Sex Steroids and proteomics

Gonadal hormone deprivation (GHD) and decline such as menopause and bilateral oophorectomy are associated with an increased risk of neurodegeneration. Yet, hormone therapies (HTs) show varying efficacy, influenced by factors such as sex, drug type, and timing of treatment relative to hormone decline. We hypothesize that the molecular environment of the brain undergoes a transition following GHD, impacting the effectiveness of HTs. Using a GHD model in mice treated with Tibolone, we conducted proteomic analysis and identified a reprogrammed response to Tibolone, a compound that stimulates estrogenic, progestogenic, and androgenic pathways...

Sex hormone-binding globulin (SHBG) is a serum glycoprotein exhibiting the unique feature of binding sex steroids with high affinity and specificity. Over the past few decades, there have been significant breakthroughs in our understanding of the function and regulation of SHBG. The biological role of SHBG has expanded from being considered a simple sex hormone transporter to being associated with several complex physiological and pathological changes in a variety of target tissues. Many factors can affect the plasma SHBG levels, with fluctuations in circulating levels affecting the development of various diseases, such as increasing the risk of developing breast cancer...

Cherax quadricarinatus exhibit sexual dimorphism, with males outpacing females in size specification and growth rate. However, there is limited understanding of the molecular mechanisms underlying sex determination and sex differentiation in crustaceans. To study the differences between intersex individuals and normal individuals, this study counted the proportion of intersex individuals in the natural population, collected the proportion of 7 different phenotypes in 200 intersex individuals, and observed the differences in tissue sections...

Epidemiological data and research highlight increased neuropathy and chronic pain prevalence among females, spanning metabolic and normometabolic contexts, including murine models. Prior findings demonstrated diverse immune and neuroimmune responses between genders in neuropathic pain (NeP), alongside distinct protein expression in sciatic nerves. This study unveils adipose tissue's (AT) role in sex-specific NeP responses after peripheral nerve injury. Metabolic assessments, metabolomics, energy expenditure evaluations, AT proteomic analyses, and adipokine mobilization depict distinct AT reactions to nerve damage...

Uterine fibroids (UFs) are benign tumors arising from the uterus, characterized by accumulation of abundant extracellular matrix (ECM) and sex steroids dependent growth. Women with symptomatic UFs have reduced quality of life and decreased labor productivity. Among the driver gene mutations identified in UFs, mutations in MED12, a component of the cyclin-dependent kinase (CDK) Mediator module, are the most common and observed in 50-80% of UFs. They are gain-of-function mutations and are more frequently observed in Black women and commonly observed even in small UFs...

BACKGROUND: Maternal vitamin B12 (B12) deficiency plays a vital role in fetal programming, as corroborated by previous studies on murine models and longitudinal human cohorts. OBJECTIVE: This study assessed the effects of diet-induced maternal B12 deficiency on F1 offspring in terms of cardiometabolic health and normalization of these effects by maternal peri-conceptional B12 supplementation. METHODS: A diet-induced maternal B12 deficient Wistar rat model was generated where female rats were either fed a control AIN-76A diet (with 0...

Progesterone is an essential steroid hormone that is required to initiate and maintain pregnancy in mammals and serves as a metabolic intermediate in the synthesis of endogenously produced steroids, including sex hormones and corticosteroids. Steroidogenic luteal cells of the corpus luteum have the tremendous capacity to synthesize progesterone. These specialized cells are highly enriched with lipid droplets that store lipid substrate which can be used for the synthesis of steroids. We recently reported that hormone-stimulated progesterone synthesis by luteal cells requires protein kinase A-dependent mobilization of cholesterol substrate from lipid droplets to mitochondria...

An erratum was issued for: Eyestalk Ablation to Increase Ovarian Maturation in Mud Crabs. The Introduction, Protocol, Discussion and References were updated. The forth sentence in the third paragraph of the Introduction has been updated from: The eyestalk ablation protocol in this work minimizes stress by using fully sedated crabs and minimizes physical injury to personnel from crab bites.  to: The eyestalk ablation protocol in this work minimizes stress by using fully anesthetized crabs and minimizes physical injury to personnel from crab bites...

Epidemiological studies have revealed sex differences in the incidence and morbidity of respiratory virus infection in the human population, and often these observations are correlated with sex differences in the quality or magnitude of the immune response. Sex differences in immunity and morbidity also are observed in animal models of respiratory virus infection, suggesting differential dominance of specific immune mechanisms. Emerging research shows intrinsic sex differences in immune cell transcriptomes, epigenomes, and proteomes that may regulate human immunity when challenged by viral infection...

OBJECTIVE: To determine whether discontinuation of delta-9-tetrahydrocannabinol (THC) use mitigates THC-associated changes in male reproductive health using a rhesus macaque model of daily THC edible consumption. DESIGN: Research animal study. SETTING: Research institute environment. PATIENT(S): Adult male rhesus macaques (age, 8-10 years; n = 6). INTERVENTION(S): Chronic daily THC edible administration at medically and recreationally relevant contemporary doses followed by cessation of THC use...

