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1.
Medicine (Baltimore). 2018 Jul;97(30):e11583. doi: 10.1097/MD.0000000000011583.

Ganglioglioma of the adenohypophysis mimicking pituitary adenoma: A case report and review of the literature.

Author information

1
Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine.
2
Brain Research Institute.
3
Collaborative Innovation Center for Brain Science, Zhejiang University, Hangzhou, Zhejiang, P.R. China.

Abstract

INTRODUCTION:

Ganglioglioma is a generally benign tumor, mostly occurring in patients <30 years old. Temporal lobe is most frequently involved. Up to now, only 3 cases were reported of ganglioglioma in the pituitary gland, all being confined to the neurohypophysis. Here, we are the first to report an adenohypophysis ganglioglioma.

CASE PRESENTATION:

A 43-year-old woman presented with chronic headache was referred to our hospital. Magnetic resonance imaging (MRI) indicated pituitary adenoma. Endoscopic transnasal transsphenoidal surgery was performed. The tumor was rich in blood supply, with tough texture, therefore only subtotal resection was conducted. Pathology analysis revealed an adenohypophysial tumor composed of dysplastic ganglion cells and neoplastic glial cells collided with nonspecific hyperplasia of pituitary cells. Immunohistochemistry revealed positive staining of synaptophysin, glial-fibrillary acidic protein, and CD34. The results were consistent with the diagnosis of ganglioglioma. After the surgery the patient recovered well except developing cerebrospinal fluid rhinorrhea, which was controlled by lumbar drainage. MRI 6 months later did not show any sign of progression.

CONCLUSION:

According to the findings of our case, concerns should be raised considering ganglioglioma as a differential diagnosis of mass located in the sellar region. Furthermore, an ideal management strategy for pituitary ganglioglioma is not known; therefore, more cases and long-term follow-up are needed to enrich our knowledge of the diagnosis, treatment, and prognosis of this rare intracranial lesion.

PMID:
30045287
PMCID:
PMC6078729
DOI:
10.1097/MD.0000000000011583
[Indexed for MEDLINE]
Free PMC Article
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2.
Toxicol Lett. 2018 Oct 1;295:41-53. doi: 10.1016/j.toxlet.2018.05.041. Epub 2018 Jun 2.

Protective mechanisms involving enhanced mitochondrial functions and mitophagy against T-2 toxin-induced toxicities in GH3 cells.

Author information

1
Department of Animal Sciences & Technology, Key Laboratory for the Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, Hubei, 430070, China.
2
Department of Animal Sciences & Technology, Laboratory of Quality & Safety Risk Assessment for Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei, 430070, China.
3
Department of Animal Sciences & Technology, Key Laboratory for the Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, Hubei, 430070, China; Department of Animal Sciences & Technology, Laboratory of Quality & Safety Risk Assessment for Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei, 430070, China. Electronic address: Wangxu@mail.hzau.edu.cn.
4
Department of Animal Sciences & Technology, Key Laboratory for the Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, Hubei, 430070, China; Department of Animal Sciences & Technology, Laboratory of Quality & Safety Risk Assessment for Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei, 430070, China. Electronic address: yuan5802@mail.hzau.edu.cn.

Abstract

T-2 toxin is the most toxic member of trichothecene mycotoxin. So far, the mechanism of mitochondrial toxicity and protective mechanism in mammalian cells against T-2 toxin are not fully understood. In this study, we aimed to investigate the cellular and mitochondrial toxicity of T-2 toxin, and the cellular protective mechanisms in rat pituitary GH3 cells. We showed that T-2 toxin significantly increased reactive oxygen species (ROS) and DNA damage and caused apoptosis in GH3 cells. T-2 toxin induced abnormal cell morphology, cytoplasm and nuclear shrinkage, nuclear fragmentation and formation of apoptotic bodies and autophagosomes. The mitochondrial degradative morphologies included local or total cristae collapse and small condensed mitochondria. T-2 toxin decreased the mitochondrial membrane potential. However, T-2 toxin significantly increased the superoxide dismutase (SOD) activity and expression of antioxidant genes glutathione peroxidase 1 (GPx-1), catalase (CAT), mitochondria-specific SOD-2 and mitochondrial uncoupling protein-1, -2 and -3 (UCP-1, 2 and 3). Interestingly, T-2 toxin increased adenosine triphosphate (ATP) levels and mitochondrial complex I activity, and increased the expression of most of mitochondrial electron transport chain subunits tested and critical transcription factors controlling mitochondrial biogenesis and mitochondrial DNA transcription and replication. T-2 toxin increased mitophagic activity by increasing the expression of mitophagy-specific proteins NIP-like protein X (NIX), PTEN-induced putative kinase protein 1 (PINK1) and E3 ubiquitin ligase Parkin. T-2 toxin activated the protective protein kinase A (PKA) signaling pathway, which activated the nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/PINK1/Parkin pathway to mediate mitophagy. Taken together, our results suggested that the mammalian cells could increase their resistance against T-2 toxin by increasing the antioxidant activity, mitophagy and mitochondrial function.

