General and comparative endocrinology最新文献

Role of gonadal soma-derived growth factor (gsdf) on sex-differentiation in Nile tilapia, Oreochromis niloticus 性腺体细胞衍生生长因子（gsdf）在尼罗罗非鱼性别分化中的作用

IF 1.7 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

General and comparative endocrinology

Pub Date : 2026-01-12 DOI: 10.1016/j.ygcen.2026.114884

Tomomitsu Arai , Sakura Tanaka , Megumi Sakon , He Gao , Shigeho Ijiri

Molecular sex differentiation is regulated by complex transcriptional dynamics. In Nile tilapia, ovarian differentiation requires the synthesis of estradiol-17β (E₂), in which forkhead box L2 (foxl2) and ovarian aromatase (cytochrome P450, family 19, subfamily A, polypeptide 1a; cyp19a1a) play critical roles, whereas gonadal soma-derived growth factor (gsdf) and doublesex and mab-3-related transcription factor 1 (dmrt1) are implicated in testicular differentiation. During the early phase of molecular sex differentiation, gsdf mRNA is expressed to a significantly higher degree in the undifferentiated gonads of XY males than in XX females. However, the molecular mechanisms by which gsdf promotes testicular differentiation remain poorly understood. We hypothesized that gsdf acts by suppressing ovarian differentiation or promoting testicular differentiation through the upregulation of dmrt1. To clarify the relationship with dmrt1, we performed fluorescent double in situ hybridization on undifferentiated gonads and testes. Furthermore, recombinant Gsdf (rGsdf) was produced and microinjected into the body cavity of XX larvae to investigate its effects on the expression of sex differentiation-related genes in undifferentiated gonads. We demonstrated that gsdf and dmrt1 were expressed in distinct cell populations in undifferentiated gonads, whereas partial co-localization occurred in certain cells within the testes. Administration of rGsdf led to a significant decrease in the expression of E₂ synthesis–related genes, including foxl2, hydroxysteroid 17-beta dehydrogenase 1 (hsd17b1), and cyp19a1a. These findings suggest that gsdf suppresses E₂ production and that its expression is regulated not only by dmrt1 but also by other factors during the molecular sex differentiation phase in Nile tilapia.

分子性别分化受复杂的转录动力学调控。尼罗罗非鱼卵巢分化需要雌二醇-17β (E2)的合成，其中叉头盒L2 （foxl2）和卵巢芳香化酶（细胞色素P450，家族19，亚家族A，多肽1a； cyp19a1a）起关键作用，而性腺体细胞衍生生长因子（gsdf）和双性和单克隆抗体-3相关转录因子1 （dmrt1）与睾丸分化有关。在分子性别分化早期，gsdf mRNA在XY雄性未分化性腺中的表达程度明显高于XX雌性。然而，gsdf促进睾丸分化的分子机制仍然知之甚少。我们假设gsdf通过上调dmrt1抑制卵巢分化或促进睾丸分化。为了阐明与dmrt1的关系，我们对未分化性腺和睾丸进行了荧光双原位杂交。制备重组Gsdf (rGsdf)，并将其微量注入XX幼虫体腔，研究其对未分化性腺性别分化相关基因表达的影响。我们证明gsdf和dmrt1在未分化性腺的不同细胞群中表达，而部分共定位发生在睾丸内的某些细胞中。rGsdf可显著降低E2合成相关基因的表达，包括foxl2、羟基类固醇17- β脱氢酶1 （hsd17b1）和cyp19a1a。这些发现表明，在尼罗罗非鱼的分子性别分化阶段，gsdf抑制E2的产生，其表达不仅受dmrt1的调控，还受其他因素的调控。

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引用次数: 0

Expression profiles of the sirtuin genes family during ovarian development and hormonal regulation in Pampus argenteus 农奴卵巢发育和激素调节过程中sirtuin基因家族的表达谱。

IF 1.7 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

General and comparative endocrinology

Pub Date : 2026-01-10 DOI: 10.1016/j.ygcen.2026.114874

Changyuan Wang , Hengwei Zhang , Yi Wang , Kai Zhang , Xinwei Wang , Xubo Wang , Chunyang Guo

