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.