17β-estradiol Levels Research Articles

The Effect of Ginger (Zingiber Officinale Roscoe) and Turmeric (Curcuma Longa) Supplementation on 17-β Estradiol Level, Quality of Life and Body Composition in Postmenopausal Women: Secondary Outcomes of a Randomized, Placebo controlled Trial

The Effect of Ginger (Zingiber Officinale Roscoe) and Turmeric (Curcuma Longa) Supplementation on 17-β Estradiol Level, Quality of Life and Body Composition in Postmenopausal Women: Secondary Outcomes of a Randomized, Placebo controlled Trial

Reproductive performance of lumpfish (Cyclopterus lumpus, L. 1758) females: Effects of integrated photoperiod and temperature manipulations on sexual maturation and spawning.

A successful control of sexual maturation is crucial for year-round production of lumpfish juveniles destined as cleaner fish in Atlantic salmon aquaculture. This study investigated the combined effects of photoperiod and temperature manipulations on sexual maturation and spawning in lumpfish females. Lumpfish juveniles were exposed to simulated natural and nine-month compressed annual photoperiods, with subsequent temperature elevation. Body weight (BW), condition factor (K), gonadosomatic index (GSI), ovarian development, plasma levels of 17β-estradiol (E2), testosterone (T) and 11-ketotestosterone (11-KT), and spawning were assessed. Compressing the natural photoperiod caused a clear increase and decrease in GSI, T, 11-KT and E2 towards and during the spawning period. Before the temperature elevation, GSI, T, 11-KT, E2 and ovarian development were advanced in the compressed photoperiod. After the temperature elevation, GSI, T, 11-KT and E2 fluctuated more in the compressed photoperiod, while in the natural photoperiod, E2 declined, and GSI, T and 11-KT increased. Spawning was advanced by 1 month in the compressed photoperiod compared to the natural photoperiod. Temperature elevation led to higher levels, earlier peaks and declines of T, 11-KT or E2 in both photoperiods, and advanced spawning by 1.5 months in the compressed photoperiod compared to the natural photoperiod. Temperature elevation also led to increased ovulation recruitment and increased cumulative weight of spawned eggs in the natural photoperiod. Compressing the natural photoperiod and elevating temperature can thus advance sexual maturation and spawning in lumpfish females. Due to the lower amounts of spawned egg weights in the high temperature compressed photoperiod, further studies on effects of photoperiod and timing of temperature manipulations on spawning, fecundity and egg quality could optimize the photothermal manipulations on lumpfish broodstock.

Effects of thiacloprid, a neonicotinoid pesticide, on rat reproductive system: Pregnancy hormone disruption and abortion trends

Thiacloprid (TCL), commonly known as Biscaya, is among the most widely used pesticides in agriculture, designed to eliminate insects by targeting their nicotinic receptors. This study explores the effects of orally administering TCL (at a dose of 50 mg/kg) on the hormone secretion crucial for pregnancy and the factors influencing abortion throughout the early, middle, and late stages of pregnancy in female rats.Following TCL exposure, there were significant increases in levels of 17β-Estradiol, prostaglandins F2α and E2, and serum oxytocin hormone in different stages of pregnancy. In contrast, progesterone and endothelin-1 serum levels notably decreased during the initial and final stages of pregnancy. Additionally, TCL led to a substantial rise in lipid peroxidation levels and a decrease in total thiol molecules and total antioxidant capacity, especially in uterine tissue. Although TCL did not significantly affect the morphological characteristics of the delivered fetuses, it notably increased the number of abortions, especially during the second and third stages of pregnancy.In summary, our findings suggest that TCL elevates the risk of abortion in pregnant rats by disrupting the secretion of hormones crucial for fertility (such as 17β-Estradiol/progesterone) and by increasing the secretion of abortion-inducing hormones like prostaglandins and oxytocin. Furthermore, these effects may be associated with disruptions in the oxidant/antioxidant balance within the ovaries and uterus.

