scholarly journals Sex hormones underlying 17a-Estradiol effects on neuroinflammation

2020 ◽  
Author(s):  
Lucas K. Debarba ◽  
Hashan Jayarathne ◽  
Richard A. Miller ◽  
Michael Garratt ◽  
Marianna Sadagurski
Keyword(s):  
Sex Hormones ◽  
Disease Onset ◽  
Brain Regions ◽  
Gonadal Hormone ◽  
Sexually Dimorphic ◽  
Hormone Production ◽  
Specific Effects ◽  
Hypothalamic Inflammation ◽  
Health And Disease ◽  
Male Specific

Abstract17-α-estradiol (17aE2) treatment extends lifespan in male mice and can reduce neuroinflammatory responses in the hypothalamus of 12-month-old males. Although 17aE2 improves longevity in males, female mice are unaffected, suggesting a sexually dimorphic pattern of lifespan regulation. We tested whether the sex-specific effects of 17aE2 on neuroinflammatory responses are mediated by sex hormones and whether hypothalamic changes extend to other brain regions in old age. Manipulating sex hormone levels through gonadectomy, we show that sex-specific effects of 17aE2 on age-associated gliosis are brain region-specific and are partially dependent on gonadal hormone production. 17aE2 treatment started at 4 months of age protected 25-month-old males from hypothalamic inflammation. Castration prior to 17aE2 exposure reduced the effect of 17aE2 on hypothalamic astrogliosis. By contrast, sex-specific changes in microgliosis with 17aE2 were not significantly affected by castration in males. While 17aE2 treatment had no effect of hypothalamic astrocytes or microglia in intact females, ovariectomy significantly increased the occurrence of hypothalamic gliosis evaluated in 25-month-old females, which was partially reduced by 17aE2. In the hippocampus, both male and female gonadally-derived hormones influenced the severity of gliosis and the responsiveness to 17aE2 in a regiondependent manner. The male-specific effects of 17aE2 correlate with changes in hypothalamic ERα expression, highlighting a receptor through which 17aE2 could act. The results of this study demonstrate that neuroinflammatory responses to 17aE2 are partially controlled by the presence of sex-specific gonads. Interactions between sex-steroids and neuroinflammation could, therefore, influence late-life health and disease onset, leading to sexual dimorphism in aging.

17-a-estradiol has sex-specific effects on neuroinflammation that are partly reversed by gonadectomy

2021 ◽  
Author(s):  
Lucas K Debarba ◽  
Hashan S M Jayarathne ◽  
Richard A Miller ◽  
Michael Garratt ◽  
Marianna Sadagurski
Keyword(s):  
Disease Onset ◽  
Brain Regions ◽  
Sexually Dimorphic ◽  
Dependent Manner ◽  
Specific Inhibition ◽  
Specific Effects ◽  
Hypothalamic Inflammation ◽  
Health And Disease ◽  
Male Specific ◽  
Lifespan Regulation

Abstract 17-α-estradiol (17aE2) treatment from 4-months of age extends lifespan in male mice and can reduce neuroinflammatory responses in the hypothalamus of 12-month-old males. Although 17aE2 improves longevity in males, female mice are unaffected, suggesting a sexually dimorphic pattern of lifespan regulation. We tested whether the sex-specific effects of 17aE2 on neuroinflammatory responses are affected by gonadal removal and whether hypothalamic changes extend to other brain regions in old age. We show that sex-specific effects of 17aE2 on age-associated gliosis are brain region-specific and are partially dependent on gonadectomy. 17aE2 treatment started at 4 months of age protected 25-month-old males from hypothalamic inflammation. Castration before 17aE2 exposure reduced the effect of 17aE2 on hypothalamic astrogliosis in males. By contrast, sex-specific inhibition of microgliosis generated by 17aE2 was not significantly affected by castration. In the hippocampus, gonadectomy influenced the severity of gliosis and the responsiveness to 17aE2 in a region-dependent manner. The male-specific effects of 17aE2 correlate with increases in hypothalamic ERα expression, specifically in gonadally intact males, consistent with the idea that 17aE2 might act through this receptor. Our results indicate that neuroinflammatory responses to 17aE2 are partially controlled by the presence of sex-specific gonads. Loss of gonadal function and age-associated neuroinflammation could, therefore, influence late-life health and disease onset, leading to sexual dimorphism in both aging and in response to drugs that modify the pace of aging.

