Research

Jump to: Review

10 pages, 2211 KiB

Open AccessArticle

Decreased Expression of Estrogen Receptors Is Associated with Tumorigenesis in Papillary Thyroid Carcinoma

by Chen-Kai Chou, Shun-Yu Chi, Yi-Yung Hung, Yi-Chien Yang, Hung-Chun Fu, Jia-He Wang, Chueh-Chen Chen and Hong-Yo Kang

Int. J. Mol. Sci. 2022, 23(3), 1015; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23031015 - 18 Jan 2022

Cited by 6 | Viewed by 1878

Abstract

Papillary thyroid carcinomas (PTC), which is derived from thyroid follicular cells, is the most commonly differentiated thyroid cancer with sex disparity. However, the role of estrogen receptors (ERs) in the pathogenesis of PTC remains unclear. The present study aimed to determine the association [...] Read more.

Papillary thyroid carcinomas (PTC), which is derived from thyroid follicular cells, is the most commonly differentiated thyroid cancer with sex disparity. However, the role of estrogen receptors (ERs) in the pathogenesis of PTC remains unclear. The present study aimed to determine the association of ER mRNA expression levels with clinicopathologic features in PTC. To that aim, the mRNA levels of ESR1 (ERα66), ESR1 (ERα36), ESR2, and G-protein-coupled estrogen receptor 1 (GPER1) in snap-frozen tissue samples from PTCs and adjacent normal thyroid tissues were determined using quantitative reverse transcription polymerase chain reaction (RT-qPCR), and the correlation between ER mRNA expression levels and clinicopathologic features was analyzed. The expression of ERα66, ERα36, ERβ, and GPER1 was lower in PTC specimens than in adjacent normal thyroid tissues. Moreover, low GPER1 expression was associated with extrathyroidal extension. There was no obvious difference in expression of ERs between PTC specimens from male and female patients. In conclusion, our findings highlight the importance of ERs in PTC tumorigenesis. Full article

(This article belongs to the Special Issue Steroid Hormones and Sex Difference in Diseases)

► Show Figures

Figure 1

26 pages, 3949 KiB

Open AccessArticle

Estradiol Protects against Noise-Induced Hearing Loss and Modulates Auditory Physiology in Female Mice

by Benjamin Shuster, Ryan Casserly, Erika Lipford, Rafal Olszewski, Béatrice Milon, Shaun Viechweg, Kanisa Davidson, Jennifer Enoch, Mark McMurray, Mark A. Rutherford, Kevin K. Ohlemiller, Michael Hoa, Didier A. Depireux, Jessica A. Mong and Ronna Hertzano

Int. J. Mol. Sci. 2021, 22(22), 12208; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222212208 - 11 Nov 2021

Cited by 19 | Viewed by 4970

Abstract

Recent studies have identified sex-differences in auditory physiology and in the susceptibility to noise-induced hearing loss (NIHL). We hypothesize that 17β-estradiol (E₂), a known modulator of auditory physiology, may underpin sex-differences in the response to noise trauma. Here, we gonadectomized B6CBAF1/J [...] Read more.

Recent studies have identified sex-differences in auditory physiology and in the susceptibility to noise-induced hearing loss (NIHL). We hypothesize that 17β-estradiol (E₂), a known modulator of auditory physiology, may underpin sex-differences in the response to noise trauma. Here, we gonadectomized B6CBAF1/J mice and used a combination of electrophysiological and histological techniques to study the effects of estrogen replacement on peripheral auditory physiology in the absence of noise exposure and on protection from NIHL. Functional analysis of auditory physiology in gonadectomized female mice revealed that E₂-treatment modulated the peripheral response to sound in the absence of changes to the endocochlear potential compared to vehicle-treatment. E₂-replacement in gonadectomized female mice protected against hearing loss following permanent threshold shift (PTS)- and temporary threshold shift (TTS)-inducing noise exposures. Histological analysis of the cochlear tissue revealed that E₂-replacement mitigated outer hair cell loss and cochlear synaptopathy following noise exposure compared to vehicle-treatment. Lastly, using fluorescent in situ hybridization, we demonstrate co-localization of estrogen receptor-2 with type-1C, high threshold spiral ganglion neurons, suggesting that the observed protection from cochlear synaptopathy may occur through E₂-mediated preservation of these neurons. Taken together, these data indicate the estrogen signaling pathways may be harnessed for the prevention and treatment of NIHL. Full article

