Endocrine regulation of ageing

Over the past 15 years it has become clear that mutations in genes that regulate endocrine signalling pathways can prolong lifespan. Lifespan can be increased by altered endocrine signalling in a group of cells or a single tissue, which indicates that crosstalk between tissues functions to coordinate ageing of the organism. These endocrine pathways might serve as targets for the manipulation of the ageing process and prevention of age-related diseases.     

Is gestational diabetes an acquired condition?

Intrvenous injection of 30 mg of streptozotocin per kg body weight induces a mild diabetes in pregnant rats (first generation); the non-fasting blood glucose is increased and the percentage of endocrine tissue and also the percentage of granulated beta cells do not increase. The fetuses of these mildly diabetic pregnant rats have an increased percentage of pancreatic endocrine tissue and there is beta-cell degranulation. The modifications in the endocrine pancreas during intrauterine life causes persistent changes in later adult life (second generation), which are not perceptible in basal conditions, but become apparent in situations stressing the beta-cell activity, such as an intravenous glucose load or pregnancy. During pregnancy in the second generation rats an increased non-fasting blood glucose and no adaptation of the beta cells is seen. This inadequate adaptation to pregnancy causes changes in the fetal endocrine pancreas of the fetuses of the third generation. From these experiments it may be concluded that gestational diabetes is an acquired condition.     

Development of the diffuse endocrine system in the chicken proventriculus

Summary The development of endocrine cells in the chicken proventriculus has been investigated using light-and electron-microscopy in conjunction with silver and immunocytochemical techniques. The first morphologically detectable endocrine cells were found in 5-day-old embryos by electron microscopy. From the 9th to the 13th day, endocrine cells in contact with the lumen of the organ could be detected both by electron and light (silver impregnation) microscopy. The number of open-type endocrine cells progressively decreased and the number of closed-type increased after this stage. Until the 16th day, endocrine cells were located exclusively in the luminal epithelium, but afterwards they appeared in progressively greater numbers in the compound glands. After hatching, long cytoplasmic processes could be seen in the endocrine cells. Immunoreactivities to regulatory substances appeared in the following order: serotonin (day-14), avian pancreatic polypeptide, glucagon and somatostatin (day-16), bombesin and neurotensin (day-18), and finally, met-enkephalin (day-21).     

Distribution of endocrine cells in the digestive tract of Alligator sinensis during the active and hibernating period

The digestive tract is the largest endocrine organ in the body; the distribution pattern of endocrine cells varies with different pathological and physiological states. The aim of the present study was to investigate the distributed density of 5-hydroxytryptamine (5-HT), gastrin (GAS), somatostatin (SS) and vasoactive intestinal peptide (VIP) immunoreactive (IR) cells in the digestive tract of Alligator sinensis during the active and hibernating period by immunohistochemical (IHC) method. The results indicated that 5-HT-IR cells were distributed throughout the entire digestive tract, which were most predominant in duodenum and jejunum. The density increased significantly in stomach and duodenum during hibernation. GAS-IR cells were limited in small stomach and small intestine. The density decreased significantly in small stomach during hibernation, while increased in duodenum. What's more, most of the endocrine cells in duodenum were generally spindle shaped with long cytoplasmic processes ending in the lumen during hibernation. SS-IR cells were limited in stomach and small stomach. The density increased in stomach while decreased in small stomach during hibernation, meanwhile, fewer IR cells occurred in small intestine. VIP-IR cells occurred in stomach and small stomach. The density decreased in small stomach, while increased in stomach during hibernation. These results indicated that the endocrine cells in different parts of digestive tract varied differently during hibernation, their changes were adaptive response to the hibernation.     

