Somatostatin (SST) is an inhibitory polypeptide hormone that plays an important role in a variety of biological processes. Somatostatin receptor 2 (SSTR2) is the most widely expressed somatostatin receptor. However, the specific cell types expressing Sstr2 in the tissues have not been investigated. In this study, we detected the expression pattern of SSTR2 protein in mouse at different development stages, including the embryonic 15.5 days and the postnatal 1, 7, 15 days as well as 3 and 6 months, by multicolour immunofluorescence analyses. We found that Sstr2 was expressed in some specific cells types of several tissues, including the neuronal cells and astrocytes in the brain, the mesenchymal cells, the hematopoietic cells, the early hematopoietic stem cells, and the B cells in the bone marrow, the macrophages, the type Ⅱ alveolar epithelial cells, and the airway ciliated cells in the lung, the epithelial cells and the neuronal cells in the intestine, the hair follicle cells, the gastric epithelial cells, the hematopoietic stem cells and the nerve fibre in the spleen, and the tubular epithelial cells in the kidney. This study identified the specific cell types expressing Sstr2 in mouse at different developmental stages, providing new insights into the physiological function of SST and SSTR2 in several cell types.
Mice ; Animals ; Receptors, Somatostatin/metabolism* ; Hematopoietic Stem Cells/metabolism* ; Epithelial Cells

Adverse experiences in early life have long-lasting negative impacts on behavior and the brain in adulthood, one of which is sleep disturbance. As the corticotropin-releasing hormone (CRH)-corticotropin-releasing hormone receptor 1 (CRHR1) system and nucleus accumbens (NAc) play important roles in both stress responses and sleep-wake regulation, in this study we investigated whether the NAc CRH-CRHR1 system mediates early-life stress-induced abnormalities in sleep-wake behavior in adult mice. Using the limited nesting and bedding material paradigm from postnatal days 2 to 9, we found that early-life stress disrupted sleep-wake behaviors during adulthood, including increased wakefulness and decreased non-rapid eye movement (NREM) sleep time during the dark period and increased rapid eye movement (REM) sleep time during the light period. The stress-induced sleep disturbances were accompanied by dendritic atrophy in the NAc and both were largely reversed by daily systemic administration of the CRHR1 antagonist antalarmin during stress exposure. Importantly, Crh overexpression in the NAc reproduced the effects of early-life stress on sleep-wake behavior and NAc morphology, whereas NAc Crhr1 knockdown reversed these effects (including increased wakefulness and reduced NREM sleep in the dark period and NAc dendritic atrophy). Together, our findings demonstrate the negative influence of early-life stress on sleep architecture and the structural plasticity of the NAc, and highlight the critical role of the NAc CRH-CRHR1 system in modulating these negative outcomes evoked by early-life stress.
Animals ; Mice ; Corticotropin-Releasing Hormone/metabolism* ; Nucleus Accumbens/metabolism* ; Receptors, Corticotropin-Releasing Hormone/metabolism* ; Sleep ; Sleep Wake Disorders ; Stress, Psychological/complications*

It is well established that increased excitability of the presympathetic neurons in the hypothalamic paraventricular nucleus (PVN) during hypertension leads to heightened sympathetic outflow and hypertension. However, the mechanism underlying the overactivation of PVN presympathetic neurons remains unclear. This study aimed to investigate the role of endogenous corticotropin-releasing factor (CRF) on the excitability of presympathetic neurons in PVN using Western blot, arterial blood pressure (ABP) and renal sympathetic nerve activity (RSNA) recording, CRISPR/Cas9 technique and patch-clamp technique. The results showed that CRF protein expression in PVN was significantly upregulated in spontaneously hypertensive rats (SHRs) compared with normotensive Wistar-Kyoto (WKY) rats. Besides, PVN administration of exogenous CRF significantly increased RSNA, heart rate and ABP in WKY rats. In contrast, knockdown of upregulated CRF in PVN of SHRs inhibited CRF expression, led to membrane potential hyperpolarization, and decreased the frequency of current-evoked firings of PVN presympathetic neurons, which were reversed by incubation of exogenous CRF. Perfusion of rat brain slices with artificial cerebrospinal fluid containing CRF receptor 1 (CRFR1) blocker, NBI-35965, or CRF receptor 2 (CRFR2) blocker, Antisauvagine-30, showed that blocking CRFR1, but not CRFR2, hyperpolarized the membrane potential and inhibited the current-evoked firing of PVN presympathetic neurons in SHRs. However, blocking CRFR1 or CRFR2 did not affect the membrane potential and current-evoked firing of presympathetic neurons in WKY rats. Overall, these findings indicate that increased endogenous CRF release from PVN CRF neurons enhances the excitability of presympathetic neurons via activation of CRFR1 in SHRs.
Rats ; Animals ; Rats, Inbred SHR ; Paraventricular Hypothalamic Nucleus/physiology* ; Receptors, Corticotropin-Releasing Hormone/metabolism* ; Rats, Inbred WKY ; Corticotropin-Releasing Hormone/metabolism* ; Neurons/physiology* ; Hypertension ; Sympathetic Nervous System