(This article belongs to the Special Issue Steroid Hormones and Sex Difference in Diseases)

► Show Figures

Figure 1

14 pages, 3294 KiB

Open AccessArticle

Hepatic LKB1 Reduces the Progression of Non-Alcoholic Fatty Liver Disease via Genomic Androgen Receptor Signaling

by Jun H. Heo, Sang R. Lee, Seong Lae Jo, Je-Won Ko, Hyo-Jung Kwon and Eui-Ju Hong

Int. J. Mol. Sci. 2021, 22(15), 7904; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22157904 - 23 Jul 2021

Cited by 3 | Viewed by 2496

Abstract

The incidence of non-alcoholic fatty liver disease (NAFLD) increases in males aged >45 years, which indicates that androgens are associated with the development and/or progression of NAFLD, although excess dietary intake is the primary causative factor. However, it is uncertain how androgens are [...] Read more.

The incidence of non-alcoholic fatty liver disease (NAFLD) increases in males aged >45 years, which indicates that androgens are associated with the development and/or progression of NAFLD, although excess dietary intake is the primary causative factor. However, it is uncertain how androgens are involved in the metabolic process of NAFLD, which is associated with the state of steatosis in hepatocytes. To investigate whether androgen receptor (AR) signaling influences NAFLD development, the state of steatosis was monitored in mouse livers and hepatocytes with or without androgens. As a result, hepatic lipid droplets, expression of AR, and phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) increased in the presence of testosterone. Concurrently, the expression of LKB1, an upstream regulator of AMPK, was increased by testosterone treatment. We observed that the fluctuation of AMPK-ACC signaling, which plays an important role in lipogenesis, depends on the presence of testosterone and AR. Additionally, we demonstrated that testosterone bound AR was recruited to the promoter of the LKB1 gene and induced LKB1 expression. Our study highlights a novel mechanism by which testosterone modulates NAFLD development by inducing the mRNA expression of LKB1. Full article

(This article belongs to the Special Issue Steroid Hormones and Sex Difference in Diseases)

► Show Figures

Figure 1

Review

Jump to: Research

20 pages, 730 KiB

Open AccessReview

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

by Ya-Ting Chang, Yung-Lung Chen and Hong-Yo Kang

Int. J. Mol. Sci. 2021, 22(16), 8776; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22168776 - 16 Aug 2021

Cited by 7 | Viewed by 3033

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Steroid Hormones and Sex Difference in Diseases)

► Show Figures

Figure 1

21 pages, 420 KiB

Open AccessReview

Sex Differences in Otolaryngology: Focus on the Emerging Role of Estrogens in Inflammatory and Pro-Resolving Responses

by Sheng-Dean Luo, Tai-Jan Chiu, Wei-Chih Chen and Ching-Shuen Wang

Int. J. Mol. Sci. 2021, 22(16), 8768; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22168768 - 16 Aug 2021

Cited by 4 | Viewed by 2756

Abstract

Otolaryngology (also known as ear, nose, and throat (ENT)) diseases can be significantly affected by the level of sex hormones, which indicates that sex differences affect the manifestation, pathophysiology, and outcomes of these diseases. Recently, increasing evidence has suggested that proinflammatory responses in [...] Read more.

