Steroid Hormones Research Articles

Responses in organs, sperm, steroid hormones and CYP450 enzyme in male mice treated by quinestrol only or in conjunction with clarithromycin

Pest rodents persistently undermine crop yields and food security. Fertility control could be a viable alternative for managing rodent populations. This study investigates the antifertility effects of various concentrations of clarithromycin combined with 1.0 mg/kg quinestrol on male rodents to determine an effective contraceptive dose that minimizes quinestrol usage, addressing key concerns such as potential environmental residue, which may impact ecological balance, and poor palatability, which could reduce ingestion and limit the sterilant’s effectiveness. Male mice were divided into five groups and administered different doses of clarithromycin or clarithromycin and quinestrol for three consecutive days, while the control group received sunflower seed oil only. After seven days, organ weights, reproductive organ weights, sperm density, serum hormone levels, and CYP3A4 content in small intestinal and liver tissues were measured to assess persistent effects. Compared with the control group, all treatment groups had significant reductions in epididymal weight, seminal vesicle weight, and serum T and LH levels. Higher concentrations of clarithromycin (2 mg/kg and 10 mg/kg) significantly impacted reproductive metrics, including sperm density, organ weights, and serum LH and testosterone levels, though complete sterilization was not achieved, with more than 60 million cauda epididymal spermatozoa remaining. However, the combination demonstrated potential as an effective strategy for male fertility control. The combination of 2.0 mg/kg clarithromycin and quinestrol can mitigate organ enlargement seen with quinestrol alone. This combination also decreased total enzyme content, thereby diminishing quinestrol’s induction of CYP3A4, which may increase the sterilization effectiveness of the treatment.

Nuclear receptor E75/NR1D2 promotes tumor malignant transformation by integrating Hippo and Notch pathways

AbstractHormone therapy resistance and the ensuing aggressive tumor progression present a significant clinical challenge. However, the mechanisms underlying the induction of tumor malignancy upon inhibition of steroid hormone signaling remain poorly understood. Here, we demonstrate that Drosophila malignant epithelial tumors show a similar reduction in ecdysone signaling, the main steroid hormone pathway. Our analysis of ecdysone-induced downstream targets reveals that overexpression of the nuclear receptor E75, particularly facilitates the malignant transformation of benign tumors. Genome-wide DNA binding profiles and biochemistry data reveal that E75 not only binds to the transcription factors of both Hippo and Notch pathways, but also exhibits widespread co-binding to their target genes, thus contributing to tumor malignancy. We further validated these findings by demonstrating that depletion of NR1D2, the mammalian homolog of E75, inhibits the activation of Hippo and Notch target genes, impeding glioblastoma progression. Together, our study unveils a novel mechanism by which hormone inhibition promotes tumor malignancy, and describes an evolutionarily conserved role of the oncogene E75/NR1D2 in integration of Hippo and Notch pathway activity during tumor progression.

Based on Serum Pharmacochemistry and Metabolomics Studied the Pharmacodynamic Material Basis and Mechanism of Rubi Fructus (Fupenzi) in Improving the Symptom of Kidney-Yang Deficiency.

Rubi fructus (Fupenzi) is the immature fruit of East China Rubi fructus, which is widely used in medicine, food, health food and other fields. Since ancient times, Fupenzi has been considered to be an important medicine for tonifying the kidney in terms of nourishing the liver and kidney, fixing essence and reducing urine, but its effective components and mechanism are not clear. In this paper, the effective components of Rubi fructus were analyzed by detecting the components of Fupenzi in vivo and in vitro. Adenine was used to replicate the model of kidney yang deficiency, and organ index, biochemical index and histopathology were used to evaluate the effect of different doses of Fupenzi on tonifying kidney yang. Metabonomics technique was used to analyze the metabolic regulation mechanism of Fupenzi in improving kidney yang deficiency syndrome. The results showed that 61 chemical constituents of Fupenzi were identified in vitro, including 18 flavonoids, 19 organic acids, 5 coumarins, 8 terpenoids, 7 amino acids and 4 other components. A total of 51 chemical components were identified, including 30 prototype components and 21 metabolic components, which may be the effective components of Fupenzi. The results of pharmacodynamics showed that compared with the model group, the renal index, testicular index and epididymal index of rats in each Fupenzi group were significantly improved (p<0.01), cAMP significantly increased (p<0.05), cGMP decreased (p<0.05) and cAMP/cGMP ratio increased significantly (p<0.05). The content of ACTH in low dose group increased significantly (p<0.05), while the content of ACTH in middle and high dose groups increased, but there was no significant difference. The results of HE staining showed that compared with the model group, the kidney, testis and epididymis of rats in each treatment group were significantly improved. In general, these changes may be mainly through primary bile acid biosynthesis, linoleic acid metabolism, steroid hormone biosynthesis, β-alanine metabolism, glutathione metabolism, porphyrin and chlorophyll metabolism, unsaturated fatty acid biosynthesis, arachidonic acid metabolism, arginine and proline metabolism and other metabolic pathways to improve adenine-induced metabolic disorders in rats with kidney-yang deficiency syndrome.

