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Aldosterone increased by chronic unpredictable mild stress damages epididymal sperm quality in young rats 慢性不可预测的轻度应激引起的醛固酮升高损害幼鼠附睾精子质量。
IF 1.7 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-09-23 DOI: 10.1016/j.ygcen.2025.114823
Tonantzi Guadalupe Osorio Pérez , Eliut Pérez-Sánchez , Vanessa Guadalupe Nolasco Garduño , Adriana Corona-Pérez , María de Lourdes Arteaga Castañeda , Rosa Angélica Lucio , Jorge Rodríguez-Antolín , Leticia Nicolás-Toledo
In young rats, aldosterone concentration increases in response to stress. Aldosterone can decrease testosterone production. We hypothesized that aldosterone impairs sperm quality, and that this impairment is reversible with 50 mg/kg of eplerenone in young rats. Forty-two young male Wistar rats (51 days old) were divided into six groups: Control, Control + vehicle (C + Veh), chronic unpredictable mild stress (CUMS), and CUMS + eplerenone at three concentrations: 25, 50, and 100 mg/kg bw, a selective aldosterone blocker (CUMS + EP) (n = 7 per each). On postnatal day 51, eplerenone was administered orally via gastric tube 2 h before the start of the stress test. The CUMS paradigm was administered once daily at various times, without repeating the stressor, over a four-week period. We evaluated the effects of chronic stress on serum testosterone concentrations, oxidative stress, apoptosis, and sperm quality. The CUMS group exhibited low testosterone levels and poor epididymal sperm quality. Compared to the CUMS group, the 50 mg/kg dose of eplerenone demonstrated significant improvements in sperm motility (28.8 %), sperm viability (36.9 %), and sperm concentration (58.9 %). In the CUMS context, the 100 mg/kg dose was toxic because it induced oxidative stress and apoptosis. Aldosterone negatively affects epididymal sperm quality by reducing testosterone-induced sperm motility, viability, and concentration. Aldosterone impairs sperm quality, which is reversible with 50 mg/kg of eplerenone. The prevention by eplerenone supports our hypothesis.
在幼鼠中,醛固酮浓度在应激反应中增加。醛固酮可以减少睾酮的产生。我们假设醛固酮会损害精子质量,并且这种损害在年轻大鼠中50 mg/kg的eplerenone是可逆的。将42只51 日龄的年轻雄性Wistar大鼠分为6组,分别为Control、Control + vehicle (C + Veh)、chronic unpredictable mild stress (CUMS)和CUMS + eplerenone(25、50和100 mg/kg bw三种浓度),选择性醛固酮阻断剂(CUMS + EP) (n = 7只)。出生后第51天,在压力测试开始前通过胃管2 h口服依普利酮。在四周的时间里,每天在不同时间进行一次CUMS范式,不重复压力源。我们评估了慢性应激对血清睾酮浓度、氧化应激、细胞凋亡和精子质量的影响。CUMS组睾酮水平低,附睾精子质量差。与CUMS组相比,50 mg/kg剂量的eplerenone显着改善了精子活力(28.8% %),精子活力(36.9% %)和精子浓度(58.9% %)。在CUMS环境中,100 mg/kg剂量是有毒的,因为它诱导氧化应激和细胞凋亡。醛固酮通过降低睾酮诱导的精子活力、活力和浓度,对附睾精子质量产生负面影响。醛固酮会损害精子质量,但服用50 毫克/公斤的依普利酮即可逆转。每个人的预防都支持了我们的假设。
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引用次数: 0
Expression of the estrogen receptor gene across the life cycle in the polychaete, Capitella teleta 雌性激素受体基因在多毛纲动物中生命周期的表达
IF 1.7 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-09-20 DOI: 10.1016/j.ygcen.2025.114821
A.M. Murillo , A.R. Lanza , M. Hendershot , E.V.W. Setton , E.C. Seaver , J.Y. Wilson
Vertebrate estrogen receptors (ERs; NR3A subfamily genes) are essential for regulating multiple biological processes in vertebrates. However, little is known about ERs (NR3D subfamily genes) in invertebrates. Capitella teleta is a marine polychaete with a single ER gene that is ligand-activated with low concentrations of estradiol in vitro; yet the physiological role of this receptor is unclear. We used whole-mount in situ hybridization to investigate spatial and temporal expression patterns of the ER in larval stages and RT-qPCR to detect temporal ER gene expression patterns across age and sex in juvenile and adults. The ER gene was expressed in the brain and foregut across multiple larval stages, suggesting a role in brain and gastrointestinal development. Whole-body juvenile ER gene expression was similar between two and six weeks of age. ER expression was similar across sex between head fragments, gastrointestinal systems, or whole bodies of sexually mature worms. These data show that the ER does not exhibit a sexually dimorphic expression as is stereotypical in vertebrates, and suggests that the ER may may not play a big role in sexual maturation in C. teleta. Collectively, ER is expressed across multiple life stages and suggests a role in brain and foregut development, and possibly a gastrointestinal function in adults. This study aids in uncovering the physiological functions of ER in lophotrochozoans.