Androgens have therapeutic potential in T2 asthma by mediating METTL3 in bronchial epithelial cells

Studies have shown that androgens can alleviate the symptoms of T2 asthma and are inversely correlated with the severity of allergic asthma. METTL3, a crucial component of m6A modification, mitigates the development of T2 asthma by inhibiting Th2 cell differentiation. However, the impact of androgens, such as dihydrotestosterone (DHT), on the progression of T2 asthma through METTL3 has yet to be investigated. At the clinical level, patients with T2 asthma exhibited reduced levels of DHT and METTL3 mRNA, along with increased levels of 17β-estradiol (E2). DHT and METTL3 were found to be negatively associated with the severity of T2 asthma, while E2 was positively associated with it. Administration of DHT and E2 in induced T2 asthma mouse models showed that DHT improved lung function, reduced airway inflammation, and inhibited Th2 cell differentiation. Interestingly, DHT reversed the damage to METTL3, whereas E2 had the opposite effect. In vitro studies of mouse bronchial epithelial cells (BECs) confirmed that METTL3-dependent m6A modification inhibited the T2 inflammatory response, and DHT inhibited Th2 cell differentiation in T2 asthma by promoting METTL3 expression in BECs. In conclusion, our study suggests that DHT has therapeutic potential for T2 asthma by regulating METTL3 in BECs.

Positive effects of a mixture of fish oil and soybean oil as a dietary lipid source on the ovarian development and health of female giant river prawn, Macrobrachium rosenbergii broodstock

Lipids are key nutrients that affect the development of the ovary in aquatic animals. This study aimed to investigate the effects of different lipid sources on the ovarian development and health of Macrobrachium rosenbergii broodstock. The M. rosenbergii broodstock, with an initial body weight of 8.07±0.74 g, were fed diets containing 5 % fish oil (FO), soya bean oil (SO), rapeseed oil (RO), coconut oil (CO), and a 1:1 mixture of fish oil and soybean oil (MO) as lipid sources for a period of 56 days. The results indicated that there were no significant differences in survival rate (SR) and hepatopancreatic index (HSI) among the different groups (P > 0.05). However, the specific growth rate (SGR) and gonadosomatic index (GSI) in the MO group were significantly higher than other groups (P < 0.05). Additionally, fatty acid levels in diets directly influenced the fatty acid composition of prawn hepatopancreas, showing a similar trend to that observed in the diet itself. Furthermore, compared to the other trial groups, haemolymph levels of 17-β estradiol (E2) and progesterone (PROG) were significantly increased in the MO group (P < 0.05). The ovarian section also exhibited better histomorphology and larger oocyte diameter in this group. Moreover, total antioxidant capacity was significantly increased in the MO group (P < 0.05). Saturated fatty acids in RO and CO groups could promote the expression of lipid synthesis-related genes fatty acid synthase (fas) and acetyl-CoA carboxylase (acc), concurrently suppressing the expression of lipid catabolism-related genes acyl-CoA oxidase-1 (acox-1) and AMP-activated protein kinase alpha (ampkα) (P < 0.05). Conversely, polyunsaturated fatty acids in the MO group significantly up-regulated the expression levels of fatty acid binding protein-3 (fabp-3) and peroxisome proliferator-activated receptor gamma (pparγ) (P < 0.05). Based on the findings of hepatopancreatic tissue structure, it was determined that the use of a single vegetable oil resulted in some damage to the hepatopancreatic tissue structure of M. rosenbergii broodstock, leading to increased oxidative stress. In conclusion, it is recommended that a 1:1 mixture of fish oil and soybean oil be used as a dietary lipid source to effectively meet the nutritional requirements during the ovarian development period of M. rosenbergii broodstock. This combination also enhances antioxidant properties, promotes the synthesis of haemolymph steroid hormones and lipid metabolism in female prawns, thereby facilitating ovarian development and overall health of M. rosenbergii broodstock.

Association of brown adipose tissue activity with circulating sex hormones and fibroblast growth factor 21 in the follicular and luteal phases in young women

BackgroundThermogenesis is influenced by fluctuations in sex hormones during the menstrual cycle in premenopausal women. The thermogenic activity and mass of brown adipose tissue (BAT) are regulated by endocrine factors, including sex hormones and fibroblast growth factor 21 (FGF21). However, the relationship between human BAT and these endocrine fluctuations within individuals remains to be elucidated. This study aimed to assess variations in BAT activity between the luteal and follicular phases and identify correlations with circulating levels of sex hormones and FGF21.MethodsHealthy young women were enrolled in an observational study. Measurement of BAT activity and blood analyses were performed in both the follicular and luteal phases. BAT activity was analyzed using thermography with 2-h cold exposure. Plasma 17β-estradiol, progesterone, and FGF21 levels were determined by enzyme-linked immunosorbent assay. A comparative analysis within individuals was conducted in 13 women to compare the follicular and luteal phases. Furthermore, sensitivity analysis was carried out in 21 women during the follicular phase only.ResultsPlasma 17β-estradiol and progesterone levels were significantly higher in the luteal phase, whereas plasma FGF21 level was significantly higher in the follicular phase. Comparison analysis found no significant differences in cold-induced BAT activity between the follicular and luteal phases in young women. Correlation analysis in both comparison and sensitivity analyses found that plasma 17β-estradiol and progesterone levels were not associated with BAT activity, whereas plasma FGF21 levels were significantly and positively correlated with BAT activity only in the follicular phase. In addition, plasma 17β-estradiol levels in the follicular phase were significantly and positively associated with plasma FGF21 levels in both the comparison and sensitivity analyses.ConclusionsThe thermogenic activity of BAT during cold exposure was comparable between the follicular and luteal phases in young women. Higher BAT activity was associated with elevated levels of plasma FGF21 only in the follicular phase, which is related to increased plasma 17β-estradiol levels.