Otolaryngology (also known as ear, nose, and throat (ENT)) diseases can be significantly affected by the level of sex hormones, which indicates that sex differences affect the manifestation, pathophysiology, and outcomes of these diseases. Recently, increasing evidence has suggested that proinflammatory responses in ENT diseases are linked to the level of sex hormones. The sex hormone receptors are present on a wide variety of immune cells; therefore, it is evident that they play crucial roles in regulating the immune system and hence affect the disease progression of ENT diseases. In this review, we focus on how sex hormones, particularly estrogens, regulate ENT diseases, such as chronic rhinosinusitis, vocal fold polyps, thyroid cancer, Sjögren’s syndrome, and head and neck cancers, from the perspectives of inflammatory responses and specialized proresolving mediator-driven resolution. This paper aims to clarify why considering sex differences in the field of basic and medical research on otolaryngology is a key component to successful therapy for both males and females in the future. Full article

(This article belongs to the Special Issue Steroid Hormones and Sex Difference in Diseases)

16 pages, 726 KiB

Open AccessReview

Sex Differences in the Triad of Acquired Sensorineural Hearing Loss

by Kuang-Hsu Lien and Chao-Hui Yang

Int. J. Mol. Sci. 2021, 22(15), 8111; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22158111 - 28 Jul 2021

Cited by 17 | Viewed by 5271

Abstract

The triad of noise-generated, drug-induced, and age-related hearing loss is the major cause of acquired sensorineural hearing loss (ASNHL) in modern society. Although these three forms of hearing loss display similar underlying mechanisms, detailed studies have revealed the presence of sex differences in [...] Read more.

The triad of noise-generated, drug-induced, and age-related hearing loss is the major cause of acquired sensorineural hearing loss (ASNHL) in modern society. Although these three forms of hearing loss display similar underlying mechanisms, detailed studies have revealed the presence of sex differences in the auditory system both in human and animal models of ASNHL. However, the sexual dimorphism of hearing varies among noise-induced hearing loss (NIHL), ototoxicity, and age-related hearing loss (ARHL). Importantly, estrogen may play an essential role in modulating the pathophysiological mechanisms in the cochlea and several reports have shown that the effects of hormone replacement therapy on hearing loss are complex. This review will summarize the clinical features of sex differences in ASNHL, compare the animal investigations of cochlear sexual dimorphism in response to the three insults, and address how estrogen affects the auditory organ at molecular levels. Full article

(This article belongs to the Special Issue Steroid Hormones and Sex Difference in Diseases)

► Show Figures

Figure 1

13 pages, 867 KiB

Open AccessReview

Androgen/Androgen Receptor Signaling in Ovarian Cancer: Molecular Regulation and Therapeutic Potentials

by Wei-Min Chung, Lumin Chen, Wei-Chun Chang, Sheng-Yuan Su, Yao-Ching Hung and Wen-Lung Ma

Int. J. Mol. Sci. 2021, 22(14), 7748; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22147748 - 20 Jul 2021

Cited by 19 | Viewed by 2885

Abstract

Ovarian cancer (OVCA) arises from three cellular origins, namely surface epithelial cells, germ cells, and stromal cells. More than 85% of OVCAs are EOCs (epithelial ovarian carcinomas), which are the most lethal gynecological malignancies. Cancer stem/progenitor cells (CSPCs) are considered to be cancer [...] Read more.

Ovarian cancer (OVCA) arises from three cellular origins, namely surface epithelial cells, germ cells, and stromal cells. More than 85% of OVCAs are EOCs (epithelial ovarian carcinomas), which are the most lethal gynecological malignancies. Cancer stem/progenitor cells (CSPCs) are considered to be cancer promoters due to their capacity for unlimited self-renewal and drug resistance. Androgen receptor (AR) belongs to the nuclear receptor superfamily and can be activated through binding to its ligand androgens. Studies have reported an association between AR expression and EOC carcinogenesis, and AR is suggested to be involved in proliferation, migration/invasion, and stemness. In addition, alternative AR activating signals, including both ligand-dependent and ligand-independent, are involved in OVCA progression. Although some clinical trials have previously been conducted to evaluate the effects of anti-androgens in EOC, no significant results have been reported. In contrast, experimental studies evaluating the effects of anti-androgen or anti-AR reagents in AR-expressing EOC models have demonstrated positive results for suppressing disease progression. Since AR is involved in complex signaling pathways and may be expressed at various levels in OVCA, the aim of this article was to provide an overview of current studies and perspectives regarding the relevance of androgen/AR roles in OVCA. Full article

