A role for hypothalamic astrocytes in dehydroepiandrosterone and estradiol regulation of gonadotropin-releasing hormone (GnRH) release by GnRH neurons

Ismail H. Zwain, Armando Arroyo, Paula Amato, Samuel S.C. Yen

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

Molecules of astrocyte origin influence gonadotropin-releasing hormone (GnRH) release and GnRH neuronal growth and differentiation. Furthermore, type 1 astrocytes express steroid receptors, presenting the possibility that steroid actions on GnRH neurons might occur via astrocytes. Utilizing GT1-7 cells, a GnRH-secreting cell line, the present study demonstrates that astrocytes mediate dehydroepiandrosterone (DHEA) or estradiol (E2) stimulated GnRH secretion. Conditioned media (CM) from astrocytes cultured for 48 h alone, with DHEA (DHEA-CM), or with E2 (E2-CM) were collected, treated with charcoal to remove steroids, and added to GT1-7 cells in culture for 12 h to test the effect on GnRH secretion. DHEA-CM and E2-CM stimulated GnRH secretion by GT1-7 cells by 4- and 3-fold, respectively. The effect of DHEA-CM on GnRH secretion by GT1-7 cells appears to be related to both DHEA and its metabolite, E2, since blocking the metabolism of DHEA into estrogen in the DHEA-treated astrocytes partially reversed the stimulatory effect of DHEA-CM. Addition of transforming growth factor (TGF)-β1-neutralizing antibody to the astrocyte cultures reversed the stimulatory effects of both DHEA-CM and E2-CM on GnRH secretion by GT1-7 cells, suggesting that TGF-β1 derived from astrocytes may be the principle mediator of E2 and DHEA effects. These data provide evidence for a novel mechanism by which circulating steroids and/or neurosteroids may modulate GnRH secretion.

Original languageEnglish (US)
Pages (from-to)375-383
Number of pages9
JournalNeuroendocrinology
Volume75
Issue number6
DOIs
StatePublished - 2002
Externally publishedYes

Keywords

  • Astrocytes
  • Gonadal steroid receptors
  • Gonadal steroids
  • Gonadotropin-releasing hormone
  • GT1-7 cell line
  • Transforming growth factor

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

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