Integrative analysis of the transcriptome, targeted metabolome, and anatomical observation provides insights into the brassinosteroids-mediated seasonal variation of cambial activity in Chinese fir

Chinese fir (Cunninghamia lanceolata) is widely planted in southern China due to its strong adaptability and fast-growing. Wood formation is derived from the periodic changes of cambial activity that is regulated by environmental cues and phytohormone signals. Brassinosteroids (BRs), a class of plant-specific steroid hormones, play central roles in modulating cambial activity and xylem development. To decipher the regulatory role of BR in the dynamic change of Chinese fir cambium, a comprehensive analysis of the transcriptome, targeted metabolome, and anatomical observation was conducted. The application of 24-epibrassinolide (EBR, 10 μM) significantly increased the cambial cell layers, resulting in the thickening of the secondary xylem. Conversely, brassinazole (Brz) treatment strikingly inhibited the xylem development by attenuating cambial activity. Moreover, 1583 up-regulated differentially expressed genes (DEGs) were shared in stages A (reactivating), C (active), and E (dormant), which were annotated into the xylem formation and BR signaling pathway. Metabolomic profiling of phytohormone indicated that the contents of brassinolide (BL, the most active BR), castasterone (CS), and typhasterol (TY) were distinctly increased in stage C. Furthermore, ClBES1/BZR1, a hub gene in the co-expression network, dramatically activated the expression of ClPAL2 and ClMYB4 by binding to their promotors. Collectively, these results elucidate the potential role of BR in dynamic changes in the cambial zone and provide insight into the regulatory mechanism of wood formation in conifers.

Modification of B-Nor Steroids Mediated by Filamentous Fungus Fusarium culmorum: Focus on 15α-Hydroxylase Activity

The metabolic activities of microorganisms to modify the chemical structures of organic compounds are an effective tool for the production of high-value steroidal drugs or active pharmaceutical ingredients (APIs). The integration of biotransformation into the synthesis of APIs can greatly reduce the number of reaction steps and achieve higher process efficiency, thus enabling their greener production. The current research efforts are focused on either the optimization of existing processes or identification of new potentially useful bioconversions. This study aimed to assess the catalytic abilities of the filamentous fungus Fusarium culmorum AM 282 to transform B-nor analogues (5(6→7)abeo compounds) of steroid hormones: androstenedione (AD), dehydroepiandrosterone (DHEA) and its acetate. Our previous studies have demonstrated that this strain is an active hydroxylating catalyst for many steroidal compounds with diverse structures. The results presented in this work showed that the hydroxylation of B-nor steroids occurred with the regio- and stereoselectivity typical of this strain in relation to the corresponding natural hormones of the standard 6:6 A/B series. After the transformations of B-nor-DHEA and its acetate, 15α-hydroxy-B-nor-DHEA was obtained as the sole product of the reaction, while the transformation of the AD analogue resulted in a mixture of its 15α- and 6α-hydroxy derivatives. A detailed analysis of the transformation course indicated that all the obtained hydroxy derivatives could be the result of the activity of the same enzyme. The presented results may provide a basis for research aimed at understanding the molecular nature of cytochrome P-450 monooxygenase from F. culmorum AM 282 with its ability for 15α-hydroxylation of steroidal compounds. An analysis of the pharmacokinetic and pharmacodynamic properties of the obtained metabolites with cheminformatics tools suggests their potential biological activity.

