Steroid Estrogens Research Articles

Sex differences in peripheral monoamine transmitter and related hormone levels in chronic stress mice with a depression-like phenotype.

BackgroundsChronic stress could induce depression-like phenotype in animal models. Previous data showed that sex differences exist after chronic stress model establishment, however, the detailed information about the difference of blood biochemical indexes is not clear. In this study, we aim to supply comparison of monoamine transmitters and related hormone markers in serum between male and female depressed mice, and in order to better understand the sex difference in transmitters and hormone levels in depression occurrence and development.MethodsSixty C57BL/6 mice (both male and female) were divided into two groups by gender. Same gender mice were then divided randomly into the non-treated control group and chronic stress group which was exposed to 8 weeks of chronic unpredictable mild stress (CUMS). Depression-like behavior was assessed with open-field test and sucrose preference test. Blood sample was collected and monoamine transmitter and related hormone in serum were measured by ELISA.ResultsThe depression-like phenotype mice model was established successfully after 8 weeks of chronic stress. The locomotion activity scores in male stressed mice declined more than that in female stressed mice, while the exploratory behavior scores in female stressed mice declined more than that in male stressed mice. Compared to non-treated control group mice, mice in the chronic stress group in response to stress showed greater declines in monoamine transmitters (5-HT, dopamine, norepinephrine) and sex hormones (androgen, estrogen, oxytocin and prolactin), while stress hormones (adrenaline, corticosterone and ACTH) were significantly increased. The decrease of norepinephrine, androgen and estrogen in female stressed mice was greater than in male stressed mice, whereas the 5-HT and oxytocin in male stressed mice decreased more than in female stressed mice, and the corticosterone in male stressed mice increased more than in female stressed mice.ConclusionSex differences of monoamine transmitter and related hormone levels in serum occurred in chronic stress induced depression-like phenotype mice model. It may provide a useful reference to guide precise antidepressant treatment in different gender population in clinical care.

Evaluation of Sex Hormone in Benign and Malignant Breast Cancer in Iraqi Women

Elevated levels of circulating estrogens and androgens are linked to higher breast cancer risk among postmenopausal women; however, little is known about hormone levels within the breast. Hormone concentrations within the breast may not be reflected in the blood and are likely important contributors to breast carcinogenesis. The present study investigated the sex hormone (Estrogen, progesterone, Prolactin and testosterone). Female patients are divided into three groups (Benign, malignant and control). Benign (B)(34 patients) is divided into sub-groups including Benign premenopausal stage (B1)(17 patients) Benign postmenopausal stage (B2) (17 patients) and Malignant (M)(34 patients), Malignant premenopausal stage (M1) (17patients) and Malignant postmenopausal stage (M2)(17patients), and control group (C) include (11) premenopausal stage (C1) and (11) postmenopausal stage (C2). The expression level of soluble sex hormone (Estrogen, progesterone, Prolactin and testosterone) in serum was determined by an ELISA. Technique. The patients attended the Center for Early Detection of Breast Tumor at an oncology teaching hospital in Medical City. The study was conducted on 15/February (2021) to 20/July (2021). The values of Estrogen hormone in premenopausal malignant M1 (34.76 ±4.26 pg/ml) decreased significantly (P≤0.05) in comparison with C1, but it was non-significant in comparison with C2 and B1. M2 (64.28 ±4.17 pg/ml) shows a non-significant increase compared with C1, but it increased significantly with C2, B2 and M1. The values of progesterone hormone B1(12.75 ±3.34ng/ml) and B2( 13.06 ±2.98 ng/ml) was non-significant(P≤0.05) in comparison with C1 (8.17 ±2.87 ng/ml) and C2(6.28 ±2.87 ng/ml).M1 (14.30 ±4.29 ng/ml) and M2 (15.76 ±4.34 ng/ml) show non-significant difference in comparison with C1,C2,B1and B2. The values of Prolactin hormone in the M1(32.07±3.56(µIU/ml)) and M2(29.42±3.16) show non-significant difference(p>0.05) with C1,C2,B1 and B2.levelsTestosterone hormone show a significant in M1(1.462 ±0.11(ng/ml)) increased (p<0.05) in comparison with C1,C2,B1,B2. M2(1.392 ±0.10(ng/ml)) increase significantly(p<0.05) in comparison with C1,C2,B1,B2 and M1. concluded from this study that the levels of estrogen increased significantly in postmenopausal malignant M2 women with breast cancer, and the levels of testosterone hormone significant increase in pre and postmenopausal breast cancer women, the levels of Prolactin and progesterone hormone showed non-significant differences in comparison with other groups. Keywords: Sex Hormone, Benign, malignant, Breast Cancer,

