Unraveling the gut-brain axis:the impact of steroid hormones and nutrition on Parkinson's disease

This comprehensive review explores the intricate relationship between nutrition,the gut microbiome,steroid hormones,and Parkinson's disease within the context of the gut-brain axis.The gut-brain axis plays a pivotal role in neurodegenerative diseases like Parkinson's disease,encompassing diverse components such as the gut microbiota,immune system,metabolism,and neural pathways.The gut microbiome,profoundly influenced by dietary factors,emerges as a key player.Nutrition during the first 1000 days of life shapes the gut microbiota composition,influencing immune responses and impacting both child development and adult health.High-fat,high-sugar diets can disrupt this delicate balance,contributing to inflammation and immune dysfunction.Exploring nutritional strategies,the Mediterranean diet's anti-inflammatory and antioxidant properties show promise in reducing Parkinson's disease risk.Microbiome-targeted dietary approaches and the ketogenic diet hold the potential in improving brain disorders.Beyond nutrition,emerging research uncovers potential interactions between steroid hormones,nutrition,and Parkinson's disease.Progesterone,with its anti-inflammatory properties and presence in the nervous system,offers a novel option for Parkinson's disease therapy.Its ability to enhance neuroprotection within the enteric nervous system presents exciting prospects.The review addresses the hypothesis thatα-synuclein aggregates originate from the gut and may enter the brain via the vagus nerve.Gastrointestinal symptoms preceding motor symptoms support this hypothesis.Dysfunctional gut-brain signaling during gut dysbiosis contributes to inflammation and neurotransmitter imbalances,emphasizing the potential of microbiota-based interventions.In summary,this review uncovers the complex web of interactions between nutrition,the gut microbiome,steroid hormones,and Parkinson's disease within the gut-brain axis framework.Understanding these connections not only offers novel therapeutic insights but also illuminates the origins of neurodegenerative diseases such as Parkinson's disease.

Gut microbiota affects the estrus return of sows by regulating the metabolism of sex steroid hormones

Background Sex hormones play important roles in the estrus return of post-weaning sows.Previous studies have demonstrated a complex and bi-directional regulation between sex hormones and gut microbiota.However,the extent to which the gut microbiota affects estrus return of post-weaning sows is largely unknown.Results In this study,we first screened 207 fecal samples from well-phenotyped sows by 16S rRNA gene sequencing and identified significant associations between microbes and estrus return of post-weaning sows.Using metagenomic sequencing data from 85 fecal samples,we identified 37 bacterial species that were significantly associated with estrus return.Normally returning sows were characterized by increased abundances of L.reuteri and P.copri and decreased abundances of B.fragilis,S.suis,and B.pseudolongum.The changes in gut microbial composition significantly altered the functional capacity of steroid hormone biosynthesis in the gut microbiome.The results were confirmed in a validation cohort.Significant changes in sex steroid hormones and related compounds were found between normal and non-return sows via metabolome analysis.An integrated analysis of differential bacterial species,metagenome,and fecal metabolome provided evidence that normal return-associated bacterial species L.reuteri and Prevotella spp.participated in the degradation of pregnenolone,progesterone,and testosterone,thereby promoting estrogen biosynthesis.Furthermore,the microbial metabolites related to sow energy and nutrient supply or metabolic disorders also showed relationships with sow estrus return.Conclusions An integrated analysis of differentially abundant bacterial species,metagenome,and fecal metabolome revealed the involvement of L.reuteri and Prevotella spp.in sow estrus return.These findings provide deep insight into the role of gut microbiota in the estrus return of post-weaning sows and the complex cross-talk between gut microbiota and sex hormones,suggesting that the manipulation of the gut microbiota could be an effective strategy to improve sow estrus return after weaning.

Transcriptome analysis reveals steroid hormones biosynthesis pathway involved in abdominal fat deposition in broilers