Sirtuins (Sirt) are a class of NAD + -dependent type III histone deacetylases that play significant roles in energy metabolism and reproductive regulation. To explore the role of the sirt genes family in the ovarian development of Pampus argenteus and its significance in artificial breeding, this study conducted a systematic investigation using phylogenetic tree analysis and real-time fluorescence quantitative PCR. Phylogenetic analysis indicated that the sirt gene of the P. argenteus was most closely related to those of Thunnus maccoyii and Thunnus. albacares. Specific expression analysis revealed that the expression levels of sirt1, sirt2, sirt5, sirt6, and sirt7 in the ovary were significantly higher than those in other tissues (P < 0.05). In the analysis of ovarian development during stage I-VI, sirt1, sirt3, and sirt5 reached their peak expression during the pre-maturation stage, while sirt6 had the highest expression in stage VI. The in vitro steroid hormone immature egg culture experiment showed that estradiol significantly inhibited the expression of sirt1, sirt2, sirt4, sirt5, sirt6 genes. Luteinizing hormone inhibited the expression of sirt1, sirt2 and sirt4, but promoted the expression of sirt3 and sirt5. Human chorionic gonadotropin slightly upregulated the expression of sirt1. Intraperitoneal injection of HCG and LH shows differential regulation on the expression of sirt genes in different brain regions, indicating that they were involved in the neuroendocrine regulatory pathway. In conclusion, the sirt genes family, especially sirt1, which showed peak expression during the critical period of early egg growth and before maturation, may promote ovarian maturation by regulating meiotic recovery and energy metabolism pathways. This study provides a theoretical basis for researching the reproductive regulation of P. argenteus and optimizing artificial breeding techniques.

Sirtuins （Sirt）是一类依赖NAD + 的III型组蛋白去乙酰化酶，在能量代谢和生殖调节中发挥重要作用。为探讨srt基因家族在阿根廷Pampus argenteus卵巢发育中的作用及其在人工育种中的意义，本研究采用系统发育树分析和实时荧光定量PCR对阿根廷Pampus argenteus进行了系统调查。系统发育分析表明，银种P. argenteus与黄颡鱼（Thunnus maccoyii）和黄颡鱼（Thunnus）的基因亲缘关系最为密切。albacares。特异性表达分析显示，sirt1、sirt2、sirt5、sirt6和sirt7在卵巢中的表达水平显著高于其他组织(P

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引用次数: 0

Development of a sandwich ELISA for serum leptin measurement in chub mackerel across reproductive stages and feeding and nutritional statuses 用夹心酶联免疫吸附试验（ELISA）测定不同繁殖阶段、饲养和营养状况的鲐鱼血清瘦素。

IF 1.7 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

General and comparative endocrinology

Pub Date : 2026-01-10 DOI: 10.1016/j.ygcen.2026.114883

Hirofumi Ohga

Leptin is an adipocyte-derived hormone that links nutritional status with endocrine and reproductive functions. However, only a limited number of teleost species allow reliable measurement of circulating leptin. In this study, we aimed to develop a specific and sensitive sandwich enzyme-linked immunosorbent assay (ELISA) for measuring serum leptin A in chub mackerel (Scomber japonicus) using two polyclonal antibodies. Validation assays confirmed high specificity, sensitivity, recovery, linearity, and parallelism, demonstrating the effectiveness of the sandwich ELISA in leptin quantification. Using the system, we analyzed leptin dynamics under several physiological conditions. Although no sex-related difference was observed in the circulating leptin levels, leptin concentrations were significantly higher in mature adults than in immature fish, suggesting its role in signaling the attainment of the threshold body weight required for reproduction. Postprandial analysis revealed a transient increase in circulating leptin at 2 h after feeding, which returned to baseline by 4 h, indicating its involvement in short-term appetite regulation. During long-term fasting, circulating leptin showed a non-significant upward trend, suggesting its possible role in metabolic responses under energy depletion. In conclusion, our study established a reliable assay system and, for the first time, characterized circulating leptin dynamics in chub mackerel. The findings could lay the foundation for future studies on nutritional and reproductive physiology of teleost fish.