scholarly journals Revealing the Influences of Sex Hormones and Sex Differences in Atrial Fibrillation and Vascular Cognitive Impairment

2021 ◽  
Vol 22 (16) ◽  
pp. 8776
Author(s):  
Ya-Ting Chang ◽  
Yung-Lung Chen ◽  
Hong-Yo Kang
Keyword(s):  
Atrial Fibrillation ◽  
Sex Differences ◽  
Cognitive Impairment ◽  
Sex Hormones ◽  
Disease Onset ◽  
Vascular Cognitive Impairment ◽  
Disease Diagnosis ◽  
Therapeutic Interventions ◽  
Organ Systems ◽  
Health And Disease

The impacts of sex differences on the biology of various organ systems and the influences of sex hormones on modulating health and disease have become increasingly relevant in clinical and biomedical research. A growing body of evidence has recently suggested fundamental sex differences in cardiovascular and cognitive function, including anatomy, pathophysiology, incidence and age of disease onset, symptoms affecting disease diagnosis, disease severity, progression, and treatment responses and outcomes. Atrial fibrillation (AF) is currently recognized as the most prevalent sustained arrhythmia and might contribute to the pathogenesis and progression of vascular cognitive impairment (VCI), including a range of cognitive deficits, from mild cognitive impairment to dementia. In this review, we describe sex-based differences and sex hormone functions in the physiology of the brain and vasculature and the pathophysiology of disorders therein, with special emphasis on AF and VCI. Deciphering how sex hormones and their receptor signaling (estrogen and androgen receptors) potentially impact on sex differences could help to reveal disease links between AF and VCI and identify therapeutic targets that may lead to potentially novel therapeutic interventions early in the disease course of AF and VCI.

scholarly journals Beneficial and Deleterious Effects of Female Sex Hormones, Oral Contraceptives, and Phytoestrogens by Immunomodulation on the Liver

2019 ◽  
Vol 20 (19) ◽  
pp. 4694
Author(s):  
Luis E. Soria-Jasso ◽  
Raquel Cariño-Cortés ◽  
Víctor Manuel Muñoz-Pérez ◽  
Elizabeth Pérez-Hernández ◽  
Nury Pérez-Hernández ◽  
...  
Keyword(s):  
Sex Hormones ◽  
Oral Contraceptives ◽  
Endocrine System ◽  
Sexually Dimorphic ◽  
Systemic Immune Response ◽  
Physiological Importance ◽  
Female Sex ◽  
Female Sex Hormones ◽  
Liver Functions ◽  
Health And Disease

The liver is considered the laboratory of the human body because of its many metabolic processes. It accomplishes diverse activities as a mixed gland and is in continuous cross-talk with the endocrine system. Not only do hormones from the gastrointestinal tract that participate in digestion regulate the liver functions, but the sex hormones also exert a strong influence on this sexually dimorphic organ, via their receptors expressed in liver, in both health and disease. Besides, the liver modifies the actions of sex hormones through their metabolism and transport proteins. Given the anatomical position and physiological importance of liver, this organ is evidenced as an immune vigilante that mediates the systemic immune response, and, in turn, the immune system regulates the hepatic functions. Such feedback is performed by cytokines. Pro-inflammatory and anti-inflammatory cytokines are strongly involved in hepatic homeostasis and in pathological states; indeed, female sex hormones, oral contraceptives, and phytoestrogens have immunomodulatory effects in the liver and the whole organism. To analyze the complex and interesting beneficial or deleterious effects of these drugs by their immunomodulatory actions in the liver can provide the basis for either their pharmacological use in therapeutic treatments or to avoid their intake in some diseases.

