Increased intake of phytoestrogens may be associated with a lower risk of cancer in the breast and several other sites, although there is controversy surrounding this activity. One of the mechanisms proposed to explain the activity of phytoestrogens is their ability to bind and activate human estrogen receptor alpha (ERalpha) and human estrogen receptor beta (ERbeta). Nine phytoestrogens were tested for their ability to transactivate ERalpha or ERbeta at a range of doses. Mammary adenocarcinoma (MCF-7) cells were co-transfected with either ERalpha or ERbeta, and an estrogen-response element was linked to a luciferase reporter gene. Dose-dependent responses were compared with the endogenous ligand 17beta-estradiol. Purified genistein, daidzein, apigenin, and coumestrol showed differential and robust transactivation of ERalpha- and ERbeta-induced transcription, with an up to 100-fold stronger activation of ERbeta. Equol, naringenin, and kaempferol were weaker agonists. When activity was evaluated against a background of 0.5 nM 17beta-estradiol, the addition of genistein, daidzein, and resveratrol superstimulated the system, while kaempferol and quercetin were antagonists at the highest doses. This transfection assay provides an excellent model to evaluate the activation of ERalpha and ERbeta by different phytoestrogens in a breast cancer context and can be used as a screening bioassay tool to evaluate the estrogenic activity of extracts of herbs and foods.

in the patient's preference of the two treatment groups or in the number of times they used their bronchodilator aerosol, or in the forced expiratory volume in one second, vital capacity, or peak expfratory flow rate in the two treatment groups. The plasma cortisol levels when the patients were on the aerosol were much higher than when they were on prednisolone. The use of inhaled aerosol steroids seems to be preferable as it eliminates the usual complications of oral steroid therapy.

SummaryBeclomethasone dipropionate differs from other steroids previously tried by inhalation in bronchial asthma in having marked topical potency and relatively weak systemic glucocorticoid effects. Experiments in human volunteer subjects demonstrating the effect of this steroid on the hypothalamo-pituitary adrenal axis (HPA axis) are described. These are part of a larger investigation into the reasons for the selectivity of beclomethasone dipropionate in bronchial asthma. From the evidence so far obtained, it may be concluded that suppression ofthe HPA axis is unlikely to occur at doses up to !-0 mg/per day by inhalation.

SummaryBeelomethasone dipropionate has recently been shown to be effective in controlling the nasal sympioms of hay fever at doses similar to those required to control bronchial asthma. Experiments in human volunteer subjects are described demonstrating the effect of this steroid by intra-nasal. and combined intra-nasal and inhaled administration on the Hypothaiamo-Pituitary-Adrenal axis (HPA axis).From tbe evidence obtained suppression ofthe HPA axis is less likely following intra-nasal administration, than after the inhaled or oral routes. It may be concluded that suppression ofthe HPA axis is unlikely unless concurrent doses in excess of I mg a day by both routes are used.

Our data demonstrate that OX2R mediates Ca -dependent amylase release in AR42J cells, suggesting that Orexins may have secretory functions in pancreatic tumor cells.