Ultrastructural and autoradiographic analysis of the cellular reactivity of the exo- and endocrine epithelium of the frog pancreas under the action of cobalt chloride]

The frog pancreatic epithelium was studied using morphometry, autoradiography and electron microscopy during the treatment with cobalt chloride (10 mg/100 g body wieght). In response to this treatment, generative changes in some exocrine cells were revealed. At the same time, those of cells, whose nuclei were in the state of DNA synthesis, increased in number. Cobalt chloride resulted in endocrine A-cells damage. A compensation of the broken endocrine A-cell function was maintained in a transformation of the exocrine epithelium into endocrine A-cells and in the appearance of intermediate acinar-islet cells, as well as in islet A-cell hyperplasia.     

六味地黄苷糖对悬吊应激小鼠生殖内分泌及免疫系统的影响

目前尚无有效可靠的抗应激药物.传统的补益中药六味地黄汤（LW）对多种类型应激所致内分泌和免疫平衡失调具有明显调节作用,但目前已上市的LW成药缺乏可靠的质量控制方法,其临床疗效的可靠程度难以估测.本课题组在前期研究中以免疫和内分泌活性评价为导向,从LW中追踪分离并组成了质量可控且安全性好的六味地黄苷糖（LW-AFC）.本文观察了悬吊应激雌性小鼠生殖内分泌及免疫系统的变化及LW-AFC的影响.结果表明,悬吊应激小鼠皮质酮升高,动情期缩短、动情间期延长,垂体LH下降,动情间期血清E2升高;脾细胞培养上清IgG含量明显降低;口服LW-AFC能显著降低血清皮质酮,升高垂体LH,且LW-AFC能明显降低动情间期血清E2,并能明显增强脾细胞IgG分泌能力.这提示,悬吊应激可导致雌性小鼠生殖内分泌功能紊乱以及免疫功能下降,口服LW-AFC具有明显调节作用,对应激所致生殖内分泌功能紊乱以及免疫功能下降具有潜在防治作用.     

Endocrine-committed progenitor cells retain their differentiation potential in the absence of neurogenin-3 expression

Neurogenin-3 (ngn-3) expression is critical for endocrine development in the developing pancreas. We found that when ngn-3 was inhibited in an E11.5 pancreas, using either morpholino antisense or siRNA, it led to a significant decrease in endocrine differentiation after seven days in culture. Endocrine differentiation was rescued when ngn-3 inhibition was withdrawn after three days of culture, suggesting that the embryonic pancreas retains progenitor cells with the ability to differentiate into endocrine cell types when ngn-3 expression recurs. To determine whether the rescue phenomenon observed after withdrawing ngn-3 antisense treatment was the result of the original endocrine-committed cells reinitiating endocrine differentiation, or was instead due to new recruitment of later progenitor cells, we blocked ngn-3 expression for only the last four days of a seven-day culture. Here, insulin-positive differentiation was slightly reduced, but there was a normal number of glucagon-positive cells. In addition, there was an increase in SOX9-positive cells in ngn-3 inhibited, as well as in ngn-3 rescued pancreata, with a significant proportion of these SOX9-positive cells co-localized with DBA, an early ductal marker. This increased number of cells with co-localization of SOX9 and DBA could indicate an increased number of endocrine progenitor cells.     

Activated Notch1 prevents differentiation of pancreatic acinar cells and attenuate endocrine development

Mice carrying loss-of-function mutations in certain Notch pathway genes display increased and accelerated pancreatic endocrine development, leading to depletion of precursor cells followed by pancreatic hypoplasia. Here, we have investigated the effect of expressing a constitutively active form of the Notch1 receptor (Notch1(ICD)) in the developing pancreas using the pdx1 promoter. At e10.5 to e12.5, we observe a disorganized pancreatic epithelium with reduced numbers of endocrine cells, confirming a repressive activity of Notch1 upon the early differentiation program. Subsequent branching morphogenesis is impaired and the pancreatic epithelium forms cyst-like structures with ductal phenotype containing a few endocrine cells but completely devoid of acinar cells. The endocrine cells that do form show abnormal expression of cell type-specific markers. Our observations show that sustained Notch1 signaling not only significantly represses endocrine development, but also fully prevents pancreatic exocrine development, suggesting that a possible role of Notch1 is to maintain the undifferentiated state of common pancreatic precursor cells.     