Hippocampus under pressure: molecular mechanisms of cognitive impairment in shr rats

In clinical studies and in animal experiments, data have been obtained indicating the association of chronic hypertension with the development of cognitive impairment. The review examines structural and biochemical changes in the hippocampus of SHR rats with genetic hypertension, which are used as a model of essential hypertension, as well as vascular dementia. The dysfunction of the hypothalamic-pituitary-adrenocortical system, observed in SHR rats at an early age, may, along with the development of hypertension, be a key factor in the damage to the hippocampus at the structural and molecular levels. Global changes at the body level (hypertension, neurohumoral dysfunction) are associated with the development of vascular pathology and destruction of the blood-brain barrier. Changes in multiple biochemical glucocorticoid-dependent processes in the hippocampus (dysfunction of steroid hormone receptors, disorders of neurotransmitter systems, BDNF deficiency, oxidative stress, neuroinflammation) are accompanied by structural changes including cellular processes of neuroinflammation (microgliosis, astrogliosis), disorders of neurogenesis in the subgranular neurogenic niche, neurodegenerative processes at the level of synapses, axons and dendrites up to neuronal cell death. The consequence of this is dysfunction of the hippocampus, a key structure of the limbic system necessary for the realization of cognitive functions. Summarizing of the available results at various levels, from the level of the organism and the structure of the brain (hippocampus) to the molecular one, allows us to confirm the translational validity of SHR rats for modeling the mechanisms of vascular dementia.

The association between metabolite profiles and impaired bone microstructure in adult growth hormone deficient rats

BackgroundAdult growth hormone deficiency (AGHD) is associated with an increased risk of fractures and impaired bone microstructure. Understanding the metabolic changes accompanying bone deterioration in AGHD might provide insights into mechanisms behind molecular changes and develop new biomarkers or nutritional strategies for bone destruction. Our study aimed to investigate the association between altered metabolite patterns and impaired bone microstructure in adult rats with growth hormone deficiency.MethodsThirty seven-week-aged adult Lewis dwarf homozygous (dw/dw) rats (five females and five males), and adult Lewis dwarf heterozygous (dw/ +) rats (five females and five males) rats were compared. Micro-computed tomography (Micro-CT) was used to examine the bone's microstructure. Hematoxylin and eosin (H&E) staining were used to quantify the histological characteristics. Liquid chromatography-mass spectrometry untargeted serum metabolomic analysis was applied in the study. ELISA was used to measure serum bone turnover markers and IGF-1 levels.ResultsAdult dw/dw rats exhibited great reductions in trabecular volume bone density (Tb.vBMD), bone volume/total volume (BV/TV), and cortical thickness (Ct. Th) compared with adult dw/ + rats (all p values < 0.05), indicating significant impairment in bone microstructure. The serum metabolite profiles revealed substantial differences between the dw/dw rats and dw/ + rats. A total of 134 differential metabolites in positive ion mode and 49 differential metabolites in negative mode were identified. Five metabolites, including Lysophosphatidylcholine(LPC) 20:3, LPC22:6, LPC22:4, cortisol and histamine levels were upregulated in dw/dw rats. The steroid hormone biosynthesis and bile secretion pathways were the main perturbed metabolic pathways. There were significant associations between differential metabolites and the impaired bone microstructure parameters, indicating that the selected metabolites might serve as potential biomarkers for deteriorated bone microstructure in AGHD.ConclusionAdult dw/dw rats exhibit impaired bone microstructure and distinct serum metabolic profiles, and the altered metabolites were significantly associated with bone microstructure destruction. This provides a new insight into understanding the mechanism of bone deterioration in AGHD patients from a metabolic perspective.

Endocannabinoid System and Metabolism: The Influences of Sex

The endocannabinoid system (ECS) is a lipid signaling system involved in numerous physiological processes, such as endocrine homeostasis, appetite control, energy balance, and metabolism. The ECS comprises endocannabinoids, their cognate receptors, and the enzymatic machinery that tightly regulates their levels within tissues. This system has been identified in various organs, including the brain and liver, in multiple mammalian and non-mammalian species. However, information regarding the sex-specific regulation of the ECS remains limited, even though increasing evidence suggests that interactions between sex steroid hormones and the ECS may ultimately modulate hepatic metabolism and energy homeostasis. Within this framework, we will review the sexual dimorphism of the ECS in various animal models, providing evidence of the crosstalk between endocannabinoids and sex hormones via different metabolic pathways. Additionally, we will underscore the importance of understanding how endocrine-disrupting chemicals and exogenous cannabinoids influence ECS-dependent metabolic pathways in a sex-specific manner.

