Chronic estradiol exposure - harmful effects on behavior, cardiovascular and reproductive functions.

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Estradiol (E2) is a female hormone that is produced largely by the ovaries, but also by the adrenal glands, fat and liver. It is present in the circulation of both males and females. Many studies in the literature have described how E2 is beneficial to the body in terms of preventing bone loss, affording protection in ischemia reperfusion injury, relieving symptoms of menopause, maintaining vaginal health and helping with ovarian failure or hypogonadism. Beneficial effects on the brain have been reported to include protection against memory loss, neuronal degeneration, changes in cognition, mood and behavior. However, the effects of E2 exposure on the neuroendocrine system have not been understood completely. This is because differences in doses, preparation and duration of exposure have produced variable results ranging from beneficial, to no change, or to detrimental. Studies in our lab over the last few years have shown that chronic exposures to low levels of E2 in young rats can produce specific effects on the neuroendocrine system. We have observed that these exposures can induce reproductive senescence, hypertension, anxiety-like behavior and cause degenerative changes in specific neuronal populations leading to hyperprolactinemia. The purpose of the review is to present evidence from the literature for these effects and to discuss the underlying molecular mechanisms.