KEYWORDS:

Antioxidant; Apoptosis; Mitochondria; Mitophagy; PGC-1; ROS

PMID:
29870751
DOI:
10.1016/j.toxlet.2018.05.041
[Indexed for MEDLINE]
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3.
PLoS One. 2018 Apr 23;13(4):e0196029. doi: 10.1371/journal.pone.0196029. eCollection 2018.

Differentiation capacities of PS-clusters, adult pituitary stem/progenitor cell clusters located in the parenchymal-niche, of the rat anterior lobe.

Author information

1
Division of Life Science, Graduate School of Agriculture, Meiji University, Kanagawa, Japan.
2
Organization for the Strategic Coordination of Research and Intellectual Property, Meiji University, Kanagawa, Japan.
3
Institute of Reproduction and Endocrinology, Meiji University, Kanagawa, Japan.
4
Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.
5
Department of Life Science, School of Agriculture, Meiji University, Kanagawa, Japan.
6
Laboratory of Anatomy and Cell Biology, Department of Health Sciences, Kyorin University, Tokyo, Japan.

Abstract

Pituitary endocrine cells are supplied by Sox2-expressing stem/progenitor cells in the anterior lobe of the adult pituitary. In relation to their microenvironment ("niche"), SOX2-positive cells exist in two types of niches; the marginal cell layer-niche and the parenchymal-niche. Recently, we isolated dense stem/progenitor cell clusters from the parenchymal-niche as parenchymal stem/progenitor cell (PS)-clusters. We classified these PS-clusters into three subtypes based on differences in S100β-expression (S100β-positive, -negative, and -mixed type), and reported that S100β-positive PS-clusters exhibited the capacity for differentiation into endocrine cells under 3-dimensional cultivation system. In the present study, we further characterized S100β-positive PS-clusters using an in vitro 2-dimensional cultivation system. The results demonstrated that S100β-positive PS-clusters in the 2-dimensional cultivation system proliferated more actively than S100β-negative clusters. Moreover, in 2-dimensional cultivation conditions, S100β-positive PS-clusters showed differentiation capacity into non-endocrine cells (Myogenin-, αSMA-, NG2-, or SOX17-positive cells) but not into endocrine cells, whereas S100β-negative PS-clusters did not. Collectively, PS-clusters were heterogeneous, exhibiting different proliferation and differentiation properties based on the difference in S100β-expression. Specifically, a part of SOX2-positive cells in the parenchymal-niche had capacities for differentiation into non-endocrine cells, and S100β-positive PS-clusters may be in more progressive stages toward differentiation than S100β-negative clusters.

PMID:
29684040
PMCID:
PMC5912746
DOI:
10.1371/journal.pone.0196029
[Indexed for MEDLINE]
Free PMC Article
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4.
Biomed Pharmacother. 2018 Jun;102:494-501. doi: 10.1016/j.biopha.2018.02.003. Epub 2018 Mar 24.

Bu-shen-zhu-yun decoction promotes synthesis and secretion of FSHβ and LHβ in anterior pituitary cells in vitro.

