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The signalling association of glucagon-like peptide-1 and its receptors in the gastrointestinal tract and GPR40 and insulin receptor in the pancreas of sheep 胰高血糖素样肽-1 及其在胃肠道中的受体与 GPR40 和胰腺中的胰岛素受体之间的信号联系。
IF 2.1 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-09-01 DOI: 10.1016/j.ygcen.2024.114602
G. Krishnan , M. Bagath , C. Devaraj , N.M. Soren

The present study was aimed at gaining insight into the signalling relationship between glucagon-like peptide-1 (GLP-1) and its receptor (GLP-1R) in the regulation of glucose metabolism. Further, to assess the role of G-protein-coupled receptor 40 (GPR40) and insulin receptor (INSR) in the pancreas of sheep that were supplemented with calcium salts of long-chain fatty acids (CSFAs). An experiment was carried out over a period of 60 days with eighteen sheep, and they were fed with a standard basal diet. The sheep were divided into three groups: CSFA0 (without CSFAs), while CSFA3 and CSFA5 were supplemented with 3 % and 5 % of CSFAs, respectively. Plasma concentrations of GLP-1, insulin, glucagon, and glucose were assessed every two weeks. At the end of the experiment, sheep were slaughtered, and samples of gastrointestinal tract (GIT) epithelial tissues and pancreas were collected to assess the relative expression of mRNA of GPR40, GLP-1R, and INSR. Postprandial GLP-1 and insulin were increased by 3.7–4.1 and 1.45–1.5 times, respectively, in the CSFAs-supplemented groups compared to CSFA0. Post-feeding, glucagon and glucose levels decreased in CSFA3 and CSFA5 compared to CSFA0. The results indicated that the supplementation of LCFAs increased the expression of GLP-1R in the GIT and pancreas, as well as the mRNA of GPR40 and INSR in the pancreas. Chemosensing of LCFAs by GPR40 in the pancreas triggers signalling transduction, and enhanced GLP-1 and GLP-1R resulted in moderately increased insulin secretion and reduced glucagon levels. These combined effects, along with the glucose-lowering effect of GLP-1, effectively lowered glucose levels in normoglycemic sheep.

