Neurodegenerative Disease: Roles for Sex, Hormones, and Oxidative Stress

Endocrinology ◽  
2021 ◽  
Author(s):  
Nathalie Sumien ◽  
J Thomas Cunningham ◽  
Delaney L Davis ◽  
Rachel Engelland ◽  
Oluwadarasimi Fadeyibi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Diseases ◽  
Sex Hormones ◽  
Intracellular Signaling ◽  
Hormone Receptors ◽  
Chromosome Complement ◽  
Sex Hormone ◽  
Stress Conditions ◽  
Signaling Cascades ◽  
Aging Men

Abstract Neurodegenerative diseases cause severe impairments in cognitive and motor function. With an increasing aging population and the onset of these diseases between 50-70 years, the consequences are bound to be devastating. While age and longevity are the main risk factors for neurodegenerative diseases, sex is also an important risk factor. Sex is multifaceted, encompassing sex chromosome complement, sex hormones (estrogens and androgens), and sex hormone receptors. Sex hormone receptors can induce various signaling cascades, ranging from genomic transcription to intracellular signaling pathways that are dependent on the health of the cell. Oxidative stress, associated with aging, can impact the health of the cell. Sex hormones can be neuroprotective under low oxidative stress conditions but not in high oxidative stress conditions. An understudied sex hormone receptor that can induce activation of oxidative stress signaling is the membrane androgen receptor (mAR). mAR can mediate NADPH oxidase (NOX) generated oxidative stress that is associated with several neurodegenerative diseases, such as Alzheimer’s disease. Further complicating this is that aging can alter sex hormone signaling. Prior to menopause, women experience more estrogens than androgens. During menopause, this sex hormone profile switches in women due to the dramatic ovarian loss of 17β-estradiol with maintained ovarian androgen (testosterone, androstenedione) production. Indeed, aging men have higher estrogens than aging women due to aromatization of androgens to estrogens. Therefore, higher activation of mAR-NOX signaling could occur in menopausal women compared to aged men, mediating the observed sex differences. Understanding these signaling cascades could provide therapeutic targets for neurodegenerative diseases.

scholarly journals Neuropharmacological Potential ofGastrodia elataBlume and Its Components

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Jung-Hee Jang ◽  
Yeonghoon Son ◽  
Seong Soo Kang ◽  
Chun-Sik Bae ◽  
Jong-Choon Kim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Brain Function ◽  
Intracellular Signaling ◽  
Inflammatory Responses ◽  
Signaling Cascades ◽  
Sedative Medication ◽  
Synthetic Chemicals ◽  
Injured Brain ◽  
Injury Models ◽  
The Brain

Research has been conducted in various fields in an attempt to develop new therapeutic agents for incurable neurodegenerative diseases.Gastrodia elataBlume (GE), a traditional herbal medicine, has been used in neurological disorders as an anticonvulsant, analgesic, and sedative medication. Several neurodegenerative models are characterized by oxidative stress and inflammation in the brain, which lead to cell death via multiple extracellular and intracellular signaling pathways. The blockade of certain signaling cascades may represent a compensatory therapy for injured brain tissue. Antioxidative and anti-inflammatory compounds isolated from natural resources have been investigated, as have various synthetic chemicals. Specifically, GE rhizome extract and its components have been shown to protect neuronal cells and recover brain function in various preclinical brain injury models by inhibiting oxidative stress and inflammatory responses. The present review discusses the neuroprotective potential of GE and its components and the related mechanisms; we also provide possible preventive and therapeutic strategies for neurodegenerative disorders using herbal resources.

scholarly journals Neuroprotective Effect of Antioxidants in the Brain

2020 ◽  
Vol 21 (19) ◽  
pp. 7152 ◽  
Author(s):  
Kyung Hee Lee ◽  
Myeounghoon Cha ◽  
Bae Hwan Lee
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Diseases ◽  
Intracellular Signaling ◽  
Neuronal Damage ◽  
Neuroprotective Effect ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
High Energy ◽  
Antioxidant Compounds ◽  
The Brain

The brain is vulnerable to excessive oxidative insults because of its abundant lipid content, high energy requirements, and weak antioxidant capacity. Reactive oxygen species (ROS) increase susceptibility to neuronal damage and functional deficits, via oxidative changes in the brain in neurodegenerative diseases. Overabundance and abnormal levels of ROS and/or overload of metals are regulated by cellular defense mechanisms, intracellular signaling, and physiological functions of antioxidants in the brain. Single and/or complex antioxidant compounds targeting oxidative stress, redox metals, and neuronal cell death have been evaluated in multiple preclinical and clinical trials as a complementary therapeutic strategy for combating oxidative stress associated with neurodegenerative diseases. Herein, we present a general analysis and overview of various antioxidants and suggest potential courses of antioxidant treatments for the neuroprotection of the brain from oxidative injury. This review focuses on enzymatic and non-enzymatic antioxidant mechanisms in the brain and examines the relative advantages and methodological concerns when assessing antioxidant compounds for the treatment of neurodegenerative disorders.

