This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this book Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wise, P. M. Articles by Rosewell, K. L. Search for Related Content PubMed PubMed Citation Articles by Wise, P. M. Articles by Rosewell, K. L.

Neuroendocrine Modulation and Repercussions of Female Reproductive Aging

Department of Physiology, University of Kentucky College of Medicine, Lexington, Kentucky 40536-0298

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 influence 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 fixed 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 neurochemical events that are critical to the preovulatory gonadotropin-releasing hormone (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 luteinizing hormone 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 estrogens. In summary, our studies show that age-related changes in the ability of estradiol to coordinate the neuroendocrine events that lead to regular preovulatory GnRH surges contribute to the onset of irregular estrous cycles and eventually to acyclicity. Furthermore, we have shown that the lack of estradiol increases the vulnerability of the brain to injury and neurodegeneration.

This article has been cited by other articles:

				V. Pilorz and S. Steinlechner Low reproductive success in Per1 and Per2 mutant mouse females due to accelerated ageing? Reproduction, April 1, 2008; 135(4): 559 - 568. [Abstract] [Full Text] [PDF]

				H.G. Burger, G.E. Hale, D.M. Robertson, and L. Dennerstein A review of hormonal changes during the menopausal transition: focus on findings from the Melbourne Women's Midlife Health Project Hum. Reprod. Update, November 1, 2007; 13(6): 559 - 565. [Abstract] [Full Text] [PDF]

				J. L. Downs and H. F. Urbanski Neuroendocrine Changes in the Aging Reproductive Axis of Female Rhesus Macaques (Macaca mulatta) Biol Reprod, October 1, 2006; 75(4): 539 - 546. [Abstract] [Full Text] [PDF]

				A. Franczak, A. Nynca, K. E. Valdez, K. M. Mizinga, and B. K. Petroff Effects of Acute and Chronic Exposure to the Aryl Hydrocarbon Receptor Agonist 2,3,7,8-Tetrachlorodibenzo-p-Dioxin on the Transition to Reproductive Senescence in Female Sprague-Dawley Rats Biol Reprod, January 1, 2006; 74(1): 125 - 130. [Abstract] [Full Text] [PDF]

				G. S. Roth, J. A. Mattison, M. A. Ottinger, M. E. Chachich, M. A. Lane, and D. K. Ingram Aging in Rhesus Monkeys: Relevance to Human Health Interventions Science, September 3, 2004; 305(5689): 1423 - 1426. [Abstract] [Full Text] [PDF]

				B.-M. Landgren, A. Collins, G. Csemiczky, H. G. Burger, L. Baksheev, and D. M. Robertson Menopause Transition: Annual Changes in Serum Hormonal Patterns over the Menstrual Cycle in Women during a Nine-Year Period Prior to Menopause J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 2763 - 2769. [Abstract] [Full Text] [PDF]