瘦素是一种脂肪细胞衍生的激素，它将营养状况与内分泌和生殖功能联系起来。然而，只有有限数量的硬骨鱼物种能够可靠地测量循环瘦素。在这项研究中，我们旨在建立一种特异性和敏感性的夹心酶联免疫吸附试验（ELISA），用于测定鲐鱼（Scomber japonicus）血清瘦素a。验证分析证实了高特异性、灵敏度、回收率、线性和平行性，证明了夹心ELISA在瘦素定量中的有效性。利用该系统，我们分析了几种生理条件下瘦素的动态变化。尽管在循环瘦素水平上没有观察到与性别相关的差异，但成年鱼的瘦素浓度明显高于未成熟鱼，这表明它在达到繁殖所需的阈值体重方面发挥着信号作用。餐后分析显示，进食后2 h循环瘦素短暂升高，4 h恢复到基线水平，表明其参与短期食欲调节。在长期禁食期间，循环瘦素呈不显著上升趋势，提示其可能在能量消耗下的代谢反应中起作用。总之，我们的研究建立了一个可靠的分析系统，并首次表征了鲐鱼循环瘦素的动态。研究结果可为今后硬骨鱼的营养和生殖生理研究奠定基础。

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引用次数: 0

Corrigendum to “Effects of endocrine disrupting compounds on growth and the growth hormone/insulin-like growth factor system of fish” [Gen. Comp. Endocrinol. 375C (2026) 114837] “内分泌干扰化合物对鱼类生长和生长激素/胰岛素样生长因子系统的影响”的更正[Gen. Comp. Endocrinol. 375C (2026) 114837]

IF 1.7 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

General and comparative endocrinology

Pub Date : 2026-01-01 DOI: 10.1016/j.ygcen.2025.114868

Mark A. Sheridan, Andrea M. Hanson

引用次数: 0

Latent trait-like component identified for bottlenose dolphin fecal glucocorticoid metabolite concentrations 宽吻海豚粪便糖皮质激素代谢物浓度的潜在性状成分鉴定。

IF 1.7 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

General and comparative endocrinology

Pub Date : 2025-12-28 DOI: 10.1016/j.ygcen.2025.114873

Lisa K. Lauderdale , Douglas A. Granger , Michael T. Walsh , Lance J. Miller

Cortisol, an end product of hypothalamic–pituitary–adrenal (HPA) axis activation, plays a critical role in responding to arousal and restoring homeostasis. Chronic or repeated activation of the HPA axis may lead to physiological dysregulation that has potential negative health consequences. Quantifying stable, trait-like components of fecal glucocorticoid metabolite concentrations in animals could have a marked effect on investigating physiological stress responses and establishing higher resolution baselines for intra-individual clinical management, yet no studies have examined latent state-trait (LST) models for any non-human animals. Using an LST model, trait and state sources of fecal glucocorticoid metabolite variation were decomposed. Fecal samples were collected from 179 common bottlenose dolphins (Tursiops truncatus) in 41 habitats in late afternoon. The fit indices were excellent suggesting that LST models can be applied to bottlenose dolphin glucocorticoid metabolite measures. Trait factors (i.e., individual specific) accounted for an estimated 49 % of the variance in glucocorticoid metabolite concentrations and state factors (i.e., day-to-day factors) accounted for an estimated 41 % of the variance. This work suggests that LST models provide valuable evidence of a trait-like component in glucocorticoid metabolites in bottlenose dolphins that can be widely used in clinical management and research settings.

皮质醇是下丘脑-垂体-肾上腺（HPA）轴激活的最终产物，在反应觉醒和恢复体内平衡中起着关键作用。慢性或反复激活下丘脑轴可能导致生理失调，具有潜在的负面健康后果。定量动物粪便糖皮质激素代谢物浓度的稳定、性状样成分可能对研究生理应激反应和建立个体内临床管理的更高分辨率基线有显著影响，但尚未有研究检验任何非人类动物的潜在状态-性状（LST）模型。利用LST模型，对粪便糖皮质激素代谢物变异的性状和状态来源进行了分解。在下午晚些时候采集了41个栖息地179只普通宽吻海豚的粪便样本。拟合指标良好，表明LST模型可用于宽吻海豚糖皮质激素代谢物的测量。性状因素（即个体特异性）估计占糖皮质激素代谢物浓度方差的49% %，状态因素（即日常因素）估计占方差的41% %。这项工作表明，LST模型为宽吻海豚糖皮质激素代谢物中的特征成分提供了有价值的证据，可以广泛用于临床管理和研究环境。