Excessive abdominal fat deposition reduces the feed efficiency and increase the cost of production in broilers.Therefore,it is an important task for poultry breeders to breed broilers with low abdominal fat.Abdominal fat deposition is a highly complex biological process,and its molecular basis remains elusive.In this study,we performed transcriptome analysis to compare gene expression profiles at different stages of abdominal fat deposition to identify the key genes and pathways involved in abdominal fat accumulation.We found that abdominal fat weight(AFW)increased gradually from day 35(D35)to 91(D91),and then decreased at day 119(D119).Accordingly,after detecting differentially expressed genes(DEGs)by comparing gene expression profiles at D35 vs.D63 and D35 vs.D91,and identifying gene modules associated with fat deposition by weighted gene co-expression network analysis(WGCNA),we performed intersection analysis of the detected DEGs and WGCNA gene modules and identified 394 and 435 intersecting genes,respectively.The results of the Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses showed that the steroid hormone biosynthesis and insulin signaling pathways were co-enriched in all intersecting genes,steroid hormones have been shown that regulated insulin signaling pathway,indicating the importance of the steroid hormone biosynthesis pathway in the development of broiler abdominal fat.We then identified 6 hub genes(ACTB,SOX9,RHOBTB2,PDLIM3,NEDD9,and DOCK4)related to abdominal fat deposition.Further analysis also revealed that there were direct interactions between 6 hub genes.SOX9 has been shown to bind to proteins required for steroid hormone receptor binding,and RHOBTB2 indirectly regulates the steroid hormones biosynthesis through cyclin factor,and ultimately affect fat deposition.Our results suggest that the genes RHOBTB2 and SOX9 play an important role in fat deposition in broilers,by regulating steroid hormone synthesis.These findings provide new targets and directions for further studies on the mechanisms of fat deposition in chicken.

Metformin:A promising clinical therapeutical approach for BPH treatment via inhibiting dysregulated steroid hormones-induced prostatic epithelial cells proliferation

The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.However,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive relationship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met’s anti-proliferative effects were blocked by AMPK inhibitor or YAP1 overexpression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

Effect of Sex Steroid Hormones on Brain Tubulin Synthesis in Castrated Male Mouse & Testis-intact Male Mouse

The effect of gonadal hormones on brain tubulin synthesis has been studied in the castrated middle-aged male mouse and testes intact oldaged male mouse.Estrogen exerts potent influences on stimulating tubulin synthesis.Treatment with estradiol benzoate or estradiol benzoate and hydroxyprogesterone caproate increase the amount of tubulin by almost 37%-43%.Administration of testosterone propionate can produce a 13%-23% increase.Both estrogen and androgen can stimulate tubulin synthesis after the critical period of brain development but, estrogen plays a stronger role than androgen in stimulating tubulin synthesis in male mouse.

Functional interactions between steroid hormones and neurotrophin BDNF

Brain-derived neurotrophic factor(BDNF),a critical neurotrophin,regulates many neuronal aspects including cell differentiation,cell survival,neurotransmission,and synaptic plasticity in the central nervous system(CNS) .Though BDNF has two types of receptors,high affinity tropomyosin-related kinase(Trk) B and low affinity p75 receptors,BDNF positively exerts its biological effects on neurons via activation of TrkB and of resultant intracellular signaling cascades including mitogenactivated protein kinase/extracellular signal-regulated protein kinase,phospholipase Cγ,and phosphoinositide 3-kinase pathways.Notably,it is possible that alteration in the expression and/or function of BDNF in the CNS is involved in the pathophysiology of various brain diseases such as stroke,Parkinson's disease,Alzheimer's disease,and mental disorders.On the other hand,glucocorticoids,stress-induced steroid hormones,also putatively contribute to the pathophysiology of depression.Interestingly,in addition to the reduction in BDNF levels due to increased glucocorticoid exposure,current reports demonstrate possible interactions between glucocorticoids and BDNF-mediated neuronal functions. Other steroid hormones,such as estrogen,are involved in not only sexual differentiation in the brain,but also numerous neuronal events including cell survival and synaptic plasticity.Furthermore,it is well known that estrogen plays a role in the pathophysiology of Parkinson's disease,Alzheimer's disease,and mental illness,while serving to regulate BDNF expression and/or function.Here,we present a broad overview of the current knowledge concerning the association between BDNF expression/function and steroid hormones(glucocorticoids and estrogen).

Analysis of 13 kinds of steroid hormones in raw milk using modified QuEChERS method combined with UPLC-QTOF-MS

Thirteen kinds of steroid hormones in raw milk（cow, goat and buffalo milk） were analyzed with ultra performance liquid chromatography-quadrupole time of flight mass spectrometry（UPLC-QTOF-MS） after extraction and cleanup with the modified Qu ECh ERS method. These steroid hormones included 17β-estradiol, estriol, estrone, diethylstilbestrol, progesterone, melengestrol acetate, megestrol acetate, chlormadinone acetate, 19-nortestosterone, metandienone, boldenone, epitestosterone, and testosterone. The limits of detection for the raw milk basing on 3 times the signal to noise ratios（S/N=3） was in range of 0.07-0.51 μg kg^–1, and the limits of quantification（basing on S/N=10 method） covered the ranges from 0.23 to 1.7 μg kg^–1. With matrix external standard method, the substances presented recoveries over the range 74.2–99.7%. Qualitative analysis was also done in the mass/mass spectrum（MS/MS） mode and each debris structure of 13 kinds of steroid hormones was achieved. The methodology was then applied in real raw milk samples which were collected in several areas of China and the progesterone was detected with high level.