Further evidence that peritraumatic 17β-estradiol levels influence chronic posttraumatic pain outcomes in women, data from both humans and animals.

Chronic posttraumatic pain (CPTP) is common after traumatic stress exposure (TSE) and disproportionately burdens women. We previously showed across 3 independent longitudinal cohort studies that, in women, increased peritraumatic 17β-estradiol (E2) levels were associated with substantially lower CPTP over 1 year. Here, we assessed this relationship in a fourth longitudinal cohort and also assessed the relationship between E2 and CPTP at additional time points post-TSE. Furthermore, we used a well-validated animal model of TSE to determine whether exogenous E2 administration protects against mechanical hypersensitivity. Using nested samples and data from the Advancing Understanding of RecOvery afteR traumA study (n = 543 samples, 389 participants), an emergency department-based prospective study of TSE survivors, we assessed the relationship between circulating E2 levels and CPTP in women and men using multivariate repeated-measures mixed modeling. Male and ovariectomized female Sprague Dawley rats were exposed to TSE and administered E2 either immediately after or 3 days post-TSE. Consistent with previous results, we observed an inverse relationship between peritraumatic E2 and longitudinal CPTP in women only (β = -0.137, P = 0.033). In animals, E2 protected against mechanical hypersensitivity in female ovariectomized rats only if administered immediately post-TSE. In conclusion, peritraumatic E2 levels, but not those at post-TSE time points, predict CPTP in women TSE survivors. Administration of E2 immediately post TSE protects against mechanical hypersensitivity in female rats. Together with previous findings, these data indicate that increased peritraumatic E2 levels in women have protective effects against CPTP development and suggest that immediate post-TSE E2 administration in women could be a promising therapeutic strategy for reducing risk of CPTP.

Identification of candidate genes and pathways involved in the establishment of sexual size dimorphism in the olive flounder (Paralichthys olivaceus) using RNA-seq

Olive flounder (Paralichthys olivaceus) is a valuable mariculture fish that shows female-biased sexual size dimorphism (SSD), yet the molecular mechanisms responsible for this phenomenon remain poorly understood. In this study, the growth differences between females and males were compared, and comparative transcriptome analyses of brains/pituitaries, livers, muscles, and gonads from 13-month-old females and males were performed. The critical time window for SSD was from 13- to 14-month-old, with females reaching significantly larger sizes than males. Muscle cell size and plasma growth hormone (GH), insulin-like growth factor 1 and 2 (IGF1, IGF2), 11-ketotestosterone (11-KT), and 17β-estradiol (E2) levels had no significant differences between the sexes of 13- and 14-month-old flounders. Furthermore, the RNA-seq data revealed differential expression in the genes encoding the receptors for these hormones, suggesting that regulation may occur at the receptor level, potentially leading to SSD during the critical window. RNA-seq analysis identified 88, 645, 414, and 15,833 differentially expressed genes between females and males in brains/pituitaries, livers, muscles, and gonads, respectively. KEGG (Kyoto Encyclopedia of Genes and Genomes) and GSEA-based KEGG analyses revealed that some pathways associated with growth and development, including “prolactin signaling pathway” in brains/pituitaries, “cell cycle”, “oocyte meiosis”, and “DNA replication” in livers, “focal adhesion”, “ECM-receptor interaction”, “protein digestion and absorption”, “arginine and proline metabolism”, and “cysteine and methionine metabolism” in muscles, and “Hippo signaling pathway” and “JAK-STAT signaling pathway” in gonads may be involved in the establishment of sexual growth differences. Notably, females had lower steroid hormone synthesis abilities than males in brains/pituitaries, livers, and gonads, indicating the importance of sex steroid hormones in the establishment of SSD. Moreover, genes including frizzled3 (fzd3) and prolactin (prl) in brains/pituitaries, and growth hormone receptor (ghr), estrogen receptor (esr1), insulin-like growth factor binding protein-3 (igfbp3), bone morphogenetic protein 8A-like (bmp8a), leptin receptor (lepr), and lipoprotein lipase-like (lpl) in livers emerge as potential candidates for the establishment of SSD. In conclusion, this study may help clarify the molecular mechanisms involved in SSD-related growth traits in flounder and provide basic data for genetic breeding of flounder.