Sex Hormone Receptors in Vocal Fold Tissue: A Theory about the Influence of Sex Hormones in the Larynx

2011 ◽  
Vol 63 (2) ◽  
pp. 77-82 ◽  
Author(s):  
Andrea Nacci ◽  
Bruno Fattori ◽  
Fabio Basolo ◽  
Maria E. Filice ◽  
Katia De Jeso ◽  
...  
Keyword(s):  
Sex Hormones ◽  
Vocal Fold ◽  
Hormone Receptors ◽  
Sex Hormone

Sex hormone receptors in varicose veins of women with premenstrual syndrome

Phlebologie ◽  
2008 ◽  
Vol 37 (02) ◽  
pp. 68-72 ◽  
Author(s):  
L. Dzieciuchowicz ◽  
M. Kotwicka ◽  
M. Gabriel ◽  
A. Szczęśniak-Chmielecka ◽  
B. Krasińska ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Sex Hormones ◽  
Hormone Receptors ◽  
Varicose Veins ◽  
Progesterone Receptors ◽  
Muscle Cells ◽  
Sex Hormone ◽  
Estrogen And Progesterone Receptors ◽  
Premenstrual Tension

SummaryThe pathogenesis of premenstrual tension syndrome is not fully understood. It has been hypothesized that the interaction between sex hormones and target organs is the key event in its pathogenesis. Aim: The purpose of the study was to examine the differences in the prevalence of smooth muscle cells with sex hormones receptors in varicose veins of women with and without premenstrual tension syndrome (PS). Patients, methods: Samples of great saphenous vein were obtained from 50 women during varicose vein surgery. They were divided into group I (20 women with clinically diagnosed PS) and group II (30 women without PS). Estrogen and progesterone receptors were detected with an immunohistochemical method. Superficial densities of smooth muscle cells positive to estrogen and progesterone receptors were analyzed with densitometric program IM-AN and automatic image analyzer Magicall. The results were compared with t-Student test. Results: There were no differences in superficial density of smooth muscle cells positive to estrogen receptors between the groups. In contradiction to this, superficial density of smooth muscle cells positive to progesterone receptors was higher in group with PS than in patients without, 343 (±171) and 240 (±123), respectively. The difference was statistically significant (p < 0.05). Conclusion: The amount of cells with sex hormone receptors, not the level of hormones, could play a role in PS pathology. Our results show that progesterone is more important than estrogen in effector organs.

scholarly journals Effect of the Combined Extracts of Herba Epimedii and Fructus Ligustri Lucidi on Sex Hormone Functional Levels in Osteoporosis Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
RenHui Liu ◽  
Xue Kang ◽  
LiPing Xu ◽  
HongLei Nian ◽  
XinWei Yang ◽  
...  
Keyword(s):  
Sex Hormones ◽  
Bone Histomorphometry ◽  
Hormone Receptors ◽  
Sex Hormone ◽  
Mineral Density ◽  
Oral Gavage ◽  
Treatment Of Osteoporosis ◽  
Fructus Ligustri Lucidi ◽  
Prevention And Treatment ◽  
Herba Epimedii

The combination of Herba Epimedii and Fructus Ligustri Lucidi has been used to treat osteoporosis for almost 50 years by Professor Shizeng Li, a famous doctor of traditional Chinese medicine (TCM). However, it is unclear whether the combination of the effective constituents of the two herbs may have a protective influence on the skeleton. In the present study, we investigated the effects of the combination extracts of Herba Epimedii and Fructus Ligustri Lucidi on rat model of osteoporosis induced by retinoic acid by gavage. With administrations of the combination extracts of the two herbs (50, 100, and 200 mg/kg/day) via oral gavage for 3 weeks, bone mineral density (BMD), femur histomorphometry, some sex hormones, and sex hormone receptors were measured. Results showed that the combined extracts could increase BMD, affect bone histomorphometry, coordinate the sex hormones at the level of hypothalamus-pituitary-gonad axis, and increase the protein and mRNA expressions of sex hormone receptors. The findings suggested that the combination extracts of Herba Epimedii and Fructus Ligustri Lucidi might be beneficial as an alternative medicine for the prevention and treatment of osteoporosis.