Distribution, ecological fate, and risks of steroid estrogens in environmental matrices

Over the past two decades, steroidal estrogens (SEs) such as 17α-ethylestradiol (EE2), 17β-estradiol (E2),17α-estradiol (17α-E2), estriol (E3) and estrone (E1) have elicited worldwide attention due to their potentially harmful effects on human health and aquatic organisms even at low concentration ng/L. Natural steroidal estrogens exhibit greater endocrine disruption potency due to their high binding effect on nuclear estrogen receptors (ER). However, less has been explored regarding their associated environmental risks and fate. A comprehensive bibliometric study of the current research status of SEs was conducted using the Web of Science to assess the development trends and current knowledge of SEs in the last two decades, from 2001 to 2021 October. The number of publications has tremendously increased from 2003 to 2021. We summarized the contamination status and the associated ecological risks of SEs in different environmental compartments. The results revealed that SEs are ubiquitous in surface waters and natural SEs are most studied. We further carried out an in-depth evaluation and synthesis of major research hotspots and the dominant SEs in the matrices were E1, 17β-E2, 17α-E2, E3 and EE2. Nonetheless, investigations of SEs in soils, groundwater, and sediments remain scarce. This study elucidates SEs distribution, toxicological risks, ecological fate and mitigation measures, which will be beneficial for future monitoring, management, and risk assessment. Further studies are recommended to assess the toxicological risks of different SEs in complex environmental matrices to pursue a more precise and holistic quantitative estimation of estrogenic risk.

Genital labial phyllodes tumour recurring during pregnancy - does pregnancy impact recurrence?

Phyllodes tumours (PT) of the vulva are uncommon tumours. The gold standard treatment for these lesions is unknown but is intuitively presumed to be wide local excision. Incomplete resection is associated with recurrence although the time to recurrence is not known. Pregnancy is hypothesised to increase recurrence due to the production of steroid hormones oestrogen and progesterone. We report on a patient who had recurrence of a PT at a rare site (labia minora) and on the contralateral side from the original lesion, during pregnancy. These findings support that oestrogen and progesterone hormones could have played a role in the recurrence of the PT although margins were not free at the initial surgery.

A novel in-situ enhancement strategy of denitrification biofilter for simultaneous removal of steroid estrogens and total nitrogen from low C/N wastewater

Widely-used denitrification biofilter (DNBF) is facing the challenge towards the simultaneous removal of steroid estrogens (SEs) and total nitrogen (TN) from secondary effluent. Herein, slow-release calcium peroxide (SR-nCP) was firstly introduced into DNBF to construct SR-nCP/biofilter to in-situ enhance the removal of SEs and TN from low carbon to nitrogen (C/N) ratio wastewater. Results showed that the SEs removal rate could reach >95 % and the effluent TN maintained <15 mg/L. Under hydraulic retention time (HRT) = 3 h, 17α-ethinyl estradiol (EE2) removal increased by 22.0 %–27.0 %, and the denitrification load increased by 123.5 % to reach (60.8 ± 4.8) g·N (m3·d)−1. Moreover, SR-nCP/biofilter improved the reduction of both endocrine disrupting and acute toxicity, and the enhancement effect was more prominent under the low HRT condition. Furthermore, Sediminibacterium and Steroidobacter were identified as core aerobic bacterium that acted on SEs degradation and anaerobic bacterium that was responsible for simultaneous removal of SEs and TN, respectively. The presented strategy exhibited a synergistic effect of oxygen and organic carbon from SR-nCP and confirmed the feasibility of the SR-nCP/biofilter for the removal of SEs and TN from low C/N wastewater, highlighting a promising in-situ enhancement method for upgrading the function of current DNBF in advanced wastewater purification.

