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      Regulation of gonadotropin-releasing hormone (GnRH) gene expression by 5alpha-dihydrotestosterone in GnRH-secreting GT1-7 hypothalamic neurons.

      1 , , , ,
      Endocrinology
      The Endocrine Society

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          Abstract

          Hypothalamic GnRH secretory neurons are precisely regulated by circulating gonadal steroids. However, the question of whether these cells are directly responsive to steroid hormones remains a central and controversial issue in reproductive science. In the present study, we demonstrate the expression of androgen receptor (AR) in a mouse hypothalamic GnRH-secreting cell line, GT1-7. AR messenger RNA was detected by Northern blot analysis of 10 microg total cellular RNA. Western blot analysis revealed a 110K AR immunoreactive band, and saturation binding analysis confirmed the presence of a high affinity low capacity androgen binding entity (Kd = 0.06 nM; Bmax = 12.4 fmol/mg protein). In addition, GT1-7 cells were found to express ARA70, an AR-specific coactivator that has been reported to enhance transactivational activity of the AR. GT1-7 cells transiently transfected with an androgen responsive MMTV-luciferase reporter construct displayed a 4.2-fold induction of luciferase reporter gene activity by 1 nM 5alpha-dihydrotestosterone (DHT), further demonstrating the presence of a functional AR. Treatment of GT1-7 cells with 1 or 10 nM DHT resulted in approximately 55% reduction in GnRH messenger RNA measured at 24 and 36 h after treatment. This repression was completely blocked by hydroxyflutamide, an AR antagonist. These results provide the first demonstration that androgen acts directly through an AR-mediated pathway to repress GnRH gene expression in hypothalamic GnRH-secreting neurons.

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          Author and article information

          Journal
          Endocrinology
          Endocrinology
          The Endocrine Society
          0013-7227
          0013-7227
          Mar 1998
          : 139
          : 3
          Affiliations
          [1 ] Department of Physiology, University of Toronto and Toronto Hospital Research Institute, Ontario, Canada. d.belsham@utoronto.ca
          Article
          10.1210/endo.139.3.5846
          9492044
          7d14fe22-c310-466b-bca3-2702a317ffd2
          History

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