Estrogen-astrocyte-luteinizing hormone-releasing hormone signaling: A role for transforming growth factor-β1

C. D. Buchanan, V. B. Mahesh, D. W. Brann

Research output: Contribution to journalArticlepeer-review

117 Scopus citations


The purpose of this study was to identify factors from astrocytes that can regulate LHRH neurosecretion. Exposure of LHRH-secreting (GT1-7) cells to conditioned media (CM) from C6 glial cells and hypothalamic astrocytes (HA) stimulated LHRH release. Assays of C6 and HA CM revealed that transforming growth factor-β1 (TGF-β1) and 3α-hydroxy-5α-pregnane-20-one (3α,5α- THP), both known LHRH secretagogues, were present in CM and their levels increased in parallel to the LHRH-releasing activity of CM. In contrast, TGF- α was undetectable in C6 or HA CM. Ultrafiltration to remove peptides with molecular weights >10 kDa virtually abolished the LHRH-releasing ability of the HA CM. Furthermore, immunoneutralization with a panspecific THF-β antibody dose-dependently attenuated the LHRH-releasing activity of the CM. Rat hypothalamus and GT1-7 cells were demonstrated to express TGF-β receptors as well as furin, an enzyme that converts latent TGF-β1 to active TGF-β1. Estrogen receptor-α and ER-β mRNA and protein were also demonstrated in HAs by reverse transcription-polymerase chain reaction and double immunofluorescence, and treatment with 17β-estradiol (17β-E2) increased both active and latent TGF-β1 levels in HA CM. The effect of 17β-E2 was completely blocked by the ER antagonist IC18280. As a whole, these studies provide evidence of a previously undescribed 17β-E2-TGF-β1- LHRH signaling pathway.

Original languageEnglish (US)
Pages (from-to)1710-1721
Number of pages12
JournalBiology of reproduction
Issue number6
StatePublished - 2000

ASJC Scopus subject areas

  • Reproductive Medicine
  • Cell Biology


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