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.

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.

The expression of Hoxa10 and its regulation by sex steroids andHB-EGF at the time of implantation in the human endometrium

Objective:The aim of this study was to determine the expression of Hoxa 10 in endometrium during the menstrual cycle and their response to sex steroids and HB-EGF.Methods:Forty endometrial samples from regularly cycling women were studied.The endometrial epithelial(EEC)and stromal(ESC)cells isolated by collagenase Ⅰ digestion and mechanical dissociation was cultured from every sample.The endometrial stromal cells(ESC)were incubated with 17-beta estradiol(10-8mol/L),medroxyprogesterone acetate(MPA)(10-6mol/L),RU486(10-8mol/L)or HB-EGF(10ng/ml)for 48 hours respectively.The expression of Hoxa10 mRNA was demonstrated by reverse transcription-polymerase chain reaction(RT-PCR).Result:Hoxa10 showed a regulated cycle phase-dependent expression pattern in stromal cells and epithelial cells.Hoxa10 expression dramatically increased during the midsecretory phase of the menstrual cycle,at the time of implantation.The expression of Hoxa10 in cultured endometrial stromal cells was stimulated by estrogen,progesterone and HB-EGF.Conclusion:The cycle phase-specific expression of Hoxa10 and up-regulated by sex steroids and HB-EGF suggests a tight regulation and establishing conditions necessary for implantation.

Mutations in Exons of the CYP17-Ⅱ Gene Affect Sex Steroid Concentration in Male Japanese Flounder(Paralichthys olivaceus)

As a specific gene of fish,cytochrome P450c17-Ⅱ(CYP17-Ⅱ) gene plays a key role in the growth,development and reproduction level of fish.In this study,the single-stranded conformational polymorphism(SSCP) technique was used to characterize polymorphisms within the coding region of CYP17-Ⅱ gene in a population of 75 male Japanese flounder(Paralichthys olivaceus).Three single nucleotide polymorphisms(SNPs) were identified in CYP17-Ⅱ gene of Japanese flounder.They were c.G594A(p.G188R),c.G939A and c.G1502A(p.G490D).SNP1(c.G594A),located in exon 4 of CYP17-Ⅱ gene,was significantly associated with gonadosomatic index(GSI).Individuals with genotype GG of SNP1 had significantly lower GSI(P < 0.05) than those with geno-type AA or AG.SNP2(c.G939A) located at the CpG island of CYP17-Ⅱ gene.The mutation changed the methylation of exon 6.Indi-viduals with genotype AA of SNP2 had significantly lower serum testosterone(T) level and hepatosomatic index(HSI) compared to those with genotype GG.The results suggested that SNP2 could influence the reproductive endocrine of male Japanese flounder.How-ever,the SNP3(c.G1502A) located in exon 9 did not affect the four measured reproductive traits.This study showed that CYP17-Ⅱ gene could be a potentially useful candidate gene for the research of genetic breeding and physiological aspects of Japanese flounder.

Breast cancer stem cells: The role of sex steroid receptors

Breast cancer(BC)is the most common cancer among women,and current available therapies often have high success rates.Nevertheless,BC might acquire drug resistance and sometimes relapse.Current knowledge about the most aggressive forms of BC points to the role of specific cells with stem properties located within BC,the so-called“BC stem cells”(BCSCs).The role of BCSCs in cancer formation,growth,invasiveness,therapy resistance and tumor recurrence is becoming increasingly clear.The growth and metastatic properties of BCSCs are regulated by different pathways,which are only partially known.Sex steroid receptors(SSRs),which are involved in BC etiology and progression,promote BCSC proliferation,dedifferentiation and migration.However,in the literature,there is incomplete information about their roles.Particularly,there are contrasting conclusions about the expression and role of the classical BC hormonal biomarkers,such as estrogen receptor alpha(ERα),together with scant,albeit promising information concerning ER beta(ERβ)and androgen receptor(AR)properties that control different transduction pathways in BCSCs.In this review,we will discuss the role that SRs expressed in BCSCs play to BC progression and recurrence and how these findings have opened new therapeutic possibilities.

<i>In-Vitro</i>Effect of Sex Steroids on Mouse Melanoma (B16F10) Cell Growth

A battery of sex steroids were used to check their effect on mouse melanoma (B16F10) cell growth in-vitro. Progesterone and its synthetic receptor antagonist RU-486 showed maximum inhibition on in-vitro melanoma cell growth [1]. Further research work showed that the inhibition by progesterone was not a toxic, spurious or non-specific effect on mouse melanoma cell growth and the inhibition by progesterone was not mediated through progesterone receptor.

