Role of astrocytes in reproduction and neuroprotection

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.