Brown kelp modulates endocrine hormones in female sprague-dawley rats and in human luteinized granulosa cells.

Epidemiological studies suggest that populations consuming typical Asian diets have a lower incidence of hormone-dependent cancers than populations consuming Western diets. These dietary differences have been mainly attributed to higher soy intakes among Asians. However, studies from our laboratory suggest that the anti-estrogenic effects of dietary kelp also may contribute to these reduced cancer rates. As a follow-up to previous findings of endocrine modulation related to kelp ingestion in a pilot study of premenopausal women, we investigated the endocrine modulating effects of kelp (Fucus vesiculosus) in female rats and human luteinized granulosa cells (hLGC). Kelp administration lengthened the rat estrous cycle from 4.3 +/- 0.96 to 5.4 +/- 1.7 d at 175 mg . kg(-1) body wt . d(-1) (P = 0.05) and to 5.9 +/- 1.9 d at 350 mg . kg(-1) . d(-1) (P = 0.002) and also led to a 100% increase in the length of diestrus (P = 0.02). Following 175 mg . kg(-1) . d(-1) treatment for 2 wk, serum 17beta-estradiol levels were reduced from 48.9 +/- 4.5 to 40.2 +/- 3.2 ng/L (P = 0.13). After 4 wk, 17beta-estradiol levels were reduced to 36.7 +/- 2.2 ng/L (P = 0.02). In hLGC, 25, 50, and 75 micromol/L treatment reduced 17beta-estradiol levels from 4732 +/- 591 to 3632 +/- 758, 3313 +/- 373, and 3060 +/- 538 ng/L, respectively. Kelp treatment also led to modest elevations in hLGC culture progesterone levels. Kelp extract inhibited the binding of estradiol to estrogen receptor alpha and beta and that of progesterone to the progesterone receptor, with IC(50) values of 42.4, 31.8, and 40.7 micromol/L, respectively. These data show endocrine modulating effects of kelp at relevant doses and suggest that dietary kelp may contribute to the lower incidence of hormone-dependent cancers among the Japanese.

[1]  J. Hébert,et al.  Algae -- a poor man's HAART? , 2004, Medical hypotheses.

[2]  S. Kim,et al.  Inhibition of HIV-1 reverse transcriptase and protease by phlorotannins from the brown alga Ecklonia cava. , 2004, Biological & pharmaceutical bulletin.

[3]  C. la Vecchia,et al.  Influence of selected hormonal and lifestyle factors on familial propensity to ovarian cancer. , 2004, Gynecologic oncology.

[4]  X. Shu,et al.  Menstrual and reproductive factors and endometrial cancer risk: Results from a population‐based case‐control study in urban Shanghai , 2004, International journal of cancer.

[5]  H. Chung,et al.  Inhibitory phlorotannins from the edible brown algaecklonia stolonifera on total reactive oxygen species (ROS) generation , 2004, Archives of pharmacal research.

[6]  T. Querec,et al.  Gonadotropin and steroid hormones stimulate proliferation of the rat ovarian surface epithelium , 2004, Journal of cellular physiology.

[7]  Roger E. Moore,et al.  Suppression of estrogen biosynthesis by procyanidin dimers in red wine and grape seeds. , 2003, Cancer research.

[8]  M. Hirose,et al.  Impact of dietary exposure to methoxychlor, genistein, or diisononyl phthalate during the perinatal period on the development of the rat endocrine/reproductive systems in later life. , 2003, Toxicology.

[9]  V. Chinchilli,et al.  A case-control study of menstrual factors in relation to breast cancer risk in African-American women. , 2003, Journal of the National Medical Association.

[10]  Valerie Beral,et al.  Breast cancer and hormone-replacement therapy in the Million Women Study , 2003, The Lancet.

[11]  A. McTiernan.  Behavioral risk factors in breast cancer: can risk be modified? , 2003, The oncologist.

[12]  V. Siskind,et al.  Ovulation and risk of epithelial ovarian cancer , 2003, International journal of cancer.

[13]  E. Damonte,et al.  Fucoidans from the brown seaweed Adenocystis utricularis: extraction methods, antiviral activity and structural studies. , 2003, Carbohydrate research.

[14]  Satoru Koyanagi,et al.  Oversulfation of fucoidan enhances its anti-angiogenic and antitumor activities. , 2003, Biochemical pharmacology.

[15]  Toshiyuki Shibata,et al.  Bactericidal activity of phlorotannins from the brown alga Ecklonia kurome. , 2002, The Journal of antimicrobial chemotherapy.

[16]  S. Chan.  A review of selective estrogen receptor modulators in the treatment of breast and endometrial cancer. , 2002, Seminars in oncology.

[17]  H. Harris,et al.  The ligand binding profiles of estrogen receptors α and β are species dependent , 2002, Steroids.

[18]  C. Pouget,et al.  Synthesis and Aromatase Inhibitory Activity of Flavanones , 2002, Pharmaceutical Research.