Effectiveness of Tri-Kaysorn-Mas Extract in Ameliorating Cognitive-like Behavior Deficits in Ovariectomized Mice via Activation of Multiple Mechanisms.

Postmenopausal women have a higher probability of experiencing cognitive alterations compared to men, suggesting that the decline in female hormones may contribute to cognitive deterioration. Thailand traditionally uses Tri-Kaysorn-Mas (TKM), a blend of three medicinal herbs, as a tonic to stimulate appetite and relieve dyspepsia. Due to its antioxidant and anti-acetylcholinesterase activities, we investigated the effects of TKM (50 and 100 mg/kg/day, p.o., for 8 weeks) on cognitive deficits and their underlying causes in an ovariectomized (OVX) mouse model of menopause. OVX mice showed cognitive impairment in the Y-maze, novel object recognition task (NORT), and Morris water maze (MWM) behavioral tests, along with atrophic changes to the uterus, altered levels of serum 17β-estradiol, and down-regulated expression of estrogen receptors (ERα and ERβ). These behavioral effects were reversed by TKM. TKM decreased malondialdehyde (MDA) levels and mitigated oxidative stress in the brain by enhancing the activity of superoxide dismutase (SOD) and catalase (CAT) and by up-regulating the antioxidant-related gene Nrf2 while down-regulating Keap1. TKM also counteracted OVX-induced neurodegeneration by enhancing the expression of the neurogenesis-related genes BDNF and CREB. The results indicate that TKM extract alleviates oxidative brain damage and neurodegeneration while enhancing cognitive behavior in OVX mice, significantly improving cognitive deficiencies related to menopause/ovariectomy through multiple targets.

Effects of 5α-reductase inhibition by dutasteride on reproductive gene expression and hormonal responses in zebrafish embryos

Steroid 5α-reductase (SRD5A) is a crucial enzyme involved in steroid metabolism, primarily converting testosterone to dihydrotestosterone (DHT). Dutasteride, an inhibitor of SRD5A types 1 and 2, is widely used for treating benign prostatic hyperplasia. An adverse outcome pathway (AOP) has been documented wherein SRD5A inhibition decreases DHT synthesis, leading to reduced levels of 17β-estradiol (E2) and vitellogenin (VTG), subsequently impairing fecundity in fish (AOP 289). However, the molecular and cellular mechanisms underlying these effects remain poorly understood. In this study, we assessed the impact of SRD5A inhibition on zebrafish embryos (Danio rerio). Exposure to dutasteride resulted in decreased DHT, E2, and VTG levels, showing a positive correlation. Dutasteride also downregulated the expression of reproduction-related genes (srd5a2, cyp19a1, esr1, esr2a, esr2b, and vtg), with interrelated reductions observed across these levels. Docking studies suggested that dutasteride's effects may operate independently of androgen receptor (AR) and estrogen receptor (ER) interactions. Furthermore, co-exposure of dutasteride (0.5 or 2 μM) with 0.5 μM DHT revealed gene expression levels comparable to the control group. These findings underscore DHT's pivotal role in modulating estrogenic function and the interplay between estrogenic and androgenic responses in vertebrates. Our proposed AOP model offers insights into mechanistic gaps, thereby enhancing current understanding and bridging knowledge disparities.