Mechanism of 17β-estradiol degradation by Rhodococcus equi via the 4,5-seco pathway and its key genes

Steroid estrogens have been detected in oceans, rivers, lakes, groundwaters, soils, and even urban water supply systems, thereby inevitably imposing serious impacts on human health and ecological safety. Indeed, many estrogen-degrading bacterial strains and degradation pathways have been reported, with the 4,5-seco pathway being particularly important. However, few studies have evaluated the use of the 4,5-seco pathway by actinomycetes to degrade 17β-estradiol (E2). In this study, 5 genes involved in E2 degradation were identified in the Rhodococcus equi DSSKP-R-001 (R-001) genome and then heterologously expressed to confirm their functions. The transformation of E2 with hsd17b14 reached 63.7% within 30 h, resulting in transformation into estrone (E1). Furthermore, we found that At1g12200-encoded flavin-binding monooxygenase (FMOAt1g12200) can transform E1 at a rate of 51.6% within 30 h and can transform E1 into 4-hydroxyestrone (4-OH E1). In addition, catA and hsaC genes were identified to further transform 4-OH E1 at a rate of 97–99%, and this reaction was accomplished by C–C cleavage at the C4 position of the A ring of 4-OH E1. This study represents the first report on the roles of these genes in estrogen degradation and provides new insights into the mechanisms of microbial estrogen metabolism and a better understanding of E2 degradation via the 4,5-seco pathway by actinomycetes.

Characteristics of Steroid Estrogen Loss, Degradation and Residues during Open-Air Dairy Manure Disposal

Steroid estrogens (SEs) are mainly derived from livestock manure, and composting is the common method of bioresource utilization. In this study, an open-air composting experiment with dairy manure was conducted to observe the degradation and loss of five SEs under the influence of different precipitation intensities and additional mixed fermentation strains. SE determination results for dairy manure after 30 days of composting indicated that the average removal rates of 17α-estradiol (E2α), estrone (E1), 17β-estradiol (E2β), 17α-ethinyl estradiol (EE2), estriol (E3), and estradiol equivalent (EEQ) were 76.67%, 71.07%, 73.88%, 92.02%, 98.77%, and 88.11%, respectively, partly due to SE runoff. The rates of SEs leaching from the open-air composting dairy manure ranged from 0.05% to 4.75% after 10 rounds of 5–60 mm/d simulated rainfall. The total leaching amount of SEs was positively correlated with rainfall, but the leaching concentrations of SEs were just the opposite. As a result of its role as a degradation intermediate of other SEs, E3 was the most prone to run off. By strengthening the action of microorganisms, the total leaching amount of EEQ increased by 5%, E3 increased by five times, and E2β also underwent a transition from a conjugated form to free. However, there were also fewer final SEs remaining in the composted product, as well as the environmental risks of conjugated SEs. These conclusions can provide beneficial suggestions and references for controlling the environmental risks of SEs in the process of composting livestock and poultry manure.

Simultaneous Quantification of Steroid Hormones Using hrLC-MS in Endocrine Tissues of Male Rats and Human Samples.

Steroid hormones play a vital role in the regulation of cellular processes, and dysregulation of these metabolites can provoke or aggravate pathological issues, such as autoimmune diseases and cancer. Regulation of steroid hormones involves different organs and biological compartments. Therefore, it is important to accurately determine their levels in tissues and biofluids to monitor changes after challenge or during disease. In this work, we have developed and optimized the extraction and quantification of 11 key members of the different steroid classes, including androgens, estrogens, progestogens and corticoids. The assay consists of a liquid/liquid extraction step and subsequent quantification by high-resolution liquid chromatography coupled time-of-flight mass spectrometry. The recoveries range between 74.2 to 126.9% and 54.9 to 110.7%, using a cell culture or urine as matrix, respectively. In general, the signal intensity loss due to matrix effect is no more than 30%. The method has been tested in relevant steroidogenic tissues in rat models and it has also been tested in human urine samples. Overall, this assay measures 11 analytes simultaneously in 6 min runtime and it has been applied in adrenal gland, testis, prostate, brain and serum from rats, and urine and extracellular vesicles from humans.