本研究旨在深入了解胰高血糖素样肽-1(GLP-1)及其受体(GLP-1R)在调节葡萄糖代谢中的信号关系。此外,本研究还评估了G蛋白偶联受体40(GPR40)和胰岛素受体(INSR)在补充长链脂肪酸钙盐(CSFAs)的绵羊胰腺中的作用。我们对 18 只绵羊进行了为期 60 天的实验,这些绵羊以标准基础日粮喂养。绵羊被分为三组:CSFA0组(不含CSFAs),CSFA3和CSFA5组分别添加3%和5%的CSFAs。每两周评估一次血浆中 GLP-1、胰岛素、胰高血糖素和葡萄糖的浓度。实验结束后,宰杀绵羊,采集胃肠道(GIT)上皮组织和胰腺样本,评估GPR40、GLP-1R和INSR mRNA的相对表达。与CSFA0相比,CSFA补充组的餐后GLP-1和胰岛素分别增加了3.7-4.1倍和1.45-1.5倍。与 CSFA0 相比,进食后 CSFA3 和 CSFA5 组的胰高血糖素和葡萄糖水平有所下降。结果表明,补充 LCFAs 增加了 GLP-1R 在胃肠道和胰腺中的表达,也增加了 GPR40 和 INSR 在胰腺中的 mRNA 表达。胰腺中的 GPR40 对 LCFAs 的化学感应触发了信号转导,GLP-1 和 GLP-1R 的增强导致胰岛素分泌适度增加,胰高血糖素水平降低。这些综合效应加上 GLP-1 的降糖作用,有效降低了血糖正常绵羊的血糖水平。
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引用次数: 0
Cloning and expression profiling of peptide YY in the brain of common carp, Cyprinus carpio 鲤鱼脑中多肽 YY 的克隆和表达谱分析。
IF 2.1 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-08-30 DOI: 10.1016/j.ygcen.2024.114600
Cheni-Chery Sudhakumari , Dharavath Bhasker , Sonika Kar, Akanksha Pranoty, Aparna Dutta-Gupta , Balasubramanian Senthilkumaran
Peptide YY (PYY) is an anorectic brain-gut pancreatic peptide that helps in feeding regulation by reducing appetite and is well characterized in mammals. The role of PYY in relation to brain is least studied in mammals as well as in lower vertebrates including fish, however high expression was evident in male reproductive tissue. In this regard, this study attempts to evaluate the significance of PYY in the brain of common carp, Cyprinus carpio. As a first step, the cDNA of PYY from brain of adult male carp was cloned. Following which expression analysis was performed using juvenile and adult fish. The differential distribution pattern in various regions of brain and ontogeny expression analysis indicated that PYY may involve in physiological processes related to brain-pituitary axis. In addition, a significant decrease in neuropeptide Y expression was observed upon PYY- endoribonuclease-prepared small interfering RNA transfection in brain cells, in vitro indicating plausible PYY-NPY interaction in brain-pituitary axis of common carp.
肽 YY(PYY)是一种厌食的脑肠胰肽,它通过降低食欲来帮助调节进食,在哺乳动物中具有很好的特征。在哺乳动物以及包括鱼类在内的低等脊椎动物中,对PYY在大脑中的作用研究得最少,但在雄性生殖组织中却有明显的高表达。因此,本研究试图评估PYY在鲤鱼大脑中的重要性。首先,亚克隆了成年雄性鲤鱼大脑中PYY的cDNA。随后,利用幼鱼和成鱼进行了表达分析。PYY在大脑各区域的不同分布模式和本体表达分析表明,PYY可能参与了与脑-垂体轴相关的生理过程。此外,体外观察到,PYY-内切核酸酶制备的小干扰 RNA 转染脑细胞后,神经肽 Y 的表达量明显下降,这表明PYY-NPY 之间可能存在相互作用。
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引用次数: 0
Revisiting the hormonal control of sexual dimorphism in chicken feathers 重新审视荷尔蒙对鸡羽毛性双态性的控制。
IF 2.1 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-08-22 DOI: 10.1016/j.ygcen.2024.114601
Li You , Kaori Nishio , Kinue Kowata , Minaru Horikawa , Hibiki Fukuchi , Maho Ogoshi , Sayaka Aizawa , Sakae Takeuchi

Sexual dimorphism in plumage is widespread among avian species. In chickens, adult females exhibit countershading, characterized by dull-colored round feathers lacking fringe on the saddle, while adult males display vibrant plumage with deeply fringed bright feathers. This dimorphism is estrogen-dependent, and administering estrogen to males transforms their showy plumage into cryptic female-like plumage. Extensive studies have shown that estrogen’s role in female plumage formation requires thyroid hormone; however, the precise mechanisms of their interaction remain unclear. In this study, we investigated the roles of estrogen and thyroid hormone in creating sexual dimorphism in the structure and coloration of saddle feathers by administering each hormone to adult males and observing the resulting changes in regenerated feathers induced by plucking. RT-PCR analysis revealed that the expression of type 3 deiodinase (DIO3), responsible for thyroid hormone inactivation, correlates with fringing. Estrogen suppressed DIO3 and agouti signaling protein (ASIP) expression while stimulating BlSK1, a marker of barbule cells, resulting in female-like feathers with mottled patterns and lacking fringes. Administration of thyroxine (T4) stimulated BlSK1 and proopiomelanocortin (POMC) expression, with no effect on ASIP, leading to the formation of solid black feathers lacking fringes. Triiodothyronine (T3) significantly increased POMC expression in pulp cells in culture. Taken together, these findings suggest that estrogen promotes the formation of solid vanes by suppressing DIO3 expression, while also inducing the formation of mottled patterns through inhibition of ASIP expression and indirect stimulation of melanocortin expression via changes in local T3 concentration. This is the first report describing molecular mechanism underlying hormonal crosstalk in creating sexual dimorphism in feathers.