Whole-body exposure to filtered fraction of diesel exhaust induced localized testicular damage through attenuated functional response of glutathione-s-transferase in adult male Wistar rats

The possible vulnerability of the male reproductive system to environmental pollutants such as air pollution necessitates a thorough investigation of the underlying mechanisms involved in the dysregulation of male reproductive function. The present study was designed to investigate the influence of the filtered fraction of diesel exhaust (predominantly comprising gases) on male reproductive function in Wistar rat model. Adult male rats were randomly assigned into three groups (n=8/group): Control (unexposed) group (CG-A), the Clean air group in WBE chamber (CAG-A), and Filtered diesel exhaust group in WBE chamber (FDG-A). The exposure protocol for CAG-A and FDG-A was 6 h/day x 5d/week x 6 weeks,evaluation of sperm parameters, testicular histopathology, quantification of hormones (testosterone, LH, FSH, 17β-Estradiol, and prolactin), and GST levels were performed. Results showed that WBE to FDE leads to a significant decline in sperm concentration (p=0.008, CG-A vs FDG-A; p=0.014, CAG-A vs FDG-A), motility (p=0.008, CG-A vs FDG-A; p=0.029, CAG-A vs FDG-A), serum testosterone (p=0.024, CG-A vs FDG-A; p=0.007, CAG-A vs FDG-A), testicular testosterone (p=0.008, CG-A vs FDG-A; p=0.028, CAG-A vs FDG-A), 17β-Estradiol (p=0.007, CG-A vs FDG-A), and GST levels (p=0.0002, CG-A vs FDG-A; p=0.0019, CAG-A vs FDG-A). These findings demonstrate the disruption of testosterone-estradiol balance in the intratesticular milieu without significant alterations in other principal pituitary hormones in adult rats exposed to FDE. The predominant presence of gaseous components in FDE can cause testicular damage due to oxidative imbalance. This underscores the causality of FDE exposure and impaired male reproductive outcomes.

An integrated network pharmacology and molecular docking approach to reveal the role of Arctigenin against Cutibacterium acnes-induced skin inflammation by targeting the CYP19A1.

Acne caused by inflammation of hair follicles and sebaceous glands is a common chronic skin disease. Arctigenin (ATG) is an extract of Arctium lappa L., which has significant anti-inflammatory effects. However, the effect and mechanism of ATG in cutaneous inflammation mediated by Cutibacterium acnes (C. acnes) has not been fully evaluated. The purpose of this study was to explore the effect and potential mechanism of ATG in the treatment of acne through network pharmacology and experimental confirmation. An acne model was established by injected live C. acnes into living mice and treated with ATG. Our data showed that ATG effectively improved acne induced by live C. acnes, which was confirmed by determining ear swelling rate, estradiol concentration and hematoxylin and eosin (H&E) staining. In addition, ATG inhibited the NLRP3 inflammasome signaling pathway in mice ear tissues and reduced the secretion of pro-inflammatory cytokines IL-1β to relieve inflammation. The results of network pharmacology and molecular docking confirmed that ATG can regulate 17β-Estradiol (E2) levels through targeted to CYP19A1, and finally inhibited skin inflammation. Taken together, our results confirmed that ATG regulated E2 secretion by targeting CYP19A1, thereby inhibiting the NLRP3 inflammasome signaling pathway and improving inflammation levels in acne mice. This study provides a basis for the feasibility of ATG in treating acne in clinical practice.

Anti-dyslipidemic effects of Pueraria lobata root and Glycine max (L.) Merrill extracts fermented with Lactiplantibacillus plantarum in ovariectomized mice.

Pueraria lobata root and Glycine max (L.) Merrill are rich in phytoestrogens. However, these bioactive ingredients have limited bioavailability due to their high molecular weight. In this study, we extracted two natural products and fermented with Lactiplantibacillus plantarum before mixing the fermented extracts (FPE-FGE). To understand whether FPE-FGE could alleviate menopause with dyslipidemia, we examined their effects on ovariectomy (OVX)-induced dyslipidemia in mice. Oral administration of the FPE-FGE (1:9, 3:7, and 9:1) did not affect safety-related biomarkers, such as uterus index (%), vagina index (%), aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, and creatinine. Furthermore, FPE-FGE (1:9, 3:7, and 9:1) increased the levels of 17β-estradiol (E2) and expression of uterus estrogen receptor β (ERβ); there was little effect on the expression of uterus estrogen receptor α (ERα), and reduced the levels of gonadotropins, such as luteinizing hormone (LH) and follicle-stimulating hormone (FSH). However, only the FPE-FGE (3:7) reduced the levels of blood lipids, including total cholesterol (TC) and LDL-cholesterol (LDL-C). Accordingly, FPE-FGE (3:7) upregulated endothelial nitric oxide synthase (eNOS), nitric oxide (NO), cyclic guanosine monophosphate (cGMP), and protein kinase G (PKG). In conclusion, FPE-FGE (3:7) attenuated themenopausal dyslipidemia by upregulating eNOS-NO-cGMP signaling pathway.

Loss of bmp15 function in the seasonal spawner Atlantic salmon results in ovulatory failure.