Author information

1
The First Clinical College, Nanjing University of Chinese Medicine, Xianlin Road, Nanjing, Jiangsu Province, 210023, China. Electronic address: jiangxiaofei78@163.com.
2
The First Clinical College, Nanjing University of Chinese Medicine, Xianlin Road, Nanjing, Jiangsu Province, 210023, China; Jiangsu Provincial Hospital of Traditional Chinese Medicine, China. Electronic address: zhouhuifang2011301@163.com.
3
Department of Obstetrics and Gynecology, Lishui Hospital of Traitional Chinese Medicine, Lishui, Zhejiang, 323000, China. Electronic address: 936391460@qq.com.
4
The First Clinical College, Nanjing University of Chinese Medicine, Xianlin Road, Nanjing, Jiangsu Province, 210023, China. Electronic address: 263522575@qq.com.
5
The First Clinical College, Nanjing University of Chinese Medicine, Xianlin Road, Nanjing, Jiangsu Province, 210023, China. Electronic address: 956030454@qq.com.
6
The First Clinical College, Nanjing University of Chinese Medicine, Xianlin Road, Nanjing, Jiangsu Province, 210023, China. Electronic address: 1335499687@qq.com.
7
The First Clinical College, Nanjing University of Chinese Medicine, Xianlin Road, Nanjing, Jiangsu Province, 210023, China; Pediatric Institution of Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: dfsjj@163.com.
8
The First Clinical College, Nanjing University of Chinese Medicine, Xianlin Road, Nanjing, Jiangsu Province, 210023, China; Pediatric Institution of Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: 710735592@qq.com.
9
The First Clinical College, Nanjing University of Chinese Medicine, Xianlin Road, Nanjing, Jiangsu Province, 210023, China; Pediatric Institution of Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: sunnyxyl1021@163.com.

Abstract

Luteal phase defects (LPD) are an important etiology of infertility which has increased in recent years. Studies have shown that bu-shen-zhu-yun decoction (BSZY-D) can lower the expression of estrogen receptor and progesterone receptor, in rats endometrium of embryonic implantation period, which upregulated by mifepristone, and improve uterine receptivity. The aim of present study was to determine the effect of BSZY-D on the synthesis and secretion of gonadotropic hormones in the anterior pituitary cells of rats. Rats were treated with saline (control) or BSZY-D two times/day for three estrous cycles by gavage. The cerebrospinal fluid (CSF) were collected for further cell treatment. The components in BSZY-D, serum and CSF were analysed by High Performance Liquid Chromatography (HPLC). Cells were either pretreated with normal CSF or BSZY-D/CSF before being stimulated with or without cetrorelix. The mRNA and proteins levels of receptors, hormones, and transcription factors were detected by RT-PCR, western blot analysis and immunostaining. We show that non-toxic concentrations of cetrorelix, a GnRH antagonist, can reduce the mRNA and protein levels of GnRHR, LH, and FSH. This effect could be reversed by the addition of BSZY-D/CSF. We also show decreased mRNA and protein expression of transcription factors, such as CREB, and Egr-1 and secretory vescicles, including SNAP-25 and Munc-18 upon treatment with cetrorelix could be reversed post co-treatment with BSZY-D/CSF. These results indicate that BSZY-D/CSF treatment led to increased levels of GnRHR, transcription factors, and secretory vesicles leading to increased secretion of FSH and LH. Thus, BSZY-D presents a promising candidate to treat luteal phase defects and infertility.

KEYWORDS:

Anterior pituitary cells; Bu-shen-zhu-yun decoction; FSH; Infertility; LH

PMID:
29579710
DOI:
10.1016/j.biopha.2018.02.003
[Indexed for MEDLINE]
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5.
Ecotoxicol Environ Saf. 2018 Jul 30;156:116-124. doi: 10.1016/j.ecoenv.2018.03.029. Epub 2018 Mar 14.

Hypothalamic-pituitary-ovarian axis perturbation in the basis of bisphenol A (BPA) reproductive toxicity in female zebrafish (Danio rerio).

Author information

1
Departamento de Farmacología, Toxicología y Medicina Legal y Forense, Facultad de Veterinaria, Universidad de Córdoba, Campus de Rabanales, Edificio Darwin, 14071 Córdoba, Spain. Electronic address: ft2moloa@uco.es.
2
Departamento de Bioquímica y Biología Molecular, Campus de Excelencia Internacional Agroalimentario CeiA3, Universidad de Córdoba, Campus de Rabanales, Edificio Severo Ochoa, 14071 Córdoba, Spain.
3
Departamento de Anatomía y Anatomía Patológica Comparadas, Facultad de Veterinaria, Universidad de Córdoba, Campus de Rabanales, Edificio de Sanidad Animal, 14071 Córdoba, Spain.
4
Departamento de Farmacología, Toxicología y Medicina Legal y Forense, Facultad de Veterinaria, Universidad de Córdoba, Campus de Rabanales, Edificio Darwin, 14071 Córdoba, Spain.