Hydroxylation and sulfation of sex steroid hormones in inflammatory liver

Sex steroids, also known as gonadal steroids, are oxidized with hydroxylation by cytochrome P450,glucuronidation by UDP-glucuronosyltransferase, sulfation by sulfotransferase, and O-methylation by catechol Omethyltransferase. Thus, it is important to determine the process by which inflammation influences metabolism of gonadal hormones. Therefore, we investigated the mechanism of metabolic enzymes against high physiologic inflammatory response in vivo to study their biochemical properties in liver diseases. In this study, C57BL/6N mice were induced with hepatic inflammation by diethylnitrosamine(DEN) exposure. We observed upregulation of Cyp19a1, Hsd17b1, Cyplal, Sult1e1 in the DEN-treated livers compared to the control-treated livers using real time PCR. Moreover, the increased Cyp19a1 and Hsd17b1 levels support the possibility that estrogen biosynthesis from androgens are accumulated during inflammatory liver diseases. Furthermore, the increased levels of Cyp1a1 and Cyp1b1 in the hydroxylation of estrogen facilitated the conversion of estrogen to 2-or 4-hydroxyestrogen,respectively. In addition, the substantial increase in the Sultlel enzyme levels could lead to sulfate conjugation of hydroxyestrogen. The present information supports the concept that inflammatory response can sequester sulfate conjugates from the endogenous steroid hormones and may suppress binding of sex steroid hormones to their receptors in the whole body.

ANNUAL CHANGES IN PLASMA LEVELS OF CORTISOL AND SEX STEROID HORMONES IN MALE RAINBOW TROUT, ONCORHYNCHUS MYKISS

The profiles of cortisol, testosterone, 11 ketotestosterone and 17α, 20β dihydroxy 4 pregnene 3 one in male rainbow trout reared under constant water temperature and natural photoperiod were determined by radioimmunoassay. Gonads of male rainbow trout reached maturity when the fish were two years old. Changes in the plasma levels of both sex steroid hormones and cortisol were closely related to the GSI. Plasma levels of testosterone, 11 ketotestosterone and 17α, 20β dihydroxy 4 pregnene 3 one showed a clear peak in the annual breeding season, when the GSI reached their maxima. Plasma cortisol levels also showed clearly seasonal changes in both two and three year old fish. The results suggest that the elevated plasma levels of cortisol may not just be due to stresses during the breeding season but have certain physiological functions in the reproduction of rainbow trout.

Gender disparity in COVID-19: Role of sex steroid hormones

The emerging pandemic of COVID-19 caused by the novel pathogenic human coronavirus SARS-CoV-2 has caused significant morbidity and mortality across the globe,prompting the scientific world to search for preventive measures to interrupt the disease process.Demographic data indicates gender-based differences in COVID-19 morbidity with better outcome amongst females.Disparity in sex-dependent morbidity and mortality in COVID-19 patients may be attributed to difference in levels of sex steroid hormones-androgens and estrogens.Evidence suggests that apart from the regulation of viral host factors,immunomodulatory and cardioprotective roles exerted by estrogen and progesterone may provide protection to females against COVID-19.Exploring the underlying mechanisms and beneficial effects of these hormones as an adjuvant to existing therapy may be a step towards improving the outcomes.This article aims to review studies demonstrating the role of sex steroidal hormones in modulating SARS-CoV-2 host factors and summarize plausible biological reasons for sex-based differences seen in COVID-19 mortality.

Study on two steroidal sex hormones in rice

Steroidal sex hormones including androgensand estrogens are important in the reproduc-tive development of mammals. A number ofstudies suggested that these steroids mighthave similar functions in plants. A latest re-search on Nongken 58s, a photoperiod-sensi-tire genie male-sterile rice (PGMR), showed

Sex Hormones and Androgen Receptor:Risk Factors of Coronary Heart Disease in Elderly Men

