2005-0825. [DOI] [PubMed] [Google Scholar]
  97. Nilsson S., Makela S., Treuter E., Tujague M., Thomsen J., Andersson G., Enmark E., Pettersson K., Warner M., Gustafsson J. A. Mechanisms of estrogen action. Physiological reviews. 2001;81:1535–1565. doi: 10.1152/physrev.2001.81.4.1535. [DOI] [PubMed] [Google Scholar]
  98. Oral E.A., Simha V., Ruiz E., Andewelt A., Premkumar A., Snell P., Wagner A. J., Paoli A.M., Reitman M. L., Taylor S. I., Gorden P., Garg A. Leptin-replacement therapy for lipodystrophy. New England Journal of Medicine. 2002;346:570–578. doi: 10.1056/NEJMoa012437. [DOI] [PubMed] [Google Scholar]
  99. Pearce L. C. Metabolic syndrome & obesity: Coepidemics could overwhelm home health care. Caring. 2003;22:24–28. [PubMed] [Google Scholar]
  100. Peet D. J., Turley S. D., Ma W., Janowski B. A., Lobaccaro J. M. A., Hammer R. E., Mangelsdorf D. J. Cholesterol and bile acid metabolism are impaired in mice lacking the nuclear oxysterol receptor lxr[alpha] Cell. 1998;93:693–704. doi: 10.1016/s0092-8674(00)81432-4. [DOI] [PubMed] [Google Scholar]
  101. Picard F., Auwerx J. Ppar(gamma) and glucose homeostasis. Annual review of nutrition. 2002;22:167–197. doi: 10.1146/annurev.nutr.22.010402.102808. [DOI] [PubMed] [Google Scholar]
  102. Poretsky L., Seto-Young D., Shrestha A., Dhillon S., Mirjany M., Liu H.-C., Yih M. C., Rosenwaks Z. Phosphatidyl-inositol-3 kinase-independent insulin action pathway(s) in the human ovary. Journal of clinical endocrinology and metabolism. 2001;86:3115–3119. doi: 10.1210/jcem.86.7.7617. [DOI] [PubMed] [Google Scholar]
  103. Pradhan A. D., Manson J. E., Rossouw J. E., Siscovick D. S., Mouton C. P., Rifai N., Wallace R. B., Jackson R. D., Pettinger M. B., Ridker P. M. Inflammatory biomarkers, hormone replacement therapy, and incident coronary heart disease: Prospective analysis from the women’s health initiative observational study. Journal of the American Medical Association. 2002;288:980–987. doi: 10.1001/jama.288.8.980. [DOI] [PubMed] [Google Scholar]
  104. Price T., O’Brien S., Welter B., George R., Anandjiwala J., Kilgore M. Estrogen regulation of adipose tissue lipoprotein lipase-possible mechanism of body fat distribution. American journal of obstetrics and gynecology. 1998;178:101–107. doi: 10.1016/s0002-9378(98)70634-9. [DOI] [PubMed] [Google Scholar]
  105. Reaven G. M. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes. 1988;37:1595–1607. doi: 10.2337/diab.37.12.1595. [DOI] [PubMed] [Google Scholar]
  106. Reckless J., Metcalfe J. C., Grainger D. J. Tamoxifen decreases cholesterol sevenfold and abolishes lipid lesion development in apolipoprotein e knockout mice. Circulation. 1997;95:1542–1548. doi: 10.1161/01.cir.95.6.1542. [DOI] [PubMed] [Google Scholar]
  107. Rosenfeld C. S., Roberts R. M., Lubahn D. B. Estrogen receptor- and aromatase-deficient mice provide insight into the roles of estrogen within the ovary and uterus. Molecular reproduction and development. 2001;59:336–346. doi: 10.1002/mrd.1039. [DOI] [PubMed] [Google Scholar]
  108. Rubin G. L., Zhao Y., Kalus A. M., Simpson E. R. Peroxisome proliferator-activated receptor gamma ligands inhibit estrogen biosynthesis in human breast adipose tissue: Possible implications for breast cancer therapy. Cancer Research. 2000;60:1604–1608. [PubMed] [Google Scholar]
  109. Sbarouni E., Flevari P., Kroupis C., Kyriakides Z. S., Koniavitou K., Kremastinos D. T. The effects of raloxifene and simvastatin on plasma lipids and endothelium. Cardiovascular Drugs and Therapy. 2003;17:319–323. doi: 10.1023/a:1027391405600. [DOI] [PubMed] [Google Scholar]
  110. Schairer C., Hill D., Sturgeon S. R., Fears T., Pollak M., Mies C., Ziegler R. G., Hoover R. N., Sherman M. E. Serum concentrations of igf-i, igfbp-3 and c-peptide and risk of hyperplasia and cancer of the breast in postmenopausal women. International Journal of Cancer. 2004;108:773–779. doi: 10.1002/ijc.11624. [DOI] [PubMed] [Google Scholar]
  111. Scheen A. J., Luyckx F. H. [metabolic syndrome: Definitions and epidemiological data] Revue médicale de Liège. 2003;58:479–484. [PubMed] [Google Scholar]