(This article belongs to the Special Issue Steroid Hormones and Sex Difference in Diseases)

► Show Figures

Figure 1

12 pages, 44242 KiB

Open AccessReview

The Effect of Castration on Peripheral Autonomic Neurons Supplying Mammalian Male Genitourinary System

by Jerzy Kaleczyc and Ewa Lepiarczyk

Int. J. Mol. Sci. 2021, 22(14), 7632; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22147632 - 16 Jul 2021

Viewed by 2215

Abstract

This review paper deals with the influence of androgens (testosterone) on pelvic autonomic pathways in male mammals. The vast majority of the relevant information has been gained in experiments involving castration (testosterone deprivation) performed in male rats, and recently, in male pigs. In [...] Read more.

This review paper deals with the influence of androgens (testosterone) on pelvic autonomic pathways in male mammals. The vast majority of the relevant information has been gained in experiments involving castration (testosterone deprivation) performed in male rats, and recently, in male pigs. In both species, testosterone significantly affects the biology of the pathway components, including the pelvic neurons. However, there are great differences between rats and pigs in this respect. The most significant alteration is that testosterone deprivation accomplished a few days after birth results some months later in the excessive loss (approximately 90%) of pelvic and urinary bladder trigone intramural neurons in the male pig, while no changes in the number of pelvic neurons are observed in male rats (rats do not have the intramural ganglia). In the castrated pigs, much greater numbers of pelvic neurons than in the non-castrated animals express CGRP, GAL, VIP (peptides known to have neuroprotective properties), and caspase 3, suggesting that neurons die due to apoptosis triggered by androgen deprivation. In contrast, only some morpho-electrophysiological changes affecting neurons following castration are found in male rats. Certain clinicopathological consequences of testosterone deprivation for the functioning of urogenital organs are also discussed. Full article

(This article belongs to the Special Issue Steroid Hormones and Sex Difference in Diseases)

► Show Figures

Figure 1

17 pages, 1621 KiB

Open AccessReview

Let’s Talk about Placental Sex, Baby: Understanding Mechanisms That Drive Female- and Male-Specific Fetal Growth and Developmental Outcomes

by Ashley S. Meakin, James S. M. Cuffe, Jack R. T. Darby, Janna L. Morrison and Vicki L. Clifton

Int. J. Mol. Sci. 2021, 22(12), 6386; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22126386 - 15 Jun 2021

Cited by 53 | Viewed by 5483

Abstract

It is well understood that sex differences exist between females and males even before they are born. These sex-dependent differences may contribute to altered growth and developmental outcomes for the fetus. Based on our initial observations in the human placenta, we hypothesised that [...] Read more.

It is well understood that sex differences exist between females and males even before they are born. These sex-dependent differences may contribute to altered growth and developmental outcomes for the fetus. Based on our initial observations in the human placenta, we hypothesised that the male prioritises growth pathways in order to maximise growth through to adulthood, thereby ensuring the greatest chance of reproductive success. However, this male-specific “evolutionary advantage” likely contributes to males being less adaptable to shifts in the in-utero environment, which then places them at a greater risk for intrauterine morbidities or mortality. Comparatively, females are more adaptable to changes in the in-utero environment at the cost of growth, which may reduce their risk of poor perinatal outcomes. The mechanisms that drive these sex-specific adaptations to a change in the in-utero environment remain unclear, but an increasing body of evidence within the field of developmental biology would suggest that alterations to placental function, as well as the feto-placental hormonal milieu, is an important contributing factor. Herein, we have addressed the current knowledge regarding sex-specific intrauterine growth differences and have examined how certain pregnancy complications may alter these female- and male-specific adaptations. Full article

(This article belongs to the Special Issue Steroid Hormones and Sex Difference in Diseases)

► Show Figures