Sex Differences in Blood Accumulation of Neurodegenerative-Related Proteins and Antioxidant Responses to Regular Physical Exercise

Physical activity has been demonstrated to improve cognitive function, thereby preventing/slowing neurodegenerative diseases (NDs). Biological responses to physical activity and vulnerabilities to NDs are emerging to be gender-related. Herein, known ND-associated markers (β-amyloid, tau, α-synuclein), main sex steroid hormones, antioxidant responses, and key gene transcription modulators were evaluated in the blood of physically active and sedentary women and men. In our hands, females presented higher basal erythrocytes β-amyloid and α-synuclein amounts than males. Regular physical activity was able to significantly reduce the erythrocyte content of β-amyloid in females and the tau levels in males, suggesting that these differences may be mediated by organizational actions of sex steroid hormones during development. Furthermore, despite a comparable plasma antioxidant capability (AOC) between males and females, in the latter group, physical activity significantly enhances AOC versus peroxynitrite radicals only. Finally, regular physical activity modulated the levels of transcription factor Nrf2 in erythrocytes, as well as the plasma concentration of the microRNA miR-195 and miR-153, suggesting the promotion of antioxidant/autophagic processes associated with ND-related proteins. Overall, these results could shed light on how cerebral adaptations to physical activity differ between males and females, especially with regard to blood accumulation of ND proteins and mechanisms of antioxidant responses to regular exercise.

17α-Ethynylestradiol alters testicular epigenetic profiles and histone-to-protamine exchange in mice

Spermatogenesis starts with the onset of puberty within the seminiferous epithelium of the testes. It is a complex process under intricate control of the endocrine system. Physiological regulations by steroid hormones in general and by estrogens in particular are due to their chemical nature prone to be disrupted by exogenous factors acting as endocrine disruptors (EDs). 17α-Ethynylestradiol (EE2) is an environmental pollutant with a confirmed ED activity and a well-known effect on spermatogenesis and chromatin remodeling in haploid germ cells. The aim of our study was to assess possible effects of two doses (2.5ng/ml; 2.5 μg/ml) of EE2 on both histone-to-protamine exchange and epigenetic profiles during spermatogenesis performing a multi/transgenerational study in mice. Our results demonstrated an impaired histone-to-protamine exchange with a significantly higher histone retention in sperm nuclei of exposed animals, when this process was accompanied by the changes of histone post-translational modifications (PTMs) abundancies with a prominent effect on H3K9Ac and partial changes in protamine 1 promoter methylation status. Furthermore, individual changes in molecular phenotypes were partially transmitted to subsequent generations, when no direct trans-generational effect was observed. Finally, the uncovered specific localization of the histone retention in sperm nuclei and their specific PTMs profile after EE2 exposure may indicate an estrogenic effect on sperm motility and early embryonic development via epigenetic mechanisms.

Differentiation of adsorption and degradation in steroid hormone micropollutants removal using electrochemical carbon nanotube membrane

The growing concern over micropollutants in aquatic ecosystems motivates the development of electrochemical membrane reactors (EMRs) as a sustainable water treatment solution. Nevertheless, the intricate interplay among adsorption/desorption, electrochemical reactions, and byproduct formation within EMR complicates the understanding of their mechanisms. Herein, the degradation of micropollutants using an EMR equipped with carbon nanotube membrane are investigated, employing isotope-labeled steroid hormone micropollutant. The integration of high-performance liquid chromatography with a flow scintillator analyzer and liquid scintillation counting techniques allows to differentiate hormone removal by concurrent adsorption and degradation. Pre-adsorption of hormone is found not to limit its subsequent degradation, attributed to the rapid adsorption kinetics and effective mass transfer of EMR. This analytical approach facilitates determining the limiting factors affecting the hormone degradation under variable conditions. Increasing the voltage from 0.6 to 1.2 V causes the degradation dynamics to transition from being controlled by electron transfer rates to an adsorption-rate-limited regime. These findings unravels some underlying mechanisms of EMR, providing valuable insights for designing electrochemical strategies for micropollutant control.

