Pars Intermedia Research Articles

Immunohistochemical study of gonadotropin-releasing hormone and somatolactin during induced spawning of Liza ramada

Introduction: Gonadotropin releasing hormone (GnRH) is a crucial regulator of gonadal development and reproduction in fish. In addition, it is a possible secretagogue of somatolactin (SL) in teleosts. Little is known about the possible association of GnRH and SL during reproduction of Liza ramada.Aim of the work: The present study was designed to investigate the GnRH and SL immunoreactivities during inducing the final stages of maturation, ovulation and spawning of Liza ramada; to assess the possible actions of these hormones on sexual maturation and spawning of teleosts.Materials and Methods: Histological and immunohistochemical techniques were generally performed to describe the immunoreactivity of both GnRH and SL during ovarian maturation and spawning of Liza ramada.Results: The mammalian GnRH (mGnRH) cell bodies were observed in the medulla oblongata. However, SL-immunoreactive (-IR) cells were detected in the pars intermedia (PI) of the pituitary gland. The GnRH-IR nerve terminals are in close contact with SL-IR pituitary cells. Importantly, the activity of both mGnRH-IR neurons and SL-IR pituitary cells were increased as reflected with the increased cell number and size during sexual maturation and spawning. The activity of these cells was more pronounced as indicated by the increased cells number and size with more immunoreactivity in pre-spawning female. During final maturation and spawning, mGnRH-IR neurons and SL cells showed an increase in the secretory activity as reflected by their small sizes, vacuolated appearance and weak immunoreactivity.Conclusions: Taken together, these findings suggest that the close contact of mGnRH-IR terminals with SL-IR cells in the pituitary, together with the concomitant changes of GnRH and SL immunoreactivity in response to progress in the reproductive events suggest that GnRH may regulate SL release and the regulation of reproductive activity in L. ramada.

Pharmacokinetics and Pharmacodynamics of Oral Pergolide Mesylate In Horses With Pituitary Pars Intermedia Dysfunction

Pharmacokinetics and Pharmacodynamics of Oral Pergolide Mesylate In Horses With Pituitary Pars Intermedia Dysfunction

Laboratory diagnosis of the endocrine causes of laminitis

Equine metabolic syndrome (EMS) and/or pituitary pars intermedia dysfunction (PPID) are identified in most horses with laminitis. In some cases of laminitis, a diagnosis of EMS or PPID is obvious from clinical signs but in others laboratory testing can be helpful to confirm the diagnosis, assess laminitis risk and monitor treatment responses. Laboratory methods for assessing PPID and EMS have their limitations but recent clinical research from a number of groups has resulted in advances — this article aims to summarise recent developments and how they can be applied in practice.

Evaluation of size and morphology of sella turcica

Introduction: One of the most commonly used cranial landmarks for cephalometric tracing is sella point. Sella point is located in the centre of sella turcica with the turcica housing the pituitary gland in the crainal base. This gland lies within the pituitary fossa and consists of the anterior lobe, the intermediate lobe and the posterior lobe. Any abnormality or pathology in the gland could manifest from an altered shape of the sella turcica to a disturbance in the regulations of glandular hormones, prolactin, growth hormones, thyroid – stimulating hormone, follicular stimulating hormone, etc. Aims and Objective: The aim of the study was to determine difference in dimensions of sella turcica in different age groups and genders, that could assist in detection and evaluation of pathological conditions. Materials and Method: Lateral cephalometric radiographs of 100 individuals (50 males and 50 females) were evaluated retrospectively. The radiographs were divided into two groups according to the subject’s age: pre-pubertal (

Fatigue in Multiple Sclerosis: Is it related to cytokines and hypothalamic-pituitary-adrenal axis?

