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.

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.

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.

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.

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.

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.

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.

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.

Associations of waist circumference with sex steroid hormones among 4031 USA children and adolescents

In the recent decades,obesity rates among children and adolescents,especially males,have increased significantly.This worldwide phenomenon is thought to significantly affect the levels of sex hormones.However,the association between waist circumference(a marker of abdominal obesity)and sex hormone levels in children and adolescents is unknown.In this study,4031 participants aged 6–19 years from the United States National Health and Nutrition Examination Survey(NHANES)in the USA were enrolled in this study.The common confounders of age,race,body mass index,educational level,family income,diabetes,and time of sample collection were also collected.The participants missing any of the above information were excluded from the study.We used multiple linear regression and other multiple statistics to assess the associations between waist circumference and serum testosterone,estradiol,sex hormone-binding globulin(SHBG),free androgen index(FAI),and testosterone/estradiol ratio(T/E2).Waist circumference remained associated with sex hormone levels in children and adolescents after controlling for covariates.As waist circumference increases,testosterone levels in children and adolescents show an overall decline after a brief increase,with the inflection point for waist circumference of 65–66 cm.In addition,waist circumference positively correlates with estradiol levels in male children(β=0.007,95%confidence interval:0.004–0.009).Moreover,circulating SHBG decreases in children and adolescents as waist circumference increases.In conclusion,this study highlighted waist circumference as a vital indicator affecting sex hormone levels in children and adolescents.

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.

Removal of steroid hormones from mariculture system using seaweed Caulerpa lentillifera

The removal of steroid hormones from the mariculture system using seaweeds(Caulerpa lentillifera,Ulva pertusa,Gracilaria lemaneiformis,and Codium fragile)was investigated.The results illustrated that both 17β-estradiol(E_(2))and 17α-ethinylestradiol(EE_(2))could be removed by the seaweeds at different levels,and the Caulerpa lentillifera was the most efficient one.More than 90%of E_(2) or EE_(2) at concentration of 10μg/L was removed by Caulerpa lentillifera within 12 h.Processes including initial quick biosorption,the following slow accumulation,and biodegradation might explain the removal mechanisms of E_(2)/EE_(2) by Caulerpa lentillifera.E_(2)/EE_(2) removal was positively related to the nutrient level and the initial concentration of steroid hormone.A significant linear relationship for E_(2) and EE_(2) existed between the initial pollutant concentration and the average removal rate.The highest removal kinetic constant(k)value was obtained at 30℃as 0.34/h for E_(2) and at 20℃as 0.28/h for EE_(2),demonstrating the promising application potential of Caulerpa lentillifera in the water purification of the industrialized mariculture system with relatively high water temperature.Simultaneous and efficient removal of E_(2) and EE_(2) by Caulerpa lentillifera was still achieved after 3 cycles in the pilot-scale experiment.The steroid hormones and nutrients in mariculture wastewater could also be simultaneously removed using Caulerpa lentillifera.These findings demonstrated that Caulerpa lentillifera was the promising seaweed for the removal of steroid hormones in mariculture systems.