Bone morphogenetic protein 15 (BMP15) is an oocyte-specific growth factor important for successful female reproduction in mammals. While mutations in BMP15/Bmp15 cause ovulatory deficiency and/or infertility in certain mammalian species, loss of bmp15 in zebrafish, a continuous spawner and the only bmp15 knockout model in fish to date, results in complete arrest of follicle development and later female-to-male sex reversal, preventing to examine effects on ovulation/fertilization. Here, we used Atlantic salmon, a seasonal spawner, and generated bmp15 mutants to investigate ovarian development and fertility. Histological and morphometric analyses revealed that in biallelic frameshift (bmp15 fs/fs) mutant ovaries, folliculogenesis started earlier, resulting in an advanced development compared to wild-type (WT) controls, accompanied by a weaker expression of the (early) oocyte-specific factor figla. This precocious ovarian development was followed in bmp15 fs/fs females by enhanced follicle atresia during vitellogenic stages. Although genes involved in steroid synthesis and signaling (star, cyp11b, cyp17a1 and esr1) were dramatically higher in late vitellogenic bmp15 fs/fs mutant ovaries, estradiol-17β plasma levels were lower than in WT counterparts, potentially reflecting compensatory changes at the level of ovarian gene expression. At spawning, bmp15 fs/fs females displayed lower gonado-somatic index values and reduced oocyte diameter, and the majority (71.4%), showed mature non-ovulating ovaries with a high degree of atresia. The remaining (28.6%) females spawned eggs but they either could not be fertilized or, upon fertilization, showed severe malformations and embryonic mortality. Our results show that Bmp15 is required for proper follicle recruitment and growth and later ovulatory success in Atlantic salmon, providing an alternative candidate target to induce sterility in farmed salmon. Moreover, since loss of bmp15 in salmon, in contrast to zebrafish, does not result in female-to-male sex change, this is the first mutant model in fish allowing further investigations on Bmp15-mediated functions in the ovulatory period.

Antipsychotic-induced prolactin elevation in premenopausal women with schizophrenia: associations with estrogen, disease severity and cognition.

Antipsychotic-induced prolactin elevation may impede protective effects of estrogens in women with schizophrenia-spectrum disorders (SSD). Our study sought to confirm whether the use of prolactin-raising antipsychotics is associated with lower estrogen levels, and to investigate how estrogen and prolactin levels relate to symptom severity and cognition in premenopausal women with SSD. This cross-sectional study included 79 premenopausal women, divided in three groups of women with SSD treated with prolactin-sparing antipsychotics (n = 21) or prolactin-raising antipsychotics (n = 27), and age-matched women without SSD (n = 31). Circulating 17β-estradiol was compared among groups. In patients, we assessed the relationship between prolactin and 17β-estradiol, and the relationships of these hormones to symptom severity and cognition, using correlation analyses and backward regression models. In women receiving prolactin-raising antipsychotics, 17β-estradiol levels were lower as compared to both other groups (H(2) = 8.34; p = 0.015), and prolactin was inversely correlated with 17β-estradiol (r=-0.42, p = 0.030). In the prolactin-raising group, 17β-estradiol correlated positively with verbal fluency (r = 0.52, p = 0.009), and 17β-estradiol and prolactin together explained 29% of the variation in processing speed (β17β-estradiol = 0.24, βprolactin=-0.45, F(2,25) = 5.98, p = 0.008). In the prolactin-sparing group, 17β-estradiol correlated negatively with depression/anxiety (r=-0.57, p = 0.014), and together with prolactin explained 26% of the variation in total symptoms (β17β-estradiol=-0.41, βprolactin = 0.32, F(2,18) = 4.44, p = 0.027). In women with SSD, antipsychotic-induced prolactin elevation was related to lower estrogen levels. Further, estrogens negatively correlated with symptom severity and positively with cognition, whereas prolactin levels correlated negatively with cognition. Our findings stress the clinical importance of maintaining healthy levels of prolactin and estrogens in women with SSD.

