Progress in salivary glands: Endocrine glands with immune functions.

The production and secretion of saliva is an essential function of the salivary glands. Saliva is a complicated liquid with different functions, including moistening, digestion, mineralization, lubrication, and mucosal protection. This review focuses on the mechanism and neural regulation of salivary secretion, and saliva is secreted in response to various stimuli, including odor, taste, vision, and mastication. The chemical and physical properties of saliva change dynamically during physiological and pathophysiological processes. Moreover, the central nervous system modulates salivary secretion and function via various neurotransmitters and neuroreceptors. Smell, vision, and taste have been investigated for the connection between salivation and brain function. The immune and endocrine functions of the salivary glands have been explored recently. Salivary glands play an essential role in innate and adaptive immunity and protection. Various immune cells such as B cells, T cells, macrophages, and dendritic cells, as well as immunoglobins like IgA and IgG have been found in salivary glands. Evidence supports the synthesis of corticosterone, testosterone, and melatonin in salivary glands. Saliva contains many potential biomarkers derived from epithelial cells, gingival crevicular fluid, and serum. High level of matrix metalloproteinases and cytokines are potential markers for oral carcinoma, infectious disease in the oral cavity, and systemic disease. Further research is required to monitor and predict potential salivary biomarkers for health and disease in clinical practice and precision medicine.

Whole-body analysis of TRPML3 (MCOLN3) expression using a GFP-reporter mouse model reveals widespread expression in secretory cells and endocrine glands.

TRPML3 (mucolipin 3, MCOLN3) is an endolysosomal cation channel belonging to the TRPML subfamily of transient receptor potential channels. Gain-of-function mutations in the Trpml3 gene cause deafness, circling behavior and coat color dilution in mice due to cell death of TRPML3-expressing hair cells of the inner ear or skin melanocytes, respectively. Furthermore, TRPML3 was found to play a role in the long term survival of cochlear hair cells (its absence contributing to presbycusis), in specialized giant lysosomes that neonatal (birth to weaning) enterocytes used for the uptake and digestion of maternal milk nutrients, and in the expulsion of exosome-encased bacteria such as uropathogenic E. coli, infecting bladder epithelial cells. Recently, TRPML3 was found to be expressed at high levels in alveolar macrophages and loss of TRPML3 results in a lung emphysema phenotype, confirmed in two independently engineered Trpml3 knockout lines. TRPML3 is not ubiquitously expressed like its relative TRPML1 and thus cellular expression of TRPML3 on a whole-tissue level remains, with the exceptions mentioned above, largely elusive. To overcome this problem, we generated a τGFP reporter mouse model for TRPML3 and compared expression data obtained from this model by immunofluorescence on tissue sections with immunohistochemistry using TRPML3 antibodies and in situ hybridization. We thus uncovered expression in several organs and distinct cell types. We confirmed TRPML3 expression in both neonatal and adult alveolar macrophages, in melanocytes of hair follicles and glabrous skin, in principle cells of the collecting duct of the neonatal and adult kidney, and in olfactory sensory neurons of the olfactory epithelium, including its fibres protruding to the glomeruli of the olfactory bulb. Additionally, we localized TRPML3 in several glands including parathyroid, thyroid, salivary, adrenal, and pituitary gland, testes and ovaries, suggestive of potential roles for the channel in secretion or uptake of different hormones.

Histological and electrophysiological evidence on the safe operation of a sharp-tip multimodal optrode during infrared neuromodulation of the rat cortex.

Infrared neuromodulation is an emerging technology in neuroscience that exploits the inherent thermal sensitivity of neurons to excite or inhibit cellular activity. Since there is limited information on the physiological response of intracortical cell population in vivo including evidence on cell damage, we aimed to create and to validate the safe operation of a microscale sharp-tip implantable optrode that can be used to suppress the activity of neuronal population with low optical power continuous wave irradiation. Effective thermal cross-section and electric properties of the multimodal microdevice was characterized in bench-top tests. The evoked multi-unit activity was monitored in the rat somatosensory cortex, and using NeuN immunocytochemistry method, quantitative analysis of neuronal density changes due to the stimulation trials was evaluated. The sharp tip implant was effectively used to suppress the firing rate of neuronal populations. Histological staining showed that neither the probe insertion nor the heating protocols alone lead to significant changes in cell density in the close vicinity of the implant with respect to the intact control region. Our study shows that intracortical stimulation with continuous-wave infrared light at 1550 nm using a sharp tip implantable optical microdevice is a safe approach to modulate the firing rate of neurons.