Cortical GABAergic inhibitory neurons are composed of three major classes, each expressing parvalbumin (PV), somatostatin (SOM) and 5-hydroxytryptamine receptor 3A (Htr3a), respectively. Htr3a
Animals ; Interneurons/metabolism* ; Mice ; Neurons/metabolism* ; Parvalbumins/metabolism* ; Receptors, Serotonin, 5-HT3/genetics* ; Serotonin ; Somatostatin/metabolism*

Objective: To explore the effects of the mu-opioid receptor (MOR) in the paraventricular nucleus (PVN) on the ejaculatory behaviors of male rats and its potential mechanisms. METHODS: Male SD rats with normal ejaculation ability were mated with female ones in hormone-induced estrus. After bilateral PVN microinjection of D-Ala-2-Me-Phe-4-Gly-ol enkephalin (DAGO) or D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) with an inserted catheter, the male animals were observed for mount latency (ML), mount frequency (MF), intromission latency (IL), intromission frequency (IF), ejaculation latency (EL), ejaculation frequency (EF), post-ejaculation interval (PEI), and intromission ratio (IR). The lumbar sympathetic nerve activity (LSNA) of the rats was recorded using the PowerLab data acquisition hardware device, and the levels of norepinephrine (NE) in the peripheral plasma were measured by ELISA following microinjection of saline or different doses of DAGO or CTAP. RESULTS: Neither CTAP nor DGAO significantly affected the ML of the male rats (P > 0.05). DGAO remarkably increased IF (P < 0.01) and MF (P < 0.01), prolonged IL (P < 0.01), EL (P < 0.01) and PEI (P < 0.01), and reduced EF (P <0.01) and IR (P < 0.05). On the contrary, CTAP markedly decreased IF (P < 0.01) and MF (P < 0.01), shortened IL (P < 0.01), EL (P < 0.01) and PFI (P < 0.01), and elevated EF (P < 0.01) and IR (P < 0.01). Additionally, DAGO decreased LSNA in a dose-dependent manner and reduced the NE level in the peripheral plasma. CTAP, however, not only offset the effects of DAGO on LSNA, but also significantly increased LSNA. CONCLUSIONS MOR in PVN inhibits ejaculatory behaviors in male rats by weakening LSNA, which has provided some theoretical evidence for the use of highly selective opioids in the treatment of premature ejaculation.
Animals ; Ejaculation ; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-/pharmacology* ; Female ; Male ; Paraventricular Hypothalamic Nucleus/physiology* ; Peptide Fragments/pharmacology* ; Rats ; Rats, Sprague-Dawley ; Receptors, Opioid, mu/physiology* ; Somatostatin/pharmacology* ; Sympathetic Nervous System/physiology*

Pancreatic neuroendocrine tumors (pNETs) are rare neoplasms arising from the pancreatic islet of Langerhans and can be functioning or non-functioning based on the clinical symptoms caused by hormonal secretions. PNETs are the second most common tumor of the pancreas and represent 1–2% of all pancreatic neoplasms. The incidence of pNETs appears to be rising and the prognosis seems to be improving, likely due to the improved treatment options. Recent updates of the World Health Organization classification and grading separate pNETs into 2 broad categories according to the histopathologic criteria, including the Ki-67 proliferative index and mitotic counts: well-differentiated NET and poorly-differentiated neuroendocrine carcinoma (NEC). The classification also incorporates a new subcategory of well-differentiated high-grade NEC (grade 3) to the well-differentiated NET category. This new classification algorithm aims to improve the prediction of the clinical outcomes and survival and help clinicians select better therapeutic strategies for patient care and management. The treatment of advanced or metastatic pNETs may include surgical resection, liver-directed therapies, and/or systemic treatments. In unresectable patients, the goals of these therapies are to palliate the tumor-related symptoms and prolong the lifespan. Systemic therapy consists of the following broad modalities: somatostatin analogues, molecular targeted therapy, systemic chemotherapy, and peptide receptor radionuclide therapy. In conclusion, pNETs are diagnosed increasingly throughout the world, usually with metastatic disease and requiring systemic therapy. Each patient should be evaluated thoroughly and discussed individually by a multidisciplinary and dedicated NET-expert team, which might consider all treatment options, including ongoing clinical trials before selecting the appropriate treatment sequence.
Carcinoma, Neuroendocrine ; Classification ; Drug Therapy ; Humans ; Incidence ; Islets of Langerhans ; Molecular Targeted Therapy ; Neuroectodermal Tumors, Primitive ; Neuroendocrine Tumors ; Pancreas ; Pancreatic Neoplasms ; Patient Care ; Prognosis ; Receptors, Peptide ; Somatostatin ; World Health Organization