脊椎动物雌激素受体(er; NR3A亚家族基因)对调节脊椎动物的多种生物过程至关重要。然而,对无脊椎动物的er (NR3D亚家族基因)知之甚少。小头藻(Capitella teleta)是一种具有单一内质网基因的海洋多毛藻,在体外用低浓度雌二醇激活配体;然而,这种受体的生理作用尚不清楚。我们采用全安装原位杂交技术研究了ER在幼虫期的时空表达模式,并采用RT-qPCR技术检测了不同年龄和性别的ER基因在幼年和成年期的时空表达模式。ER基因在多个幼虫阶段的大脑和前肠中表达,表明其在大脑和胃肠道发育中起作用。幼鼠全身ER基因表达在2周龄和6周龄之间相似。在性成熟蠕虫的头部碎片、胃肠道系统或整个身体之间,ER的表达在性别上是相似的。这些数据表明,内质网并没有表现出脊椎动物中典型的两性二态表达,这表明内质网在C. teleta的性成熟中可能没有发挥重要作用。总的来说,ER在生命的多个阶段表达,表明其在大脑和前肠发育中起作用,并可能在成人的胃肠道功能中起作用。本研究有助于揭示光线虫内质网的生理功能。
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引用次数: 0
Identification and functional characterization of relaxin-like gonad stimulating peptide in the sea cucumber, Stichopus horrens 海参中松驰素样性腺刺激肽的鉴定及功能表征。
IF 1.7 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-09-18 DOI: 10.1016/j.ygcen.2025.114819
Tyler R. Goodearly , An Wirth-Yap , Bradley K. Fox , Hidekazu Katayama , Andre P. Seale
In the state of Hawaiʻi, there is rising interest in the culture of native sea cucumbers, such as Stichopus horrens; however, current production is hindered by a limited understanding of their reproductive biology. Originally described in starfish, relaxin-like gonad stimulating peptide (RGP) has been characterized and used to induce oocyte maturation and spawning in sea cucumbers. For the first time using S. horrens specifically, we identified the RGP (Sh-RGP) coding sequence through de novo transcriptomics, synthesized the mature peptide, and investigated its role in inducing oocyte maturation in vitro, and spawning in vivo. The Sh-RGP precursor gene encodes a single mature peptide composed of two amino acid chains. The B- and A-chains contain two and four cysteine residues, respectively, resulting in an intra-chain linkage on the A-chain and two disulfide connections between the two chains. A synthetic Sh-RGP was produced from solid-phase peptide synthesis, bonded, and isolated by reverse-phase HPLC. A tissue distribution analysis revealed that shrgp mRNA expression is highest (P < 0.001) in the neural ring. In vitro, Sh-RGP (0.1–10 μM) induced germinal vesicle breakdown in oocytes incubated with gonadal tissue in time and concentration-dependent fashions. When injected with Sh-RGP (∼4.5 μg/kg body weight), all mature male and female sea cucumbers spawned within 39 min of treatment. Overall, these results indicate that Sh-RGP induces oocyte maturation and spawning and provide a framework for integrating transcriptomics and functional assays to elucidate and validate endogenous species-specific reproductive hormones that can be used to address barriers in sea cucumber aquaculture.