羽色的两性异形在鸟类物种中很普遍。在鸡中,成年雌性表现为反阴影,其特征是鞍部缺乏流苏的暗色圆形羽毛,而成年雄性则表现为带有深流苏亮色羽毛的鲜艳羽色。这种二态性依赖于雌激素,给雄鸡施用雌激素会使其艳丽的羽毛变成隐蔽的雌性羽毛。大量研究表明,雌激素在雌性羽毛形成过程中的作用需要甲状腺激素;然而,它们之间相互作用的确切机制仍不清楚。在这项研究中,我们通过给成年雄鸟注射雌激素和甲状腺激素,并观察拔毛后再生羽毛的变化,研究了雌激素和甲状腺激素在鞍羽结构和颜色的性双态性形成过程中的作用。RT-PCR分析表明,负责甲状腺激素灭活的3型脱碘酶(DIO3)的表达与流苏相关。雌激素抑制了DIO3和Agouti信号蛋白(ASIP)的表达,同时刺激了钩毛细胞标记物BlSK1的表达,导致雌鸟羽毛呈斑驳状,缺乏流苏。甲状腺素(T4)刺激了BlSK1和原绒毛膜促皮质素(POMC)的表达,但对ASIP没有影响,从而形成了没有流苏的纯黑色羽毛。三碘甲状腺原氨酸(T3)能显著增加培养的髓细胞中 POMC 的表达。综上所述,这些研究结果表明,雌激素通过抑制DIO3的表达来促进实心叶片的形成,同时也通过抑制ASIP的表达和通过局部T3浓度的变化间接刺激黑皮质素的表达来诱导斑纹的形成。这是第一份描述荷尔蒙相互影响导致羽毛性双态性的分子机制的报告。
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引用次数: 0
The annual ovarian cycle in Northern pit vipers (Bothrops atrox) using serum steroids and ultrasound of the female reproductive tract 利用血清类固醇和雌性生殖道超声波研究北方蝮蛇(Bothrops atrox)的年卵巢周期。
IF 2.1 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-08-10 DOI: 10.1016/j.ygcen.2024.114599
Samira Emanuela Maria Vieira , Kathleen Fernandes Grego , Marcel Henrique Blank , Gabriel Augusto Novaes , Giovanni Perez Machado da Silveira , Sávio Stefanini Sant’Anna , Ricardo José Garcia Pereira

Knowledge on hormonal regulation of reproductive cycles in viperid snakes is still incipient, especially when it comes to females and tropical species. There is an urgent need to understand the reproduction of venomous snakes to improve assisted reproduction techniques and optimize the maintenance of these animals in captivity. With this in mind, we monitored Northern pit viper females year-round throughout different seasons via serum levels of progesterone (P4) and estradiol (E2) in conjunction with ultrasound examinations. Ovarian follicles were classified according to their size and stage of vitellogenesis in F-I and F-II (non-vitellogenic phase) or in F-III and F-IV (vitellogenic phase). During autumn and winter, five adult males were rotated among these females for reproductive pairing, which resulted in 17 copulations and 2 pregnancies in the first year and 12 copulations and 5 pregnancies in the second year. Then, we assessed changes in P4 and E2 levels according to seasons, predominant ovarian structures and the presence of embryos or eggs in the oviduct. Our findings showed high levels of E2 when a greater number of vitellogenic follicles were detected, indicating a possible influence of E2 on vitellogenesis and higher levels of P4 whenever eggs and embryos were visualized in the oviduct, implying its role in maintaining pregnancy. Descriptive analysis of the vipers’ ovarian cycles revealed a greater number of vitellogenic follicles during winter, probably as a result of increases in E2; whereas pregnancies occurred predominantly in spring, under the influence of P4. The use of ultrasound images, as a minimally invasive methodology, associated with serum steroid levels has proven to be an efficient approach in the reproductive monitoring of Northern pit vipers in vivo. In addition, these data suggest that female pit vipers under human care display a seasonal reproductive cycle, despite earlier studies involving captive males of the species indicating a lack of seasonality in sperm production and quality.

