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MINIREVIEW

Aging-Related Changes in Ovarian Hormones, Their Receptors, and Neuroendocrine Function

Tandra R. Chakraborty^* and Andrea C. Gore^,1

^* Fishberg Research Center for Neurobiology, Mount Sinai School of Medicine, New York, New York 10029; and Division of Pharmacology/Toxicology, College of Pharmacy, Institute for Neuroscience, and Institute for Cellular & Molecular Biology, University of Texas at Austin, Austin, Texas 78712

To whom requests for reprints should be addressed at ¹ Division of Pharmacology/ Toxicology, University of Texas at Austin, Austin, TX 78712. E-mail: andrea.gore{at}mail.utexas.edu

Ovarian steroid hormones exert a broad range of effects on the body and brain. In the nervous system, estrogen and progesterone have crucial feedback actions on the hypothalamic neurons that drive the reproductive axis. In addition, hormones exert a variety of actions on other traditionally nonreproductive functions such as cognition, learning and memory, neuroprotection, mood and affective behavior, and locomotor activity. The actions of hormones on the hypothalamus are largely mediated by their nuclear hormone receptors, the two estrogen receptors, ER and ERß, and the two progesterone receptor isoforms, PR-A and PR-B. Thus, changes in the circulating concentrations of estrogens and progestins during the life cycle can result in differential activation of their receptors. Furthermore, changes in the numbers, activity, and distribution of hypothalamic ERs and PRs can occur as a function of developmental age. The purpose of this article is to review the literature on the causes and consequences of alterations in steroid hormones, their neural receptors, and their interactions on reproductive senescence. We have also discussed several important experimental design considerations, focusing on rodent models in current use for understanding the mechanisms of menopause in women.

Key Words: estrogen receptor • progesterone receptor • aging • menopause • neuroendocrine • hypothalamus

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