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Attenuation of Preoptic Area Glutamate Release Correlates with Reduced Luteinizing Hormone Secretion in Middle-Aged Female Rats

Department of Obstetrics and Gynecology, Division of Reproductive Medicine and Infertility (G.S.N.-P., N.F.S.) and Department of Neuroscience (A.M.E.), Albert Einstein College of Medicine, Bronx, New York 10461; and Levine Neuroscience Laboratory, Department of Neurology (G.D.Z.), University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medial School, Piscataway, New Jersey 08854

Address all correspondence and requests for reprints to: Genevieve S. Neal-Perry, Department of Obstetrics and Gynecology, Division of Reproductive Medicine and Infertility, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461.

Glutamate (Glu) and its receptors are involved in the maturation and maintenance of the neural mechanisms governing the preovulatory LH surge of young, reproductive-aged rodents and nonhuman primates. Little is known about the role of Glu in the delayed onset and reduced peak amplitude of the LH surge that characterizes female rodents during early reproductive senescence. The present study tested the hypothesis that the delayed and attenuated LH surge observed in middle-aged female rats is associated with altered hypothalamic Glu release. We used intracerebral microdialysis in young (3–4 months) and middle-aged (9–11 months) female rats to monitor changes in medial preoptic area Glu release and jugular vein catheters to monitor changes in serum LH levels. All animals were ovariectomized and injected with estradiol and progesterone in doses sufficient to produce a robust LH surge in most (70%) young rats. In both young and middle-aged females that surged, extracellular Glu levels were higher than in those that did not surge. Among animals that surged, the onset of the LH surge was significantly delayed, and the amplitude of the surge was significantly reduced in middle-aged compared with young rats. Middle-aged females also had significantly reduced extracellular Glu levels throughout the day of the LH surge when compared with young females. These data strongly suggest that age-related hypothalamic dysfunction contributes to reproductive aging independent of gonadal failure. We propose that reduced medial preoptic area Glu transmission contributes to reproductive aging by attenuating excitatory input to GnRH neurons.

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