Objective To investigate the variation of sex hormone and its receptor level in elderly male patients with coronary heart disease (CHD) and to evaluate the correlations between CHD and sex hormone as well as sex hormone receptor. Methods Altogether 139 male CHD patients (CHD group) aged 60-92 years and 400 healthy men (control group) aged 60-90 years were included in this cross sectional study. The plasma concentrations of dehydroepiandrosterone sulfate (DHEAS),total testosterone (TT),free testosterone (FT),estradiol (E2),sex hormone binding globulin (SHBG),luteinizing hormone (LH),and follicle-stimulating hormone (FSH) were measured. The androgen receptor (AR) was tested by flow cytometry. Correlations between CHD and levels of sex hormones and AR were analyzed. Results Compared with the control group,the levels of DHEAS,TT,FT,SHBG,and the fluorescence intensity of AR in the CHD group significantly reduced (P<0.05),while the levels of FSH and E2 significantly increased (P<0.01). Age was negatively correlated with TT (r=-0.28,P=0.00) and FT (r=-0.17,P=0.01),while it was positively correlated with SHBG (r=0.14,P=0.04) and E2 (r=0.33,P=0.00). AR fluorescence intensity was negatively correlated with systolic blood pressure (r=-0.12,P=0.01). Binary logistic regression analysis showed that TT,SHBG,and AR were all negatively correlated with CHD (P<0.05). Conclusions Elderly male patients with CHD are found to have low levels of DHEAS,TT,FT,SHBG,and AR,while high concentrations of E2 and FSH. Low levels of TT and SHBG may be the potential risk factors of CHD in elderly men.

WJSC 6^(th) Anniversary Special Issues(2):Mesenchymal stem cells Differentiation of mesenchymal stem cells into gonad and adrenal steroidogenic cells

Hormone replacement therapy is necessary for patients with adrenal and gonadal failure.Steroid hormone treatment is also employed in aging people for sex hormone deficiency.These patients undergo such therapies,which have associated risks,for their entire life.Stem cells represent an innovative tool for tissue regeneration and the possibility of solving these problems.Among various stem cell types,mesenchymal stem cells have the potential to differentiate into steroidogenic cells both in vivo and in vitro.In particular,they can effectively be differentiated into steroidogenic cells by expressing nuclear receptor 5A subfamily proteins(steroidogenic factor-1 and liver receptor homolog-1)with the aid of cAMP.This approach will provide a source of cells for future regenerative medicine for the treatment of diseases caused by steroidogenesis deficiencies.It can also represent a useful tool for studying the molecular mechanisms of steroidogenesis and its related diseases.

CORRELATION OF STEROID HORMONE RECEPTORS AND CLINICAL PATHOLOGICAL FEATURES WITH PROGNOSIS OF HUMAN BREAST CANCER

Clinical, pathological features and steroid hormone receptors (SR) including receptors of estrogen (ER), progesterone (PR) and androgen (AR) were observed in 58 cases of breast carcinoma, and related to patient 5- year survival rate through stratification and multivariatc analysis. The results showed that histologic tumor type and grading, lymphnode status, ER value and patient age took more important role in patient survival, and SR, especially, conferred survival advantage in advanced cases with tumor size larger than 2 cm, node involved, or TNM Stage Ⅱ-Ⅲ.

Hormones in Poultry Production: Scientific Facts

The following article has been retracted due to the investigation of complaints received against it. The Editorial Board found that substantial portions of the text came from other published papers. The scientific community takes a very strong view on this matter, and the Open Journal of Animal Sciences treats all unethical behavior seriously. This paper published in Vol.4 No.5, 228-236, 2014 has been removed from this site. Title: Hormones in Poultry Production: Scientific Facts Authors: Wagner Azis Garcia de Araújo, Tarcisio Sim&otildees Pereira Agostinho, Nielton Cezar Ton, Luiz Fernando Teixeira

Leptin effects on the hypothalamic-pituitary-gonadal axis by activating proopiomelanocortin neurons Correlation between regulatory effects and duration