Increased DNMT1 acetylation leads to global DNA methylation suppression in follicular granulosa cells during reproductive aging in mammals

With increasing age, the reproductive performance of women and female animals declines. However, the molecular mechanisms underlying ovarian aging and age-related fertility decline remain unclear. Granulosa cells (GCs) are suspected to play an important role in reproductive aging, and their proliferation, apoptosis, and steroid hormone secretion are used to determine the fate of follicles and ovarian function. First, we found that the proliferative ability of GCs from the old mouse group (10-month-old) decreased compared with that from the young mouse group (6-week-old), and cell cycle arrest occurred in old mice. To investigate changes in protein modification, we compared the levels of protein acetylation in GCs from young and old mice. We found that the K1118, K1120, K1122, and K1124 sites of DNA methyltransferase 1 (DNMT1) were increasingly acetylated with age, resulting in a decrease in DNMT1 protein expression. Therefore, we performed whole-genome methylation sequencing of GCs in the two groups and found that the CG methylation levels in the old group were lower than those in the young group. Furthermore, the inhibition of DNMT1 expression in GCs resulted in cell cycle arrest. This study revealed the dynamics and importance of protein acetylation and DNA methylation in GCs during reproductive aging. The findings provide a theoretical basis for studying the mechanism of reproductive aging in mammals.

20-Hydroxyecdysone Boosts Energy Production and Biosynthetic Processes in Non-Transformed Mouse Cells

20-Hydroxyecdysone (20E) is an arthropod steroid hormone that possesses a number of beneficial pharmacological activities in humans, including anabolic, antioxidant, hypoglycemic, cardioprotective, hepatoprotective, neuroprotective, and antineoplastic properties, etc. While several studies have explored the anabolic activity of 20E in muscle cells, they have concentrated on its effects on myofibril size, protein biosynthesis intensity, and myostatin expression, without assessing energy metabolism. In this research, we have demonstrated that 20E boosts both catabolism and anabolism, coupling energy-producing and biosynthetic metabolic processes in mouse myoblasts and fibroblasts in the same way. Using a transcriptomic approach, we identified the 20E-mediated up-regulation of genes involved in different metabolic processes. Further experiments revealed that 20E increased the levels of enzymes involved in glycolysis and one-carbon metabolism. It also increased the uptake of glucose, glycolysis, respiration, the production of ATP, and global protein biosynthesis in mouse myoblasts and fibroblasts. This phenomenon involves the PI3K/AKT/mTOR signaling pathway. Taken together, the observed 20E-dependent upregulation of energy metabolism may be the main reason for 20E’s well-known anabolic activity.

The associations between exposure to mixed environmental endocrine disruptors and sex steroid hormones in men: a comparison of different statistical models

In recent years, worldwide fertility rates have continued to decrease. Humans are frequently exposed to a combination of environmental endocrine disruptors, which can cause male reproductive disorders. The study employed three distinct analytical models to examine the correlation between exposure to a combination of 25 chemicals and sex steroid hormone levels in adult males. This involved evaluating 12 chemicals and their metabolites from personal care and consumer products, as well as 13 metabolites linked to phthalates and plasticisers. The study analysed 25 chemicals and 3 measured sex steroid hormone outcomes, as well as two calculated hormonal outcomes (free androgen index, TT/E2 ratio) in 1262 adult men who participated in the National Health and Nutrition Examination Survey (NHANES) 2013–2016 in the United States. The study employed several statistical methods to estimate the relationships between single chemicals or chemical blends and sex hormones. These methods included linear regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine (BKMR) regression. The results of the linear regression analysis indicate that chemical exposure has a negative correlation with E2, TT, and FAI, and a positive correlation with SHBG and TT/E2. The mixture effect analyses using the WQS and BKMR models further confirmed that BP3, MECPP, and MECOP were the most highly weighted chemical mixtures. The analyses also suggested that there were differences in the effects of different concentrations of EDCs on sex steroid hormones. Exposure to environmental endocrine-disrupting chemicals (EDCs) has been found to have a negative correlation with estradiol and total testosterone, as well as FAI. Conversely, this exposure has been found to have a positive correlation with sex hormone binding globulin and the TT/E2 ratio. The study also revealed differences in the effects of different concentrations of EDCs.