Adsorption and desorption of steroid hormones on saline soil

Soil organic matter content was the main driving factor affecting adsorption and desorption process of 17β-estradiol(E2)and 17α-ethynylestradiol(EE2)on saline soil.The adsorption and desorption of E2 and EE2 on three saline soils showed the similar behavior that soil with the highest organic content possessed the highest adsorption capacity and the lowest desorption capacity for E2 and EE2.The adsorption capacity of untreated soil samples(with organic matter)was larger than that of soil samples without organic matter.For soil with the largest adsorption capacity,adsorption capacity of E2/EE2 on the untreated soil and soil colloid(with organic matter)respectively reached 0.15/0.30μg/g and 0.16/0.33μg/g while the soil and soil colloid without organic matter hardly adsorbed pollutants.The adsorption capacity of E2/EE2 at the initial concentration of 100μg/L was 25/15 times higher than that at the initial concentration of 5μg/L.E2 and EE2 had the same adsorption sites on saline soil while EE2 possessed higher competition intensity for adsorption sites than E2.Pseudo-first-order model(R^(2)=0.995–0.986)and Langmuir model(R^(2)=0.989–0.999)could better fit the adsorption process of E2 or EE2.The thermodynamic study further showed that the adsorption of E2/EE2 on saline soil was a spontaneous exothermic process.The desorption capacity of EE2/E2 accounted for 40%/78%of the total adsorption capacity to possibly exert potential risk to the groundwater.The variation of the salinity led to the variation of soil organic carbon which subsequently changed the adsorption and desorption behaviors of endocrine disrupting chemicals in coastal saline soil.This study provides a new insight on the interfacial behavior of endocrine disrupting chemicals on saline soil.

Effect of Combination Regimen of Low-dose Gossypol Acetic Acid with Steroid Hormones on Expression of Protein Kinase C alpha (PKC-α) and Cyclin D1 in Rat Testes

Objective To investigate the contraceptive mechanism of combination regimen of low- dose gossypol acetic acid （GA） with steroid hormones [desogestre/ethinylestradiol/ testosterone undeeanote（DSG/EE/TU）]. Methods Adult male rats were randomly divided into four groups. Group GH： rats were fed orally with gossypol acetic acid （GA, 12.5 mg/kg） and desogestrel （DSG, 0.125 mg/kg）/ ethinylestradiol （EE, 0.025 mg/kg）/testosterone undecanoate （TU, 100 mg/kg per day, qd X4 weeks or 10 weeks）; group G： a single dose of GA （12.5 mg/kg per day, qd X 4 weeks or I0 weeks）; group H： the same dosage of DSG/EE/TUas in group GH; group C： rats were treated with vehicle （1% methyl cellulose） as the control. Expression of protein kinase C alpha （PKC-a） and cyclin D1 in rat testes were tested mainly by immunohistochemistry （IHC） and Western blotting. Results IHC results showed that protein PKC- a was expressed mainly in interstitial tissue of testis among seminiferous tubule. The expression of PKC-oc in groups H and GH at week 10 was decreased greatly compared with that in group C. The protein cyclin D1 was expressed mainly in residual body of seminiferous tubule eavosurface and interstitial tissue among seminiferous tubule of testis. Western blotting results showed that the expression of PKC-a in groups H and GH at week 10 was decreased significantly compared with that in group C （P〈0.05）. The expression of cyclin D1 in groups G, H or GH at week 10 rose significantly compared with that in group C （P 〈0.05）.Conclusion The administration of low-dose gossypol acetic acid with steroid hormones for 10 weeks can decrease the expression of PKC-a greatly.

Isolation and characterization of a bacterial strain that efficiently degrades sex steroid hormones

A bacterial strain,ZY3,growing on sex steroid hormones as the sole source of carbon and energy was isolated from the sewage treatment plant of a prophylactic steroids factory.ZY3 degrades the 3-methoxy-17b-hydroxy-1,3,5(10),8(9)-d-4-estren(MHE).This strain was preli-minarily identified as Raoultella sp.ZY3 according to its morphology and its 16S rRNA gene sequence.During the experimental period(72 h),the optimum temperature,pH and 3-MHE concentration for the degradation of hydride by the strain ZY3 were 35°C,10 and 10 mg/L,respectively.The degradation rate of the sex steroid hormones increased to 87%and 85% after the addition of maltose and peptone,respectively.

THE EVALUATION METHODS OF VELVET ANTLER AND THE DETERMINATION OF NUCLEOSIDES AND STEROID HORMONES IN DIFFERENT PARTS FROM SIKA DEER AND RED DEER

Velvet antler is an important and precious traditional Chinese animal medicine,and was used for strengthening the kidney,anti-fatigue,improving sexual function and so on.But the evaluation methods of velvet antler and the scientific evidence for the use of antler is insufficient.Materials and Vacuum freeze drier was used for dehydration of the fresh antler at-60.,6 pa for 24 h.