Carbon Nanodots with Solvatochromic Photoluminescence for the Electrochemical Determination of Estrogenic Steroids

Herein, we utilized carbon nanodots (R-CNDs) for the electrochemical detection of estrogens in tap and natural water samples and simulated effluents from Swedish waste water treatment plants (WWTPs). R-CNDs were prepared from 2-aminophenol by solvothermal synthesis and used as a modifier for chitosan-based selective membranes. The data obtained from atomic force microscopy and transmission electron microscopy suggest a spherical morphology of the R-CNDs with lateral size in the range of 3–8 nm and the height of 1–8 nm. In contrast to most other known carbon nanodots, R-CNDs are soluble in various organic solvents, including apolar, and less soluble in water. Small nanodots (3 nm) are more hydrophilic than large ones (6–8 nm) and can be separated from the bulk suspension of R-CNDs in heptane by their extraction into a water/ethanol mixture. Suspensions of large R-CNDs in apolar solvents exhibit green photoluminescence, while small R-CNDs in polar solvents have orange. This phenomenon was attributed to a solvatochromic rather than to a quantum effect. The R-CNDs were embedded on a chitosan-modified pencil electrode and the electrode was applied for voltammetric determination of four abandoned estrogens: estrone, estradiol, estriol, and ethynyl estradiol. The sensor demonstrates a group-selective response to the estrogens with a detection limit of 17.0 nmol L–1. It can be applied to determine the estrogens in the range of 0.05–4.6 μmol L–1 in the presence of typical interfering bioactive compounds, such as paracetamol, uric acid, progesterone, sulfamethoxazole, trimethoprim, ibuprofen, and caffeine. The developed sensors show repeatability and reproducibility values of 1.8–3.4% and 4.3%, respectively. The efficiency was proved by application for tap and lake water samples, where the recovery range was found to be 93–100%. The low cost, stability, and high sensitivity and selectivity of fabricated sensors make R-CNDs a perspective modifier for electrochemical sensors for the detection of estrogen microquantities in variable water samples.

Self-polymerized polydopamine-imprinted layer-coated carbon dots as a fluorescent sensor for selective and sensitive detection of 17β-oestradiol

The compound 17β-oestradiol (E2) is a steroidal oestrogen used extensively in food processing and animal husbandry. As E2 is well-known as a typical endocrine disrupting chemical, its release, penetration, and exposure create serious environmental concerns. Carbon dots (CDs) have attracted great attention due to their excellent fluorescent and non-toxic properties. To help improve the selectivity of CDs, they can be combined with molecularly-imprinted polymers (MIPs). In light of the limitations involved in the fabrication of MIP layer on CDs (e.g., time consumption and low controllability of imprinted layer), the mussel inspired dopamine self-polymerization can be considered as an alternative option. As functional monomer in molecular imprinted technology, dopamine can be used efficiently to polymerize in weak alkaline condition (e.g., formation of polydopamine). In this research, a new method was developed for selective and sensitive fluorescent detection of E2 based on self-polymerization of dopamine (functional monomer) on fluorescent carbon dots (CDs@MI-PDA). The developed sensor selectively binds with E2 to quench the fluorescence intensity of CDs by photo-induced electron transfer. The sensor showcases a detection limit of E2 as 0.34 ng/mL with a linearity over 1–50 ng/mL. Furthermore, the probe was successfully applied to water (tap and river water) and milk samples with recoveries of 96.4–102.2 %. This study is expected to open a new path for the development of a simple and convenient detection approach for E2 present in complex matrices.

Gender-Diverse Inclusion in Immunological Research: Benefits to Science and Health.

The differences between male and female immune systems are an under-researched field, ripe for discovery. This is evidenced by the stark sex biases seen in autoimmunity and infectious disease. Both the sex hormones (oestrogen and testosterone), as well as the sex chromosomes have been demonstrated to impact immune responses, in multiple ways. Historical shortcomings in reporting basic and clinical scientific findings in a sex-disaggregated manner have led not only to limited discovery of disease aetiology, but to potential inaccuracies in the estimation of the effects of diseases or interventions on females and gender-diverse groups. Here we propose not only that research subjects should include both cis-gender men and cis-gender women, but also transgender and gender-diverse people alongside them. The known interaction between the hormonal milieu and the sex chromosomes is inseparable in cis-gender human research, without the confounders of puberty and age. By inclusion of those pursuing hormonal affirmation of their gender identity- the individual and interactive investigation of hormones and chromosomes is permitted. Not only does this allow for a fine-tuned dissection of these individual effects, but it allows for discovery that is both pertinent and relevant to a far wider portion of the population. There is an unmet need for detailed treatment follow-up of the transgender community- little is known of the potential benefits and risks of hormonal supplementation on the immune system, nor indeed on many other health and disease outcomes. Our research team has pioneered the inclusion of gender-diverse persons in our basic research in adolescent autoimmune rheumatic diseases. We review here the many avenues that remain unexplored, and suggest ways in which other groups and teams can broaden their horizons and invest in a future for medicine that is both fruitful and inclusive.