有关毒蛇生殖周期的激素调节的知识仍处于起步阶段,尤其是在雌性和热带物种方面。目前迫切需要了解毒蛇的繁殖情况,以改进辅助繁殖技术,优化人工饲养这些动物。有鉴于此,我们通过血清中的孕酮(P4)和雌二醇(E2)水平,结合超声波检查,对北蝮蛇雌性在不同季节进行全年监测。根据卵泡的大小和卵黄发生阶段将卵泡分为 F-I 和 F-II(非卵黄发生期)或 F-III 和 F-IV(卵黄发生期)。在秋冬季,五只成年雄性雌性轮流进行生殖配对,结果第一年交配 17 次,怀孕 2 次,第二年交配 12 次,怀孕 5 次。然后,我们根据季节、主要卵巢结构和输卵管中胚胎或卵子的存在情况,评估了P4和E2水平的变化。我们的研究结果表明,当检测到较多的卵黄发生卵泡时,E2的水平较高,这表明E2可能对卵黄发生有影响;而当在输卵管中看到卵子和胚胎时,P4的水平较高,这意味着它在维持妊娠中的作用。对蝰蛇卵巢周期的描述性分析表明,冬季卵黄发生卵泡的数量较多,这可能是 E2 增加的结果;而怀孕主要发生在春季,这是受 P4 影响的结果。事实证明,使用超声波图像这种微创方法,并结合血清类固醇水平,是监测北方蝮蛇体内生殖情况的有效方法。此外,这些数据还表明,人类饲养的雌性蝮蛇表现出季节性生殖周期,尽管早先对圈养雄性蝮蛇的研究表明精子的产生和质量没有季节性。
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引用次数: 0
Temperature-driven changes in the neuroendocrine axis of the blue crab Callinectes sapidus during the molt cycle 青蟹蜕壳周期中神经内分泌轴在温度驱动下的变化。
IF 2.1 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-08-08 DOI: 10.1016/j.ygcen.2024.114598
Daniela Dantas David , Giovanna Zanetti , José Araújo Souto-Neto , Cristhian David Sua-Cespedes , José Thalles Lacerda , Ana Maria de Lauro Castrucci

Environmental cues such as temperature induce macroscopic changes in the molting cycle of crustaceans, however, the physiological mechanisms behind these changes remain unclearWe aimed to investigate the regulatory mechanisms in the intermolt and premolt stages of the Callinectes sapidus molt cycle in response to thermal stimuli. The concentration of ecdysteroids and lipids in the hemolymph, and the expression of heat shock proteins (HSPs) and molt key genes were assessed at 19 °C, 24 °C and 29 °C. The premolt animals exhibited a much larger response to the colder temperature than intermolt animals. Ecdysteroids decreased drastically in premolt animals, whereas the expression of their hepatopancreas receptor (CasEcR) increased, possibly compensating for the low hemolymphatic levels at 19 °C. This decrease might be due to increased HSPs and inhibited ecdysteroidogenesis in the Y-organ. In addition, the molting-inhibiting hormone expression in the X-organ/sinus gland (XO/SG) remained constant between temperatures and stages, suggesting it is constitutive in this species. Lipid concentration in the hemolymph, and the expression of CasEcR and CasHSP90 in the XO/SG were influenced by the molting stage, not temperature. On the other hand, the expression of HSPs in the hepatopancreas is the result of the interaction between the two factors evaluated in the study. Our results demonstrated that temperature is an effective modulator of responses related to the molting cycle at the endocrine level and that temperature below the control condition caused a greater effect on the evaluated responses compared to the thermostable condition, especially when the animal was in the premolt stage.

温度等环境线索会引起甲壳动物蜕皮周期的宏观变化,然而这些变化背后的生理机制仍不清楚。在19 °C、24 °C和29 °C条件下,我们评估了血淋巴中蜕皮激素和脂质的浓度,以及热休克蛋白(HSPs)和蜕皮关键基因的表达。与蜕皮间期动物相比,蜕皮前期动物对低温的反应更大。预蜕皮动物的蜕皮激素急剧下降,而其肝胰腺受体(CasEcR)的表达却增加了,这可能是对19 °C时低血淋巴水平的补偿。这种减少可能是由于 HSPs 增加和 Y-器官中的蜕皮激素生成受到抑制。此外,X器官/窦腺(XO/SG)中蜕皮抑制激素的表达在不同温度和阶段保持不变,表明它在该物种中是组成型的。血淋巴中的脂质浓度以及 XO/SG 中 CasEcR 和 CasHSP90 的表达受蜕皮阶段的影响,而不受温度的影响。另一方面,肝胰腺中 HSPs 的表达是本研究评估的两个因素相互作用的结果。我们的研究结果表明,在内分泌水平上,温度是蜕皮周期相关反应的有效调节器,与恒温条件相比,低于控制条件的温度对所评估反应的影响更大,尤其是当动物处于蜕皮前阶段时。
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引用次数: 0
Proteome-wide neuropeptide identification using NeuroPeptide-HMMer (NP-HMMer) 利用 NeuroPeptide-HMMer (NP-HMMer) 进行全蛋白质组神经肽鉴定。
IF 2.1 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-07-29 DOI: 10.1016/j.ygcen.2024.114597
Meet Zandawala , Muhammad Bilal Amir , Joel Shin , Won C. Yim , Luis Alfonso Yañez Guerra

