17α-Estradiol Exerts Neuroprotective Effects on SK-N-SH Cells

Abstract

Estradiol (E2) has been shown to exert organizational, neurotrophic, and neuroprotective effects in the CNS. The present study assessed the specificity of the neuroprotective effects of estradiol for the potent 17␤-isomer. SK-N-SH cells from a human neuroblastoma cell line, which we have shown to be estrogen-responsive, were cultured at low or high plating density. Then cells were exposed to 17␤-E2 (0.2 or 2 nM), 17␣-E2 (0.2 or 2 nM), or cholesterol, testosterone, dihydrotestosterone, progesterone, or corticosterone (all at 2 nM). Cultures were insulted by serum deprivation, which caused a profound loss of cells. At 1 or 2 d of serum deprivation and steroid hormone replacement, the protection afforded cells by the steroid addition was assessed. Serum deprivation killed ϳ90% of cells cultured at both low and high plating density. Both 17␣-and 17␤-E2 provided protection of SK-N-SH cells at either plating density. Further, a 10-fold molar excess of tamoxifen antagonized only approximately one-third of the neuroprotective effects of either isomer of estradiol, and a 100-fold excess of tamoxifen had no additional effect on the neuroprotection by 17␤-E2. By contrast, none of the other steroids tested protected cells from the insult of serum deprivation. These results indicate that the neuroprotective effects of estrogens are not attributable to the general steroid structure, and the majority of the neuroprotection may not be mediated via a tamoxifenantagonized receptor mechanism.

17β-Estradiol upregulates and activates WOX1/WWOXv1 and WOX2/WWOXv2 in vitro: potential role in cancerous progression of breast and prostate to a premetastatic state in vivo

“…Under similar conditions, E 2 could not induce apoptosis of Mv1Lu and other cells tested in this study. Estrogen is generally considered to exert neuroprotection (Gangolli et al, 1997;Green et al, 1997;Gridley et al, 1998;Garcia-Segura et al, 2001;Wise, 2002) and protect breast tissues from apoptosis (Gompel et al, 2000;review). However, at high doses estrogen may induce apoptosis (Song and Santen, 2003;review).…”

“…E 2 induced phosphorylation of nuclear p53 in MDA-MB-231 but not in MDA-MB-435S cells (Figure 5b). p53 levels in (Gangolli et al, 1997;Green et al, 1997;Gridley et al, 1998). Mechanism of this regard is unknown.…”

Hydroxytamoxifen protects against oxidative stress in brain mitochondria

“…Indeed, some animal studies indicate the existence of dose-related biphasic effects of estradiol [47,48]. Some effects are lost at higher concentrations [47,48], whereas others require high doses [49]. These dose-related effects could be taken as an advantage to possibly dissociate some activities in the target tissue.…”

Estrogen actions on mitochondria—Physiological and pathological implications

“…Following our first report of neuroprotection with estrogens in an animal model of ischemia (Simpkins et al, 1997a, we and other have demonstrated that estrogens protects the brain from ischemic damage induced by transient cerebral ischemia (Alkayed et al, 1998;Rusa et al, 1999;Hurn and Macrae, 2000;Shi et al, 2001,Sampei et al, 2000, permanent cerebral ischemia (Dubal et al, 1998Yang et al, 2001), subarachnoid hemorrhage , and global ischemia (He et al, 2002). The protective effects of estrogens are seen with 17β-estradiol, as well as non-feminizing estrogens, such as 17α-estradiol , ENT-estradiol , and 2-adamantyl-estrone (Liu et al, 2002).…”