scholarly journals PDF-1 neuropeptide signaling regulates sexually dimorphic gene expression in shared sensory neurons of C. elegans

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Zoë A Hilbert ◽  
Dennis H Kim
Keyword(s):  
Sexually Dimorphic ◽  
Specific Expression ◽  
C Elegans ◽  
Pigment Dispersing Factor ◽  
Behavioral Decision ◽  
Specific Effects ◽  
Sexually Dimorphic Expression ◽  
Male Specific ◽  
Dimorphic Gene Expression ◽  
Dimorphic Expression

Sexually dimorphic behaviors are a feature common to species across the animal kingdom, however how such behaviors are generated from mostly sex-shared nervous systems is not well understood. Building on our previous work which described the sexually dimorphic expression of a neuroendocrine ligand, DAF-7, and its role in behavioral decision-making in C. elegans (Hilbert and Kim, 2017), we show here that sex-specific expression of daf-7 is regulated by another neuroendocrine ligand, Pigment Dispersing Factor (PDF-1), which has previously been implicated in regulating male-specific behavior (Barrios et al., 2012). Our analysis revealed that PDF-1 signaling acts sex- and cell-specifically in the ASJ neurons to regulate the expression of daf-7, and we show that differences in PDFR-1 receptor activity account for the sex-specific effects of this pathway. Our data suggest that modulation of the sex-shared nervous system by a cascade of neuroendocrine signals can shape sexually dimorphic behaviors.

scholarly journals A sexually dimorphic neuroendocrine cascade acts through shared sensory neurons to regulate behavior inC. elegans

2018 ◽  
Author(s):  
Zoë A. Hilbert ◽  
Dennis H. Kim
Keyword(s):  
Sexually Dimorphic ◽  
Animal Kingdom ◽  
Specific Expression ◽  
C Elegans ◽  
Pigment Dispersing Factor ◽  
Behavioral Decision ◽  
Specific Effects ◽  
Sexually Dimorphic Expression ◽  
Male Specific ◽  
Dimorphic Expression

ABSTRACTSexually dimorphic behaviors are observed in species across the animal kingdom, however the relative contributions of sex-specific and sex-shared nervous systems to such behaviors are not fully understood. Building on our previous work which described the sexually dimorphic expression of a neuroendocrine ligand, DAF-7, and its role in behavioral decision-making inC. elegans(Hilbert and Kim, 2017), we show here that sex-specific expression ofdaf-7is regulated by another neuroendocrine ligand, Pigment Dispersing Factor (PDF-1), which has previously been implicated in regulating male-specific behavior (Barrios et al., 2012). Our analysis revealed that PDF-1 acts sex- and cell-specifically in the ASJ neurons to regulate the expression ofdaf-7and we show that differences in the expression of the PDFR-1 receptor account for the sex-specific effects of this pathway. Our data suggest that modulation of the sex-shared nervous system by neuroendocrine signaling pathways can play a role in shaping sexually dimorphic behaviors.

scholarly journals Estrogen mediates sex differences in preoptic neuropeptide and pituitary hormone production in medaka

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Junpei Yamashita ◽  
Yuji Nishiike ◽  
Thomas Fleming ◽  
Daichi Kayo ◽  
Kataaki Okubo
Keyword(s):  
Anterior Pituitary ◽  
Pituitary Hormones ◽  
Pituitary Hormone ◽  
Sexually Dimorphic ◽  
Hormone Production ◽  
Anterior Pituitary Hormones ◽  
Vertebrate Brain ◽  
Pituitary Adenylate Cyclase ◽  
Evolutionarily Conserved ◽  
Sexually Dimorphic Expression