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引用次数: 0

Life after precocious male maturation in a semelparous salmonid: A physiological perspective in Chinook salmon, Oncorhynchus tshawytscha 半产鲑鱼雄性早熟后的生活：奇努克鲑鱼的生理学视角。

IF 1.7 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

General and comparative endocrinology

Pub Date : 2025-12-16 DOI: 10.1016/j.ygcen.2025.114872

Donald A. Larsen , Mollie A. Middleton , Deborah L. Harstad , Dina K. Spangenberg , Abby E. Fuhrman

Spring Chinook salmon, Oncorhynchus tshawytscha, are typically semelparous, dying after a single lifetime spawning event. However, observations of survival following maturation in males that mature at age-1 (common names: precocious parr or microjacks) have been documented, but little is known regarding their post-maturation physiology. In this investigation, mature microjacks were fed either a high or low winter ration to examine potential effects of feeding regime on mortality, smoltification and rematuration the following year. We measured a series of physiological factors including survival, size, percent whole body solid (an index of whole body lipid), and gill Na+/K+-ATPase activity (an index of smoltification). We also analyzed a series of maturation indices including plasma 11-ketotestosterone (11-KT), gonadosomatic index (GSI), pituitary follicle stimulating hormone (fshb) and luteinizing hormone (lhb) beta-subunit mRNA, and testicular histology in male fish following maturation as microjacks. In both treatments, the proportion of males that survived (High Ration: 0.91, Low Ration: 0.87) and rematured (High Ration: 1.0, Low Ration: 1.0) was very high, more indicative of iteroparity than semelparity. The low winter ration may have caused a slight delay in rematuration as evidenced by delayed fshb expression and 11-KT secretion in the spring. However, there was no evidence microjacks smolted in the spring after maturation at age-1. From a fisheries conservation perspective, the potential for iteroparity in microjacks (survival to remature at age-2) means it is possible they contribute genetically more than once when breeding in the natural environment.

春季奇努克鲑鱼，Oncorhynchus tshawytscha，通常是半产的，在一生的一次产卵事件后死亡。然而，在1岁成熟的雄性（俗称：早熟的同伴或微杰克）成熟后的存活率有文献记载，但对其成熟后的生理机能知之甚少。在这项研究中，研究人员给成熟的微千头鱼喂高或低的冬季口粮，以研究喂养方式对次年微千头鱼死亡率、孵化和再成熟的潜在影响。我们测量了一系列生理因素，包括存活率、大小、全身固体百分比（全身脂质指数）和鳃Na+/K+- atp酶活性（smoltification指数）。我们还分析了一系列成熟指标，包括血浆11-酮睾酮（11-KT）、促性腺指数（GSI）、垂体促卵泡激素（fshb）和黄体生成素(lhb) β亚基mRNA，以及雄性鱼成熟后的睾丸组织学。在两种处理中，成活率（高比率：0.91，低比率：0.87）和再成熟率（高比率：1.0，低比率：1.0）都非常高，更能说明雌雄同体而非半胚。较低的冬季口粮可能会导致再成熟的轻微延迟，这可以从春季fshb表达和11-KT分泌的延迟中得到证明。然而，没有证据表明，在1岁成熟后的春天，微杰克会产卵。从渔业保护的角度来看，微千斤顶的潜在互变性（存活到2岁再成熟）意味着它们在自然环境中繁殖时可能不止一次地贡献基因。

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引用次数: 0

Amiodarone disrupts thyroid hormone signaling networks governing early heart development in the chick embryo 胺碘酮破坏控制小鸡胚胎早期心脏发育的甲状腺激素信号网络。