BackgroundFatigue is a common symptom of Multiple Sclerosis (MS) that diminishes the quality of life of patients, but its exact mechanism remains poorly understood. There is not a generally adopted scale to determine MS fatigue. Studies that investigated physiopathology of fatigue symptom have shown dysregulation of hypothalamic-pituitaryadrenal (HPA) axis. In the current study, we aimed to compare the results obtained with two separate scales, namely the Fatigue Severity Scale (FSS) and the Neurological Fatigue Index-Multiple Sclerosis (NFI-MS), and assess the relationship between fatigue and serum IL-1β, TNF-α, IL-35, IL-2, IL-10, ACTH, cortisol, α-MSH, β-MSH, γ-MSH and CLIP (Corticotropinlike intermediate lobe peptide) in MS patients categorized as fatigued and non-fatigued on the basis of FSS scores. MethodsFor the study, a total of 54 (29 females, 25 males) patients diagnosed with RRMS including 26 with fatigue symptom (48.1%), and 26 healthy controls (13 females, 13 males) were enrolled. A FSS score ≥36 was considered as cut-off score to separate fatigued patients from nonfatigued patients. ResultsA significant positive correlation was determined between FSS score and NFI-MS scale, NFI-MS 1, NFI-MS 2, NFI-MS 3 and NFI-MS 4 scores. IL-1β, IL-10 and TNF-α levels did not differ between patient and control groups. IL-35 and IL-2 levels were significantly higher among MS patients (p<0.01). However, no difference was observed between fatigued and nonfatigued patients in the cytokines and HPA parameters studied. ACTH, cortisol and α-MSH were significantly higher in MS group (p=0.02, p<0.01 and p<0.01, respectively). CLIP level was significantly low in MS patient group (p<0.01). ConclusionNFI-MS scale is equally sensitive as FSS scale for assessment of MS fatigue; thus, it may also be widely used to evaluate that symptom. Generally HPA axis is hyperactive in MS patients, but it is not correlated with fatigue in our study. For the first time, levels of CLIP (a type of melanocortin) are studied, and determined to be lower among MS patients. Elevated levels of IL-35 and IL-2 suggest that these cytokines may have a prominent role in MS pathophysiology and can be investigated as potential targets for development of novel therapies.

Immunocytochemical identification and ontogeny of adenohypophyseal cells in a cave fish, Phreatichthys andruzzii (Cypriniformes: Cyprinidae).

The morphogenesis of the pituitary gland and the chronological appearance of adenohypophyseal cells were investigated for the first time in the Somalian cave fish Phreatichthys andruzzii by immunocytochemistry. The adult adenohypophysis contained: a rostral pars distalis, with prolactin (PRL) cells arranged in follicles and adrenocorticotropic (ACTH) cells, a proximal pars distalis with somatotropic (GH), β-thyrotropic (TSH), β-gonadotropic type I (FSH) and type II (LH) cells and a pars intermedia with α-somatolactin (SL), α-melanotropic (MSH) and β-endorphin (END) cells. All regions were deeply penetrated by neurohypophyseal branches. At hatching (24 h post-fertilization) the pituitary was an oval cell mass, close to the ventral margin of diencephalon. The first immunoreactive cells appeared as follows: PRL at 0·5 days after hatching (dah), GH and SL at 1·5 dah, END at 2 dah, TSH, ACTH and MSH at 2·5 dah, FSH at 28 dah and LH at 90 dah. The neurohypophysis appeared at 5 dah and branched extensively inside the adenohypophysis at 130 dah, but there was no boundary between rostral pars distalis and proximal pars distalis at this stage. The potential indices of prolactin and growth hormone production increased until 28 and 60 dah, respectively. The potential index of growth hormone production correlated positively with total length. Activity of PRL and GH cells, measured as ratio of cell area to nucleus area, was significantly higher in juveniles than in larvae.

Interchangeable Roles for E2F Transcriptional Repression by the Retinoblastoma Protein and p27KIP1-Cyclin-Dependent Kinase Regulation in Cell Cycle Control and Tumor Suppression.