AbstractThe preoptic area (POA) is one of the most evolutionarily conserved regions of the vertebrate brain and contains subsets of neuropeptide-expressing neurons. Here we found in the teleost medaka that two neuropeptides belonging to the secretin family, pituitary adenylate cyclase-activating polypeptide (Pacap) and vasoactive intestinal peptide (Vip), exhibit opposite patterns of sexually dimorphic expression in the same population of POA neurons that project to the anterior pituitary: Pacap is male-biased, whereas Vip is female-biased. Estrogen secreted by the ovary in adulthood was found to attenuate Pacap expression and, conversely, stimulate Vip expression in the female POA, thereby establishing and maintaining their opposite sexual dimorphism. Pituitary organ culture experiments demonstrated that both Pacap and Vip can markedly alter the expression of various anterior pituitary hormones. Collectively, these findings show that males and females use alternative preoptic neuropeptides to regulate anterior pituitary hormones as a result of their different estrogen milieu.

scholarly journals Sex‐specific effects of wind on the flight decisions of a sexually dimorphic soaring bird

2020 ◽  
Vol 89 (8) ◽  
pp. 1811-1823 ◽  
Author(s):  
Thomas A. Clay ◽  
Rocío Joo ◽  
Henri Weimerskirch ◽  
Richard A. Phillips ◽  
Olivier Ouden ◽  
...  
Keyword(s):  
Sexually Dimorphic ◽  
Specific Effects

Subset-Specific Effects of Sex Hormones and Pituitary Gonadotropins on Human Lymphocyte Proliferation in Vitro

1993 ◽  
Vol 66 (3) ◽  
pp. 201-211 ◽  
Author(s):  
Balu H. Athreya ◽  
Jonathan Pletcher ◽  
Francesco Zulian ◽  
David B. Weiner ◽  
William V. Williams
Keyword(s):  
Sex Hormones ◽  
Human Lymphocyte ◽  
Lymphocyte Proliferation ◽  
Specific Effects ◽  
Proliferation In Vitro

The melanocortin-3 receptor is a pharmacological target for the regulation of anorexia

2021 ◽  
Vol 13 (590) ◽  
pp. eabd6434
Author(s):  
Patrick Sweeney ◽  
Michelle N. Bedenbaugh ◽  
Jose Maldonado ◽  
Pauline Pan ◽  
Katelyn Fowler ◽  
...  
Keyword(s):  
Sexual Dimorphism ◽  
Feeding Behavior ◽  
Critical Role ◽  
Brain Regions ◽  
Sexually Dimorphic ◽  
Male And Female ◽  
Female Mice ◽  
Bidirectional Regulation ◽  
Fear And Anxiety ◽  
Agouti Related Protein

Ablation of hypothalamic AgRP (Agouti-related protein) neurons is known to lead to fatal anorexia, whereas their activation stimulates voracious feeding and suppresses other motivational states including fear and anxiety. Despite the critical role of AgRP neurons in bidirectionally controlling feeding, there are currently no therapeutics available specifically targeting this circuitry. The melanocortin-3 receptor (MC3R) is expressed in multiple brain regions and exhibits sexual dimorphism of expression in some of those regions in both mice and humans. MC3R deletion produced multiple forms of sexually dimorphic anorexia that resembled aspects of human anorexia nervosa. However, there was no sexual dimorphism in the expression of MC3R in AgRP neurons, 97% of which expressed MC3R. Chemogenetic manipulation of arcuate MC3R neurons and pharmacologic manipulation of MC3R each exerted potent bidirectional regulation over feeding behavior in male and female mice, whereas global ablation of MC3R-expressing cells produced fatal anorexia. Pharmacological effects of MC3R compounds on feeding were dependent on intact AgRP circuitry in the mice. Thus, the dominant effect of MC3R appears to be the regulation of the AgRP circuitry in both male and female mice, with sexually dimorphic sites playing specialized and subordinate roles in feeding behavior. Therefore, MC3R is a potential therapeutic target for disorders characterized by anorexia, as well as a potential target for weight loss therapeutics.

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