Biological Effects and Markers of Exposure to Xenosteroids and Selective Estrogen Receptor Modulators (SERMs) at the Hypothalamic-Pituitary Unit
Estrogen is a pivotal factor in the regulation of a wide array of biological systems, in both the male and the female, which include not only the reproductive axis but also bone, the cardiovascular system, adipose tissue and the brain. In recent years, the biological effects and mechanisms of action of estrogen have been deeply revisited, and extensive efforts have been made to better understand both the physiology and pathophysiology of estrogen actions in different target tissues. In this context, a major concern has recently emerged about the potential deleterious effects on human and wildlife health of a wide array of natural and synthetic compounds with sex steroid-like (mostly estrogenic) bioactivities; these compounds are globally termed xenosteroids. In addition, synthetic drugs have been developed with combined estrogenic and anti-estrogenic actions, depending on the cellular context. These molecules, collectively named selective estrogen receptor modulators (SERMs), are provided with obvious pharmacological applications, but they may also serve in the characterization of the complex mode of action of estrogen in different physiological systems. Similarly, estrogen receptor (ER)-selective ligands have been recently identified or engineered, thus providing an experimental tool to dissect out the contribution of each of the two major ER isoforms (ERot and ERP) in signaling the plethora of estrogen effects in multiple target tissues. The hypothalamic- pituitary (HP) unit is highly sensitive to the actions of estrogen, although several aspects of estrogen effects upon the development and regulation of the HP unit remain partially unknown. The aim of this review is to provide a comprehensive overview of our recent work in the identification of molecular mechanisms and markers of exposure to xenoestrogens, as well as in the analysis of the biological effects of SERMs and ER-selective ligands at the HP unit.
KeywordsEstrogen Receptor Estradiol Benzoate Neonatal Exposure Estradiol Benzoate Antiestrogenic Action
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