Animals ; Diethylhexyl Phthalate ; toxicity ; Female ; Ovary ; drug effects ; metabolism ; ultrastructure ; Rats, Sprague-Dawley ; Receptors, LH ; metabolism ; Receptors, LHRH ; metabolism ; Toxicity Tests

Methylphenidate (MPH) is the most preferred drug for treatment of the attention deficit hyperactivity disorder (ADHD). Here, we aimed to discuss the possible effects and mechanisms of MPH on precocious puberty (PP) via a case series with seven children who had normal body mass index. In this case series we evaluated seven children with ADHD, who had received MPH for at least 6 months (0.5 mg/kg/dose three times a day, maximum 60 mg) and admitted to Department of Pediatric Endocrinology with PP symptoms. The mean age was 8.16 years. Basal hormonal levels (luteinizing hormone [LH], follicle stimulating hormone, and estrogen/testosterone) were within normal range. Results of LH-releasing hormone stimulation tests demonstrated central pubertal responses. Glutamine, dopamine and noradrenaline are most important excitatory neurotransmitters that have a role at the beginning of puberty. The effect of MPH, cumulating dopamine and noradrenaline in the synaptic gap could be associated with the acceleration of puberty with the excitatory effect of dopamine’s gonadotropin-releasing hormone (GnRH) release, excitatory effect of noradrenaline’s GnRH release and the disappearance of GnRH receptor expression suppressor effect on prolactin disinhibitory effect.
Acceleration ; Adolescent ; Attention Deficit Disorder with Hyperactivity ; Body Mass Index ; Child ; Dopamine ; Endocrinology ; Follicle Stimulating Hormone ; Glutamine ; Gonadotropin-Releasing Hormone ; Humans ; Methylphenidate ; Neurotransmitter Agents ; Norepinephrine ; Prolactin ; Puberty ; Puberty, Precocious ; Receptors, LHRH ; Reference Values

Radiomics handles imaging biomarker from high-throughput feature extraction through complex pattern recognition that is difficult for human to process. Recent medical paradigms are rapidly changing to personalized medicine, including molecular targeted therapy, immunotherapy, and theranostics, and the importance of biomarkers for these is growing day by day. Even though biopsy continues to gold standard for tumor assessment in personalized medicine, imaging is expected to complement biopsy because it allows whole tumor evaluation, whole body evaluation, and non-invasive and repetitive evaluation. Radiomics is known as a useful method to get imaging biomarkers related to intratumor heterogeneity in molecular targeted therapy as well as one-size-fits-all therapy. It is also expected to be useful in new paradigms such as immunotherapy and somatostatin receptor (SSTR) or prostate-specific membrane antigen (PSMA)-targeted theranostics. Radiomics research should move to multimodality (CT, MR, PET, etc.), multicenter, and prospective studies from current single modality, single institution, and retrospective studies. Image-quality harmonization, intertumor heterogeneity, and integrative analysis of information from different scales are thought to be important keywords in future radiomics research. It is clear that radiomics will play an important role in personalized medicine.
Biomarkers ; Biopsy ; Complement System Proteins ; Humans ; Immunotherapy ; Membranes ; Methods ; Molecular Targeted Therapy ; Population Characteristics ; Precision Medicine ; Prospective Studies ; Receptors, Somatostatin ; Retrospective Studies ; Theranostic Nanomedicine ; Weights and Measures

Immunoglobulin G4 (IgG4)–related diseases are a spectrum of systemic inflammatory conditions of unknown etiology, which are characterized by infiltration of tissues by IgG4 plasma cells and sclerosing inflammation (Cheuk and Chan Adv Anat Pathol 17:303-32, 2010). Although this condition was initially described in relation to autoimmune pancreatitis, now it has been reported in almost every organ system of body (Zen and Nakanuma Am J Surg Pathol 34:1812-9, 2010, Masaki et al. Ann Rheuma Dis 68:1310-5, 2009). Orbital involvement by IgG4 disease can involve extraocular muscles (EOM), lacrimal glands, conjunctiva, eyelids, infraorbital nerve, orbital fat, and nasolacrimal system (McNab and McKelvie. Ophthal Plast Reconstr Surg 31:167-78, 2015, Katsura et al. Neuroradiology 54:873-82, 2012). The basis of using ⁶⁸Ga-DOTANOC PET/CT in IgG4 orbital disease is the known expression of somatostatin receptors in chronic inflammatory cells (Cuccurullo et al. Indian J Radiol Imaging 27:509-16, 2017) and also avidity shown previously in other IgG4-related diseases (Cheng et al. Clin Nucl Med 43:773-6, 2018).
Conjunctiva ; Eyelids ; Immunoglobulin G ; Immunoglobulins ; Inflammation ; Lacrimal Apparatus ; Muscles ; Orbit ; Orbital Diseases ; Pancreatitis ; Plasma Cells ; Positron-Emission Tomography and Computed Tomography ; Receptors, Somatostatin