Role of astrocytes in reproduction and neuroprotection

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

Hypothalamic astrocytes secrete TGF-β and 3α,5α-tetrahydro progesterone (3α,5α-THP) in culture. When the astrocyte-conditioned medium (ACM) was incubated with the hypothalamic cell line GT1-7, it resulted in the secretion of GnRH. Immunoneutralization with TGF-β antibody or ultrafilteration with a 10 kDa cut off filter resulted in attenuation of the GnRH releasing ability of ACM, indicating that TGF-β was a major factor involved with GnRH release. Treatment with estrogens increases TGF-β secretion. These observations indicate a significant role of astrocytes in GnRH secretion. Serum-deprivation results in the death of GT1-7 neurons in culture and addition of ACM or TGF-β to the culture, attenuates cell death. The mechanism of protection from cell death appears to involve phosphorylation of MKK4, JNK, c-JunSer63, and enhancement of AP-1 binding. Co-administration of JNK inhibitors, but not MEK inhibitors attenuated ACM or TGF-β-induced c-JunSer63 phosphorylation and their neuroprotective effects. These studies suggest that astrocytes can protect neurons, at least in part, by the release of TGF-β and activation of a c-Jun/AP-1 protective pathway.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalMolecular and Cellular Endocrinology
Volume246
Issue number1-2
DOIs
StatePublished - Feb 26 2006

Fingerprint

Astrocytes
Reproduction
Conditioned Culture Medium
Gonadotropin-Releasing Hormone
Phosphorylation
Transcription Factor AP-1
Cell death
Neurons
Cell Death
Mitogen-Activated Protein Kinase Kinases
Neuroprotective Agents
Neuroprotection
Progesterone
Estrogens
Chemical activation
Cells
Cell Line
Antibodies
Serum

Keywords

  • Astrocytes
  • C-Jun/AP-1
  • Estradiol-17β
  • GnRH
  • Neuroprotection
  • TGF-β

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Cite this

Role of astrocytes in reproduction and neuroprotection. / Mahesh, Virendra B.; Dhandapani, Krishnan Michael; Brann, Darrell W.

In: Molecular and Cellular Endocrinology, Vol. 246, No. 1-2, 26.02.2006, p. 1-9.

Research output: Contribution to journalArticle

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