Deep eutectic supramolecular polymers based HPLC stationary phase: Green synthesis strategy and promising application prospects

BackgroundDeep eutectic solvents (DESs) have been widely and significantly applied in various fields due to their outstanding features such as low cost, easy preparation and good biodegradability. As novel derivatives of DESs, deep eutectic supramolecular polymers (DESPs) combine the macroscopic state of DESs with the covalent interactions of supramolecular polymers, which also possess the properties of DESs as multifunctional materials. Therefore, DESPs are believed to be promising candidates for separation science. However, there are no studies on the application of DESPs as stationary phases for HPLC analysis. ResultsIn this work, a novel DESP based HPLC stationary phase (Poly(DES)@SiO2) was developed for the first time through a green synthesis method by using DES as the polymerization monomer as well as the reaction medium. The results manifest that this novel Poly(DES)@SiO2 column can well interact with analytes through various mechanisms, and realize selective separation of a wide range of structurally similar hydrophilic/hydrophobic substances. More importantly, the separation of hydrophobic analytes on the Poly(DES)@SiO2 column is less time-consuming with fewer organic eluent, although the column efficiency is slightly lower than that of commercial C18 column. Furthermore, the Poly(DES)@SiO2 column exhibits excellent mechanical stability and satisfactory separation repeatability for steroid hormones. Therefore, a reliable method was established for detecting steroid hormones in actual samples with the recoveries ranging from 94.56 % to 103.84 %, which can meet the detection needs of commonly seen steroid hormones in food and the environment. SignificanceIn summary, this work provides some valuable theoretical references for the synthesis of new DESP based stationary phases through a green and facile strategy, and meanwhile, verifies the feasibility of DESP for effective HPLC separations. In addition, the promising application prospect of DESP based stationary phases in the analysis of complex samples has also been demonstrated, expanding the potential application of DES in separation science.

A multidisciplinary approach in the treatment of thoracic endometriosis

Purpose. To familiarize gynecologists with the clinical presentation, diagnosis and basic principles of treatment of thoracic endometriosis (TE).Materials and Methods. The article presents a review of publications based on the results of search in electronic resources PubMed, Elibrary, EMBASE. The own clinical observation of the patient with TE is also presented.Results. The clinical picture of TE can be different, in many patients it is asymptomatic. The typical symptom of TE is menstrual cycle-related, usually right-sided pain in the thoracic, scapular or shoulder area. Chest X-rays, computed tomography (CT), magnetic resonance imaging (MRI) and bronchoscopy are used in diagnosis. The gold standard for definitive diagnosis and effective treatment is video-assisted thoracoscopic surgery (VATS). As with pelvic disease, the first-line therapy for TE is medication to suppress ovarian steroid hormone production. Surgical treatment should be considered in patients with refractory or recurrent TE and in acute life-threatening conditions.Conclusion. Management of patients with thoracic endometriosis requires an interdisciplinary approach involving gynecologists and thoracic surgeons.

Wen-Shen-Tong-Luo-Zhi-Tong-Decoction inhibits bone loss in senile osteoporosis model mice by promoting testosterone production

Ethnopharmacological relevanceWen-Shen-Tong-Luo-Zhi-Tong-Decoction (WSTLZTD) is a traditional Chinese medicine formula, and its effectiveness in the treatment of senile osteoporosis(SOP) has been confirmed by clinical studies. However, the underlying mechanism of WSTLZTD in SOP is unclear. Aim of the studyThis study aimed to clarify the unique effects of Wen-Shen-Tong-Luo-Zhi-Tong-Decoction(WSTLZTD) on senile osteoporosis(SOP) and its underlying mechanisms. Materials and methodsSAMP6 mice were treated with varying doses of WSTLZTD as the SOP model. Bone loss was evaluated by micro-CT, HE, OCN immunohistochemistry staining, and serum Trap level. Metabolomics studies serum metabolites. ELISA, qPCR, and immunofluorescence were utilized to measure testosterone levels in mouse testis. The effect of testosterone on the mitochondrial energy metabolism of BMSCs was investigated using ROS generation, NAD+/NADH ratio, and WB. Cell senescence was examined by β-galactosidase staining and WB. The effect of TM3 cell conditioned media (CM) on mitochondrial energy metabolism and BMSCs osteogenesis were studied using ALP, ARS, ROS staining, the NAD+/NADH, and WB. ResultsWSTLZTD effectively reversed bone loss in SOP model mice, resulting in better bone microstructure, increased BMD, BV/TV, Tb.n, Tb.Th and, and decreased Tb.Sp. WSTLZTD can increase OCN expression and decrease Trap levels. Network pharmacology data suggest that WSTLZTD regulates steroid hormone production, cellular senescence, inflammation. Metabolomic data indicate that WSTLZTD increases testosterone production or metabolism-related metabolites. WSTLZTD enhanced testosterone production and the mRNA expression of genes involved in testosterone synthesis. Testosterone inhibited the decline in osteogenic differentiation and mitochondrial energy metabolism of senescent BMSCs. The decreased testosterone production in senescent TM3 is reversed by WSTLZTD. CM derived from WSTLZTD-treated TM3 cells promoted osteogenic differentiation and mitochondrial energy metabolism of BMSCs. ConclusionsBy increasing testosterone production, WSTLZTD may promote mitochondrial energy metabolism and osteogenic differentiation of senescent BMSCs, thereby exerting its anti-SOP effect.