[Characterization of Endocrine Glands Involved in Erdheim-Chester Disease].

Objective To investigate the clinical and imaging characteristics of endocrine glands involved in Erdheim-Chester disease (ECD).Methods A retrospective analysis was performed on 48 ECD cases pathologically diagnosed from January 2014 to October 2020 in Peking Union Medical College Hospital,including 22 cases of endocrine gland involvement.The clinical,imaging,and pathological characteristics were summarized. Results Pituitary was involved in 17 cases (17/48,35.4%),adrenal gland in 8 cases (8/48,16.7%),and both pituitary and adrenal gland in 3 cases (3/48,6.25%).The most common symptom in patients with pituitary involvement was central diabetes insipidus (13/17,76.5%),and the T1-weighted imaging showed posterior pituitary hypersignal disappearance,pituitary stalk thickening,and abnormally enhanced pituitary nodules.The most common symptom in patients with adrenal gland involvement was adrenal function reduction (3/8,37.5%),and the CT scanning showed diffuse thickening of adrenal glands.BRAF V600E mutation was positive in 13 (13/22,59.1%) cases with ECD involving endocrine glands.Conclusion Pituitary and adrenal glands are the most common sites of ECD involving endocrine glands.A definite diagnosis can be achieved by combining clinical,imaging,and pathological characteristics for timely treatment.

Endocrine and metabolic complications of COVID-19: lessons learned and future prospects.

Coronavirus disease 2019 (COVID-19) is well known for its respiratory complications; however, it can also cause extrapulmonary manifestations, including cardiovascular, thrombotic, renal, gastrointestinal, neurologic, and endocrinological symptoms. Endocrinological complications of COVID-19 are rare but can considerably impact the outcome of the patients. Moreover, preexisting endocrinologic disorders can affect the severity of COVID-19. Thyroid, pancreas, adrenal, neuroendocrine, gonadal, and parathyroid glands are the main endocrinologic organs that can be targeted by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Endocrinological complications of COVID-19 are rare but can significantly deteriorate the patients' prognosis. Understanding the interaction between COVID-19 and the endocrine system can provide a potential treatment option to improve the outcome of COVID-19. In this article, we aim to review the short-term and long-term organ-based endocrinological complications of COVID-19, the pathophysiology, the influence of each complication on COVID-19 prognosis, and potential therapeutic interventions based on current published data. Moreover, current clinical trials of potential endocrinological interventions to develop therapeutic strategies for COVID-19 have been discussed.

Cell Networks in Endocrine/Neuroendocrine Gland Function.

Reproduction, growth, stress, and metabolism are determined by endocrine/neuroendocrine systems that regulate circulating hormone concentrations. All these systems generate rhythms and changes in hormone pulsatility observed in a variety of pathophysiological states. Thus, the output of endocrine/neuroendocrine systems must be regulated within a narrow window of effective hormone concentrations but must also maintain a capacity for plasticity to respond to changing physiological demands. Remarkably most endocrinologists still have a "textbook" view of endocrine gland organization which has emanated from 20th century histological studies on thin 2D tissue sections. However, 21st -century technological advances, including in-depth 3D imaging of specific cell types have vastly changed our knowledge. We now know that various levels of multicellular organization can be found across different glands, that organizational motifs can vary between species and can be modified to enhance or decrease hormonal release. This article focuses on how the organization of cells regulates hormone output using three endocrine/neuroendocrine glands that present different levels of organization and complexity: the adrenal medulla, with a single neuroendocrine cell type; the anterior pituitary, with multiple intermingled cell types; and the pancreas with multiple intermingled cell types organized into distinct functional units. We give an overview of recent methodologies that allow the study of the different components within endocrine systems, particularly their temporal and spatial relationships. We believe the emerging findings about network organization, and its impact on hormone secretion, are crucial to understanding how homeostatic regulation of endocrine axes is carried out within endocrine organs themselves. © 2022 American Physiological Society. Compr Physiol 12:3371-3415, 2022.

