Withania somnifera inhibits photorefractoriness which triggers neuronal apoptosis in both pre-optic and paraventricular hypothalamic area of Coturnix coturnix japonica: involvement of oxidative stress induced p53 dependent Caspase-3 mediated low immunoreactivity of estrogen receptor alpha.

Light has a very important function in the regulation of the normal physiology including the neuroendocrine system, biological rhythms, cognitive behavior, etc. The variation in photoperiod acts as a stressor due to imbalance in endogenous hormones. Estrogen and its receptors ER alpha and beta play a vital role in the control of stress response in birds. The study investigates the estrogenic effects of a well-known medicinal plant Withania somnifera (WS), mediated by estrogen receptor alpha (ERα) in the hypothalamic pre-optic area (POA) and paraventricular nuclei (PVN). Further the study elucidates its anti-oxidants and anti-apoptotic activities in the brain of Japanese quail. To validate this hypothesis, mature male quails were exposed to long day length for 3 months and then transferred to intermediate day length to become photorefractory (PR) while controls were still continued under long daylength. Supplementation of WS root extract in PR quail increases plasma estrogen and lowers corticosterone. Further, in PR quail the variation in light downregulates immunoreactivity of ERα, oxidative stress and antioxidant enzyme activities i.e. superoxide dismutase and catalase in the brain. Neuronal apoptosis was observed in the POA and PVN of PR quail as indicated by the abundant expression of Caspase-3 and p53 which reduces after the administration of WS root extract. The neuronal population also found to decrease in PR although it increased in WS administered quails. Further, the study concluded that change in photoperiod from 3 months exposure of 16L: 8D to 13.5L: 10.5D directly activates neuronal apoptosis via expression of Caspase3 and p53 expression in the brain and increases neuronal and gonadal oxidative stress while WS root extract reverses them via enhanced estrogen and its receptor ERα expression in the hypothalamic pre-optic and PVN area of Japanese quail.

Expression of estrogen receptor alpha in response to stress and estrogen antagonist tamoxifen in the shell gland of Gallus gallus domesticus: involvement of anti-oxidant system and estrogen.

Animals are frequently exposed to various kinds of environmental stressors and estrogen is known to play important role in stress response besides its crucial role in regulation of cellular proliferation, metabolic activity and reproduction. The study investigates the estrogen antagonist, tamoxifen (TM), mediated estrogen receptor alpha (ERα) expression, to modulate stress induced parameters in chickens. The study further explores the activity of superoxide dismutase (SOD), catalase and glutathione peroxidase (GPX) and malonaldehyde (MDA) in brain, ovary and shell gland during water deprivation (WD) and tamoxifen administration in sexually mature chicken. WD and TM administration both decrease the plasma estradiol while WD increases corticosterone. WD also elevates MDA concentration in the brain, ovary and shell gland while TM lowers it. WD and TM administration lowers the specific activity of SOD in brain and shell gland. In contrast, WD increases the specific activity of catalase, GPx and GR in the brain and shell gland, while TM decreases it. It appears that endogenous estradiol plays a crucial role in expression of antioxidant enzymes and tamoxifen acts as an antioxidant by reducing the oxidative stress in chicken. Abundant expression of ERα has been observed in the shell gland of egg laying birds while stress like water deprivation and TM down-regulates its expression. Thus, it can be concluded that expression of ERα in shell gland plays a predominant role in mediating estrogen action in response to water deprivation stress and tamoxifen.

Expression of estrogen receptor alpha in developing brain, ovary and shell gland of Gallus gallus domesticus: Impact of stress and estrogen.

Estrogen plays a central role in the control of reproductive behaviour and in the regulation of neuroendocrine system. To elucidate the mechanism by which it controls the stress-modulated functions, it is important to understand how estrogenic effects are mediated. The distribution of estrogen receptor alpha (ERα) protein in brain, ovary and shell gland of chickens has been investigated. Immature chickens were taken and randomly divided into four groups. First group served as control (C), second water deprived for two days (WD), third treated with estradiol benzoate (E) and fourth treated with estradiol benzoate followed by water deprivation during last two days of treatment (E + WD). The dose of estradiol benzoate administered for 15 days was 0.5 mg/100 g. Immuno-fluorescent localization demonstrated the presence of ER alpha (ERα) in hypothalamic area, principally the pre-optic area on estrogen administration. However, ERα expression in brain decreased on water deprivation. ERα expression was observed highly in granulosa and thecal cells of E and E + WD ovary compared to immature while least on water deprivation. Similarly, ERα expression was abundant in tunica muscularis and epithelial cells of E and E + WD shell gland while lesser in WD. Plasma estradiol significantly increased in E and E + WD group while decreased on water deprivation. Plasma corticosterone decreased significantly in E and E + WD group while increased in WD. Therefore, we conclude that administration of estradiol in stress decreases corticosterone induced sensitivity mediated by an increased expression of ERα in brain, ovary and shell gland. It appears that negative feedback regulation is involved between HPA-axis and HPG- axis during stress in chickens.