Highly sensitive and group-targeting detection of steroid estrogens in water environment using a valid oligonucleotide class-specific editing technique

Steroid environmental estrogens (SEEs) are often coexist in water, require complex analytical techniques for separation and monitoring. However, aptamer-based chemical detection often only recognizes one of them, and the detection of SEEs is still a huge challenge. Herein, a group-targeting aptamer with the ability to recognize SEEs was constructed using efficient oligonucleotide class-specific editing technology, and a photoelectrochemical aptasensor capable of detecting the class of SEEs was established. A quantitative analysis of highly toxic SEEs in the environment and carrying similar core carbon skeleton, including 17β-estradiol, esterone, estriol and ethinylestradiol, was performed. The detection limit was as low as 0.1 nM with a response time of only 15 min. Specifically, this method exhibited high anti-interference with different complex media existing. Combining the theoretical calculations with a variety of spectral experiments, the Π-Π stacking and hydrogen bond synergistic interactions between the photoelectric interface and the three ring structures on SEEs and the hydroxyl group of ring 1 were analyzed in depth. Besides, the conformational changes of loose base helix structure and the free rotation limitation of oligonucleotides after the recognition of SEEs at the molecular level were also elucidated, facilitating the transfer of electrons on the surface of the photoelectrode.

The Hepatoprotective and Hepatotoxic Roles of Sex and Sex-Related Hormones

Most liver diseases, including acute liver injury, drug-induced liver injury, viral hepatitis, metabolic liver diseases, and end-stage liver diseases, are strongly linked with hormonal influences. Thus, delineating the clinical manifestation and underlying mechanisms of the “sexual dimorphism” is critical for providing hints for the prevention, management, and treatment of those diseases. Whether the sex hormones (androgen, estrogen, and progesterone) and sex-related hormones (gonadotrophin-releasing hormone, luteinizing hormone, follicle-stimulating hormone, and prolactin) play protective or toxic roles in the liver depends on the biological sex, disease stage, precipitating factor, and even the psychiatric status. Lifestyle factors, such as obesity, alcohol drinking, and smoking, also drastically affect the involving mechanisms of those hormones in liver diseases. Hormones deliver their hepatic regulatory signals primarily via classical and non-classical receptors in different liver cell types. Exogenous sex/sex-related hormone therapy may serve as a novel strategy for metabolic liver disease, cirrhosis, and liver cancer. However, the undesired hormone-induced liver injury should be carefully studied in pre-clinical models and monitored in clinical applications. This issue is particularly important for menopause females with hormone replacement therapy (HRT) and transgender populations who want to receive gender-affirming hormone therapy (GAHT). In conclusion, basic and clinical studies are warranted to depict the detailed hepatoprotective and hepatotoxic mechanisms of sex/sex-related hormones in liver disease. Prolactin holds a promising perspective in treating metabolic and advanced liver diseases.

A specialized Hsp90 co-chaperone network regulates steroid hormone receptor response to ligand.

SUMMARYHeat shock protein-90 (Hsp90) chaperone machinery is involved in the stability and activity of its client proteins. The chaperone function of Hsp90 is regulated by co-chaperones and post-translational modifications. Although structural evidence exists for Hsp90 interaction with clients, our understanding of the impact of Hsp90 chaperone function toward client activity in cells remains elusive. Here, we dissect the impact of recently identified higher eukaryotic co-chaperones, FNIP1/2 (FNIPs) and Tsc1, toward Hsp90 client activity. Our data show that Tsc1 and FNIP2 form mutually exclusive complexes with FNIP1, and that unlike Tsc1, FNIP1/2 interact with the catalytic residue of Hsp90. Functionally, these co-chaperone complexes increase the affinity of the steroid hormone receptors glucocorticoid receptor and estrogen receptor to their ligands in vivo. We provide a model for the responsiveness of the steroid hormone receptor activation upon ligand binding as a consequence of their association with specific Hsp90:co-chaperone subpopulations.

Thyroid Hormones Enhance the Growth of Estrogen Receptor-Positive Breast Cancers.

