Abstract：
:Hypothalamic astrocytes secrete TGF-beta and 3 alpha,5 alpha-tetrahydro progesterone (3 alpha,5 alpha-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-beta antibody or ultra-filteration with a 10 kDa cut off filter resulted in attenuation of the GnRH releasing ability of ACM, indicating that TGF-beta was a major factor involved with GnRH release. Treatment with estrogens increases TGF-beta 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-beta to the culture, attenuates cell death. The mechanism of protection from cell death appears to involve phosphorylation of MKK4, JNK, c-Jun(Ser63), and enhancement of AP-1 binding. Co-administration of JNK inhibitors, but not MEK inhibitors attenuated ACM or TGF-beta-induced c-Jun(Ser63) phosphorylation and their neuroprotective effects. These studies suggest that astrocytes can protect neurons, at least in part, by the release of TGF-beta and activation of a c-Jun/AP-1 protective pathway.
journal_name
Mol Cell Endocrinoljournal_title
Molecular and cellular endocrinologyauthors
Mahesh VB,Dhandapani KM,Brann DWdoi
10.1016/j.mce.2005.11.017keywords:
subject
Has Abstractpub_date
2006-02-26 00:00:00pages
1-9issue
1-2eissn
0303-7207issn
1872-8057pii
S0303-7207(05)00421-1journal_volume
246pub_type
杂志文章,评审abstract：:Incubation of pituitary GH1 cells with N'-methylnicotinamide, nicotinamide and 3-acetylpyridine which inhibit nuclear ADP-ribosylation and/or the cellular concentration of its substrate NAD+ reduced the amount of nuclear thyroid hormone receptors in a time- and dose-dependent manner without altering the affinity of th...
journal_title：Molecular and cellular endocrinology
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journal_title：Molecular and cellular endocrinology
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journal_title：Molecular and cellular endocrinology
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pub_type： 杂志文章,评审
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journal_title：Molecular and cellular endocrinology
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journal_title：Molecular and cellular endocrinology
pub_type： 杂志文章,评审
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journal_title：Molecular and cellular endocrinology
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