Protective Actions of 17 β

Steroid hormones synthesized in and secreted from peripheral endocrine glands pass through the blood-brain barrier and play a role in the central nervous system. In addition, the brain possesses an inherent endocrine system and synthesizes steroid hormones known as neurosteroids. Increasing evidence shows that neuroactive steroids protect the central nervous system from various harmful stimuli. Reports show that the neuroprotective actions of steroid hormones attenuate oxidative stress. In this review, we summarize the antioxidative effects of neuroactive steroids, especially 17β-estradiol and progesterone, on neuronal injury in the central nervous system under various pathological conditions, and then describe our recent findings concerning the neuroprotective actions of 17β-estradiol and progesterone on oxidative neuronal injury induced by organometallic compounds, tributyltin, and methylmercury

Estrogen and Mitochondrial Function in Disease

Anecdotal and scientific evidence suggest that the sex hormone estrogen provides significant health benefits in women. Women have higher estrogen levels than men. Circulating estrogen reaches its highest level during the reproductive period and steadily declines with the onset of menopause. The role of estrogen and estrogen receptors in both cellular physiology and pathophysiology has been controversial. Estrogen has anti-inflammatory and anti-oxidant effects, which preserve cell viability during cardiovascular incidents, but it enhances disease progression in the context of breast cancer. Estrogen mediates these responses via activation of estrogen receptor subtypes located in the cell membrane, nucleus, and mitochondrion. Further, transcription of nuclear and mitochondrial genes by estrogen yields products that play an important role in regulating mitochondrial function. Mitochondria are part of a highly dynamic network and undergo fission and fusion, produce cellular energy, adenosine 5′ triphosphate (ATP), and regulate cell death. Herein, we review the cell and receptor specific effects of estrogen on mitochondrial structure, function, and cell death under normal physiological conditions and in the context of cardiovascular disease, inflammation, neurodegeneration, and cancer. Further research is needed to elucidate the specific role of estrogenic control of mitochondria in health and disease

Mitochondrial and sex steroid hormone crosstalk during aging

Decline in circulating sex steroid hormones accompanies several age-associated pathologies which may influence human healthspan. Mitochondria play important roles in biosynthesis of sex steroid hormones, and these hormones can also regulate mitochondrial function. Understanding the cross talk between mitochondria and sex steroid hormones may provide insights into the pathologies associated with aging. The aim of this review is to summarize the current knowledge regarding the interplay between mitochondria and sex steroid hormones during the aging process. The review describes the effect of mitochondria on sex steroid hormone production in the gonads, and then enumerates the contribution of sex steroid hormones on mitochondrial function in hormone responsive cells. Decline in sex steroid hormones and accumulation of mitochondrial damage may create a positive feedback loop that contributes to the progressive degeneration in tissue function during aging. The review further speculates whether regulation between mitochondrial function and sex steroid hormone action can potentially influence healthspan

Mechanisms of Estrogens’ Dose-Dependent Neuroprotective and Neurodamaging Effects in Experimental Models of Cerebral Ischemia

Ever since the hypothesis was put forward that estrogens could protect against cerebral ischemia, numerous studies have investigated the mechanisms of their effects. Despite initial studies showing ameliorating effects, later trials in both humans and animals have yielded contrasting results regarding the fundamental issue of whether estrogens are neuroprotective or neurodamaging. Therefore, investigations of the possible mechanisms of estrogen actions in brain ischemia have been difficult to assess. A recently published systematic review from our laboratory indicates that the dichotomy in experimental rat studies may be caused by the use of insufficiently validated estrogen administration methods resulting in serum hormone concentrations far from those intended, and that physiological estrogen concentrations are neuroprotective while supraphysiological concentrations augment the damage from cerebral ischemia. This evidence offers a new perspective on the mechanisms of estrogens’ actions in cerebral ischemia, and also has a direct bearing on the hormone replacement therapy debate. Estrogens affect their target organs by several different pathways and receptors, and the mechanisms proposed for their effects on stroke probably prevail in different concentration ranges. In the current article, previously suggested neuroprotective and neurodamaging mechanisms are reviewed in a hormone concentration perspective in an effort to provide a mechanistic framework for the dose-dependent paradoxical effects of estrogens in stroke. It is concluded that five protective mechanisms, namely decreased apoptosis, growth factor regulation, vascular modulation, indirect antioxidant properties and decreased inflammation, and the proposed damaging mechanism of increased inflammation, are currently supported by experiments performed in optimal biological settings