Thyroid disorders have been associated with breast cancer. In fact, breast cancer is the most common secondary malignancy in female patients with thyroid cancer (1). Moreover, hyperthyroidism is associated with an 11% increased risk of breast cancer in women (2). Importantly, up to 30% of patients with breast cancer are treated with thyroid hormone replacement therapy (THRT) for overt or subclinical hypothyroidism (3). These observations, coupled with the preclinical data showing growth stimulatory effects of thyroid hormones (THs) in various cancer models (4), formed the rationale for the study by Wahdan-Alaswad et al. aimed at investigating the role of THRT on the outcome of patients with nonmetastatic breast cancer (3). The authors conducted an observational study analyzing the association between THRT, disease-free survival (DFS), and disease-specific survival (DSS) in two cohorts of patients with nonmetastatic breast cancer. The first cohort consistent of 820 patients followed for a median of 10 years and treated for breast cancer between 1962 and1993, with THRT implemented in 69 patients. The second cohort included 160 patients treated more recently (between 2006 and 2009) and followed for a median of 8.8 years, with 50 patients exposed to THRT. The data on the age, tumor size, presence or absence of steroid (estrogen and/or progesterone) receptors (SR+/SR-), and treatment regimen were incorporated in the multivariate model analyzing the association between DFS/DSS and THRT at 5 and 10 years. To better understand the results of the observational cohort study, the authors performed functional in vitro and in vivo experiments to investigate the molecular mechanisms underlying TH effects on breast cancer cells and to test the interactions between estrogen receptors (ERs) and TH receptors (THRs). In patients with SR+ breast cancer, THRT was associated with a significantly increased risk of recurrence (DFS RR, 2.9; P<0.001) and death (DSS RR, 3.4; P<0.001), independent of age, tumor size and grade, while THRT in patients with SR- breast cancer was not associated with worse outcomes. Moreover, patients with SR+ breast cancer undergoing therapy with aromatase inhibitor combined with THRT were characterized by a shorter DFS (P<0.042) and a higher 10-year recurrence rate of 14%, as compared with 2% in patient treated with the aromatase inhibitor alone.The functional in vitro and in vivo studies revealed growth stimulatory effects of monotherapy with TH or estrogens that were further potentiated with combination therapy in ER+ breast cancer cell lines and mice xenografts. The RNA-Seq analysis revealed that combination therapy was associated with a significant activation of the cell cycle, mismatch repair, homologous recombination, and DNA replication signaling, as well as induced thyroid-specific genes and estrogen-mediated signatures. These effects were abrogated by the knockdown or inhibition of ER and/or THRa, suggesting that cross-talk and nuclear colocalization of ERs and THRs are major drivers of pro-oncogenic signaling in the ER+ breast cancer model. The study reveals clinically significant associations between THRT and worse outcomes in patients with nonmetastatic SR+ breast cancer that are likely driven by interactions between the nuclear ERs and THRs, leading to upregulation of pro-oncogenic signaling. These results suggest that overuse of THRT in patients with hypothyroidism and concurrent breast cancer should be avoided.

Novel roles of luteinizing hormone (LH) in tissue regeneration-associated functions in endometrial stem cells

Luteinizing hormone (LH) stimulates the synthesis and secretion of the key steroid hormone estrogen, which subsequently promotes ovarian follicular growth and development. Therefore, the administration of exogenous LH to achieve superovulation (multiple ovulations) and an LH surge is commonly used as the most effective therapeutic option in a majority of in vitro fertilization (IVF) clinics. However, a relatively low pregnancy rate (between 20% and 35%) is one of the most challenging aspects of LH-based infertility treatment. Furthermore, the major cause of this low pregnancy rate in LH-based infertility treatment remains unidentified. Recent studies have shown that endometrial stem cell loss or deficiency can significantly decrease tissue regeneration ability during the menstrual cycle and reduce endometrial receptivity. In this context, we postulated that the low pregnancy rates following LH-based ovarian hyperactivation may be the result of the adverse effects of consecutive exogenous LH administration on endometrial stem cells. To the best of our knowledge, this study revealed for the first time that in addition to its previously reported roles in stimulating ovarian functions through the pituitary-gonadal axis, LH brings about the extragonadal suppression of various tissue regeneration-associated functions in endometrial stem cells, such as self-renewal, migration ability, multilineage differentiation potential, and pluripotency/stemness, by inhibiting pro-survival Akt and ERK1/2 signaling pathways in vitro and in vivo, and as a consequence, it decreases the endometrial receptivity.