The mammalian G1-S phase transition is controlled by the opposing forces of cyclin-dependent kinases (CDK) and the retinoblastoma protein (pRB). Here, we present evidence for systems-level control of cell cycle arrest by pRB-E2F and p27-CDK regulation. By introducing a point mutant allele of pRB that is defective for E2F repression (Rb1G) into a p27KIP1 null background (Cdkn1b-/-), both E2F transcriptional repression and CDK regulation are compromised. These double-mutant Rb1G/G; Cdkn1b-/- mice are viable and phenocopy Rb1+/- mice in developing pituitary adenocarcinomas, even though neither single mutant strain is cancer prone. Combined loss of pRB-E2F transcriptional regulation and p27KIP1 leads to defective proliferative control in response to various types of DNA damage. In addition, Rb1G/G; Cdkn1b-/- fibroblasts immortalize faster in culture and more frequently than either single mutant genotype. Importantly, the synthetic DNA damage arrest defect caused by Rb1G/G; Cdkn1b-/- mutations is evident in the developing intermediate pituitary lobe where tumors ultimately arise. Our work identifies a unique relationship between pRB-E2F and p27-CDK control and offers in vivo evidence that pRB is capable of cell cycle control through E2F-independent effects.

Cloning of POMC cDNA and the stress response in Coilia nasus

PDF HTML阅读 XML下载 导出引用 引用提醒 刀鲚POMC基因的cDNA克隆及其应激应答 DOI: 作者: 作者单位: 1. 农业部淡水渔业健康养殖重点实验室, 浙江省淡水水产遗传育种重点实验室, 浙江省淡水水产研究所, 浙江 湖州 313001;2. 中国水产科学研究院 淡水渔业研究中心, 农业部淡水渔业和种质资源利用重点实验室, 江苏 无锡 214081 作者简介: 杜富宽(1983-),男,助理研究员.E-mail:adublg@126.com 通讯作者: 中图分类号: S96 基金项目: 农业部淡水渔业健康养殖重点实验室开放课题（ZJK2014003）；中国水产科学研究院淡水渔业研究中心中央级公益性科研院所基本科研业务费专项资金（2015JBFR06）；江苏省科技支撑项目（BE2014307）. Cloning of POMC cDNA and the stress response in Coilia nasus Author: Affiliation: 1. Key Laboratory of Healthy and Freshwater Aquaculture, Ministry of Agriculture;Key Laboratory of Freshwater Aquaculture Genetic and Breeding of Zhejiang Province, Zhejiang Institute of Freshwater Fisheries, Huzhou 313001, China;2. Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture;Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, China Fund Project: 摘要 | 图/表 | 访问统计 | 参考文献 | 相似文献 | 引证文献 | 资源附件 | 文章评论 摘要:为了研究刀鲚（POMC基因的cDNA全长。刀鲚基因的cDNA全长2030 bp，编码区699 bp，编码232个氨基酸。二级结构预测显示，刀鲚POMC包括信号肽（signal peptide）、N末端区（N-terminal region，NPP）、促肾上腺皮质激素结构域（adrenocorticotropic hormone，ACTH）、γ-脂解素（-EP）结构域。运用荧光定量的方法检测了该基因在刀鲚不同组织中的表达分布。结果显示，基因的表达量显著下降（<0.05），6 h的表达量恢复至应激前。基因在脂肪代谢及应激调控中发挥重要的功能，本研究结果可为该基因在刀鲚后续育种及应激调控工作提供重要基础。 Abstract:The estuarine tapertail anchovy () is widely distributed in the Yangtze River, the coastal waters of China and Korea, and the Ariake Sound of Japan. It is a commercially important species because of its nutritive value and popularity. However, excess fishing and changes in aquatic ecology have almost caused extinction of this species in the middle reaches of the Yangtze River. In recent years, several studies have been performed on pond breeding and artificial propagation, and larval rearing techniques have been established. Thus, the threat to is very sensitive to stress, which often results in death and huge economic losses. Little is known about the mechanism by which loading stress causes death in fish. Pro-opiomelanocortin (POMC) is synthesized in the corticotrophs and melanotrophs of the anterior and intermediate lobes of the pituitary, respectively, as well as in peptidergic neurons in the arcuate nucleus of the hypothalamus. It is post-translationally cleaved into peptide hormones, including adrenocorticotrophic hormone, -melanocyte stimulating hormone (MSH), N-POMC, and -LPH) in tissue- and cell dependent manners. These peptides exhibit different physiological functions, such as promoting ovarian maturation, lipolysis, inhibiting fat accumulation, regulating osmotic pressure, and reacting to stressors. We cloned the and determined that the full-length cDNA is 1212 bp long, with a 699 bp open reading frame that encoded a 232 amino acid protein. The POMC protein is predicted to contain the typical POMC domains of a signal peptide sequence, the N-terminal region, and the adrenocorticotrophic hormone, -EP domains. Gene expression patterns were detected in different tissues by quantitative reverse transcription-polymerasechain reaction. was expressed strongly in the brain and relatively highly in the gill, kidney, and testis, whereas it was expressed at low levels in the liver, spleen, intestine, head kidney, muscle, and ovary. <0.05) and was significantly up regulated 4 h and 6 h after transport ( expression returned to the control level before stress. The gene plays an important role regulating fat metabolism and stress. Our results provide important clues for breeding and stress control studies in . 参考文献 相似文献 引证文献