Expression status of mRNA for sex hormone receptors in human dental pulp cells and the response to sex hormones in the cells

2013 ◽  
Vol 58 (8) ◽  
pp. 943-950 ◽  
Author(s):  
Tomohiro Inaba ◽  
Tomoko Kobayashi ◽  
Takeo W. Tsutsui ◽  
Masaaki Ogawa ◽  
Minoru Uchida ◽  
...  
Keyword(s):  
Sex Hormones ◽  
Dental Pulp ◽  
Hormone Receptors ◽  
Sex Hormone ◽  
Dental Pulp Cells ◽  
Human Dental Pulp Cells ◽  
Human Dental Pulp ◽  
Pulp Cells ◽  
Expression Status

scholarly journals Mechanistic Pathways of Sex Differences in Cardiovascular Disease

2017 ◽  
Vol 97 (1) ◽  
pp. 1-37 ◽  
Author(s):  
Vera Regitz-Zagrosek ◽  
Georgios Kararigas
Keyword(s):  
Sex Differences ◽  
Sex Hormones ◽  
Intracellular Signaling ◽  
Hormone Receptors ◽  
Pressure Overload ◽  
New Drugs ◽  
Cellular Processes ◽  
Cardiovascular Cells ◽  
Artery Disease ◽  
Underlying Mechanisms

Major differences between men and women exist in epidemiology, manifestation, pathophysiology, treatment, and outcome of cardiovascular diseases (CVD), such as coronary artery disease, pressure overload, hypertension, cardiomyopathy, and heart failure. Corresponding sex differences have been studied in a number of animal models, and mechanistic investigations have been undertaken to analyze the observed sex differences. We summarize the biological mechanisms of sex differences in CVD focusing on three main areas, i.e., genetic mechanisms, epigenetic mechanisms, as well as sex hormones and their receptors. We discuss relevant subtypes of sex hormone receptors, as well as genomic and nongenomic, activational and organizational effects of sex hormones. We describe the interaction of sex hormones with intracellular signaling relevant for cardiovascular cells and the cardiovascular system. Sex, sex hormones, and their receptors may affect a number of cellular processes by their synergistic action on multiple targets. We discuss in detail sex differences in organelle function and in biological processes. We conclude that there is a need for a more detailed understanding of sex differences and their underlying mechanisms, which holds the potential to design new drugs that target sex-specific cardiovascular mechanisms and affect phenotypes. The comparison of both sexes may lead to the identification of protective or maladaptive mechanisms in one sex that could serve as a novel therapeutic target in one sex or in both.

scholarly journals Sexual Dimorphism in the Regulation of Estrogen, Progesterone, and Androgen Receptors by Sex Steroids in the Rat Airway Smooth Muscle Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Abraham Zarazúa ◽  
Aliesha González-Arenas ◽  
Gabriela Ramírez-Vélez ◽  
Blanca Bazán-Perkins ◽  
Christian Guerra-Araiza ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Sex Hormones ◽  
Airway Smooth Muscle ◽  
Hormone Receptors ◽  
Muscle Cells ◽  
Sex Hormone ◽  
Male Rats ◽  
Airway Smooth Muscle Cells

The role of sex hormones in lung is known. The three main sex steroid receptors, estrogen, progesterone, and androgen, have not been sufficiently studied in airway smooth muscle cells (ASMC), and the sex hormone regulation on these receptors is unknown. We examined the presence and regulation of sex hormone receptors in female and male rat ASMC by Western blotting and flow cytometry. Gonadectomized rats were treated with 17β-estradiol, progesterone, 17β-estradiol + progesterone, or testosterone. ASMC were enzymatically isolated from tracheas and bronchi. The experiments were performed with double staining flow cytometry (anti-α-actin smooth muscle and antibodies to each hormone receptor). ERα, ERβ, tPR, and AR were detected in females or males. ERαwas upregulated by E2 and T and downregulated by P4 in females; in males, ERαwas downregulated by P4, E + P, and T. ERβwas downregulated by each treatment in females, and only by E + P and T in males. tPR was downregulated by P4, E + P, and T in females. No hormonal regulation was observed in male receptors. AR was downregulated in males treated with E + P and T. We have shown the occurrence of sex hormone receptors in ASMC and their regulation by the sex hormones in female and male rats.

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