Successful placentation requires delicate communication between the endometrium and trophoblasts. The invasion and integration of trophoblasts into the endometrium during early pregnancy is crucial to placentation. Dysregulation of these functions is associated with various pregnancy complications, such as miscarriage and preeclampsia. The endometrial microenvironment has an important influence on trophoblast cell functions. The precise effect of the endometrial gland secretome on trophoblast functions remains uncertain...

The causative agent of Chagas disease (CD), Trypanosoma cruzi , claims thousands of lives each year. Current diagnostic tools are insufficient to ensure parasitological detection in chronically infected patients has been achieved. A host-derived metabolic signature able to distinguish CD patients from uninfected individuals and assess antiparasitic treatment efficiency is introduced. Serum samples were collected from chronic CD patients, prior to and three years after treatment, and subjected to untargeted metabolomics analysis against demographically matched CD-negative controls...

OBJECTIVE: Obesity is common in highland areas owing to lifestyle alterations. There are pieces of evidence to suggest that both obesity and hypoxia may promote oxidative stress, leading to hypogonadism in males. These findings indicate an increased risk of hypogonadism in obese males following hypoxia exposure. However, the mechanisms underlying the disease process remain unclear. The current study aims to explore the mechanism of testosterone production dysfunction in obese male mice exposed to a chronic high-altitude hypoxia environment...

Leydig cells produce testosterone, a hormone essential for male sex differentiation and spermatogenesis. The pituitary hormone, LH, stimulates testosterone production in Leydig cells by increasing the intracellular cAMP levels, which leads to the activation of various kinases and transcription factors, ultimately stimulating the expression of the genes involved in steroidogenesis. The second messenger, cAMP, is subsequently degraded to AMP, and the increase in the intracellular AMP levels activates AMP-dependent protein kinase (AMPK)...

The risk of high-grade gliomas is lower in young females, however, its incidence enhances after menopause, suggesting potential protective roles of female sex hormones. Hormone oscillations after menopause have received attention as a possible risk factor. Little is known about risk factors for adult gliomas. We examined the association of the aging brain after menopause, determining the risk of gliomas with proteomics and the MALDI-MSI experiment. Menopause caused low neurotransmitter levels such as GABA and ACH, high inflammatory factor levels like il-1β, and increased lipid metabolism-related levels like triglycerides in the brain...

CONTEXT: Cervical excision is a risk factor for preterm birth. This suggests that the cervix plays an essential role in the maintenance of pregnancy. OBJECTIVE: We investigated the role of the cervix through proteomic analysis of cervicovaginal fluid (CVF) from pregnant women after trachelectomy surgery, the natural model of a lack of cervix. METHODS: The proteome compositions of CVF in pregnant women after trachelectomy were compared to those in control pregnant women by liquid chromatography-tandem mass spectrometry and label-free relative quantification...

The placenta is a vital fetal organ that plays an important role in maintaining fetal sex hormone homeostasis. Xenobiotics can alter placental sex-steroidogenic enzymes and transporters, including enzymes such as aromatase (CYP19A1) and the hydroxysteroid dehydrogenases (HSDs) but studying how compounds disrupt in vivo placental metabolism is complex. Utilizing high-throughput in vitro models is critical to predict the disruption of placental sex-steroidogenic enzymes and transporters, particularly by drug candidates in the early stages of drug discovery...

The placenta is a critical fetal endocrine organ that plays an important role in fetal development, xenobiotic detoxification, and sex steroid homeostasis. Although the importance of the placenta in endocrine homeostasis is known, the effect of endocrine disruptors, like phthalates, on placental endocrine function needs further exploration. A common phthalate that expectant mothers can be exposed to is di-ethylhexyl phthalate (DEHP) which is used to make flexible plastics. We aim to determine the effect of DEHP on the androgen related proteome in JEG-3 placental cell model...

Acetaminophen (APAP) is the most used medication for pain and fever in pregnancy, but recent studies have elucidated in uteroAPAP as an endocrine disruptor associated with neurocognitive disorders. The placenta is a vital endocrine organ and disruption in metabolic pathways have been associated with adverse fetal neurodevelopment such as attention deficit hyperactivity disorder (ADHD) and autism. The aim of this study was to investigate the effect of APAP treatment on androgen pathways in JEG-3 placental cells...

INTRODUCTION: Gender affirming hormone therapy (GAHT) is increasingly used by transgender individuals and leads to shifts in sex hormone levels. Skeletal muscle is highly responsive to hormone activity, with limited data on the effects of GAHT on different human tissues. Here, we present the protocol for the GAME study (the effects of <u>G</u>ender <u>A</u>ffirming hormone therapy on skeletal <u>M</u>uscle training and <u>E</u>pigenetics), which aims to uncover the effects of GAHT on skeletal muscle 'omic' profiles (methylomics, transcriptomics, proteomics, metabolomics) and markers of skeletal muscle health and fitness...