Anatomical Correlates of Neuropsychological Deficits Among Patients With the Cerebellar Stroke.

ObjectiveTo investigate the anatomical correlates of the neuropsychological deficits in patients with the cerebellar stroke.MethodsWe screened patients who were admitted to the National Rehabilitation Center with the cerebellar stroke between October 2012 and November 2016. The patients with the cerebellar stroke who underwent neuropsychological testing for which the Seoul Neuropsychological Screening Battery (SNSB) or the SNSB-II were enrolled. The neuropsychological function capacities were compared in accordance with the stroke type (hemorrhagic vs. ischemic) and the location (right/left anterior, right/left posterior intermediate, right/left posterior lateral lobe, and vermis). Mean z-scores were computed to compare the patient performances with the population averages.ResultsTwenty-six patients (15 with ischemic stroke and 11 with hemorrhagic stroke) with a mean age of 54.8±16.6 years were assessed 8.8±9.2 months after the stroke. Differences in the neuropsychological functioning according to the stroke type were not observed. All of the numerical subtests of the stroke patients showed significantly poorer performances compared with the population averages (mean z-score <0), and some of the subtests revealed abnormal performances in attention-, visuospatial function-, memory-, and frontal/executive function-related tasks (mean z-score <−1). The patients with the presence of a lesion in the right posterior intermediate lobe of the cerebellum showed a poorer performance in the subtests evaluating the executive function including the Korean-version Stroop Test (p=0.04), the Digit Symbol Coding Test (p=0.01), and the Korean-version Trail Making Test (p=0.02) compared with the patients without that lesion.ConclusionThe present study confirms that the cerebellar stroke affects the neuropsychological functioning which is associated with the anatomical site of stroke.

Pituitary Pars Intermedia Dysfunction (PPID) – Is there a correlation between severity of clinical signs and plasma ACTH concentrations in horses?

Pituitary Pars Intermedia Dysfunction (PPID) – Is there a correlation between severity of clinical signs and plasma ACTH concentrations in horses?

Distribution of Corticotrophin-Releasing Factor Type 1 Receptor-Like Immunoreactivity in the Rat Pituitary.

Corticotrophin-releasing factor (CRF) regulates the hypothalamic-pituitary-adrenal axis response to stress through its type 1 receptor (CRF1 ) in the corticotrophs of the anterior pituitary. Although CRF1 mRNA expression has been confirmed in the rat pituitary, the distribution pattern of CRF1 protein in the pituitary has not been reported. Therefore, we generated an antiserum against the amino acid fragment corresponding to the 177-188 sequence of the first extracellular loop of the rat CRF1 . Using the antiserum, CRF1 -like immunoreactivity (CRF1 -LI) was detected in the anterior lobe cells of the rat pituitary where some of them expressed intense signals. CRF1 -LI also appeared in the intermediate lobe cells and on the fibre-like elements of the posterior lobe of the pituitary. Dual immunofluorescence labelling showed that corticotrophs exhibited the highest percentage of CRF1 (male: 27.1±3.0%, female: 18.0±3.0%), followed by lactotrophs (male: 6.7±3.0%, female: 12.1±1.3%), gonadotrophs (male: 2.6±1.0%, female: 7.5±0.5%), thyrotrophs (male: 2.9±0.1%, female: 5.3±1.2%) and somatotrophs (male: 1.1±0.3%, female: 1.2±0.5%). The percentage of CRF1 -LI-positive cells that were corticotrophs was significantly higher in male rats than in female rats, whereas CRF1 -LI-positive lactotrophs and gonadotrophs were significantly higher in female rats than in male rats. Almost all of the melanotrophs were positive for CRF1 in the intermediate lobe (98.9±0.2%). CRF1 -LI and the percentage of CRF1 -LI in corticotrophs were decreased in the anterior pituitary, and the distribution patterns were altered from a diffuse to punctate one by adrenalectomy; the changes were restored by treatment with dexamethasone (100μg/kg bw). These results suggest that CRF1 is involved in the modulation of the functions of the pituitary; moreover, protein expression and the distribution patterns of CRF1 are regulated by glucocorticoids in the rat anterior pituitary.