Ethylene oxide derived glycol ethers: A review of the alkyl glycol ethers potential to cause endocrine disruption.

The 'ethylene glycol ethers' (EGE) are a broad family of solvents and hydraulic fluids produced through the reaction of ethylene oxide and a monoalcohol. Certain EGE derived from methanol and ethanol are well known to cause toxicity to the testes and fetotoxicity and that this is caused by the common metabolites methoxy and ethoxyacetic acid, respectively. There have been numerous published claims that EGE fall into the category of 'endocrine disruptors' often without substantiated evidence. This review systematically evaluates all of the available and relevant in vitro and in vivo data across this family of substances using an approach based around the EFSA/ECHA 2018 guidance for the identification of endocrine disruptors. The conclusion reached is that there is no significant evidence to show that EGE target any endocrine organs or perturb endocrine pathways and that any toxicity that is seen occurs by non-endocrine modes of action.

Loss of imprinting of the Igf2-H19 ICR1 enhances placental endocrine capacity via sex-specific alterations in signalling pathways in the mouse.

Imprinting control region (ICR1) controls the expression of the Igf2 and H19 genes in a parent-of-origin specific manner. Appropriate expression of the Igf2-H19 locus is fundamental for normal fetal development, yet the importance of ICR1 in the placental production of hormones that promote maternal nutrient allocation to the fetus is unknown. To address this, we used a novel mouse model to selectively delete ICR1 in the endocrine junctional zone (Jz) of the mouse placenta (Jz-ΔICR1). The Jz-ΔICR1 mice exhibit increased Igf2 and decreased H19 expression specifically in the Jz. This was accompanied by an expansion of Jz endocrine cell types due to enhanced rates of proliferation and increased expression of pregnancy-specific glycoprotein 23 in the placenta of both fetal sexes. However, changes in the endocrine phenotype of the placenta were related to sexually-dimorphic alterations to the abundance of Igf2 receptors and downstream signalling pathways (Pi3k-Akt and Mapk). There was no effect of Jz-ΔICR1 on the expression of targets of the H19-embedded miR-675 or on fetal weight. Our results demonstrate that ICR1 controls placental endocrine capacity via sex-dependent changes in signalling.

COVID-19 autopsy cases: detection of virus in endocrine tissues.

PURPOSE: The SARS-CoV-2 genome has been detected in a variety of human samples including blood, urine, semen, and faeces. However, evidence of virus presence in tissues other than lung are limited. METHODS: We investigated whether SARS-CoV-2 could be detected in 50 autoptic specimens of endocrine organs from 29 patients who died of COVID-19. RESULTS: The virus was detected in 25 specimens including ten abdominal subcutaneous adipose tissue samples (62%), six testes (67%), and nine thyroid (36%) samples. The analysis of multiple endocrine organ samples obtained from the same patients showed that, in virus-positive cases, the viral genome was consistently detected in all but two matched specimens. CONCLUSION: Our findings show that the virus spread into endocrine organs is a common event in severe cases. Further studies should assess the rate of the phenomenon in clinically mild cases. The potential long-term effects of COVID-19 on endocrine functions should be taken into consideration.

The heart, an endocrine gland: Natriuretic peptides.

The natriuretic peptide family consists of three biologically active peptides: atrial natriuretic peptide (ANP), brain (or B-type) natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). ANP and BNP, secreted by the heart, act as cardiac hormones, whereas CNP is an endothelial peptide. The aim of this manuscript is to review the production, action mechanisms, effects and clinical applications of natriuretic peptides.

Corpuscles of Stannius development requires FGF signaling.