Sex Steroids and Breast Cancer: An Overview

Sex steroids, also known as sex hormones are synthesized naturally by the gonads (ovaries or testes). The two main classes of sex steroids, androgens and estrogens, are crucial hormones for the proper development and function of the body;they regulate sexual differentiation, the secondary sex characteristics, and sexual habits. They are also well known to influence many common cancers, especially hormonally driven cancers such as breast and prostate cancer. In this report, we review the association of sex steroids with cancer and the potential use of endocrine manipulation in cancer therapy as well as the limitations and challenges faced in this field.

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.

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.

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.

Sex steroids of black scabbardfish,Aphanopus carbo,in relation to reproductive and migratory dynamics

Black scabbardfish,Aphanopus carbo,is a commercially important species that takes distant migrations throughout its life cycle.Sex steroids were measured by radioimmunoassay in the blood plasma of specimens caught off the Madeira Archipelago and mainland Portugal to link this species migratory path with its reproductive cycle.Furthermore,a pilot study using Mozambique tilapia(Oreochromis mossambicus)was designed to evaluate the effect of sample freshness on steroid levels because black scabbardfish blood was collected at separate times after specimens were caught.The changes in T and 11-KT concentrations between the time of blood extraction and the time after preservation did not statistically differ among the different methods applied.Therefore,measured black scabbardfish steroid concentrations were directly used in the subsequent data analyses.In females,E2 and in T concentrations peaked at a late stage of vitellogenesis.E2 concentration was significantly different between females caught off each area.Clustering E2 and T concentrations from all developing females resulted in the separation of two distinct groups,independently of their geographical area.In males,T and 11-KT were not significantly different between maturity stages.The hepatosomatic index of males caught off mainland Portugal was relatively high.This may reflect a mechanism for storing energy that will later be consumed during migration to the spawning grounds.The trend of sex steroids concentrations throughout the sexual maturation of the species is consistent with the morphological indicators and shows evidence of the reproductive and migratory pattern hypothesised for the black scabbardfish in NE Atlantic.

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.

The influence of sex steroid hormones on the response to trauma and burn injury

Trauma and related sequelae result in disturbance of homeostatic mechanisms frequently leading to cellular dysfunction and ultimately organ and system failure. Regardless of the type and severity of injury, gender dimorphism in outcomes following trauma have been reported, with females having lower mortality than males, suggesting that sex steroid hormones (SSH) play an important role in the response of body systems to trauma. In addition, several clinical and experimental studies have demonstrated the effects of SSH on the clinical course and outcomes following injury. Animal studies have reported the ability of SSH to modulate immune, inflammatory, metabolic and organ responses following traumatic injury. This indicates that homeostatic mechanisms, via direct and indirect pathways, can be maintained by SSH at local and systemic levels and hence result in more favourable prognosis. Here, we discuss the role and mechanisms by which SSH modulates the response of the body to injury by maintaining various processes and organ functions. Such properties of sex hormones represent potential novel therapeutic strategies and further our understanding of current therapies used following injury such as oxandrolone in burn-injured patients.

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

17β-HSD14 基因在魁蚶性腺发育过程中的表达特征

为探究性类固醇激素合成相关基因17β-羟类固醇脱氢酶14(17β-hydroxysteroid dehydrogenase 14,17β-HSD14)在魁蚶(Scapharca broughtonii)性腺发育过程中的作用,本研究从魁蚶转录组中筛选并验证了17β-HSD14基因序列,通过原位杂交和实时荧光定量PCR检测了该基因在魁蚶中的组织定位及性腺发育过程中表达变化规律。结果显示:17β-HSD14基因的编码区序列长度为822 bp,编码273个氨基酸;原位杂交实验在魁蚶卵巢的成熟卵细胞、滤泡壁和精巢中的精原细胞、精子以及其他组织的细胞中都检测到了17β-HSD14基因的阳性杂交信号;qRT-PCR结果表明,17β-HSD14基因的表达随其性腺发育而产生变化,在形成期(Ⅰ期)到增殖期(Ⅱ期)的过程中呈上升趋势,成熟期(Ⅲ期)至耗尽期(Ⅴ期)呈下降趋势,且在卵巢组织中的表达量显著高于精巢组织。综上,17β-HSD14基因与魁蚶的性腺发育密切相关,可能对其性腺发育、功能维持和成熟具有重要的作用。