Daidzein: A review of pharmacological effects

Background: Daidzein is an isoflavone with extensive nutritious value and is mainly extracted from soy plants. It is also called phytoestrogen due to its structural similarity to the human hormone estrogen. However, daidzein is distinct from estrogen due to the specificity of the estrogen receptor (ER) complex. In recent years, the pharmacological properties of daidzein have been extensively investigated and considerable progress has been made. The present review aims to evaluate the pharmacological effects and mechanisms of daidzein as reported in scientific literature.Materials and Methods: Studies were identified as reported in PubMed, Elsevier, Scholar, and Springer over the last ten years and this resulted in the identification of 112 papers.Results: Daidzein is reported to play a significant role in the prevention and treatment of a variety of diseases such as cancer, cardiovascular disease, diabetes, osteoporosis, skin disease, and neurodegenerative disease. This pharmacological activity is attributed to various metabolites including equol and trihydroxy isoflavone.Conclusion: Daidzein appears to play a significant role in the prevention of a variety of diseases and has the potential of being used in a clinical setting. However, further research is needed to understand its molecular mechanisms and safety for use in humans.Keywords: Plant, natural product, phytoestrogen, pharmacolog

Neuroprotective Effects of 17β-Estradiol Rely on Estrogen Receptor Membrane Initiated Signals

Besides its crucial role in many physiological events, 17β-estradiol (E2) exerts protective effects in the central nervous system. The E2 effects are not restricted to the brain areas related with the control of reproductive function, but rather are widespread throughout the developing and the adult brain. E2 actions are mediated through estrogen receptors (i.e., ERα and ERβ) belonging to the nuclear receptor super-family. As members of the ligand-regulated transcription factor family, classically, the actions of ERs in the brain were thought to mediate only the E2 long-term transcriptional effects. However, a growing body of evidence highlighted rapid, membrane initiated E2 effects in the brain that are independent of ER transcriptional activities and are involved in E2-induced neuroprotection. The aim of this review is to focus on the rapid effects of E2 in the brain highlighting the specific role of the signaling pathway(s) of the ERβ subtype in the neuroprotective actions of E2

DAIDZEIN: A REVIEW OF PHARMACOLOGICAL EFFECTS

Background: Daidzein is an isoflavone with extensive nutritious value and is mainly extracted from soy plants. It is also called phytoestrogen due to its structural similarity to the human hormone estrogen. However, daidzein is distinct from estrogen due to the specificity of the estrogen receptor (ER) complex. In recent years, the pharmacological properties of daidzein have been extensively investigated and considerable progress has been made. The present review aims to evaluate the pharmacological effects and mechanisms of daidzein as reported in scientific literature. Materials and Methods: Studies were identified as reported in PubMed, Elsevier, Scholar, and Springer over the last ten years and this resulted in the identification of 112 papers. Results: Daidzein is reported to play a significant role in the prevention and treatment of a variety of diseases such as cancer, cardiovascular disease, diabetes, osteoporosis, skin disease, and neurodegenerative disease. This pharmacological activity is attributed to various metabolites including equol and trihydroxy isoflavone. Conclusion: Daidzein appears to play a significant role in the prevention of a variety of diseases and has the potential of being used in a clinical setting. However, further research is needed to understand its molecular mechanisms and safety for use in humans. Keywords: Plant, natural product, phytoestrogen, pharmacolog

Sex and Sex Hormones in Tissue Homeostasis

Women are not small men. Sex-specific differences do not only affect the classical target organs of sexual differentiation and reproduction, but have been found to involve most, if not all the organs and tissues in the body. One of the consequences of this dimorphism is that diseases manifest in a sex- and gender-specific way. Key to maintenance of a healthy state is functioning tissue able to cope with insults. Regulated death of damaged cells and replacement with new cells by proliferation is a prerequisite for maintaining tissue function taking place at different pace in the different organs. The intent of this chapter is to review current evidence for sex-specific differences in tissue homeostasis focusing on the variability of hormone exposure characteristic for the female reproductive life stages

17β-Estradiol as a Neuroprotective Agent

The pathophysiology of neurodegeneration in the central nervous system is complex and multifactorial in nature and yet to be fully understood. Broad-spectrum neuroprotective agents with multiple mechanisms of action rather than a single druggable target are, therefore, highly desirable. The main human estrogen, 17β-estradiol, can also be considered a neurosteroid as it forms de novo in the central nervous system, and it possesses beneficial effects against practically all critical contributors to neurodegeneration to collectively thwart both the initiation and the progression of neuronal cell death. This chapter details the main aspects of the hormone’s genomic and non-genomic actions important to protect the highly vulnerably neurons of the central nervous system, as well as translational efforts to successfully realize its powerful neuroprotective potential in clinical setting while ensuring both therapeutic safety and efficacy