The corpuscles of Stannius (CS) represent a unique endocrine organ of teleostean fish that secrets stanniocalcin-1 (Stc1) to maintain calcium homeostasis. Appearing at 20-25 somite stage in the distal zebrafish pronephros, stc1-expressing cells undergo apical constriction, and are subsequently extruded to form a distinct gland on top of the distal pronephric tubules at 50 â€‹h post fertilization (hpf). Several transcription factors (e.g. Hnf1b, Irx3b, Tbx2a/b) and signaling pathways (e.g. Notch) control CS development. We report now that Fgf signaling is required to commit tubular epithelial cells to differentiate into stc1-expressing CS cells. Inhibition of Fgf signaling by SU5402, dominant-negative Fgfr1, or depletion of fgf8a prevented CS formation and stc1 expression. Ablation experiments revealed that CS have the ability to partially regenerate via active cell migration involving extensive filopodia and lamellipodia formation. Activation of Wnt signaling curtailed stc1 expression, but had no effect on CS formation. Thus, our observations identify Fgf signaling as a crucial component of CS cell fate commitment.

Analysis of the proportion and clinical characteristics of obstructive sleep apnea in women with polycystic ovary syndrome.

PURPOSE: To investigate the proportion and clinical characteristics of obstructive sleep apnea (OSA) in Chinese patients with polycystic ovarian syndrome (PCOS) through home sleep apnea test (HSAT) and to evaluate the reproductive endocrine and metabolic characteristics in these patients. METHODS: The study was a cross-sectional analysis of infertile PCOS patients who underwent sleep respiratory monitoring between January and December 2019 at Peking University Third Hospital Reproductive Medical Center and respiratory and critical care medicine department. The prevalence of OSA, body mass index (BMI), menstruation, reproductive endocrine, and metabolic characteristics were collected in patients with PCOS. Logistic regression was performed to identify significant relationships among these factors and OSA. RESULTS: Amont 328 patients with PCOS, the prevalence of OSA was 40% (131/328), and six cases (5%) were severe. Univariate analysis showed that BMI and blood pressure were significantly higher in patients with OSA than in those without OSA (P < 0.05), whereas the anti-Mullerian hormone was lower than that in patients without OSA. In terms of glucose and lipid metabolism, the glycosylated hemoglobin (HbA1c), fasting plasma glucose, and fasting insulin levels were significantly higher in patients with PCOS and comorbid OSA than in those without OSA (all P < 0.05). Patients with OSA also had higher triglyceride, low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein levels and lower high-density lipoprotein cholesterol levels (P < 0.05). Logistic regression analysis revealed that higher BMI, elevated serum testosterone, and decreased high-density lipoprotein cholesterol (HDL-C) are correlated with occurrence of OSA (P < 0.05). CONCLUSION: OSA in patients with PCOS was associated with multiple alterations in indexes of reproductive endocrine and metabolic disorders.

The Determination of Efficacy of CircuCare on Blood Circulation and Metabolism: An Animal Model Study.

OBJECTIVES: To determine whether feeding CircuCare to rats improves blood circulation, metabolism, immune regulation, endocrine activity, and oxidative stress. METHODS: 28 eight-week-old male Sprague-Dawley rats were evenly randomized into control and experimental groups. The control group was fed with ordinary drinking water, while the experimental group was fed with CircuCare at a daily dose of 93.75 mg per 300 g of body weight over eight weeks. Both groups were subjected to a swimming test, and blood samples were taken to observe any variations in various biochemical parameters before and after the test. Key Findings. The experimental group's mean swimming exhaustion duration was 53.2% longer and had a significantly higher lactic acid removal ratio. Their mean prostaglandin E2 level and mean glucose, cortisol, and glutathione level (30 minutes after swimming test) were also significantly higher. No undesirable impacts from CircuCare relating to general blood biochemistry values and bone mineral density were reported. CONCLUSIONS: The present results show that CircuCare can be safely used to increase stamina and exercise capability, expedite the metabolism of lactic acid, accelerate muscle repair, and promote the antioxidant activity of cells in rats.