Neuropeptides are essential neuronal signaling molecules that orchestrate animal behavior and physiology via actions within the nervous system and on peripheral tissues. Due to the small size of biologically active mature peptides, their identification on a proteome-wide scale poses a significant challenge using existing bioinformatics tools like BLAST. To address this, we have developed NeuroPeptide-HMMer (NP-HMMer), a hidden Markov model (HMM)-based tool to facilitate neuropeptide discovery, especially in underexplored invertebrates. NP-HMMer utilizes manually curated HMMs for 46 neuropeptide families, enabling rapid and accurate identification of neuropeptides. Validation of NP-HMMer on Drosophila melanogaster, Daphnia pulex, Tribolium castaneum and Tenebrio molitor demonstrated its effectiveness in identifying known neuropeptides across diverse arthropods. Additionally, we showcase the utility of NP-HMMer by discovering novel neuropeptides in Priapulida and Rotifera, identifying 22 and 19 new peptides, respectively. This tool represents a significant advancement in neuropeptide research, offering a robust method for annotating neuropeptides across diverse proteomes and providing insights into the evolutionary conservation of neuropeptide signaling pathways.

神经肽是重要的神经元信号分子,通过在神经系统和外周组织中的作用协调动物的行为和生理。由于具有生物活性的成熟多肽体积很小,因此使用现有的生物信息学工具(如 BLAST)在整个蛋白质组范围内鉴定这些多肽是一项巨大的挑战。为了解决这个问题,我们开发了基于隐马尔可夫模型(HMM)的工具 NeuroPeptide-HMMer(NP-HMMer),以促进神经肽的发现,尤其是在未充分开发的无脊椎动物中。NP-HMMer 利用人工编辑的 46 个神经肽家族的 HMM,能够快速准确地识别神经肽。NP-HMMer 在黑腹果蝇、水蚤、蓖麻蒺藜和栉水母上的验证表明,它能有效识别各种节肢动物的已知神经肽。此外,我们还发现了 Priapulida 和轮虫的新型神经肽,分别鉴定出 22 和 19 种新肽,从而展示了 NP-HMMer 的实用性。该工具代表了神经肽研究的一大进步,提供了一种强大的方法来注释不同蛋白质组中的神经肽,并为神经肽信号通路的进化保护提供了见解。
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引用次数: 0
Editorial for the special issue in GCE 为 GCE 特刊撰写社论。
IF 2.1 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-07-25 DOI: 10.1016/j.ygcen.2024.114596
Constantinos C. Mylonas (special editor), Rüdiger Schulz (special editor), Julien Bobe (special editor), Francesc Piferrer (special editor)
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引用次数: 0
Early-life glucocorticoids accelerate lymphocyte count senescence in roe deer 生命早期的糖皮质激素加速了狍子淋巴细胞数量的衰老。
IF 2.1 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-07-24 DOI: 10.1016/j.ygcen.2024.114595
Lucas D. Lalande , Gilles Bourgoin , Jeffrey Carbillet , Louise Cheynel , François Debias , Hubert Ferté , Jean-Michel Gaillard , Rebecca Garcia , Jean-François Lemaître , Rupert Palme , Maryline Pellerin , Carole Peroz , Benjamin Rey , Pauline Vuarin , Emmanuelle Gilot-Fromont

