Estrogen-regulated developmental neuronal apoptosis is determined by estrogen receptor subtype and the Fas/Fas ligand system
✍ Scribed by Nilsen, Jon ;Mor, Gil ;Naftolin, Frederick
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- English
- Weight
- 365 KB
- Volume
- 43
- Category
- Article
- ISSN
- 0022-3034
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✦ Synopsis
Adult sexual dimorphism in neuronal cell number is controlled by estrogen exposure during a tightly defined period of rat brain development. The mechanisms of estrogen's effect are unknown; one possibility is regulation of programmed cell death (apoptosis). In this study we have shown that estradiol can function as a neuroprotective agent or an inducer of apoptosis, depending on the estrogen receptor-subtype present in the cell. Thus, ER␣ has a neuroprotective effect, while ER mediates the induction of apoptosis in neuronal cells. Moreover, we show that estrogen-in-duced apoptosis through ER- requires the expression of Fas-and Fas ligand (FasL) proteins, since the absence of FasL in neurons prevents this effect. Furthermore, we demonstrate that microglia-secreted products induce the expression of FasL necessary to mediate estradiol-ER apoptotic effect. These findings may explain the dichotomous effect of fetal estradiol on the adult neuronal number.