  112. Sesti G., Sciacqua A., Cardellini M., Marini M. A., Maio R., Vatrano M., Succurro E., Lauro R., Federici M., Perticone F. Plasma concentration of IGF-1 is independently associated with insulin sensitivity in subjects with different degrees of glucose tolerance. Diabetes Care. 2005;28:120–125. doi: 10.2337/diacare.28.1.120. [DOI] [PubMed] [Google Scholar]
  113. Shimomura I., Hammer R. E., Ikemoto S., Brown M. S., Goldstein J. L. Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy. Nature. 1999;401:73–76. doi: 10.1038/43448. [DOI] [PubMed] [Google Scholar]
  114. Shutt D. A., Cox R. I. Steroid and phyto-oestrogen binding to sheep uterine receptors in vitro. Journal of Endocrinology. 1972;52:299–310. doi: 10.1677/joe.0.0520299. [DOI] [PubMed] [Google Scholar]
  115. Slattery M. L., Ballard-Barbash R., Edwards S., Caan B. J., Potter J. D. Body mass index and colon cancer: An evaluation of the modifying effects of estrogen (united states) Cancer Causes Control. 2003;14:75–84. doi: 10.1023/a:1022545017867. [DOI] [PubMed] [Google Scholar]
  116. Sorenson R., Brelje T., Roth C. Effects of steroid and lactogenic hormones on islets of langerhans: A new hypothesis for the role of pregnancy steroids in the adaptation of islets to pregnancy. Endocrinology. 1993;133:2227–2234. doi: 10.1210/endo.133.5.8404674. [DOI] [PubMed] [Google Scholar]
  117. Stein B., Yang M.X. Repression of the interleukin-6 promoter by estrogen receptor is mediated by nf-kappa b and c/ebp beta. Molecular and cellular biology. 1995;15:4971–4979. doi: 10.1128/mcb.15.9.4971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  118. Stephen R. L., Gustafsson M. C. U., Jarvis M., Tatoud R., Marshall B. R., Knight D., Ehrenborg E., Harris A. L., Wolf C. R., Palmer C. N. A. Activation of peroxisome proliferator-activated receptor lta stimulates the proliferation of human breast and prostate cancer cell lines. Cancer Research. 2004;64:3162–3170. doi: 10.1158/0008-5472.can-03-2760. [DOI] [PubMed] [Google Scholar]
  119. Stulnig T. M., Steffensen K. R., Gao H., Reimers M., Dahlman-Wright K., Schuster G. U., Gustafsson J.-A. Novel roles of liver x receptors exposed by gene expression profiling in liver and adipose tissue. Molecular pharmacology. 2002;62:1299–1305. doi: 10.1124/mol.62.6.1299. [DOI] [PubMed] [Google Scholar]
  120. SutterDub M. T. Preliminary report: Effects of female sex hormones on insulin secretion by the perfused rat pancreas. Journal of Physiology. 1976;72:795–800. [PubMed] [Google Scholar]
  121. Swan J. W., Anker S.D., Walton C., Godsland I. F., Clark A. L., Leyva F., Stevenson J. C., Coats A. J. Insulin resistance in chronic heart failure: Relation to severity and etiology of heart failure. Journal of the American College of Cardiology. 1997;30:527–532. doi: 10.1016/s0735-1097(97)00185-x. [DOI] [PubMed] [Google Scholar]
  122. Szkudelski T., Nogowski L., Pruszynska-Oszmalek E., Kaczmarek P., Szkudelska K. Genistein restricts leptin secretion from rat adipocytes. Journal of steroid biochemistry and molecular biology. 2005;96:301–307. doi: 10.1016/j.jsbmb.2005.04.033. [DOI] [PubMed] [Google Scholar]
  123. Taegtmeyer H., McNulty P., Young M. E. Adaptation and maladaptation of the heart in diabetes: Part i: General concepts. Circulation. 2002;105:1727–1733. doi: 10.1161/01.cir.0000012466.50373.e8. [DOI] [PubMed] [Google Scholar]
  124. Tesone M., Chazenbalk G. D., Ballejos G., Charreau E. H. Estrogen receptor in rat pancreatic islets. Journal of Steroid Biochemistry. 1979;11:1309–1314. doi: 10.1016/0022-4731(79)90201-2. [DOI] [PubMed] [Google Scholar]
  125. Torrisi R., Baglietto L., Johansson H., Veronesi G., Bonanni B., Guerrieri-Gonzaga A., Ballardini B., Decensi A. Effect of raloxifene on igf-i and igfbp-3 in postmenopausal women with breast cancer. British Journal of Cancer. 2001;85:1838–1841. doi: 10.1054/bjoc.2001.2191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  126. Tracy, R. P., (2003) Inflammation, the metabolic syndrome and cardiovascular risk.International Journal of clinical practice Suppl, 10–17. [PubMed]
