HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 79/5/878    most recent biolreprod.108.069831v1 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 journal Similar articles in PubMed Alert me to new issues of the journal My Folders Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Neal-Perry, G. S. Articles by Etgen, A. M. Search for Related Content PubMed PubMed Citation Articles by Neal-Perry, G. S. Articles by Etgen, A. M. Agricola Articles by Neal-Perry, G. S. Articles by Etgen, A. M.

Restoration of the Luteinizing Hormone Surge in Middle-Aged Female Rats by Altering the Balance of GABA and Glutamate Transmission in the Medial Preoptic Area¹

Division of Reproductive Medicine and Infertility,³ Department of Obstetrics and Gynecology, and Department of Neuroscience,⁴ Albert Einstein College of Medicine, Bronx, New York 10461 Department of Neurology,⁵ Levine Neuroscience Laboratory, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854

ABSTRACT

Hypothalamic glutamate and gamma-aminobutyric acid (GABA) neurotransmission are involved in the ovarian hormone-induced GnRH-LH surge in rodents. We previously reported that middle-aged rats have significantly less glutamate release in the medial preoptic area than young rats on the day of the LH surge. The present study tested the hypothesis that the delayed and attenuated LH surge in ovariohysterectomized middle-aged rats primed with ovarian steroids results from reduced hypothalamic glutamate and increased GABA_A neurotransmission. Microdialysis results show that middle-aged rats with attenuated LH surges had reduced extracellular glutamate and increased extracellular GABA levels in the medial preoptic area compared with young rats. Blocking GABA_A receptors with bicuculline or inhibiting synaptic glutamate reuptake with L-trans-pyrrolidine-2,4-dicarboxylic acid increased extracellular Glu in the medial preoptic area and partially restored LH surge amplitude in middle-aged rats without altering LH surge onset. Complete recovery of LH surge amplitude was observed in middle-aged rats treated with the combination of bicuculline and L-trans-pyrrolidine-2,4-dicarboxylic acid. This treatment also restored the extracellular glutamate:GABA ratio in the medial preoptic area of middle-aged rats to the level of young rats. Immunoblot analysis revealed that estradiol and progesterone treatment reduced SLC32A1(formerly known as vesicular GABA transporter) levels and increased SLC17A6 (formerly known as vesicular glutamate transporter 2) levels in the anterior hypothalamus of ovariohysterectomized young but not middle-aged rats. These data suggest that both reduced availability of glutamate and increased activation of GABA_A receptors under estrogen-positive feedback conditions contribute to the age-related delay in onset and attenuated amplitude of the LH surge..

aging, estradiol, GABA_A receptors, glutamate, gonadotropin-releasing hormone neurons, hypothalamus, luteinizing hormone

¹Supported by National Institutes of Health grants T32 HD40135 and RO1 HD29856, the Robert Wood Johnson Foundation, and the American Federation for Aging Research.

Correspondence: ²Genevieve S. Neal-Perry, Department of Obstetrics and Gynecology, Division of Reproductive Medicine and Infertility, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461. FAX: 718 430 8586; e-mail: sienna3598{at}aol.com