Neoplasia endócrina múltipla tipo 2A: relato de caso / Multiple endocrine neoplasia type 2A: a case report / Neoplasia endocrina múltiple tipo 2A: reporte de caso

As neoplasias endócrinas múltiplas (NEM) são síndromes genéticas autossômicas dominantes implicadas no desenvolvimento de neoplasias benignas ou malignas, envolvendo ao menos duas glândulas endócrinas. Entre seus subtipos, está a NEM2A, que consiste em carcinoma medular de tireoide (CMT), feocromocitoma e hiperparatireoidismo. Este texto apresente o relato de caso de um paciente de 40 anos, previamente hígido, que passou a apresentar episódios de cefaleia associada a sudorese profusa, vômitos e taquicardia. Evoluiu com distensão abdominal intensa após alimentação por via oral, perda ponderal, desnutrição, astenia, obstipação, humor deprimido e picos pressóricos. Exames laboratoriais evidenciaram alterações dos hormônios tireoidianos, PTH e hormônios da adrenal. Foi levantada a suspeita clínica de NEM2A, posteriormente corroborada pelos diagnósticos anatomopatológicos de feocromocitoma e CMT, associados à presença de hiperparatireoidismo. Foi possível concluir que, a despeito de sua baixa prevalência na população geral, a NEM é uma síndrome clínica de grande relevância, tendo em vista os impactos para os pacientes e famílias acometidas. Dessa forma, é necessário que os profissionais de saúde tenham conhecimento acerca da síndrome e que o Sistema Único de Saúde (SUS) esteja apto a assistir aos pacientes portadores de NEM, possibilitando diagnóstico precoce e tratamento adequado.

Multiple endocrine neoplasias (MEN) are dominant autosomal genetic syndromes involved in the development of benign or malignant tumors in at least two endocrine glands. MEN2A is one of its subtypes, which consists of medullary thyroid carcinoma (MTC), pheochromocytoma, and hyperparathyroidism. This study reports the case of a healthy 40-year-old male patient presenting with episodes of headache associated with profuse sweating, vomiting, and tachycardia. The patient evolved with severe abdominal distension after oral feeding, weight loss, malnutrition, asthenia, constipation, depressed mood, and pressure peaks. Laboratory tests showed abnormalities in thyroid, parathyroid (PTH), and adrenal hormones ­ thus raising the hypothesis of MEN2A, which was later corroborated by the histological diagnosis of pheochromocytoma and MTC, associated with hyperparathyroidism. The results indicate that, despite its low prevalence in the general population, MEN has a great impact on affected patients and families, thus being a relevant clinical syndrome. For enabling early diagnosis and adequate treatment, health professionals must be familiarized with such a condition, and the Brazilian Unified Health System (SUS) must be able to assist affected patients.

Las neoplasias endocrinas múltiples (NEM) son síndromes genéticos autosómicos dominantes involucrados en el desarrollo de neoplasias benignas o malignas, que afectan al menos dos glándulas endocrinas. Entre sus subtipos se encuentra NEM2A, que consiste en carcinoma medular de tiroides (CMT), feocromocitoma e hiperparatiroidismo. Este es un reporte de caso de un paciente de 40 años de edad, previamente sano, que comenzó a presentar episodios de cefalea asociada a sudoración profusa, vómitos y taquicardia. Evolucionó con distensión abdominal severa después de alimentarse, pérdida de peso, desnutrición, astenia, estreñimiento, estado de ánimo deprimido y picos de presión. Las pruebas de laboratorio mostraron alteraciones en las hormonas tiroideas, PTH y hormonas suprarrenales. Se planteó la hipótesis de MEN2A, posteriormente corroborada por el diagnóstico anatomopatológico de feocromocitoma y CMT, asociado a hiperparatiroidismo. Se pudo concluir que, a pesar de su baja prevalencia en la población general, el NEM es un síndrome clínico de gran relevancia, dado el impacto que tiene en los pacientes y familiares afectados. Por tanto, es necesario que los profesionales sanitarios tengan conocimiento sobre el síndrome y que el Sistema Único de Salud (SUS) sea capaz de asistir a los pacientes con NEM, posibilitándoles diagnóstico precoz y tratamiento adecuado.

Histone Variant H2A.J Is Enriched in Luminal Epithelial Gland Cells.