  127. Tran T. T., Medline A., Bruce W. R. Insulin promotion of colon tumors in rats. Cancer epidemiology, biomarkers & prevention. 1996;5:1013–1015. [PubMed] [Google Scholar]
  128. Tsuchida A., Yamauchi T., Kadowaki T. Nuclear receptors as targets for drug development: Molecular mechanisms for regulation of obesity and insulin resistance by peroxisome proliferator-activated receptor gamma, creb-binding protein, and adiponectin. Journal of pharmacological sciences. 2005;97:164–170. doi: 10.1254/jphs.fmj04008x2. [DOI] [PubMed] [Google Scholar]
  129. Unger R. H. Lipid overload and overflow: Metabolic trauma and the metabolic syndrome. Trends in endocrinology and metabolism. 2003;14:398–403. doi: 10.1016/j.tem.2003.09.008. [DOI] [PubMed] [Google Scholar]
  130. Schouw Y. T., Kleijn M. J., Peeters P. H., Grobbee D. E. Phyto-oestrogens and cardiovascular disease risk. Nutrition, metabolism, and cardiovascular diseases. 2000;10:154–167. [PubMed] [Google Scholar]
  131. Veldman R. G., Frolich M., Pincus S. M., Veldhuis J. D., Roelfsema F. Hyperleptinemia in women with cushing’s disease is driven by high-amplitude pulsatile, but orderly and eurhythmic, leptin secretion. European journal of endocrinology. 2001;144:21–27. doi: 10.1530/eje.0.1440021. [DOI] [PubMed] [Google Scholar]
  132. Wang X., Kilgore M. W. Signal cross-talk between estrogen receptor alpha and beta and the peroxisome proliferator-activated receptor gamma1 in mda-mb-231 and mcf-7 breast cancer cells. Molecular and cellular endocrinology. 2002;194:123–133. doi: 10.1016/s0303-7207(02)00154-5. [DOI] [PubMed] [Google Scholar]
  133. Wauters M., Considine R. V., Gaal L. F. Human leptin: From an adipocyte hormone to an endocrine mediator. European journal of endocrinology. 2000;143:293–311. doi: 10.1530/eje.0.1430293. [DOI] [PubMed] [Google Scholar]
  134. Woodside J. V., Campbell M. J., Denholm E. E., Newton L., Honour J. W., Morton M. S., Young I. S., Leathem A. J. C. Short-term phytoestrogen supplementation alters insulinlike growth factor profile but not lipid or antioxidant status. Journal of Nutritional Biochemistry. 2006;17:211–215. doi: 10.1016/j.jnutbio.2005.08.001. [DOI] [PubMed] [Google Scholar]
  135. Yamauchi T., Tobe K., Tamemoto H., Ueki K., Kaburagi Y., Yamamoto-Honda R., Takahashi Y., Yoshizawa F., Aizawa S., Akanuma Y., Sonenberg N., Yazaki Y., Kadowaki T. Insulin signalling and insulin actions in the muscles and livers of insulin-resistant, insulin receptor substrate 1-deficient mice. Molecular and cellular biology. 1996;16:3074–3084. doi: 10.1128/mcb.16.6.3074. [DOI] [PMC free article] [PubMed] [Google Scholar]
  136. Yang S. X., Zhu Q., Ma X. M., Sasso D., Prestwood K., Kuchel G. A., Diaz Padilla N., Hack C. E. Estrogen replacement raises rat crp without evidence of complement activation. Endocrine research. 2005;31:121–132. doi: 10.1080/07435800500229268. [DOI] [PubMed] [Google Scholar]
  137. Zhang S., Li X., Burghardt R., Smith R., Safe S. H. Role of estrogen receptor (er) alpha in insulin-like growth factor (igf)-i-induced responses in mcf-7 breast cancer cells. Journal of Molecular Endocrinology. 2005;35:433–447. doi: 10.1677/jme.1.01858. [DOI] [PubMed] [Google Scholar]
  138. Zhou J., Anderson K., Bievre M., Ng S., Bondy C. A. Primate mammary gland insulin-like growth factor system: Cellular localization and regulation by sex steroids. Journal of investigative medicine. 2001;49:47–55. doi: 10.2310/6650.2001.34090. [DOI] [PubMed] [Google Scholar]
  139. Zhou Y. T., Wang Z. W., Higa M., Newgard C. B., Unger R. H. Reversing adipocyte differentiation: Implications for treatment of obesity. Proceedings of the National Academy of Sciences of the United States of America. 1999;96:2391–2395. doi: 10.1073/pnas.96.5.2391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  140. Zhu B.T., Conney A. H. Functional role of estrogen metabolism in target cells: Review and perspectives. Carcinogenesis. 1998;19:1–27. doi: 10.1093/carcin/19.1.1. [DOI] [PubMed] [Google Scholar]

Articles from Genes & Nutrition are provided here courtesy of BMC

RESOURCES