Revisiting the specific and potentially independent role of the gonad in hormone regulation and reproductive behavior.

Gonadal sex steroid hormones are well-studied modulators of reproductive physiology and behavior. Recent behavioral endocrinology research has focused on how the brain dynamically responds to - and may even produce - sex steroids, but the gonadal tissues that primarily release these hormones receive much less attention as a potential mediator of behavioral variation. This Commentary revisits mechanisms by which the reproductive hypothalamic-pituitary-gonadal (HPG) axis can be modulated specifically at the gonadal level. These mechanisms include those that may allow the gonad to be regulated independently of the HPG axis, such as receptors for non-HPG hormones, neural inputs and local production of conventional 'neuropeptides'. Here, I highlight studies that examine variation in these gonadal mechanisms in diverse taxa, with an emphasis on recent transcriptomic work. I then outline how future work can establish functional roles of gonadal mechanisms in reproductive behavior and evaluate gonad responsiveness to environmental cues. When integrated with neural mechanisms, further investigation of gonadal hormone regulation can yield new insight into the control and evolution of steroid-mediated traits, including behavior.

Infanticide is driven by unfamiliarity with offspring location and associated with androgenic shifts in mimic poison frogs

Infanticide is widespread across the animal kingdom, but the physiological drivers of infanticide versus care or neglect are relatively unexplored. Here, we identified salient environmental and physiological antecedents of infanticide in the mimic poison frog (Ranitomeya imitator), a biparental amphibian in which female parents feed their tadpoles unfertilized eggs. Specifically, we explored potential environmental cues influencing infant-directed behavior by evaluating changes in the frequency of food provisioning and tadpole mortality after either cross-fostering tadpoles between family units or displacing tadpoles within the terraria of their parents. We found that changes in offspring location reduce care and increase infanticide. Specifically, parents fed their displaced offspring less and, in some instances, tadpole mortality increased. We also investigated whether care and infanticide were related to changes in steroid hormone concentrations in an unfamiliar setting. Infanticide of fertilized eggs and hatchlings in the new territory included cannibalism and was associated with lower testosterone concentrations, but not with changes in corticosterone. Overall, our results support earlier findings that familiarity with offspring location drives parental investment in poison frogs, while indicating an association between low androgen levels and infanticidal behavior in an amphibian.

Exploring the pharmacological mechanism of fermented Eucommia ulmoides leaf extract in the treatment of cisplatin-induced kidney injury in mice: Integrated traditional pharmacology, metabolomics and network pharmacology

Cisplatin (CP) is a widely utilized anticancer drug, which also produces significant side effects, notably acute kidney injury (AKI). Fermented Eucommia ulmoides leaf (FEUL), a medicinal and edible Chinese herbal remedy, is known for its renoprotective properties. However, the effect and underlying mechanism of FEUL in AKI therapy have remained largely unexplored. This research aimed to elucidate the protective roles of FEUL in an AKI mouse model through biochemical assays, histopathological examinations, and investigating the underlying mechanisms based on metabolomics and network pharmacology. The findings demonstrated that pretreatment with orally administered FEUL significantly reduced blood urea nitrogen (BUN), and serum creatinine (SCr) levels, and ameliorated CP-induced kidney histopathological injuries. Moreover, FEUL attenuated CP-induced endoplasmic reticulum (ER) stress by reducing the protein expressions of PERK, IRE 1α, GRP78, ATF6, ATF4, and CHOP. The metabolomics results indicated that a total of 31 metabolites, involved in taurine and hypotaurine metabolism, lysine degradation, and steroid hormone biosynthesis, were altered after FEUL administration. Furthermore, metabolomics integrated with network pharmacology revealed that 8 targets, 4 metabolites, and 3 key pathways including steroid hormone biosynthesis, purine metabolism, and tryptophan metabolism were the main mechanisms of FEUL in treating CP-induced AKI. These findings suggested that FEUL could offer valuable insights for potential CP-induced AKI treatment strategies.