Involvement of DNA methylation in regulating rat Prop1 gene expression during pituitary organogenesis.

PROP1 is a pituitary specific transcription factor that plays a crucial role in pituitary organogenesis. The Prop1 shows varied expression patterns that promptly emerge and then fade during the early embryonic period. However, the regulatory mechanisms governing Prop1 expression remain unclear. Here, we investigated whether Prop1 was under epigenetic regulation by DNA methylation. Bisulfite sequencing was performed on DNA obtained from the pituitary glands and livers of rats on embryonic days (E) 13.5 and E14.5, and postnatal days (P) 4 and P30. The methylation of CpG sites in seven regions from 3-kb upstream of the Prop1 transcription start site through to its second intron were examined. Certain differences in CpG-methylation levels were observed in Region-1 (–2772 b to –2355 b), Region-4 (–198 b to +286 b), Region-5 (+671 b to +990 b), and Region-6 (+1113 b to +1273 b) based on comparisons between pituitary and liver DNA on E13.5. DNA methylation in pituitary glands on E14.5, P4, and P30 was generally similar to that observed in in the pituitary gland on E13.5, whereas the anterior and intermediate lobes of the pituitary gland on P4 and P30 showed only small differences. These results indicate that Prop1 is under regulation by CpG methylation during the early period of pituitary primordium development around E13.5.

S100β-Positive Cells of Mesenchymal Origin Reside in the Anterior Lobe of the Embryonic Pituitary Gland.

The anterior and intermediate lobes of the pituitary gland develop through invagination of the oral ectoderm and as they are endocrine tissues, they participate in the maintenance of vital functions via the synthesis and secretion of numerous hormones. We recently observed that several extrapituitary cells invade the anterior lobe of the developing pituitary gland. This raised the question of the origin(s) of these S100β-positive cells, which are not classic endocrine cells but instead comprise a heterogeneous cell population with plural roles, especially as stem/progenitor cells. To better understand the roles of these S100β-positive cells, we performed immunohistochemical analysis using several markers in S100β/GFP-TG rats, which express GFP in S100β-expressing cells under control of the S100β promoter. GFP-positive cells were present as mesenchymal cells surrounding the developing pituitary gland and at Atwell's recess but were not present in the anterior lobe on embryonic day 15.5. These cells were negative for SOX2, a pituitary stem/progenitor marker, and PRRX1, a mesenchyme and pituitary stem/progenitor marker. However, three days later, GFP-positive and PRRX1-positive (but SOX2-negative) cells were observed in the parenchyma of the anterior lobe. Furthermore, some GFP-positive cells were positive for vimentin, p75, isolectin B4, DESMIN, and Ki67. These data suggest that S100β-positive cells of extrapituitary origin invade the anterior lobe, undergoing proliferation and diverse transformation during pituitary organogenesis.

Identification of marker genes for pars tuberalis morphogenesis in chick embryo: expression of Cytokine-like 1 and Gap junction protein alpha 5 in pars tuberalis.