在夏威夷,人们对当地海参(如Stichopus horrens)的养殖兴趣日益浓厚,然而,由于对其生殖生物学的了解有限,目前的生产受到阻碍。松弛素样性腺刺激肽(RGP)最初是在海星中发现的,现已被鉴定并用于诱导海参卵母细胞成熟和产卵。本研究首次以黄貂鱼为研究对象,通过从头转录组学方法鉴定了其RGP (Sh-RGP)编码序列,合成了其成熟肽,并研究了其在体外诱导卵母细胞成熟和体内产卵中的作用。Sh-RGP前体基因编码由两条氨基酸链组成的单个成熟肽。B链和a链分别含有两个和四个半胱氨酸残基,导致a链上的链内连接和两条链之间的两个二硫连接。采用固相多肽法合成合成Sh-RGP,通过反相高效液相色谱法进行键合和分离。组织分布分析显示shrgp mRNA表达量最高(P
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引用次数: 0
Photoperiod-dependent expression of ‘Cocaine- and amphetamine-regulated transcript peptide’ and ‘Neuropeptide Y’ in the brain of anuran Minervarya syhadrensis “可卡因和安非他明调节的转录肽”和“神经肽Y”在阿纳乌尔的大脑中的光周期依赖性表达。
IF 1.7 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-09-17 DOI: 10.1016/j.ygcen.2025.114820
Ketaki Shetye , Sneha Sagarkar , Swapnil Shewale , Amul Sakharkar , Shobha Bhargava , Richa Ashma
Anurans exhibit diurnal behavioral patterns; however, the expression of neuropeptides that modulate these activities remains unexplored. This study investigates day-night expression patterns of Cocaine- and Amphetamine-Regulated Transcript Peptide (CARTp) and Neuropeptide Y (NPY) in the brain of nocturnal frog, Minervarya syhadrensis. Frogs were sacrificed at different timepoints (1) under normal day-night conditions (2) after exposure to 24 h darkness and (3) 24 h light. Brain tissues, including the olfactory system, were collected for immunohistochemical analysis. Photoperiod-dependent alterations in expression of CART and NPY were observed in various brain regions. According to cosine analysis, the oscillation was seen only in the olfactory epithelium (OE) with maxima at 11:00. In anteroventral tegmentum (AV), CARTp and NPY expression were highest at midnight. In few brain regions, NPY or CARTp oscillations were observed. NPY oscillations were seen in preoptic area (POA), with a peak at noon, and in suprachiasmatic nucleus (SCN), anterior ventral hypothalamus (AvHy), and nucleus isthmus (NI) highest expression was at midnight. In Edinger-Westphal nucleus (EW) and posterior ventral hypothalamus (PvHy) CARTp upregulation was observed at midnight. CARTp fluctuated in OE, PvHy, and EW on light exposure, while changes in NPY expression were seen in OE, POA and SCN. Photoperiod-dependent fluctuations in both peptides were noted in OE and AV. While on exposure to darkness, CARTp expression decreased in AV, PvHy, and EW, and NPY expression was affected in AV, POA, SCN, AvHy, and NI. These results suggest neuropeptides in anurans exhibit photoperiod-dependent differential expression, potentially regulating physiological functions and behavioral patterns.