Bisphenol S causes excessive estrogen synthesis by activating FSHR and the downstream cAMP/PKA signaling pathway

Estrogen excess in females has been linked to a diverse array of chronic and acute diseases. Emerging research shows that exposure to estrogen-like compounds such as bisphenol S leads to increases in 17β-estradiol levels, but the mechanism of action is unclear. The aim of this study was to reveal the underlying signaling pathway-mediated mechanisms, target site and target molecule of action of bisphenol S causing excessive estrogen synthesis. Human ovarian granulosa cells SVOG were exposed to bisphenol S at environmentally relevant concentrations (1 μg/L, 10 μg/L, and 100 μg/L) for 48 h. The results confirms that bisphenol S accumulates mainly on the cell membrane, binds to follicle stimulating hormone receptor (FSHR) located on the cell membrane, and subsequently activates the downstream cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) signaling pathway, leading to enhanced conversion of testosterone to 17β-estradiol. This study deepens our knowledge of the mechanisms of environmental factors in pathogenesis of hyperestrogenism.

Oral dehydroepiandrosterone supplementation enhances osteoporotic fracture healing in the OVX rats

Osteoporosis easily causes delayed fracture union, even non-union. It has been demonstrated that dehydroepiandrosterone (DHEA) supplementation can increase estrogen levels and improve bone mineral density (BMD) in the elderly, while the role of DHEA on fracture healing remains unknown. This study aimed to elucidate the impact of DHEA supplementation on osteoporotic fracture healing. Seventy-two female Sprague-Dawley rats were used. Forty-eight rats received ovariectomy (OVX), and the remaining rats received a sham OVX operation (sham group). A right transverse femoral osteotomy was performed in all rats at 12 weeks post-OVX. OVX rats were randomly allocated into 2 groups (n = 24 in each group): (i) ovariectomized rats (control group) and (ii) ovariectomized rats treated with DHEA (DHEA group, 5 mg/kg/day). The DHEA supplementation was initiated on the first day post-fracture for 3, 6, and 12 weeks. Fracture healing was evaluated by radiography, histology, biomechanical analysis, and dual-energy X-ray absorptiometry (DEXA). Serum biomarkers were analyzed using enzyme-linked immunosorbent assay (ELISA). At 3 and 6 weeks, radiographs revealed reduced calluses formation and lower radiographic scores in the control group than in other groups. The sham and DHEA groups showed higher BMD and bone mineral content (BMC) at the fracture site than the control group after fracture. Histological analysis revealed the fracture callus was remodeled better in the sham and DHEA groups than in the control group. At the early phase of healing, DHEA supplementation increased osteoblast number, callus area, and cartilage area than the control group. An increased bone area was observed in the DHEA group than in the control group at the late phase of healing. Additionally, improved biomechanical characteristics were observed in both the sham and DHEA groups than those in the control group post-fracture. ELISA showed higher levels of insulin-like growth factor-1 (IGF-1) and 17β-estradiol (E2) in the DHEA group than in the control group post-fracture. Furthermore, the DHEA group exhibited significantly elevated alkaline phosphatase (ALP) and osteocalcin (OC) levels compared to the control group at 6 and 12 weeks. The DHEA group and the control group did not exhibit a notable difference in TRAP-5b levels. The present study demonstrated that the DHEA treatment has a favorable impact on osteoporotic fracture healing by enhancing callus formation, consolidation, and strength in the OVX rats.

Impact of Cyclic Strain on Elastin Synthesis in a 3D Human Myometrial Culture Model.

The synthesis and assembly of mature, organized elastic fibers remains a limitation to the clinical use of many engineered tissue replacements. There is a critical need for a more in-depth understanding of elastogenesis regulation for the advancement of methods to induce and guide production of elastic matrix structures in engineered tissues that meet the structural and functional requirements of native tissue. The dramatic increase in elastic fibers through normal pregnancy has led us to explore the potential role of mechanical stretch in combination with pregnancy levels of the steroid hormones 17β-estradiol and progesterone on elastic fiber production by human uterine myometrial smooth muscle cells in a three-dimensional (3D) culture model. Opposed to a single strain regimen, we sought to better understand how the amplitude and frequency parameters of cyclic strain influence elastic fiber production in these myometrial tissue constructs (MTC). Mechanical stretch was applied to MTC at a range of strain amplitudes (5%, 10%, and 15% at 0.5 Hz frequency) and frequencies (0.1 Hz, 0.5 Hz, 1 Hz, and constant 0 Hz at 10% amplitude), with and without pregnancy-level hormones, for 6 days. MTC were assessed for cell proliferation, matrix elastin protein content, and expression of the main elastic fiber genes, tropoelastin (ELN) and fibrillin-1 (FBN1). Significant increases in elastin protein and ELN and FBN1 mRNA were produced from samples subjected to a 0.5 Hz, 10% strain regimen, as well as samples stretched at higher amplitude (15%, 0.5 Hz) and higher frequency (1 Hz, 10%); however, no significant effects because of third-trimester mimetic hormone treatment were determined. These results establish that a minimum level of strain is required to stimulate the synthesis of elastic fiber components in our culture model and show this response can be similarly enhanced by increasing either the amplitude or frequency parameter of applied strain. Further, our results demonstrate strain alone is sufficient to stimulate elastic fiber production and suggest hormones may not be a significant factor in regulating elastin synthesis. This 3D culture model will provide a useful tool to further investigate mechanisms underlying pregnancy-induced de novo elastic fiber synthesis and assembly by uterine smooth muscle cells.