The adenohypophysis is formed from the oral ectoderm and consists of the pars distalis (PD), pars intermedia, and pars tuberalis (PT). The mechanisms of PD development have been extensively studied, and the cellular differentiation of the PD is well understood. However, the morphogenesis and differentiation of the PT are still unclear, and the genes expressed during PT development remain largely unknown. We have explored genes specifically expressed in the PT during embryonic development and analyzed their spatiotemporal expression patterns. Microarray analysis of laser-captured PT and PD tissues obtained from chick embryos on embryonic day 10 (E10.0) has shown high expression of Cytokine-like 1 (CYTL1) and Gap junction protein alpha 5 (GJA5) genes in the PT. Detailed analysis of these spatiotemporal expression patterns during chick embryo development by in situ hybridization has revealed that CYTL1 mRNA first appears in the lateral head ectoderm and ventral head ectoderm at E1.5. The expression of CYTL1 moves into Rathke's pouch at E2.5 and is then localized in the PT primordium where it is continuously expressed until E12.0. GJA5 mRNA is transiently detected in the PT primordium from E6.0 to E12.0, whereas its expression is not detected in the PD during development. Thus, these genes might be involved in the regulation mechanisms of PT development and could be useful markers for PT development.

Melatonin Receptor 1 Deficiency Affects Feeding Dynamics and Pro-Opiomelanocortin Expression in the Arcuate Nucleus and Pituitary of Mice

Background/Methods: Melatonin, the neurohormone for darkness, mediates photoperiod-dependent changes in physiology and behavior by targeting specific membrane-bound receptors (MT1 and MT2). In the present study, we investigated the impact of MT1 receptor deficiency on feeding behavior, locomotor activity and mRNA expression levels encoding for the polypeptide pro-opiomelanocortin (Pomc) and neuropeptide Y (Npy) in the hypothalamic arcuate nucleus (ARC) and the adenohypophysis [pars distalis (PD) and pars intermedia (PI)] in a comparison between wild-type (WT) and MT1-deficient (MT1-/-) mice. Results: The MT1-/- mice spent significantly more time feeding than the WT mice, while the general locomotor behavior, body weight and the total amount of food consumed did not differ between both genotypes. The nocturnal expression levels of Pomc in the ARC and PD were significantly higher in WT as compared to MT1-/- mice and exogenous melatonin administered during the light phase stimulated Pomc expression in WT mice only. No differences were found between WT and MT1-/- mice with regard to Pomc expression levels in the PI. Conclusion: Thus, the MT1-mediated signaling stimulates Pomc expression in a region-specific pattern. Since the MT1-mediated changes in Pomc expression do not elicit direct orexigenic or anorexigenic effects, such effects are obviously mediated by regulatory systems downstream of the Pomc mRNA (e.g. cleavage and release of POMC derivatives), which are independent of MT1 signaling.

Stellate Cell Networks in the Teleost Pituitary.

The folliculostellate cells of the mammalian pituitary are non-endocrine cells that are implicated in long-distance communication and paracrine signaling, but to date, these cells have yet to be characterized in teleosts. We found that the stellate cells of the teleost pituitary share many common attributes with mammalian folliculostellate cells. By labeling of stellate cells in live preparations of tilapia pituitaries we investigated their distribution, association with other endocrine cells and their anatomical and functional coupling. In the pars intermedia, stellate cells were arranged around neuronal bundles and their processes extended into the pars distalis. Within the pars distalis, stellate cells formed close associations with FSH cells and, to a lesser degree, with GH and LH cells, suggesting differential paracrine regulation of the two gonadotrope populations. The production of follistatin by stellate cells further corroborates the notion of a paracrine role on FSH release. We also found stellate cells to form gap junctions that enabled dye transfer to neighboring stellate cells, implicating that these cells form a large-scale network that connects distant parts of the pituitary. Our findings represent the first wide-scale study of stellate cells in teleosts and provide valuable information regarding their functional roles in pituitary function.

NG2 targets tumorigenic Rb inactivation in Pit1-lineage pituitary cells.