Laryngeal endocrine cells: topographic distribution and adaptation to chronic hypercapnic hypoxia

The morphology, topographic distribution, effects of denervation, and exposure to hypercapnic hypoxia of endocrine cells were examined in rat larynx. The endocrine cells, which were immunoreactive for protein gene product 9.5 (PGP 9.5) and calcitonin gene-related peptide (CGRP), were observed within the epithelial layer of the laryngeal cavity and in the laryngeal gland, while solitary endocrine cells with apical and/or basal cytoplasmic processes appeared near the glottis. After denervation of the left cervical vagosympathetic trunk and the superior laryngeal nerve, the number of mucosal endocrine cells in the denervated side was not significantly different from that in the intact side. After exposure to hypercapnic hypoxia for 3 months, the number of endocrine cells with PGP 9.5 and CGRP was markedly increased. In conclusion, the secretion of laryngeal endocrine cells may be stimulated by CO2 rather than O2. Furthermore, the endocrine cells and the sensory and autonomic nervous system may regulate each other by an axon reflex mechanism. Endocrine cells appear to play a very important role in the local regulation of the laryngeal mucosa.     

Gastric mucosal cellular changes induced by indomethacin (NSAID) in male albino rats

Indomethacin (2 mg/100 g body weight), induces haemorrhagic gastric ulcers in albino rats. The incidence and severity of ulceration increased with starvation period. Indomethacin caused little or no effect on the cellular and the nuclear diameter of parietal and chief cells while reduction was observed in mucus and endocrine cells. The effect was enhanced with increased duration of starvation. Both mucous and endocrine cells decreased in their number after 72 hr of starvation. Thus prolonged starvation enhanced the gastric mucosal damage induced by indomethacin.     

内分泌疾病血浆氨基酸的模式

内分泌疾病血浆氨基酸的模式蒋滢,黄美英,何达纯ＰｌａｓｍａＦｒｅｅＡｍｉｎｏＡｃｉｄｉｎＥｎｄｏｃｒｉｎｅＤｉｓｅａｓｅｓ￥ＪｉａｎｇＹｉｎｇ;ＨｉｉａｎｇＭｅｉｙｉｎｇａｎｄＨｅＤａｃｈｕｎ（ＤｅｐａｒｔｍｅｎｔｏｆＢｉｏｃｈｅｍｉｓｔｒｙ,Ｓｕｚ...     

脂肪组织功能失调在动脉血栓相关疾病中的作用

肥胖与代谢综合征是传统心血管疾病的危险因素.多项临床研究表明,肥胖也会增加患血栓性疾病(如急性心肌梗死和脑卒中)的风险.脂肪组织与血小板反应性增加和高凝状态形成以及纤溶功能降低等存在着重要联系.脂肪组织还是一个高度活跃的内分泌器官,其表达和分泌具有重要功能的脂肪因子和脂质代谢物参与调控全身代谢.深入地了解脂肪组织的内分...     

Effect of acute hypoxia on the renin and erythropoietin activities of the blood serum in rats

A comparative study of renin and erythropoietin content in the blood serum of rats with "endocrine" kidneys and changes in their activity following the action of specific erythropoietic stimulus (4-hour hypoxia) has been conducted. The presence of "endocrine" kidneys increased renin and erythropoietin activity in such animals. Acute hypoxia produced further increase in erythropoietin titre in the blood serum, with renin remaining at the same level. Possible differences in the mechanisms of renin and erythropoietin biogenesis in the kidneys are considered.     