H2A.J is a poorly studied mammalian-specific variant of histone H2A. We used immunohistochemistry to study its localization in various human and mouse tissues. H2A.J showed cell-type specific expression with a striking enrichment in luminal epithelial cells of multiple glands including those of breast, prostate, pancreas, thyroid, stomach, and salivary glands. H2A.J was also highly expressed in many carcinoma cell lines and in particular, those derived from luminal breast and prostate cancer. H2A.J thus appears to be a novel marker for luminal epithelial cancers. Knocking-out the H2AFJ gene in T47D luminal breast cancer cells reduced the expression of several estrogen-responsive genes which may explain its putative tumorigenic role in luminal-B breast cancer.

Body-fat sensor triggers ribosome maturation in the steroidogenic gland to initiate sexual maturation in Drosophila.

Fat stores are critical for reproductive success and may govern maturation initiation. Here, we report that signaling and sensing fat sufficiency for sexual maturation commitment requires the lipid carrier apolipophorin in fat cells and Sema1a in the neuroendocrine prothoracic gland (PG). Larvae lacking apolpp or Sema1a fail to initiate maturation despite accruing sufficient fat stores, and they continue gaining weight until death. Mechanistically, sensing peripheral body-fat levels via the apolipophorin/Sema1a axis regulates endocytosis, endoplasmic reticulum remodeling, and ribosomal maturation for the acquisition of the PG cells' high biosynthetic and secretory capacity. Downstream of apolipophorin/Sema1a, leptin-like upd2 triggers the cessation of feeding and initiates sexual maturation. Human Leptin in the insect PG substitutes for upd2, preventing obesity and triggering maturation downstream of Sema1a. These data show how peripheral fat levels regulate the control of the maturation decision-making process via remodeling of endomembranes and ribosomal biogenesis in gland cells.

Placental endocrine function shapes cerebellar development and social behavior.

Compromised placental function or premature loss has been linked to diverse neurodevelopmental disorders. Here we show that placenta allopregnanolone (ALLO), a progesterone-derived GABA-A receptor (GABAAR) modulator, reduction alters neurodevelopment in a sex-linked manner. A new conditional mouse model, in which the gene encoding ALLO's synthetic enzyme (akr1c14) is specifically deleted in trophoblasts, directly demonstrated that placental ALLO insufficiency led to cerebellar white matter abnormalities that correlated with autistic-like behavior only in male offspring. A single injection of ALLO or muscimol, a GABAAR agonist, during late gestation abolished these alterations. Comparison of male and female human preterm infant cerebellum also showed sex-linked myelination marker alteration, suggesting similarities between mouse placental ALLO insufficiency and human preterm brain development. This study reveals a new role for a placental hormone in shaping brain regions and behaviors in a sex-linked manner. Placental hormone replacement might offer novel therapeutic opportunities to prevent later neurobehavioral disorders.

Inflammatory repercussions in female steroid responsive glands after perinatal exposure to bisphenol A and 17-ß estradiol.

The mammary gland (MG) and female prostate are plastic reproductive organs which are highly responsive to hormones. Thus, endocrine disruptors, such as bisphenol A (BPA) and exogenous estrogens, negatively affect glandular homeostasis. In addition to previously described alterations, changes in inflammatory markers expression also trigger the development of a microenvironment that contributes to tumor progression. The current work aimed to evaluate the inflammatory responses of the MG and prostate gland to BPA (50 µg/kg) and 17-ß estradiol (35 µg/kg) exposure during the perinatal window of susceptibility. The results showed that at 6 months of age there was an increase in the number of phospho-STAT3 (P-STAT3) positive cells in the female prostate from animals perinatally exposed to 50 µg/kg BPA daily. In addition, the number of macrophages increased in these animals in comparison with nonexposed animals, as shown by the F4/80 marker. Despite an increase in the incidence of lobuloalveolar and intraductal hyperplasia, the MG did not show any difference in the expression of the four inflammatory markers evaluated: tumor necrosis factor-α, COX-2, P-STAT3, and F4/80. Analysis of both glands from the same animal led to the conclusion that exposure to endocrine disruptors during the perinatal window of susceptibility leads to different inflammatory responses in different reproductive organs. As the prostate is more susceptible to these inflammatory mechanisms, it is reasonable to affirm that possible neoplastic alterations in this organ are related to changes in the inflammatory pattern of the stroma, a characteristic that is not evident in the MG.