无尾动物表现出每日的行为模式;然而,调节这些活动的神经肽的表达仍未被探索。本研究研究了可卡因和安非他明调节转录肽(CARTp)和神经肽Y (NPY)在夜行蛙脑中的昼夜表达模式。在(1)正常昼夜条件下(2)暴露于24 h黑暗和(3)24 h光照后的不同时间点处死青蛙。收集包括嗅觉系统在内的脑组织进行免疫组织化学分析。在不同脑区观察到CART和NPY表达的光周期依赖性改变。余弦分析显示,振荡仅出现在嗅上皮(OE),在11:00时振荡最大。在腹前被盖(AV)中,CARTp和NPY在午夜表达最高。在少数脑区,观察到NPY或CARTp振荡。NPY在视前区(POA)出现振荡,中午达到峰值,视交叉上核(SCN)、下丘脑前腹侧(AvHy)和峡核(NI)在午夜表达最高。午夜时分,Edinger-Westphal核(EW)和下丘脑后腹侧(PvHy)出现CARTp上调。CARTp在OE、PvHy和EW中随光照变化而波动,而NPY在OE、POA和SCN中表达变化。在OE和AV中发现了这两种肽的光周期依赖性波动。当暴露于黑暗时,AV、PvHy和EW中的CARTp表达减少,AV、POA、SCN、AvHy和NI中的NPY表达受到影响。这些结果表明,神经肽在无尾动物中表现出光周期依赖的差异表达,可能调节生理功能和行为模式。
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引用次数: 0
Corticotropin-releasing hormone enhances the responsivity of macrophages to inflammation in zebrafish 促肾上腺皮质激素释放激素增强斑马鱼巨噬细胞对炎症的反应性。
IF 1.7 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-09-14 DOI: 10.1016/j.ygcen.2025.114815
Joeri van Heijningen , Laura H.M. van der Pluijm , Marcel J.M. Schaaf , Erin Faught
The immunomodulatory role of steroid stress hormones, such as cortisol, are well characterized; however, less is known about how other stress hormones affect the immune system. Release of central corticotropin-releasing hormone (Crh) will result in an indirect anti-inflammatory effect due to the stimulation of cortisol production. Conversely, peripheral release of Crh is thought to directly exhibit proinflammatory effects on leukocytes. This suggests that the peripheral Crh system promotes inflammation, rather than suppresses it, but the molecular mechanisms are not well defined. To test the hypothesis that Crh will stimulate immune function, we used the zebrafish animal model and assessed leukocyte migration towards a wound as a readout of inflammatory capacity. We show that not only is crhr1 regulated during inflammation, but that it directly modulates the leukocyte population localized to a wound site. In particular, it enhances pro-inflammatory macrophage recruitment through the Cxcr3.2/Cxcr11aa signalling axis. Taken together, this work further contributes to our understanding of how Crh, and stress as a whole, can impact immune system function.
类固醇应激激素(如皮质醇)的免疫调节作用已被很好地描述;然而,人们对其他应激激素如何影响免疫系统知之甚少。中枢促肾上腺皮质激素释放激素(Crh)的释放会由于刺激皮质醇的产生而产生间接的抗炎作用。相反,外周Crh的释放被认为直接表现出对白细胞的促炎作用。这表明外周Crh系统促进炎症,而不是抑制炎症,但分子机制尚不明确。为了验证Crh会刺激免疫功能的假设,我们使用斑马鱼动物模型并评估白细胞向伤口的迁移作为炎症能力的读数。我们发现,crhr1不仅在炎症过程中受到调节,而且还直接调节伤口部位的白细胞群。特别是,它通过Cxcr3.2/Cxcr11aa信号轴增强促炎巨噬细胞募集。综上所述,这项工作进一步有助于我们了解Crh和整体压力如何影响免疫系统功能。
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引用次数: 0
Hair cortisol as an indicator of chronic stress in Eurasian otters (Lutra lutra): Evaluating influencing variations 毛发皮质醇作为欧亚水獭慢性应激的指标(Lutra Lutra):评估影响变异。
IF 1.7 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-09-13 DOI: 10.1016/j.ygcen.2025.114816
Jee Hyun Kim , Hyejin Kang , Bong Kyun Kim , Mi-Sook Min , Seung Aee Ma , Je-Yoel Cho
Glucocorticoids such as cortisol are secreted via the HPA axis to maintain homeostasis and respond to stress, but chronic over-activation can impair health and survival. Cortisol accumulation in the hair is particularly useful because it reflects long-term stress, making it a valuable physiological indicator for species conservation and management. However, as variables such as housing conditions, age class, sex, hair color, and disease can affect hair cortisol concentration (HCC), ignoring these variables may lead to inaccuracies in chronic stress evaluation. This study measured HCCs in 33 Eurasian otters (Lutra lutra), an