BACKGROUND：Leptin preserves reproductive functions by stimulating hypothalamic-pituitary-gonadal axis activities at different levels.Some interneurons play an important role in leptin regulation of the gonadal axis.It remains uncertain whether leptin regulates reproductive functions by activating proopiomelanocortin （POMC） neurons.OBJECTIVE：To investigate leptin effects on secretory function of the neuroendocrine-gonadal axis by activating POMC neurons and to observe and verify the relationship between leptin effects and various time points.DESIGN,TIME AND SETTING：The randomized,controlled,animal study was performed at the Basic Institute of Chengde Medical University and the Research Room of Reproductive Immunology of National Research Institute for Family Planning from June to September 2008.MATERIALS：Leptin （Peprotech,USA）,a-melanocyte stimulating hormone and rabbit anti-POMC polyclonal antibody （SC-20148） （Santa Cruz Biotechnology,USA）,follicle stimulating hormone,luteinizing hormone,and gonadotropin releasing hormone enzyme-labeled immunosorbent assay （ELISA） kit （ADL,USA） were used in the present study.METHODS：A total of 60 healthy,female,adult,Wistar rats received 17 （3-estradiol for 5 consecutive days at 15 days after ovariectomy.The rats were randomly assigned to physiological saline （n= 35）,leptin （n = 35）,and a-melanocyte stimulating hormone （n = 20） groups.MAIN OUTCOME MEASURES：Changes in gonadotropin releasing hormone,luteinizing hormone,and follicle stimulating hormone were compared following intraventricular injection of physiological saline,leptin,and a-melanocyte stimulating hormone at various time points.Changes in POMC mRNA and protein expression in the hypothalamus were measured following physiological saline and leptin injection via the lateral ventricle.RESULTS：Compared to the physiological saline group,leptin and a-melanocyte stimulating hormone affected secretion in the hypothalamus-pituitary axis.Leptin affected secretion of gonadotropin releasing hormone,luteinizing hormone,and follicle stimulating hormone,whereas a-melanocyte stimulating hormone inhibited secretion of these hormones.Compared to the physiological saline group,POMC mRNA expression was significantly increased in the hypothalamus at 2 and 4 hours after leptin injection （P〈 0.05）,but expression recovered to physiological saline group levels at 6 hours after injection （P 〉 0.05）.POMC protein expression was significantly increased in the hypothalamus at 4 and 6 hours after leptin injection （P〈 0.05）.CONCLUSION：Leptin affects secretory function of the neuroendocrine-gonadal axis through combined effects on POMC neurons and other pathways.Results suggested that the regulatory effects of POMC neurons were later compared to other neurons.

Does the use of double hormone replacement therapy for trauma patient organ donors improve organ recovery for transplant

BACKGROUND With an ongoing demand for transplantable organs,optimization of donor management protocols,specifically in trauma populations,is important for obta-ining a high yield of viable organs per patient.Endocrine management of brain-dead potential organ donors(BPODs)is controversial,leading to heterogeneous clinical management approaches.Previous studies have shown that when levo-thyroxine was combined with other treatments,including steroids,vasopressin,and insulin,BPODs had better organ recovery and survival outcomes were increased for transplant recipients.AIM To determine if levothyroxine use in combination with steroids in BPODs increased the number of organs donated in trauma patients.METHODS A retrospective review of adult BPODs from a single level 1 trauma center over ten years was performed.Exclusion criteria included patients who were not solid organ donors,patients who were not declared brain dead(donation after circulatory death),and patients who did not receive steroids in their hospital course.Levothyroxine and steroid administration,the number of organs donated,the types of organs donated,and demographic information were recorded.Univariate analyses were performed with P<0.05 considered to be statistically significant.RESULTS A total of 88 patients met inclusion criteria,69(78%)of whom received levothyroxine and steroids(ST/LT group)vs 19(22%)receiving steroids without levothyroxine(ST group).No differences were observed between the groups for gender,race,pertinent injury factors,age,or other hormone therapies used(P>0.05).In the ST/LT group,68.1%(n=47)donated a high yield(3-5)of organ types per donor compared to 42.1%(n=8)in the ST group(P=0.038).There was no difference in the total number of organ types donated between the groups(P=0.068).CONCLUSION This study suggests that combining levothyroxine and steroid administration increases high-yield organ donation per donor in BPODs in the trauma patient population.Limitations to this study include the retrospective design and the relatively small number of organ donors who met inclusion criteria.This study is unique in that it mitigates steroid administration as a confounding variable and focuses specifically on the adjunctive use of levothyroxine.

Mechanisms of Immune Tolerance and Inflammation via Gonadal Steroid Hormones in Preterm Birth

In 2019,preterm births(PTB)accounted for approximately 0.66 million deaths globally.PTB is also associated with a significantly higher risk of mortality and long-term complications for newborns.Long-term studies associated several factors,including disruption of immune tolerance and inflammation,with PTB.However,the pathogenesis of PTB remains unclear.Gonadal steroid hormones are critical for pregnancy maintenance and regulation of immune and inflammatory responses.However,it is not clear how unbalanced gonadal steroid hormones,such as imbalanced estrogen/androgen or estrogen/progesterone contribute to PTB.In this review,we discuss how gonadal steroid hormones mediate dysfunction in immune tolerance and inflammatory responses,which are known to promote the occurrence of PTB,and provide insight into PTB prediction.

Study on Correlation of Sex Steroid Hormone Level With Gonadal Development in Amphioxus

Zhang Zhi-yi et al.demonstrated that sex steroid hormone exists in the maturegonads(ovaries and testes)of amphioxus.So far,it is not clear whether the content ofsex steroid hormone changes correlatively with the different stages of gonadal developmentof amphioxus,like vertebrate.Therefore,the present study has an important theoreticalsignificance for understanding the gonadal development and hormonal regulation inamphioxus.