Immunosenescence corresponds to the progressive decline of immune functions with increasing age. Although it is critical to understand what modulates such a decline, the ecological and physiological drivers of immunosenescence remain poorly understood in the wild. Among them, the level of glucocorticoids (GCs) during early life are good candidates to modulate immunosenescence patterns because these hormones can have long-term consequences on individual physiology. Indeed, GCs act as regulators of energy allocation to ensure allostasis, are part of the stress response triggered by unpredictable events and have immunosuppressive effects when chronically elevated. We used longitudinal data collected over two decades in two populations of roe deer (Capreolus capreolus) to test whether higher baseline GC levels measured within the first year of life were associated with a more pronounced immunosenescence and parasite susceptibility. We first assessed immunosenescence trajectories in these populations facing contrasting environmental conditions. Then, we found that juvenile GC levels can modulate lymphocyte trajectory. Lymphocyte depletion was accelerated late in life when GCs were elevated early in life. Although the exact mechanism remains to be elucidated, it could involve a role of GCs on thymic characteristics. In addition, elevated GC levels in juveniles were associated with a higher abundance of lung parasites during adulthood for individuals born during bad years, suggesting short-term negative effects of GCs on juvenile immunity, having in turn long-lasting consequences on adult parasite load, depending on juvenile environmental conditions. These findings offer promising research directions in assessing the carry-over consequences of GCs on life-history traits in the wild.

免疫衰老是指随着年龄的增长,免疫功能逐渐下降。尽管了解是什么因素调节了这种衰退至关重要,但对野生动物免疫衰老的生态和生理驱动因素仍然知之甚少。其中,生命早期的糖皮质激素(GCs)水平是调节免疫衰老模式的良好候选因素,因为这些激素会对个体生理产生长期影响。事实上,糖皮质激素是能量分配的调节剂,可确保异位平衡,是不可预测事件引发的应激反应的一部分,并且在长期升高时具有免疫抑制作用。我们利用在两个狍子种群中收集到的长达二十年的纵向数据,检验了在狍子出生后第一年测量到的较高基线 GC 水平是否与更明显的免疫衰老和寄生虫易感性有关。我们首先评估了这些面临截然不同环境条件的种群的免疫衰老轨迹。然后,我们发现幼年的 GC 水平可以调节淋巴细胞的轨迹。当 GC 在生命早期升高时,淋巴细胞在生命晚期会加速耗竭。虽然确切的机制仍有待阐明,但这可能与 GCs 对胸腺特征的作用有关。此外,幼年时期 GC 水平的升高与坏年出生的个体成年后肺部寄生虫数量的增加有关,这表明 GC 对幼年时期的免疫力有短期的负面影响,反过来又会对成年后的寄生虫数量产生长期影响,这取决于幼年时期的环境条件。这些发现为评估GCs对野外生活史特征的影响提供了很有前景的研究方向。
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引用次数: 0
Effects and action mechanism of gonadotropins on ovarian follicular cells: A novel role of Sphingosine-1-Phosphate (S1P). A review 促性腺激素对卵泡细胞的影响和作用机制:1-磷酸腺苷(S1P)的新作用。综述。
IF 2.1 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-07-22 DOI: 10.1016/j.ygcen.2024.114593
A. Guzmán , A.M. Rosales-Torres , Z.B. Medina-Moctezuma , D. González-Aretia , C.G. Hernández-Coronado

Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) control antral follicular growth by regulating several processes, such as the synthesis of hormones and signaling molecules, proliferation, survival, apoptosis, luteinization, and ovulation. To exert these effects, gonadotropins bind to their respective Gs protein-coupled receptors, activating the protein kinase A (PKA) pathway or recruiting Gq proteins to activate protein kinase C (PKC) signaling. Although the action mechanism of FSH and LH is clear, recently, it has been shown that both gonadotropins promote the synthesis of sphingosine-1-phosphate (S1P) in granulosa and theca cells through the activation of sphingosine kinase 1. Moreover, the inhibition of SPHKs reduces S1P synthesis, cell viability, and the proliferation of follicular cells in response to gonadotropins, and the addition of S1P to the culture medium increases the proliferation of granulosa and theca cells without apparent effects on sexual steroid synthesis. Therefore, we consider that S1P is a crucial signaling molecule that complements the canonical gonadotropin pathway to promote the proliferation and viability of granulosa and theca cells.