IF 1.7 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

General and comparative endocrinology

Pub Date : 2025-12-14 DOI: 10.1016/j.ygcen.2025.114871

Juhi Vaishnav , Aashi Maurya , Varun Varadarajan , Suresh Balakrishnan

Thyroid hormones (THs) are indispensable regulators of vertebrate embryogenesis, orchestrating signaling networks that direct cardiac morphogenesis. To investigate how disruption of this pathway impacts early development, fertilized Gallus domesticus eggs were exposed to amiodarone, a potent TH receptor (THR) antagonist and deiodinase inhibitor. Treated embryos displayed pronounced defects, including impaired heart looping, edema, increased apoptotic regions and sustained bradycardia during Hamburger-Hamilton stages 12 to 18. By day 10, histology revealed significant thinning of ventricular and atrial walls, with the compact ventricular layer reduced by ∼22 % while trabeculae were relatively preserved. These changes were accompanied by reduced acetylcholinesterase activity, indicating impaired neurocardiac regulation. Molecular analyses showed broad downregulation of WNT11, GATA4/5, TBX20, HAND2, BMP4, SHH, FGF8, MYOD, and MYOSIN, together with decreased PCNA and compensatory upregulation of GATA6. Interestingly, discrepancies between transcript and protein levels suggested post-transcriptional control under hypothyroid conditions. In silico promoter scanning identified thyroid hormone response elements within HAND2, GATA6, TBX5, PITX2, and BMP4, linking maternal TH signaling directly to lateral plate mesoderm gene networks. Flow cytometry and whole-mount immunolocalization confirmed reduced expression and altered localization of MYOD and MYOSIN, including loss of the normal heart-tube–restricted MYOD signal. Collectively, these findings establish that TH signaling networks coordinate structural, functional, and molecular programs essential for early cardiogenesis. Amiodarone-induced THR blockade recapitulates developmental hypothyroidism, providing mechanistic insight into how maternal TH deficiency or endocrine-disrupting exposures may contribute to congenital heart defects.

甲状腺激素（THs）是脊椎动物胚胎发生不可缺少的调节因子，协调指导心脏形态发生的信号网络。为了研究这一途径的破坏如何影响早期发育，我们将受精卵暴露于胺碘酮（一种有效的TH受体拮抗剂和去碘酶抑制剂）中。经过处理的胚胎表现出明显的缺陷，包括心循环受损、水肿、凋亡区域增加和持续的心动过缓。第10天，组织学显示心室和心房壁明显变薄，紧凑的心室层减少了~ 22% %，而小梁相对保留。这些变化伴随着乙酰胆碱酯酶活性降低，表明神经心脏调节受损。分子分析显示WNT11、GATA4/5、TBX20、HAND2、BMP4、SHH、FGF8、MYOD和MYOSIN广泛下调，PCNA降低，GATA6代偿上调。有趣的是，转录物和蛋白水平之间的差异表明在甲状腺功能减退的情况下存在转录后控制。在硅启动子扫描中发现了HAND2、GATA6、TBX5、PITX2和BMP4中的甲状腺激素应答元件，将母体TH信号直接与侧板中胚层基因网络联系起来。流式细胞术和全挂免疫定位证实MYOD和MYOSIN的表达减少和定位改变，包括正常的心脏管受限MYOD信号的丧失。总的来说，这些发现表明TH信号网络协调了早期心脏发生所必需的结构、功能和分子程序。胺碘酮诱导的THR阻断再现了发育性甲状腺功能减退，为母体THR缺乏或内分泌干扰暴露可能导致先天性心脏缺陷提供了机制见解。

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引用次数: 0

Hierarchical regulation of steroid synthesis in ovarian follicles drives progesterone surge in cloudy catshark 卵巢卵泡中类固醇合成的分级调节驱动云猫鲨孕酮激增。

IF 1.7 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

General and comparative endocrinology

Pub Date : 2025-12-13 DOI: 10.1016/j.ygcen.2025.114870

Ryotaro Inoue , Mai Kawano , Koya Shimoyama , Momoko Saito , Shogo Arimura , Kotaro Tokunaga , Wataru Takagi , Marty Kwok Shing Wong , Susumu Hyodo

We previously demonstrated that two major hormonal phases, testosterone (T)-phase and progesterone (P4)-phase, which are marked by high plasma T and P4, respectively, appeared in each egg-laying cycle of cloudy catshark. In the present study, the mechanisms underlying the cyclical fluctuations of sex steroids were investigated by follicular steroid measurement and gene expression analyses in vivo and in vitro. In the ovary of catshark, a hierarchical pattern of follicles of increasing sizes is present. Estradiol (E2) was produced by early vitellogenic follicles, while T was produced by mid- to late-vitellogenic follicles. The production of T was downregulated in the follicles at P4-phase, concomitant with the significant decreases in expression of cyp17a1 gene encoding P450c17, an enzyme converting P4 to androgen. Meanwhile, P4 was exclusively produced by preovulatory F1 follicles only at P4-phase, which was related in time to a marked upregulation of steroidogenic acute regulatory protein 2 (star2), suggesting that star2 is a key regulatory factor for inducing the P4 surge. Our newly established in vitro follicle culture system confirmed the secretion of E2, T and P4 from follicles at the different hierarchical stages. These findings provide clear evidence that follicular hierarchy is an important driver of the cyclical secretion of steroid hormones by follicles, and of circulating steroids in plasma, in the cloudy catshark.