endangered species, to examine whether housing type (wild vs. captive), age, and sex affect HCCs. The results showed that juveniles had significantly higher HCCs than adults, suggesting that age may be a factor influencing HCC. However, no significant differences in HCC were found with respect to sex or housing type. Additionally, two of the individuals with exceptionally high HCC were confirmed to have been affected by disease. We propose that standardizing age class in HCC analysis is necessary, and that other important factors potentially influencing HCC variability should also be considered. In particular, disease has been suggested as a possible factor affecting HCC, and such factors may have an even greater impact on HCC variability. Although no significant differences were found regarding housing type and sex, these factors may be more clearly identified through future studies involving a broader range of housing environments and a larger sample size. However, despite the potential of HCC as a promising indicator of long-term stress, a limitation of this study is that its physiological validity has not yet been sufficiently verified in Eurasian otters. Therefore, the results of this study should be interpreted with caution. Nevertheless, by analyzing key factors influencing HCC, this study provides important foundational data for understanding the effects of housing type, sex, and age on long-term stress assessment.
糖皮质激素(如皮质醇)通过下丘脑轴分泌,以维持体内平衡并对压力作出反应,但慢性过度激活会损害健康和生存。毛发中的皮质醇积累特别有用,因为它反映了长期的压力,使其成为物种保护和管理的有价值的生理指标。然而,由于住房条件、年龄、性别、发色和疾病等变量会影响毛发皮质醇浓度(HCC),忽略这些变量可能导致慢性压力评估不准确。本研究测量了33只欧亚水獭(Lutra Lutra)(一种濒危物种)的hcc,以检查住房类型(野生与圈养)、年龄和性别是否影响hcc。结果显示,青少年HCC明显高于成人,提示年龄可能是影响HCC的一个因素。然而,HCC在性别或住房类型方面没有显著差异。此外,两名HCC异常高的个体被证实受到疾病的影响。我们建议在HCC分析中标准化年龄分类是必要的,并且还应考虑其他可能影响HCC变异性的重要因素。特别是,疾病被认为是影响HCC的一个可能因素,而这些因素可能对HCC变异性有更大的影响。虽然在住房类型和性别方面没有发现显著的差异,但这些因素可以通过涉及更广泛的住房环境和更大样本量的未来研究更清楚地确定。然而,尽管HCC有可能作为长期应激的一个有希望的指标,但本研究的一个局限性是其生理有效性尚未在欧亚水獭中得到充分验证。因此,本研究结果应谨慎解读。然而,通过分析影响HCC的关键因素,本研究为了解住房类型、性别和年龄对长期应激评估的影响提供了重要的基础数据。
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引用次数: 0
Putative genes coding for pituitary adenylate cyclase-activating polypeptide and immunohistochemical localization of their mature peptides in the brain-pituitary axis of the inshore hagfish Eptatretus burgeri 伯氏盲鳗脑-垂体轴垂体腺苷酸环化酶激活多肽的推定基因编码及其成熟肽的免疫组织化学定位。
IF 1.7 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-09-13 DOI: 10.1016/j.ygcen.2025.114817
Masafumi Amano , Shima Furuya , Naoyuki Yamamoto , Yoko Yamaguchi , Toshio Sekiguchi , Tomohiro Osugi
Hagfish and lampreys, which are both members of the class Agnatha, are widely considered to represent one of the most basal evolutionary lineages of vertebrates. Pituitary adenylate cyclase-activating polypeptide (PACAP) and growth hormone-releasing hormone (GHRH) are both members of the secretin/PACAP family. We searched the Ensembl database for putative PACAP and GHRH sequences in the inshore hagfish, Eptatretus burgeri. We identified three putative GHRH/PACAP precursors (hagfish-1/2/3) whose expression in various tissues, including the brain, was confirmed using RNA sequencing. The hagfish-1 precursor encodes both GHRH/PRP (PACAP-related peptide) and PACAP, whereas the hagfish-2 and −3 precursors encod only PACAP. Of the three putative hagfish PACAPs, PACAP-2, encoded by hagfish-2, showed relatively high identity (77.8%) and similarity (85.2%) with PACAP from other species. In contrast, hagfish GHRH/PRP