前列腺癌内分泌治疗现状

前列腺癌(prostatecancerPC)是欧美国家男性发病率最高的恶性肿瘤,近年来其在我国的发病率也逐年升高。雄激素在PC的发生、发展过程中扮演着重要的角色,所以内分泌治疗一直是前列腺癌研究领域的重点,但是其可能诱发激素非依赖型PC这也是临床医学面临的一大问题。本文就前列腺癌内分泌治疗的分类、作用机制、用药策略及临床效果等作一综述。     

PD-L1 Expression in Normal Endocrine Tissues Is Not Increased Despite High Incidence of PD-1 Inhibitor-Associated Endocrinopathies

ObjectiveTreatment with immune-checkpoint inhibitors often results in endocrine immune-related adverse events (irAEs), affecting the pituitary, thyroid, adrenal, and parathyroid glands and pancreas. The mechanism underlying the endocrine irAEs has not been fully elucidated, and it remains unclear why endocrine organs are so commonly affected. In the present study, we evaluated immunostaining patterns of programmed death-ligand 1 (PD-L1) in normal endocrine tissues to determine whether increased expression may explain the predilection of endocrinopathies in patients treated with programmed cell death-1 inhibitors.MethodsNormal formalin-fixed paraffin-embedded endocrine tissues (pituitary, thyroid, adrenal, pancreas, and parathyroid) were collected from our hospital’s pathology tissue archive. The tissues were assessed for membranous and cytoplasmic PD-L1 immunostaining using the Dako 22C3 pharmDx assay on an automated staining platform.ResultsWe examined 49 endocrine tissues, including 12 thyroid, 5 pancreatic, 17 adrenal, 5 parathyroid, and 10 pituitary samples. Samples with less than 1% membranous PD-L1–positive cells were considered negative, while those with more than 1% of PD-L1 membranous staining were considered positive. Immunostaining result of immune-related cells was also evaluated, considering the cytoplasmic PD-L1–positive cells with the same cutoff of 1%. None of the endocrine tissues demonstrated PD-L1 positivity higher than 1% in the relevant cells.ConclusionWhile our results do not suggest a role of PD-L1 expression in the pathogenesis of endocrine irAEs, they may serve as a basis for future studies further investigating the mechanisms of autoimmune, inflammatory, or malignant endocrine conditions.     

The Current Status of Preclinical Endocrine Education in U.S. Medical Schools

ObjectiveTo characterize the current landscape of preclinical medical endocrine education in U.S. allopathic medical schools.MethodsU.S. endocrine curriculum directors were asked to voluntarily complete a 16-question email survey surveying the status of endocrine preclinical education at their medical school.ResultsSixty-nine of 155 (45%) endocrine block director respondents completed the online survey between July 2021 and September 2021. A larger incoming class, a longer duration of the endocrine curriculum, and the offering of a separate endocrine curriculum (ie apart from the teaching of other organ systems) were each independently associated with an increased number of faculty teaching the course. Schools that used a gland-/organ-based curriculum only and those that used a combination of gland-/organ-based curriculum with topic-based curriculum differed significantly in their use of large lectures, small groups, and several curriculum components, including point of care glucose testing, continuous glucose monitoring, and insulin pumps.ConclusionThis survey study reports the current landscape of preclinical endocrine education in the United States and describes opportunities to improve interest in pursuing endocrinology as a career.     

Seasonal changes in testicular contents and plasma concentrations of androgens in the desert gerbil (Gerbillus gerbillus)

Gerbils were caught in the Béni-Abbès area (Algeria). Testicular endocrine activity was highest in spring (testicular wt 298 +/- 10 mg; seminal vesicle wt 603 +/- 62 mg; testicular testosterone and androstenedione content 9.2 +/- 1.7 and 0.5 +/- 0.1 ng/testis; plasma testosterone 832 +/- 200 pg/ml). Values decreased in summer, were lowest in late summer and in autumn (84 +/- 17 mg; 40 +/- 14 mg; 0.20 +/- 0.06 and 0.02 +/- 0.01 ng/testis; 228 +/- 54 pg/ml, respectively) and increased again in winter (December-January). The onset of testicular endocrine activity was concomitant with the lowest temperatures and the shortest photoperiod; it increased when temperatures and daylength were increasing and began to decline when temperatures and photoperiod were still maximal. These seasonal changes in the endocrine activity of the testis of the gerbil differ from those of the sand rat inhabiting the same area.