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Neuroendocrine mechanisms for reproductive senescence in the female rat

Gonadotropin-releasing hormone neurons

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Abstract

Reproductive aging in female rats is characterized by profound alterations in the neuroendocrine axis. The preovulatory luteinizing hormone (LH) surge is attenuated, and preovulatory expression of the immediate early gene fos in gonadotropin-releasing hormone (GnRH) neurons is substantially reduced in middleaged compared with young rats. We tested the hypothesis that alterations in GnRH gene expression may be correlated with the attenuation of the LH surge and may be a possible mechanism involved in neuroendocrine senescent changes. Sprague-Dawley rats ages 4 to 5 mo (young), 12–14 mo (middle-aged), or 25 to 26 mo (old) were killed at 10:00 am or 3:00 pm on proestrus, the day of the LH surge, or diestrus I in cycling rats, and on persistent estrus or persistent diestrus in acyclic rats. RNase protection assays of GnRH mRNA and GnRH primary transcript were performed. GnRH mRNA levels in creased significantly with age, whereas GnRH primary transcripts levels, and index of GnRH gene transcription, decreased in old compared to young and middle-aged rats. This latter result suggests that an age-related change in GnRH mRNA levels occurs independently of a change in gene transcription, indicating a potential posttranscriptional mechanism. On proestrus, GnRH mRNA levels increased significantly from 10:00 am to 3:00 pm in young rats. This was in contrast to proestrous middle-aged rats, in which this afternoon increase in GnRH mRNA levels was not observed. Thus, the normal afternoon increase in GnRH mRNA levels on proestrus is disrupted by middle age and may represent a substrate for the attenuation of the preovulatory GnRH/LH surge that occurs in rats of this age, prior to reproductive failure.

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Authors and Affiliations

  1. Fishberg Research Center for Neurobiology, Mount Sinai School of Medicine, New York, NY

    Andrea C. Gore Ph.D., Twethida Oung, Shouyee Yung & Roxana A. Flagg

  2. Henry L. Schwartz Department of Geriatrics and Adult Development, Mounts Sinai School of Medicine, New York, NY

    Andrea C. Gore Ph.D.

  3. Department of Biological Sciences, University of Wisconsin-Whitewater, Whitewater, WI

    Michael J. Woller

  4. Neurobiology of Aging Laboratories, Mount Sinai School of Medicine, Box 1639, 10029, New York, NY

    Andrea C. Gore Ph.D., Twethida Oung, Shouyee Yung & Roxana A. Flagg

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  1. Andrea C. Gore Ph.D.
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  2. Twethida Oung
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Correspondence to Andrea C. Gore Ph.D..

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Gore, A.C., Oung, T., Yung, S. et al. Neuroendocrine mechanisms for reproductive senescence in the female rat. Endocr 13, 315–323 (2000). https://doi.org/10.1385/ENDO:13:3:315

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