encoded by hagfish-1 showed low identity (27.3%) and similarity (50.3%) with other GHRHs, and low identity (26.7%) and similarity (46.7%) with other PRPs. Phylogenetic analysis confirmed that the hagfish-2 sequence clustered within the same clade as lamprey PACAP. PACAP-like-immunoreactive (ir) cell bodies and dense punctate fibers have been detected in several brain regions, including the preoptic area, infundibular nucleus of the hypothalamus, midbrain tegmentum, and medulla oblongata. In the pituitary gland, PACAP-like-ir fibers were observed in the dorsal wall of the neurohypophysis. GHRH/PRP immunoreactivity was also observed in the medulla oblongata. The present study demonstrated that PACAP-like- and GHRH/PRP-like peptides are expressed in the brain of the inshore hagfish E. burgeri.
盲鳗和七鳃鳗都是阿格纳塔纲的成员,被广泛认为是脊椎动物最基础的进化谱系之一。垂体腺苷酸环化酶激活多肽(PACAP)和生长激素释放激素(GHRH)都是分泌素/PACAP家族的成员。我们在Ensembl数据库中搜索了近岸盲鳗(Eptatretus burgeri)的推定PACAP和GHRH序列。我们确定了三种推定的GHRH/PACAP前体(hagfish-1/2/3),它们在包括大脑在内的各种组织中表达,并通过RNA测序得到证实。hagfish-1前体编码GHRH/PRP (PACAP相关肽)和PACAP,而hagfish-2和-3前体仅编码PACAP。在三种可能的盲鳗PACAP中,由盲鳗2编码的PACAP-2与其他物种的PACAP具有较高的同源性(77.8%)和相似性(85.2%)。相比之下,hagfish-1编码的盲鳗GHRH/PRP与其他GHRHs的同源性(27.3%)和相似性(50.3%)较低,与其他PRPs的同源性(26.7%)和相似性(46.7%)较低。系统发育分析证实,hagfish-2序列与七鳃鳗PACAP属于同一进化支。pacap样免疫反应(ir)细胞体和密集的点状纤维在几个脑区被检测到,包括视前区、下丘脑基底核、中脑被盖和延髓。脑垂体神经垂体背壁可见PACAP-like-ir纤维。在延髓中也观察到GHRH/PRP免疫反应性。本研究证实了在伯氏盲鳗的大脑中有pacap样肽和GHRH/ prp样肽的表达。
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引用次数: 0
Ad4bp/sf-1 regulates cyp11b1 and cyp17a1 in the Asian catfish, Clarias batrachus Ad4bp/sf-1调节亚洲鲶鱼(Clarias batrachus)的cyp11b1和cyp17a1。
IF 1.7 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-09-12 DOI: 10.1016/j.ygcen.2025.114818
Sonika Kar, Balasubramanian Senthilkumaran
Testicular function in fish is mediated by steroids, with cytochrome P450 11B1, mitochondrial, or 11β-hydroxylase, encoded by cyp11b1, and cytochrome P450 17A1, or 17α-hydroxylase/17,20-lyase, encoded by cyp17a1, being key steroidogenic enzymes. However, the regulation of cyp11b1 and cyp17a1 has not yet been studied in fish. To address this, the 5′ upstream regions of cyp11b1 and cyp17a1 from catfish, Clarias batrachus, were cloned and sequenced. Predicted putative transcription factor binding sites included Ad4bp/sf-1, Foxp1, Pax1, Pax2, Gata1, and Oct1 in both promoter fragments. Luciferase reporter assays in TM3 mouse Leydig cells, with and without human chorionic gonadotropin (hCG) induction, showed significant promoter activity in constructs containing ad4bp/sf-1 and foxp1, but not with the other transcription factors. Site-directed mutagenesis and chromatin immunoprecipitation further confirmed the binding of Ad4bp/sf-1 to the promoters of both cyp11b1 and cyp17a1, while Foxp1 binding was observed only in the cyp11b1 promoter. Immunolocalization of Ad4bp/sf-1 revealed its presence in interstitial/Leydig cells and also in the testicular lumen. The expression of ad4bp/sf-1 increased after hCG induction in vivo and following 11-ketotestosterone (11-KT)/methyl testosterone stimulation in vitro, indicating gonadotropin- and androgen-dependent regulation. Additionally, transient gene silencing of ad4bp/sf1 using small interfering RNA (siRNA) decreased the expression of cyp11b1, cyp17a1, and foxp1, suggesting co-regulation. Finally, decreased serum testosterone and 11-KT levels upon ad4bp/sf-1 siRNA silencing further support its role in regulating male steroidogenesis in males.