The response of steroid estrogens bioavailability to various sorption mechanisms by soil organic matter extracted with sequential alkaline-extraction method from an agriculture soil

The long-term groundwater contamination risks posed by steroidal estrogens (SEs) in animal-manured agricultural soils are closely associated with the soil organic matter (SOM) content and composition. In this study, the bioavailability of estrone (E1) and 17β-estradiol (17β-E2) under different sorption mechanism in humic acids (HA1 and HA2) and humin (HM) extracted with sequential alkaline-extraction technique (SAET) were examined. These SOMs extracted by SAET showed various properties and sorption characteristics for SEs. The alkyl carbon and condensed SOM increased during SAET, but aromatic carbon decreased and the same trend for polarity. Quick sorption was the major SEs sorption mechanism on HA1 and HA2, which contributed more than 69%; whilst slow sorption rate was about 50% in soil and HM. The logKoc values were proportional to the TOC of SOM according to Freundlich fitting, and the sorption capacity of sorbent for E1 and 17β-E2 was related to the logKow values, indicating that the main mechanism controlling the SEs sorption was hydrophobic interaction. The larger micropore volume of HM and soil was more conducive to the micropore filling of SEs. Meanwhile, the specific sorption of SEs on condensed domain of SOM was the main reason for the strong desorption hysteresis and slow sorption in HM and soil. The SEs degradation rate was positively correlated with the contribution rate of quick adsorption and negatively correlated with the contribution rate of slow adsorption, indicating that the bioavailability of SEs sorbed by hydrophobic interaction was higher than that of micropore filling or specific sorption, which was also the reason for the low bioavailability of SEs in HM and soil. This work confirms the regulation of on-site SOM compositions and their properties on SEs sorption and bioavailability. Characterization of these details is crucial for the improved prediction of long-term risks to groundwater.

Progesterone and its receptor signaling in cervical remodeling: Mechanisms of physiological actions and therapeutic implications

The remodeling of the cervix from a closed rigid structure to one that can open sufficiently for passage of a term infant is achieved by a complex series of molecular events that in large part are regulated by the steroid hormones progesterone and estrogen. Among hormonal influences, progesterone exerts a dominant role for most of pregnancy to initiate a loss of tissue strength yet maintain competence in a phase termed softening. Equally important are the molecular events that abrogate progesterone function in late pregnancy to allow a loss of tissue competence and strength during cervical ripening and dilation. In this review, we focus on current understanding by which progesterone receptor signaling for the majority of pregnancy followed by a loss/shift in progesterone receptor action at the end of pregnancy, collectively ensure cervical remodeling as necessary for successful parturition.

The Regulation of Adipose Tissue Health by Estrogens.

Obesity and its’ associated metabolic diseases such as type 2 diabetes and cardiometabolic disorders are significant health problems confronting many countries. A major driver for developing obesity and metabolic dysfunction is the uncontrolled expansion of white adipose tissue (WAT). Specifically, the pathophysiological expansion of visceral WAT is often associated with metabolic dysfunction due to changes in adipokine secretion profiles, reduced vascularization, increased fibrosis, and enrichment of pro-inflammatory immune cells. A critical determinate of body fat distribution and WAT health is the sex steroid estrogen. The bioavailability of estrogen appears to favor metabolically healthy subcutaneous fat over visceral fat growth while protecting against changes in metabolic dysfunction. Our review will focus on the role of estrogen on body fat partitioning, WAT homeostasis, adipogenesis, adipocyte progenitor cell (APC) function, and thermogenesis to control WAT health and systemic metabolism.

Steroid profiling in brain and plasma of adult zebra finches following traumatic brain injury

Traumatic brain injury (TBI) is a serious health concern and a leading cause of death. Emerging evidence strongly suggests that steroid hormones (estrogens, androgens, and progesterone) modulate TBI outcomes by regulating inflammation, oxidative stress, free radical production, and extracellular calcium levels. Despite this growing body of evidence on steroid-mediated neuroprotection, very little is known about the local synthesis of these steroids following injury. Here, we examine the effect of TBI on local neurosteroid levels around the site of injury and in plasma in adult male and female zebra finches. Using ultrasensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS), we examined estrogens, androgens, and progesterone in the entopallium and plasma of injured and uninjured animals. Three days after injury, elevated levels of 17β-estradiol (E2 ), estrone (E1 ), and testosterone (T) were detected near injured brain tissue with a corresponding increase in E2 also detected in plasma. Taken together, these results provide further evidence that TBI alters neurosteroid levels and are consistent with studies showing that neurosteroids provide neuroprotection following injury.