卵泡刺激素(FSH)和黄体生成素(LH)通过调节激素和信号分子的合成、增殖、存活、凋亡、黄体化和排卵等多个过程来控制前卵泡的生长。为了发挥这些作用,促性腺激素与各自的Gs蛋白偶联受体结合,激活蛋白激酶A(PKA)途径或招募Gq蛋白激活蛋白激酶C(PKC)信号传导。尽管 FSH 和 LH 的作用机制已经明确,但最近的研究表明,这两种促性腺激素都能通过激活鞘磷脂激酶 1 促进颗粒细胞和癌细胞中鞘磷脂-1-磷酸(S1P)的合成。此外,抑制 SPHKs 会降低 S1P 的合成、细胞活力和卵泡细胞对促性腺激素的增殖反应,而在培养基中添加 S1P 会增加颗粒细胞和癌细胞的增殖,但对性类固醇的合成无明显影响。因此,我们认为S1P是一种重要的信号分子,它补充了典型的促性腺激素途径,促进颗粒细胞和theca细胞的增殖和活力。
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引用次数: 0
Characterization of corazonin signaling in a molluscan model species, Lymnaea stagnalis 软体动物模式物种锚鳋中珊瑚皂苷信号转导的特征。
IF 2.1 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-07-22 DOI: 10.1016/j.ygcen.2024.114594
István Fodor , Tomohiro Osugi , Shin Matsubara , Akira Shiraishi , Tsuyoshi Kawada , Zsolt Pirger , Honoo Satake

In recent years, new concepts have emerged regarding the nomenclature, functions, and relationships of different peptide families of the gonadotropin-releasing hormone (GnRH) superfamily. One of the main driving forces for this originated from the emerging evidence that neuropeptides previously called molluscan GnRH are multifunctional and should be classified as corazonin (CRZ). However, research articles still appear that use incorrect nomenclature and attribute the same function to molluscan CRZs as vertebrate GnRHs. The aim of the present study was to further support the recent interpretation of the origin and function of the GnRH superfamily. Towards this goal, we report the characterization of CRZ signaling system in the molluscan model species, the great pond snail (Lymnaea stagnalis). We detected a CRZ-receptor-like sequence (Lym-CRZR) by homology-searching in the Lymnaea transcriptomes and the deduced amino acid sequence showed high sequence similarity to GnRH receptors and CRZ receptors. Molecular phylogenetic tree analysis demonstrated that Lym-CRZR is included in the cluster of molluscan CRZRs. Lym-CRZR transiently transfected into HEK293 cells was found to be localized at the plasma membrane, confirming that it functions as a membrane receptor, like other G protein-coupled receptors. The signaling assays revealed that the previously identified Lym-CRZ neuropeptide stimulated intracellular Ca2+ mobilization in a dose-dependent manner, but not cyclic AMP production, in HEK293 cells transfected with Lym-CRZR. Finally, we demonstrated a wide tissue distribution of Lym-CRZR. These results suggest that Lym-CRZ is a multifunctional peptide and provide further insights into the evolution of the GnRH neuropeptide superfamily. The present study also supports the notion that previously termed molluscan “GnRH” should be classified as “CRZ”.

近年来,关于促性腺激素释放激素(GnRH)超家族不同肽家族的命名、功能和关系出现了新的概念。其中一个主要推动力来自于新出现的证据,即以前被称为软体动物 GnRH 的神经肽具有多功能性,应归类为珊瑚素(CRZ)。然而,仍有一些研究文章使用错误的命名法,将软体动物的 CRZ 与脊椎动物的 GnRH 赋予相同的功能。本研究的目的是进一步支持最近对 GnRH 超家族起源和功能的解释。为此,我们报告了软体动物模式物种大塘螺(Lymnaea stagnalis)中 CRZ 信号系统的特征。通过同源搜索,我们在大塘鳢转录组中发现了一个类似 CRZ 受体的序列(Lym-CRZR),其推导出的氨基酸序列与 GnRH 受体和 CRZ 受体的序列相似度很高。分子系统树分析表明,Lym-CRZR属于软体动物CRZR群。瞬时转染到 HEK293 细胞中的 Lym-CRZR 被发现定位于质膜,这证实了它与其他 G 蛋白偶联受体一样是一种膜受体。信号传导实验显示,在转染了 Lym-CRZR 的 HEK293 细胞中,先前确定的 Lym-CRZ 神经肽能以剂量依赖的方式刺激细胞内 Ca2+ 的调动,但不能刺激环 AMP 的产生。最后,我们证实了 Lym-CRZR 在组织中的广泛分布。这些结果表明,Lym-CRZ 是一种多功能肽,并进一步揭示了 GnRH 神经肽超家族的进化过程。本研究还支持了之前被称为软体动物 "GnRH "的物质应归类为 "CRZ "的观点。
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General and comparative endocrinology
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