鱼类睾丸功能是由类固醇介导的,cyp11b1编码的细胞色素P450 11B1,线粒体酶,或11β-羟化酶,和cyp17a1编码的细胞色素P450 17A1,或17α-羟化酶/17,20-裂解酶,是关键的类固醇生成酶。然而,cyp11b1和cyp17a1的调控尚未在鱼类中进行研究。为了解决这个问题,我们克隆了鲶鱼Clarias batrachus的cyp11b1和cyp17a1的5'上游区域并对其进行了测序。预测的转录因子结合位点包括两个启动子片段中的Ad4bp/sf-1、Foxp1、Pax1、Pax2、Gata1和Oct1。在TM3小鼠间质细胞中,无论是否诱导人绒毛膜促性腺激素(hCG),荧光素酶报告基因检测显示,在含有ad4bp/sf-1和foxp1的构建体中,启动子活性显著,而在其他转录因子中,启动子活性不显著。位点定向突变和染色质免疫沉淀进一步证实了Ad4bp/sf-1与cyp11b1和cyp17a1启动子的结合,而Foxp1仅与cyp11b1启动子结合。Ad4bp/sf-1的免疫定位显示其存在于间质/间质细胞和睾丸管腔中。体内hCG诱导和体外11-酮睾酮(11-KT)/甲基睾酮刺激后ad4bp/sf-1的表达增加,表明促性腺激素和雄激素依赖性调节。此外,使用小干扰RNA (small interfering RNA, siRNA)对ad4bp/sf1进行短暂的基因沉默,可以降低cyp11b1、cyp17a1和foxp1的表达,表明这是共同调控的。最后,ad4bp/sf-1 siRNA沉默后血清睾酮和11-KT水平下降,进一步支持其在调节男性类固醇生成中的作用。
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引用次数: 0
Genotype for hypocretin receptor (hcrtr2) affects appetite in zebrafish 下丘脑分泌素受体(hcrtr2)基因型影响斑马鱼的食欲。
IF 1.7 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-09-02 DOI: 10.1016/j.ygcen.2025.114808
Nathan Lewandowski, Miranda Brainard, Chelsea Kalb, Ashley Wong, Qin Liu, Richard Londraville
We investigated the role of hypocretin receptor in signaling appetite in zebrafish (Danio rerio). Hypocretin is a small neuropeptide known for its effects on circadian rhythm and appetite. Wild-type and heterozygous hu2098 (knockout for hcrtr2) zebrafish were raised to adulthood (3–4 months post fertilization) and genotyped. Feeding rate was measured directly using a novel technique that analyzed images of fish feeding continuously on brine shrimp, in which all individual brine shrimp were identified in a tank with a feeding fish. Fish were food restricted for 19–29 h before a feeding session, and feeding rate was determined by the regression of brine shrimp consumed/min over an eight-minute feeding period. Utilizing a mixed-effects ANCOVA model and accounting for mass as a covariate, heterozygous fish (hcrtr2+/hcrtr2-) ate brine shrimp at a significantly faster rate (mean 23.4 ± 12.6 shrimp/min, n = 12) than wildtype fish (hcrtr2+/hcrtr2+) (20.5 ± 13.8 shrimp/min, p = 0.033, n = 11). These results support a role for hcrtr2 in appetite regulation.
