lec 21 aging.pptx - Reproductive Aging 37 (a review of...

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1 Overview of the neuroendocrine control of reproduction: E2 - and + feedbacks, preovulatory GnRH and LH release, preovulatory surge of LH and ovulation Reproductive aging (menopause) is brought about by a decline in the activation of the GnRH system to the positive feedback of E2 to induce preovulatory surges of LH Reproductive failure associated with aging is linked to disfunction of hypothalamic clock genes Reproductive Aging 37 (a review of general endocrinology) S ± E ? Today’s lecture control and “story lines” S ± E ?
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2 Neuroendocrine modulation and repercussions of female reproductive aging. PM Wise, MJ Smith, DB Dubal, ME Wilson, SW Rau, AB Cashion, M Bottner and KL Rosewell, Dept of Physiology, College of Medicine, Lexington, Kentucky 40536-0208. The Endocrine Society (2002). The menopause marks the end of a woman's reproductive life. During the postmenopausal period, plasma estrogen concentrations decrease dramatically and remain low for the rest of her life, unless she chooses to take hormone replacement therapy. During the past 20 years, we have learned that changes in the central nervous system are associated with and may in f uence the timing of the menopause in women. Recently, it has become clear that estrogens act on more than just the hypothalamus, pituitary, ovary, and other reproductive organs. In fact, they play roles in a wide variety of nonreproductive functions. With the increasing life span of humans from approximately 50 to 80 years and the relatively F xed age of the menopause, a larger number of women will spend over one third of their lives in the postmenopausal state. It is not surprising that interest has increased in factors that govern the timing of the menopause and the repercussions of the lack of estrogen on multiple aspects of women's health. We have used animal models to better understand the complex interactions between the ovary and the brain that lead to the menopause and the repercussions of the hypoestrogenic state. Our results show that when rats reach middle age, the patterns and synchrony of multiple neuro- chemical events that are critical to the preovulatory GnRH surge undergo subtle changes. The precision of rhythmic pattern of neurotransmitter dynamics depends on the presence of estradiol. Responsiveness to this hormone decreases in middle-aged rats. The lack of precision in the coordination in the output of neural signals leads to a delay and attenuation of the LH surge, which lead to irregular estrous cyclicity and, ultimately, to the cessation of reproductive cycles. We also have examined the impact of the lack of estrogen on the vulnerability of the brain to injury. Our work establishes that the absence of estradiol increases the extent of cell death after stroke-like injury and that treatment with low physiological levels of estradiol are profoundly neuroprotective. We have begun to explore the cellular and molecular mechanisms that underlie this novel nonreproductive action of
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lec 21 aging.pptx - Reproductive Aging 37 (a review of...

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