我们之前已经证明，阴云猫鲨在每个产蛋周期中出现两个主要的激素阶段，睾酮(T)期和孕酮（P4）期，它们分别以高血浆T和P4为标志。在本研究中，通过体内和体外卵泡类固醇测量和基因表达分析，探讨了性类固醇周期性波动的机制。在猫鲨的卵巢中，卵泡大小逐渐增大，呈等级结构。雌二醇（E2）由早期卵黄形成的卵泡产生，而T由中晚期卵黄形成的卵泡产生。在P4期，卵泡中T的产生下调，同时编码P450c17（一种将P4转化为雄激素的酶）的cyp17a1基因的表达显著降低。同时，排卵前F1卵泡仅在P4期产生P4，这与甾体源性急性调节蛋白2 （star2）的显著上调在时间上相关，表明star2是诱导P4激增的关键调节因子。我们新建立的卵泡体外培养系统证实了不同层次阶段卵泡分泌E2、T和P4。这些发现提供了明确的证据，表明卵泡等级是卵泡周期性分泌类固醇激素和血浆循环类固醇激素的重要驱动因素。

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引用次数: 0

IDENTIFICATION of NLP-5 and NLP-6 as potential ligands for the NPR-9 receptor in Caenorhabditis elegans 秀丽隐杆线虫NPR-9受体潜在配体NLP-5和NLP-6的鉴定

IF 1.7 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

General and comparative endocrinology

Pub Date : 2025-12-06 DOI: 10.1016/j.ygcen.2025.114869

Foroozan Torki, William G. Bendena, Ian D. Chin-Sang

Neuropeptides in Caenorhabditis elegans regulate physiological and behavioural responses to environmental cues, influencing locomotion, feeding, and fat storage via interactions with G-protein coupled receptors (GPCRs). C. elegans expresses a diverse repertoire of neuropeptides, including FMRFamide-related peptides, neuropeptide-like peptides (NLPs), and insulin-like peptides (INSs). Among these, the galanin/allatostatin-like GPCR, NPR-9, localized in the AIB interneurons, regulates locomotory behaviours (roaming and dwelling) and fat accumulation by inhibiting AIB activity. Recent studies identified NLP-1 as a ligand for NPR-9, modulating behaviour through direct receptor interaction. However, our research explored whether other neuropeptides, specifically NLP-5 and NLP-6 (allatostatin A-type/galanin-like neuropeptides), could also function as NPR-9 ligands, despite evidence suggesting NLP-1 as the primary ligand. In this study, we characterized phenotypes associated with NPR-9 receptor function, including Omega turns, roaming, and fat accumulation. Loss-of-function mutations in nlp-5, nlp-6, and nlp-1 exhibited behavioural phenotypes similar to npr-9 mutants, suggesting that NLP-5 and NLP-6 may act as additional ligands for NPR-9 or affect NPR-9 signalling. Furthermore, double-mutant analyses with candidate ligand genes suppressed phenotypes associated with NPR-9 overexpression, reinforcing the hypothesis that these neuropeptides may regulate NPR-9-mediated signalling.

秀丽隐杆线虫中的神经肽调节对环境信号的生理和行为反应，通过与g蛋白偶联受体（gpcr）的相互作用影响运动、摄食和脂肪储存。秀丽隐杆线虫表达多种神经肽，包括fmrfamily相关肽、神经肽样肽（nlp）和胰岛素样肽（ins）。其中，甘丙肽/allatostatin样GPCR， NPR-9，定位于AIB中间神经元，通过抑制AIB活性调节运动行为（漫游和居住）和脂肪积累。最近的研究发现NLP-1是NPR-9的配体，通过受体直接相互作用调节行为。然而，我们的研究探索了其他神经肽，特别是NLP-5和NLP-6 （allatostatin a型/丙氨酸样神经肽）是否也可以作为NPR-9的配体，尽管有证据表明NLP-1是主要的配体。在这项研究中，我们描述了与NPR-9受体功能相关的表型，包括Omega旋转、漫游和脂肪积累。nlp-5、nlp-6和nlp-1的功能丧失突变表现出与npr-9突变相似的行为表型，这表明nlp-5和nlp-6可能作为npr-9的附加配体或影响npr-9的信号传导。此外，候选配体基因的双突变分析抑制了与NPR-9过表达相关的表型，加强了这些神经肽可能调节NPR-9介导的信号传导的假设。

