The effects of glutamate can be attenuated by estradiol via estrogen receptor dependent pathway in rat adrenal pheochromocytoma cells

Abstract

Estrogens have been suggested to exhibit neuroprotective activities against several insults including beta-amyloid and glutamate, one of the excitatory neurotransmitters in the central nervous system. In the present study, we showed that exposure to glutamate not only inhibited the cell growth of exponentially growing rat pheochromocytoma PC12 cells in a time- and dose-dependent manner, but also influenced cell adherence capacity. Glutamate-induced growth inhibition was significantly attenuated by the co-administration of estradiol in PC12 cells. Pre-exposure of the PC12 cells to the estradiol was not required for protection against glutamate-induced growth inhibition. Administration of anti-estrogen ICI182,780 efficiently blocked the neuroprotective effects of estradiol. Glutamate-induced changes in cell adherence, on the other hand, were not significantly affected by estradiol. These data indicate that the neuroprotective effects of estradiol against glutamate-induced insults in PC12 cells, at least in part, involve estrogen receptor-dependent pathways.

Opposite effects of tamoxifen on metabolic syndrome‐induced bladder and prostate alterations: A role for GPR30/GPER?

“…The latter reached statistically significant only at a concentration of estradiol that is in the high physiological range (1 nM), at least in the male. In addition, the pure classical ER antagonist ICI 182,780 did not blocked, but even increased, 17β‐estradiol (1 nM)‐induced IL‐8 release in the spent medium. It is interesting to note that ICI 182,780 acts as GPER agonist in several tissues .…”

GPR30 estrogen receptor agonists induce mechanical hyperalgesia in the rat

“…However, ICI 182,780 has also recently been shown to bind and activate GPR30 at concentrations between 1 and 10 µ m (Filardo et al ., 2002; Boulware et al ., 2005; Thomas et al ., 2005). Importantly, ICI 182,780 is first of all known to inhibit estrogen functions mediated by the classical estrogen receptors ERα and ERβ (DeFriend et al ., 1994; Molinari et al ., 2000; Chan et al ., 2007). Therefore, we complemented our pharmacological studies by using this GPR30 agonist and simultaneous inhibitor of ERα and ERβ.…”

“…To substantiate the finding that the novel estrogen receptor GPR30 apparently mediates the recently described effect of estrogen on nociceptive neurons, we used a second agonist of GPR30, which simultaneously blocks signalling through ERα and ‐β, ICI 182,780 (DeFriend et al ., 1994; Molinari et al ., 2000; Chan et al ., 2007). The behavioural experiments established a clear dose‐dependence for intradermal ICI 182,780 to produce mechanical hyperalgesia (ICI 182,780 dissolved to 10 mg/mL in 100% DMSO, diluted to final concentration in 2.5 µL in PBS; final concentration of DMSO 10%) into hind paws of male rats.…”

Protective effect of estrogen on apoptosis in a cell culture model of Parkinson's disease

“…19 Estrogen is also found to bind to specific membrane receptors to regulate gene transcription, influencing the balance of the cell death suppression gene and cell-death-accelerating gene. [20][21][22] Bcl-x is a member of the Bcl-2 family with apoptosis suppression being its major function. ICE is a proteinase whose main action is to mediate cell death.…”