我们研究了下丘脑分泌素受体在斑马鱼(Danio rerio)食欲信号中的作用。下丘脑泌素是一种小的神经肽,以其对昼夜节律和食欲的影响而闻名。将野生型和杂合型hu2098(敲除hcrtr2)斑马鱼饲养至成年(受精后3-4 个月)并进行基因分型。采用一种新技术直接测量摄食率,该技术分析了鱼类连续摄食卤虾的图像,其中所有个体的卤虾被识别在一个有喂食鱼的水箱中。鱼在饲喂前限制进食19-29 h,摄食率由8分钟的摄食周期内消耗的卤虾/分钟的回归来确定。利用mixed-effects ANCOVA模型和会计质量作为协变量,杂合的鱼(hcrtr2 + / hcrtr2)以更快的速度吃盐水虾(平均23.4 ±12.6 虾/分钟,n = 12)比野生型的鱼(hcrtr2 + / hcrtr2 +)(20.5 ±13.8 虾/分钟,p = 0.033 n = 11)。这些结果支持hcrtr2在食欲调节中的作用。
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引用次数: 0
The role of the Steroidogenesis-Associated gene cyp11a in regulating gonadal development in Hyriopsis cumingii. 甾体激素生成相关基因cyp11a在三角帆蚌性腺发育调控中的作用。
IF 1.7 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-09-01 Epub Date: 2025-07-30 DOI: 10.1016/j.ygcen.2025.114789
Liusiqiao Tang, Zongyu Liu, Mulian Cao, Yingrui Mao, Guiling Wang

The Cyp11a gene is essential for steroid hormone synthesis, which is closely associated with gonadal development. To explore the role of Cyp11a in the gonadal development of Hyriopsis cumingii, we cloned the 2951 bp H. cumingii Cyp11a gene (Hccyp11a), which includes a 2376 bp open reading frame (ORF) encoding 791 amino acids. Phylogenetic analysis revealed that HcCYP11A is closely related to other molluskan homologs. Tissue distribution analysis showed that Hccyp11a was predominantly expressed in the gonad, with significantly higher expression in the ovary compared to the testis (p < 0.01). In juveniles, Hccyp11a expression peaked at 5 months of age. In the gonads of 12-, 24-, and 36-month-old individuals, Hccyp11a consistently exhibited higher expression in females. During ovarian development, Hccyp11a expression was highest at the ovulation stage. In situ hybridization localized Hccyp11a mRNA to the follicular wall and oocytes. RNA interference of female Hccyp11a significantly reduced the expression of Hsd3b and Srd5a1 genes, estradiol (E2) and methyltestosterone (MT) levels. Female H. cumingii were exposed to low (40 ng/L) and high (200 ng/L) concentrations of 17α-methyltestosterone (17α-MT) and 17β-estradiol (17β-E2) for 24 d. Low concentrations of 17α-MT and high concentrations of both 17α-MT and 17β-E2 significantly increased (p < 0.05) Hccyp11a expression. These findings suggest that Hccyp11a is involved in sex hormone synthesis and may regulate gonadal development in H. cumingii through its effects on steroidogenic gene expression and hormone levels.

Cyp11a基因对类固醇激素的合成至关重要,与性腺发育密切相关。为了探索Cyp11a在三角帆蚌性腺发育中的作用,我们克隆了2951 bp的三角帆蚌Cyp11a基因(Hccyp11a),其中包括一个2376 bp的开放阅读框(ORF),编码791个氨基酸。系统发育分析表明,HcCYP11A与其他软体动物同源物密切相关。组织分布分析显示,Hccyp11a主要在性腺中表达,在卵巢中的表达明显高于睾丸(p
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引用次数: 0
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General and comparative endocrinology
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