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引用次数: 0

Potential role of COUP-TF in regulating major yolk protein gene expression in sea urchin COUP-TF在海胆主要卵黄蛋白基因表达调控中的潜在作用

IF 1.7 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

General and comparative endocrinology

Pub Date : 2025-12-06 DOI: 10.1016/j.ygcen.2025.114867

Ichiro Higuchi , Shiori Tsue , Yudai Kitano , Osamu Nishimiya , Masashi Hosokawa , Fumiaki Beppu , Kazuhiro Ura , Yasuaki Takagi

Major yolk protein (MYP) serves as a critical nutrient reservoir for gonadal development in sea urchins, but the transcriptional regulation of its encoding gene remains largely uncharacterized. Here, we cloned and analyzed the MYP promoter from Mesocentrotus nudus and found two conserved elements with putative binding sites for the orphan nuclear receptor COUP-TF (chicken ovalbumin upstream promoter-transcription factor). We cloned the full-length cDNA encoding COUP-TF from M. nudus (MnCOUP-TF). The cDNA encoded a 472-amino acid protein highly homologous to other COUP-TF/SVP subfamily members. RT-PCR and qPCR analyses revealed that transcripts of both MnCOUP-TF and MYP were present in several tissues, including gonads, and their levels exhibited a significant positive correlation during gonadal maturation (R² = 0.6764, p < 0.01). Electrophoretic mobility shift assays demonstrated specific binding of MnCOUP-TF to the MYP promoter, and transactivation assays showed that MnCOUP-TF activates transcription through these sites. Furthermore, total lipids extracted from gonadal tissue enhanced MnCOUP-TF–dependent reporter activity in a dose-dependent manner. This enhancement was comparable to the effect of 9-cis-retinoic acid, a compound known to activate COUP-TF at high concentrations, although it is not considered to be a physiological COUP-TF ligand. These results suggest that MnCOUP-TF regulates MYP expression in a ligand-dependent manner and that endogenous activators may be present in gonadal lipids. To our knowledge, this is the first molecular evidence implicating COUP-TF in yolk protein gene regulation in sea urchins, providing new insights into nuclear receptor-mediated control of reproduction in marine invertebrates.

主要卵黄蛋白（Major蛋黄蛋白，MYP）是海胆性腺发育的重要营养储备，但其编码基因的转录调控在很大程度上尚不清楚。在这里，我们克隆并分析了裸鸡中心虾的MYP启动子，发现了两个保守的元件，它们与孤儿核受体COUP-TF（鸡卵白蛋白上游启动子转录因子）有可能的结合位点。我们从裸鼠中克隆了编码COUP-TF的全长cDNA （MnCOUP-TF）。该cDNA编码了一个472个氨基酸的蛋白，与其他COUP-TF/SVP亚家族成员高度同源。RT-PCR和qPCR分析显示，MnCOUP-TF和MYP转录本均存在于包括性腺在内的多种组织中，其水平在性腺成熟过程中呈显著正相关（R2 = 0.6764, p < 0.01）。电泳迁移率转移实验表明MnCOUP-TF与MYP启动子特异性结合，反式激活实验表明MnCOUP-TF通过这些位点激活转录。此外，从性腺组织中提取的总脂质以剂量依赖的方式增强了mncoup - tf依赖的报告细胞活性。这种增强与9-顺式维甲酸的作用相当，9-顺式维甲酸是一种已知在高浓度下激活COUP-TF的化合物，尽管它不被认为是一种生理上的COUP-TF配体。这些结果表明，MnCOUP-TF以配体依赖的方式调节MYP的表达，内源性激活剂可能存在于性腺脂质中。据我们所知，这是暗示COUP-TF参与海胆卵黄蛋白基因调控的第一个分子证据，为核受体介导的海洋无脊椎动物生殖控制提供了新的见解。

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