The proteoglycan neuron-glial antigen 2 (NG2) is expressed by oligodendrocyte progenitors, pericytes, and some cancerous cells where it is implicated in tumor development. We examined mice with NG2-driven pRb inactivation. Unexpectedly, NG2-Cre:pRb(flox/flox) mice developed pituitary tumors with high penetrance. Adenohypophysial neoplasms developed initially as multifocal lesions; by 1 year, large tumors showed brain invasion. Immunohistochemistry identified these as Pit1-lineage neoplasms, with variable immunoreactivity for growth hormone, prolactin, thyrotropin, and α-subunit of glycoprotein hormones. Other than modest hyperprolactinemia, circulating hormone levels were not elevated. To determine the role of NG2 in the pituitary, we investigated NG2 expression. Immunoreactivity was identified in anterior and posterior lobes but not in the intermediate lobe of the mouse pituitary; in the adenohypophysis, folliculostellate cells had the strongest NG2 immunoreactivity but showed no proliferation in response to Rb inactivation. Pit1-positive adenohypophysial cells were positive for NG2, but corticotroph and gonadotroph cells were negative. RT-PCR revealed NG2 expression in normal human pituitary and human pituitary tumors; immunohistochemistry localized NG2 in nontumorous human adenohypophysis with strongest positivity in folliculostellate cells, and in tumors of all types except corticotrophs. Functional studies in GH4 mammosomatotrophs showed that NG2 increases prolactin (PRL), reduces growth hormone (GH) expression, and enhances cell adhesion without influencing proliferation. In conclusion, NG2-driven pRb inactivation results in pituitary tumors that mimic endocrinologically inactive Pit1-lineage human pituitary tumors. This model identifies a role for NG2 in pituitary cell-type-specific functions and unmasks a protective role from Rb inactivation in folliculostellate cells; it can be used for further research, including preclinical testing of novel therapies.

Endosphenoidal coil for intraoperative magnetic resonance imaging of the pituitary gland during transsphenoidal surgery.

OBJECTIVE Pituitary MR imaging fails to detect over 50% of microadenomas in Cushing's disease and nearly 80% of cases of dural microinvasion. Surface coils can generate exceptionally high-resolution images of the immediately adjacent tissues. To improve imaging of the pituitary gland, a receive-only surface coil that can be placed within the sphenoid sinus (the endosphenoidal coil [ESC]) during transsphenoidal surgery (TSS) was developed and assessed. METHODS Five cadaver heads were used for preclinical testing of the ESC. The ESC (a double-turn, 12-mm-diameter surface coil made from 1-mm-diameter copper wire) was developed to obtain images in a 1.5-T MR scanner. The ESC was placed (via a standard sublabial TSS approach) on the anterior sella face. Clinical MR scans were obtained using the 8-channel head coil and ESC as the receiver coils. Using the ESC, ultra-high-resolution, 3D, balanced fast field echo (BFFE) and T1-weighted imaging were performed at resolutions of 0.25 × 0.25 × 0.50 mm3 and 0.15 × 0.15 × 0.30 mm3, respectively. RESULTS Region-of-interest analysis indicated a 10-fold increase in the signal-to-noise ratio (SNR) of the pituitary when using the ESC compared with the 8-channel head coil. ESC-related improvements (p < 0.01) in the SNR were inversely proportional to the distance from the ESC tip to the anterior pituitary gland surface. High-resolution BFFE MR imaging obtained using ESC revealed a number of anatomical features critical to pituitary surgery that were not visible on 8-channel MR imaging, including the pituitary capsule, the intercavernous sinus, and microcalcifications in the pars intermedia. These ESC imaging findings were confirmed by the pathological correlation with whole-mount pituitary sections. CONCLUSIONS ESC can significantly improve SNR in the sellar region intraoperatively using current 1.5-T MR imaging platforms. Improvement in SNR can provide images of the sella and surrounding structures with unprecedented resolution. Clinical use of this ESC may allow for MR imaging detection of previously occult pituitary adenomas and identify microscopic invasion of the dura or cavernous sinus.

Abstract B45: Piptandenia africana and Nauclea latifolia protect against N-Nitrosodiethylamine induced hepatic tumors in Wistar rats