Occurrence and fate of endogenous steroid hormones,alkylphenol ethoxylates, bisphenol A and phthalates in municipal sewage treatment systems

Steroid hormones, alkylphenol ethoxylates（APEOs） and phthalic acid esters（PAEs） are emerging endocrine disrupting chemicals（EDCs） that can interfere with the endocrine function in organisms at low concentrations. The occurrence, distribution behavior, removal rate and the fate of 31 target EDCs in sewage treatment plants, which consist of various treatment facilities and receiving water in Hong Kong, were investigated. Estrone,nonylphenol-di-ethoxylate and diethyl phthalate were found to be dominant in each group of influent samples with concentrations ranging from 11–33, 747–3945 and 445–4635 ng/L,respectively. Conversely, progesterone, nonylphenol-mono-ethoxylate and bis（2-ethylhexyl）phthalate were the most abundant in dewatered sludge, with concentrations ranging from 0.9–237, 75–19,743 and 4310–37,016 ng/g（dry weight）. The removal rates of primary sedimentation and disinfection approaches were lower than 30% for most of the chemicals,while those of activated sludge and reverse osmosis were greater than 80% for more than two-thirds of the compounds, noticeably decreasing the estrogenic risk of sewage discharged into the environment. Steroid hormones were removed via biological degradation, while some APEOs and PAEs adsorbed to the sludge. Victoria Harbor poses a low to medium estrogenic risk mainly contributed by estrone and estradiol and deserves attention.

Drug synergistic antifertility effect of combined administration of low-dose gossypol with steroid hormones in rats

Background Our previous studies suggested that low-dose gossypol combined with steroid hormones has a reversible antifertility role in adult male rats, and the course of treatment was shorter than that of either gossypol or steroid hormones alone. This result suggested that low-dose gossypol and steroid hormones have a drug synergistic effect on antifertility. The aim of the study was to find the target organs of the antifertility synergistic effect of the combined regimen. Methods Thirty-two adult male rats were divided into four groups randomly： group GH,

Co-administration of Mixed Steroid Hormones can Enhance the Recovery of Spermatogenesis Damaged by Gossypol Acetic Acid in Adult Rats

Objective To determine whether co-administration of mixed steriod hormones can enhance the restoration of spermatogenesis damaged by gossypol acetic acid （GA）. Methods Adult male Wistar rats were treated daily for 8 weeks with GA at 50mg/kg plus testosterone undercanoate （100 mg/kg）/desogestrel （0.125 mg/kg）/mini-dose ethinylestradiol （0.025 mg/kg） （TU/DSG/EE）, followed by a period of 9 weeks for recovery. Control animals were administered the same dose of GA or TU/DSG/EE, and vehicle, respectively. Testis weight, testicular sperm head count and histological analysis were utilized to assess the spermatogenesis. Results At the end of the 9-week reovery period, in rats given GA alone, spermato- genesis steadily declined. However, when rats received combined hormone adminis- tration during GA treatment, this decline was prevented and an complete recovery of spermagenesis occurred. The haploid spermatids and spermatocytes was not to be protected but to be more aggravatedly damaged. The excellent recovery must have resulted from that the hormone treatment could protect the ability of stem spermatogonia to differentialte and evolve progressively into mature spermatozoa. In addition, the concentrations of serum LH, FSH and intratesticular testosteron （ITT） notably decreased after 2 or 8 weeks of treatment, then returned to control levels at the end of 9-week recovery period.Conclusion Steriod hormone treatment enhaces the recovery of spermatogenesis through preventing seminiferous epithelim from GA-induced destructive damage in rats. The enhanced recovery was closely associated with the marked suppression in intratesticular testosteron （ITT）.

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