Sex-steroid hormones relate to cerebellar structure and functional connectivity across adulthood.

Aging involves complex biological changes that affect disease susceptibility and aging trajectories. Although females typically live longer than males, they have a higher susceptibility to diseases like Alzheimer's, speculated to be influenced by menopause, and reduced ovarian hormone production. Understanding sex-specific differences is crucial for personalized medical interventions and gender equality in health. Our study aims to elucidate sex differences in regional cerebellar structure and connectivity during normal aging by investigating both structural and functional connectivity variations, with a focus on investigating these differences in the context of sex-steroid hormones. The study included 138 participants (mean age = 57(13.3) years, age range = 35-86 years, 54% women). The cohort was divided into three groups: 38 early middle-aged individuals (EMA) (mean age = 41(4.7) years), 48 late middle-aged individuals (LMA) (mean age = 58(4) years), and 42 older adults (OA) (mean age = 72(6.3) years). All participants underwent MRI scans, and saliva samples were collected for sex-steroid hormone quantification (17β-estradiol (E), progesterone (P), and testosterone (T)). We found less connectivity in females between Lobule I-IV and the cuneus, and greater connectivity in females between Crus I, Crus II, and the precuneus with increased age. Higher 17β-estradiol levels were linked to greater connectivity in Crus I and Crus II cerebellar subregions. Analyzing all participants together, testosterone was associated with both higher and lower connectivity in Lobule I-IV and Crus I, respectively, while higher progesterone levels were linked to lower connectivity in females. Structural differences were observed, with EMA males having larger volumes compared to LMA and OA groups, particularly in the right I-IV, right Crus I, right V, and right VI. EMA females showed higher volumes in the right lobules V and VI. These results highlight the significant role of sex hormones in modulating cerebellar connectivity and structure across adulthood, emphasizing the need to consider sex and hormonal status in neuroimaging studies to better understand age-related cognitive decline and neurological disorders.

Environmentally relevant estrogens impaired spermatogenesis and sexual behaviors in male and female zebrafish

Environmental estrogens (EEs) are found extensively in natural waters and negatively affect fish reproduction. Research on the reproductive toxicity of EEs mixtures in fish at environmentally relevant concentrations is scarce. In this study, adult male zebrafish were exposed for 60 days to EES (a mixture of EEs), EE2-low (5.55 ng/L, with an estrogenic potency equal to EES), and EE2-high (11.1 ng/L). After exposure, the expression levels of vtg1, vtg3, and esr1 in the livers in EES-treated fish remained unaltered, whereas they were significantly increased in EE2-treated fish. Both EE2-high and EES exposures notably reduced the gonad somatic index and sperm count. A disrupted spermatogenesis was also observed in the testes of EE2-high- and EES-exposed fish, along with an alteration in the expression of genes associated with spermatogonial proliferation (pcna, nanog), cell cycle transition (cyclinb1, cyclind1), and meiosis (aldh1a2, cyp26a1, sycp3). Both EE2 and EES significantly lowered plasma 11-ketotestosterone levels in males, likely by inhibiting the expression level of genes for its synthesis (scc, cyp17a1 and cyp11b2), and increased 17β-estradiol (E2) levels, possibly through upregulating the expression of cyp19a1a. A significant increase in tnfrsf1a expression and the tnfrsf1a/tnfrsf1b ratio in EE2-high and EES-treated males also suggests increased apoptosis via the extrinsic pathway. Further investigation showed that both EE2-high and EES diminished the sexual behavior of male fish, accompanied with reduced E2 levels in the brain and the expression of genes in the kisspeptin/gonadotropin-releasing hormone system. Interestingly, the sexual behavior of unexposed females paired with treated males was also reduced, indicating a synergistic effect. This study suggests that EES have a more severe impact on reproduction than EE2-low, and EEs could interfere not only with spermatogenesis in fish, but also with the sexual behaviors of both exposed males and their female partners, thereby leading to a more significant disruption in fish reproduction.