Abstract In vitro studies on crude extracts of Piptandenia africana (PA) and Nauclea latifolia (NL) showed promising anti proliferative effects on Hela, MCF7 and ICMST-6 cell lines. Furtherance to these finding, we examined the anti-tumorigenic effect of NL and PA on N-nitrosodiethylamine (DEN) induced hepatic tumors in Wistar rats as potential phytotherapeutic candidates for cancer prevention and treatment. Five groups of rats (n=5) were co-treated as follows for 60 days: Control (1), DEN only (25μg/g body wt.) (2), DEN+PA (3), DEN+ NL (4) and DEN+PA+NL (5). The serum was assessed for markers of toxicity: alanine and aspartate transaminase (ALT and AST) and alkaline phosphatase (ALP). Total bilirubin (TB) conjugated bilirubin (CB) and creatinine were also examined. Numbers, volumes and sizes of DEN-induced tumors were estimated in harvested livers using a DelcastTM caliper. Sections of liver were examined for histopathological changes and hepatic antioxidants profiles: glutathione peroxide (GPx), superoxide dismutase (SOD), glutathione -s- transferase (GST), catalase and reduced glutathione (GSH). Decreases (p&amp;lt;0.05) in food consumption and body weight were observed in grp 2 rats and had mean tumor of one (T1), in the largest lobe (LL) of their liver. In grp 3, two rats had (T0) but three other rats had (T1) each on the LL of their livers. Grp 4, one rat had (T1) on the LL, while two other rats had (T3) and (T1) on the liver’s smallest lobe (SL). Two rats had (T0), one rat had (T1) on the LL of grp 5 rats, one rat had (T3) on LL and (T2) and (T1) on the intermediate lobe (IL) while the last rat had (T0) on LL and (T1) on SL. Mean blood glucose (±S.D) level in grp2 rats was highest (87.5±5.1) compared to all other treated rats. Hepatic GPx, SOD, GST, catalase and GSH levels suggested that grp2 treated rats had lower levels of antioxidant activities compared to grp 1 and 3. Grp 4 rats exhibited higher antioxidant activity relative to animals in grp 3 and grp 2. In addition markers (AST, ALT and ALP, TB and CB) of hepatotoxicity were highest in grp 4 relative to all other groups. Histopathology of liver sections showed severe portal cellular infiltration by mononuclear cells, congestion and multiple foci of severe hepatic necrosis in grp 2, compared to the grp 1. In contrast grp 3 exhibited mild portal cellular infiltration with moderate Kupffer cell hyperplasia. Grp 4 animals presented with severe but diffuse vacuolar degeneration and necrosis of hepatocytes. Mild portal congestion, occasioned by cellular infiltration by mononuclear cells was observed in grp 5 rats. PA and NL co-treatment mitigated DEN-induced hepatic tumorigenesis in rats. PA and NL exhibited phytotherapuetic properties supporting earlier in vitro findings. This may be relevant in preventing hepatic tumor formation and may serve as potential chemoprevention agents. Elucidating the phytochemistry and mechanistic mode of actions of PA and NL are required. Citation Format: Queen-Esther E. Akinade, Sarah O. Nwozo, Olubunmi A. Akinwumi, Solomon E. Owumi. Piptandenia africana and Nauclea latifolia protect against N-Nitrosodiethylamine induced hepatic tumors in Wistar rats. [abstract]. In: Proceedings of the Fourth AACR International Conference on Frontiers in Basic Cancer Research; 2015 Oct 23-26; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2016;76(3 Suppl):Abstract nr B45.

All Hormone-Producing Cell Types of the Pituitary Intermediate and Anterior Lobes Derive From Prop1-Expressing Progenitors.

Mutations in PROP1, the most common known cause of combined pituitary hormone deficiency in humans, can result in the progressive loss of all hormones of the pituitary anterior lobe. In mice, Prop1 mutations result in the failure to initiate transcription of Pou1f1 (also known as Pit1) and lack somatotropins, lactotropins, and thyrotropins. The basis for this species difference is unknown. We hypothesized that Prop1 is expressed in a progenitor cell that can develop into all anterior lobe cell types, and not just the somatotropes, thyrotropes, and lactotropes, which are collectively known as the PIT1 lineage. To test this idea, we produced a transgenic Prop1-cre mouse line and conducted lineage-tracing experiments of Prop1-expressing cells. The results reveal that all hormone-secreting cell types of both the anterior and intermediate lobes are descended from Prop1-expressing progenitors. The Prop1-cre mice also provide a valuable genetic reagent with a unique spatial and temporal expression for generating tissue-specific gene rearrangements early in pituitary gland development. We also determined that the minimal essential sequences for reliable Prop1 expression lie within 10 kilobases of the mouse gene and demonstrated that human PROP1 can substitute functionally for mouse Prop1. These studies enhance our understanding of the pathophysiology of disease in patients with PROP1 mutations.