[19]  K. Anderson,et al.  Decreased ovarian hormones during a soya diet: implications for breast cancer prevention. , 2000, Cancer research.

[20]  P. Schedin,et al.  Estrous Cycle Regulation of Mammary Epithelial Cell Proliferation, Differentiation, and Death in the Sprague-Dawley Rat: A Model for Investigating the Role of Estrous Cycling in Mammary Carcinogenesis , 2000, Journal of Mammary Gland Biology and Neoplasia.

[21]  J. Overstreet,et al.  2,3,7,8-Tetrachlorodibenzo-p-Dioxin Decreases Estradiol Production Without Altering the Enzyme Activity of Cytochrome P450 Aromatase of Human Luteinized Granulosa Cells In Vitro1 , 2000, Biology of reproduction.

[22]  C. Corbin,et al.  Changes in Testosterone Metabolism Associated with the Evolution of Placental and Gonadal Isozymes of Porcine Aromatase Cytochrome P4501. , 1999, Endocrinology.

[23]  Masahide Takahashi,et al.  Wakame Seaweed Suppresses the Proliferation of 7,12‐Dimethylbenz(a)‐anthracene‐induced Mammary Tumors in Rats , 1999, Japanese journal of cancer research : Gann.

[24]  A. Riva,et al.  Reproductive effects of dietary soy in female Wistar rats. , 1999, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[25]  Jacques Ferlay,et al.  Estimates of the worldwide incidence of 25 major cancers in 1990 , 1999, International journal of cancer.

[26]  S. Safe,et al.  Ah receptor agonists as endocrine disruptors: antiestrogenic activity and mechanisms. , 1998, Toxicology letters.

[27]  R. Hoover,et al.  Serum hormone levels in relation to reproductive and lifestyle factors in postmenopausal women (United States) , 1998, Cancer Causes & Control.

[28]  A. Conney,et al.  Effect of dietary 2(3)-tert-butyl-4-hydroxyanisole on the metabolism and action of estradiol and estrone in female CD-1 mice. , 1997, Cancer research.

[29]  D. Edwards,et al.  Binding of [3H]progesterone to the human progesterone receptor: differences between individual and mixed isoforms. , 1996, Endocrinology.

[30]  J. Overstreet,et al.  2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) modulates function of human luteinizing granulosa cells via cAMP signaling and early reduction of glucose transporting activity. , 1996, Reproductive toxicology.

[31]  K. Setchell,et al.  Biological effects of a diet of soy protein rich in isoflavones on the menstrual cycle of premenopausal women. , 1994, The American journal of clinical nutrition.

[32]  M. Vega,et al.  Progesterone synthesis by human luteal cells: modulation by estradiol. , 1994, The Journal of clinical endocrinology and metabolism.

[33]  B. Fisch,et al.  Effects of oestrogen on progesterone synthesis and arachidonic acid metabolism in human luteal cells , 1994, Clinical endocrinology.

[34]  N. Koszewski,et al.  Hormone- and DNA-binding mechanisms of the recombinant human estrogen receptor. , 1993, Biochemistry.

[35]  J. Roser,et al.  Gonadotropin releasing hormone (GnRH) induced luteinizing hormone (LH) secretion from perifused equine pituitaries. , 1991, Domestic animal endocrinology.

[36]  M. Pike,et al.  Sex hormones in women in rural China and in Britain. , 1990, British Journal of Cancer.

[37]  M. Pike,et al.  Serum oestrogen levels in postmenopausal women: comparison of American whites and Japanese in Japan. , 1990, British Journal of Cancer.

[38]  J. Everett.  Neurobiology of reproduction in the female rat. A fifty-year perspective. , 1989, Monographs on endocrinology.

[39]  D. N. Kirk,et al.  Nonsteroidal estrogens of dietary origin: possible roles in hormone-dependent disease. , 1984, The American journal of clinical nutrition.

[40]  R. Gelman,et al.  Dietary seaweed (Laminaria) and mammary carcinogenesis in rats. , 1984, Cancer research.

[41]  J. Le Bail,et al.  Aromatase and 17beta-hydroxysteroid dehydrogenase inhibition by flavonoids. , 1998, Cancer letters.

[42]  M. Roessler,et al.  Initial uterine alterations caused by developmental exposure to tamoxifen. , 1997, Reproductive toxicology.

[43]  J L Kelsey,et al.  Reproductive factors and breast cancer. , 1993, Epidemiologic reviews.

[44]  E. Simpson,et al.  Assay of aromatase activity. , 1991, Methods in enzymology.

[45]  H. Olsson,et al.  Retrospective assessment of menstrual cycle length in patients with breast cancer, in patients with benign breast disease, and in women without breast disease. , 1983, Journal of the National Cancer Institute.

[46]  M. Ragan,et al.  Physodes and the phenolic compounds of brown algae. Isolation and characterization of phloroglucinol polymers from Fucus vesiculosus (L.) , 1976, Canadian journal of biochemistry.