Equol (7-hydroxy-3[4'hydroxyphenyl]-chroman) is the major metabolite of the phytoestrogen daidzein, one of the main isoflavones found abundantly in soybeans and soy foods. Equol may be an important biologically active molecule based on recent studies demonstrating that equol can modulate reproductive function. In this study, we examined the effects of equol on prostate growth and LH secretion and determined some of the mechanisms by which it might act. Administration of equol to intact male rats for 4-7 days reduced ventral prostate and epididymal weight and increased circulating LH levels. Using binding assays, we determined that equol specifically binds 5alpha-dihydrotestosterone (DHT), but not testosterone, dehydroepiandrosterone, or estrogen with high affinity. Equol does not bind the prostatic androgen receptor, and has a modest affinity for recombinant estrogen receptor (ER) beta, and no affinity for ERalpha. In castrated male rats treated with DHT, concomitant treatment with equol blocked DHT's trophic effects on the ventral prostate gland growth and inhibitory feedback effects on plasma LH levels without changes in circulating DHT. Therefore, equol can bind circulating DHT and sequester it from the androgen receptor, thus altering growth and physiological hormone responses that are regulated by androgens. These data suggest a novel model to explain equol's biological properties. The significance of equol's ability to specifically bind and sequester DHT from the androgen receptor have important ramifications in health and disease and may indicate a broad and important usage for equol in the treatment of androgen-mediated pathologies.

The hormonal response to stress is enhanced by oestrogen but inhibited by androgens. To determine underlying changes in activity of neuropeptide neurones in the paraventricular nucleus of the hypothalamus (PVN), we examined the effect of oestrogen and androgen treatment on restraint-induced c-fos mRNA, corticotropin-releasing hormone (CRH) heteronuclear RNA, and arginine vasopressin hnRNA expression in the PVN. Male rats were gonadectomized and injected with oestradiol benzoate (EB) or dihydrotestosterone propionate (DHTP; s.c., daily for 4 days). Rats were stressed by restraint for 10 min or 30 min before killing. Other rats were stressed for 30 min and then returned to their home cage for 20 min before killing. Corticosterone and adrenocorticotropic hormone responses to restraint stress were signi®cantly greater in EB-treated rats and lower in DHTP-treated rats at the 30-min timepoint compared to controls. c-fos mRNA increases following stress were augmented by EB but inhibited by DHTP. CRH hnRNA expression increased signi®cantly in the PVN in response to restraint stress, and this increase was augmented by EB treatment, but decreased by DHTP treatment. Vasopressin hnRNA expression was also increased in response to stress, and this increase was attenuated by DHTP. These ®ndings indicate that gonadal hormones in¯uence the reactivity of the hypothalamic-pituitary adrenal axis to stress.Stressful events, either actual or perceived, activate neurones within the paraventricular nucleus (PVN) of the hypothalamus, resulting in the enhanced synthesis and secretion of hypothalamic neuropeptides (1±3). The major secretogogues regulating the hypothalamic-pituitary adrenal axis (HPA axis) are corticotopin-releasing hormone (CRH) and arginine vasopressin. These neuropeptides can subsequently act alone or in concert to stimulate the synthesis and release of adrenocorticotropic hormone (ACTH) from anterior pituitary corticotrophs. ACTH drives adrenal cortical hormone secretion. HPA axis activity is subsequently terminated by negative feedback in which the major inhibitory tone comes from circulating corticosterone.There exists a sex difference in HPA function due at least in part to circulating sex steroid hormones (1±3). When stressed, females display a more robust HPA response than males (1±5). It appears that, in males, androgens act to inhibit (3±5) whereas, in females, oestrogens function to enhance (1±3) the activity of the HPA axis. This is in contrast to behavioural responses to stress where oestrogen appears to reduce fear related behaviour, but androgens enhance their appearance (2).Endocrine manipulation studies in females show that ovariectomy can reduce the stress-induced secretion of ACTH and corticosterone. This can be reversed via oestrogen administration (1±3). However, the precise mechanisms by which oestrogen enhances levels of ACTH and corticosterone are not completely understood. Some evidence indicates that oestrogen directly in¯uences cellular activity and gene expression within neurosecretory neurones ...

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