饲料中DHA与EPA比例对星斑川鲽雌鱼性类固醇激素及繁育性能的影响

为了探索饲料中DHA与EPA比例对星斑川鲽(Platichthys stellatus)雌性亲鱼繁育性能的影响,配制等氮等脂含不同DHA与EPA比例(0.65、1.33、2.12、3.08和3.92)饲料5组,每组设3重复,室内循环水系统养殖,试验周期90 d,试验结束后取亲鱼血清及性腺检测。结果表明,随着饲料DHA与EPA比值的升高,亲鱼雌二醇(E 2)呈先升后降趋势,DHA与EPA比值为1.33时,促进作用显著(P<0.05)。性腺中FSHR、StAR和芳香化酶表达量也显著高于对照组(P<0.05);添加DHA和EPA后亲鱼的绝对繁殖力显著提高,但DHA与EPA比值为1.33效果更显著(P<0.05);在DHA与EPA比值为0.65、1.33组和2.12时,雌鱼性腺中单不饱和脂肪酸的含量显著高于其他组(P<0.05),n-6多不饱和脂肪酸出现显著下降(P<0.05),n-3多不饱和脂肪酸明显上升,差异显著(P<0.05)。由此可见,饲料中添加DHA和EPA能有效促进星斑川鲽雌性亲鱼的性腺发育,DHA与EPA比值为1.33时能提高亲鱼E 2分泌,FSHR、StAR和芳香化酶表达以及单不饱和脂肪酸的吸收,增加性腺发育能量供给,促进亲鱼性腺成熟,提高繁育性能。

不同催产剂型对人工培育巴马拟缨鱼性腺及性激素水平的影响

为探究不同催产剂催产人工养殖巴马拟缨鱼性激素水平变化,设置4个剂量处理组,分别为:A组(LHRH-A315μg+HCG 3000 IU+DOM 15 mg)/kg、B组(LHRH-A39μg+HCG 2000 IU+DOM 10 mg)/kg、C组(LHRH-A33μg+HCG 1000 IU+DOM5 mg)/kg和D组(鱼用高效鱼用催产剂800活性单位+HCG 2500 IU)/kg;雄鱼剂量为雌鱼的1/2。催产前所采集雌雄鱼样本作为对照组M。结果表明,A组催产剂的剂型及配比,有助于提高人工养殖巴马拟缨鱼雌二醇、雌三醇水平,进而促进人工培育条件下的卵巢发育;B组催产剂利于巴马拟缨鱼雌酮水平;人工养殖巴马拟缨鱼亲本,对D组催产剂敏感性较低,D组催产剂不利于提高亲鱼雌激素水平,其中B组和C组更利于促进人工培育条件下的卵巢发育成熟。各组催产剂的剂型及配比,均促进了人工培育的巴马拟缨鱼雄性亲本精巢发育,其中A组的剂型为最佳剂型。指出,雌性亲本尚未完全成熟,影响巴马拟缨鱼产卵排精刺激的重要因素,还有待进一步研究。

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.

性类固醇激素在近江牡蛎性腺发育周期的分布特征

性类固醇激素在脊椎动物的性别分化、生长发育、生殖代谢等过程中发挥着重要的生理作用,但是目前对软体动物性类固醇激素的了解还十分有限。本研究结合组织学方法根据性腺发育状态将近江牡蛎性腺划分为三个组别,即前期(Ⅰ期)、中期(Ⅱ期)和后期(Ⅲ期),并利用酶联免疫吸附测定(ELISA)分析了孕酮、睾酮、雌二醇三种重要的性类固醇激素在性腺三个时期的变化特征。结果表明:性腺中孕酮、睾酮和雌二醇含量范围分别是22.2~346.6 pg·g^(-1)、1.9~28.7 pg·g^(-1)和23.2~258.1 pg·g^(-1);且平均含量雌二醇>孕酮>睾酮,分别为所测激素总含量的57%、40%和3%。近江牡蛎卵巢中孕酮含量在Ⅰ期和Ⅲ期显著高于精巢,精巢中睾酮含量在Ⅰ期显著高于卵巢,卵巢中雌二醇含量在Ⅱ期和Ⅲ期显著高于精巢。三种激素含量的变化在雌雄间和不同发育阶段都具有明显差异,表明性类固醇激素在近江牡蛎性别分化以及性腺发育过程中发挥了重要作用。该研究结果丰富了性类固醇激素在双壳贝类中的研究资料,可为制定近江牡蛎苗种繁育策略提供参考。