Abstract

Thousands of safety-related studies have been published on bisphenol A (BPA), an ubiquitous environmental pollutant with estrogenic activity and many other potential biological effects. In recent years, BPA exposure has been shown to cause anovulation and infertility through irreversible alteration of the hypothalamic-pituitary-gonadal axis in several organisms, including fish and mammals. Recently, the European Chemical Agency classified BPA as a "substance of very high concern" because of its endocrine-disrupting properties, which have serious effects on human health. Given the risk of exposure to BPA as a pollutant in the environment, food, and drinking water, the objective of our study was to assess the effects of this compound on the adeno-hypophysis by means of a histopathological and morphometric study of the gonadotroph cells. In addition, using quantitative real-time PCR (qRT-PCR) assays, we analyzed the changes in the expression of Cyp19b (an aromatase gene). Zebrafish were randomly distributed into five groups: a control group and 4 treated groups which were exposed to different BPA concentrations (1, 10, 100 and 1000 µg/L). The effects of the different doses on Cyp19b mRNA molecules followed a non-monotonic curve, with the 1 and 1000 µg/L doses causing dramatic decreases in the number of Cyp19b transcripts while the doses of 10 and 100 µg/L caused important increases. The consequences might be deregulation of gonadotropic hormones causing degeneration of gonadotropic cells, as observed in BPA treated animals. This is the first study in which the gonadotroph cells have been evaluated using histomorphological endpoints after BPA exposure in zebrafish.

KEYWORDS:

Adeno-hypophysis; Cyp19b; Endocrine-disrupting chemical; Fish; Gonadotroph cell

PMID:
29549734
DOI:
10.1016/j.ecoenv.2018.03.029
[Indexed for MEDLINE]
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6.
PLoS One. 2018 Mar 13;13(3):e0194300. doi: 10.1371/journal.pone.0194300. eCollection 2018.

Regulation of FSH expression by differentially expressed miR-186-5p in rat anterior adenohypophyseal cells.

Author information

1
Department of Laboratory Animals, College of Animal Sciences, Jilin University, Changchun, Jilin, P.R. China.

Abstract

Follicle-stimulating hormone (FSH) has key roles in animal reproduction, including spermatogenesis and ovarian maturation. Many factors influence FSH secretion. However, despite the broad functions of microRNAs (miRNAs) via the regulation of target genes, little is known about their roles in FSH secretion. Our previous results suggested that miR-186-5p targets the 3' UTR of FSHb; therefore, we examined whether miR-186-5p could regulate FSH secretion in rat anterior adenohypophyseal cells. miR-186-5p was transfected into rat anterior pituitary cells. The expression of FSHb and the secretion of FSH were examined by RT-qPCR and ELISA. A miR-186-5p mimic decreased the expression of FSHb compared with expression in the control group and decreased FSH secretion. In contrast, both the mRNA levels and secretion of FSH increased in response to miR-186-5p inhibitors. Our results demonstrate that miR-186-5p regulates FSH secretion by directly targeting the FSHb 3' UTR, providing additional functional evidence for the importance of miRNAs in the regulation of animal reproduction.

PMID:
29534107
PMCID:
PMC5849326
DOI:
10.1371/journal.pone.0194300
[Indexed for MEDLINE]
Free PMC Article
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7.
Pituitary. 2018 Aug;21(4):443. doi: 10.1007/s11102-018-0879-1.

Immunohistochemistry for transcription factor T-Pit as a tool in diagnostics of corticotroph pituitary tumours.

Author information

1
Uppsala University, Uppsala, Sweden. olivera.casar-borota@igp.uu.se.
2
University of Oslo, Oslo, Norway.
3
Uppsala University, Uppsala, Sweden.

Comment on

PMID:
29468382
DOI:
10.1007/s11102-018-0879-1
[Indexed for MEDLINE]
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8.
Tissue Cell. 2018 Feb;50:96-103. doi: 10.1016/j.tice.2017.12.008. Epub 2017 Dec 27.

Nintedanib effects on delaying cancer progression and decreasing COX-2 and IL-17 in the prostate anterior lobe in TRAMP mice.

Author information

1
Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), São Paulo, Brazil.
2
Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), São Paulo, Brazil. Electronic address: quitete@unicamp.br.

Abstract

Prostate cancer is the most prevalent type of cancer in men around the world. Due to its high incidence, new therapies have been evaluated, including drugs capable of inhibiting the FGF/VEGF pathways, as Nintedanib. The aim herein was to evaluate the Nintedanib therapeutic effects on morphology and COX-2 and IL-17 levels in the prostate anterior lobe in different grades of the tumor progression in TRAMP mice. Animals were treated with Nintedanib at a dose of 10 mg/kg/day in initial and intermediate grades of tumor development. At the end of treatment, the prostate anterior lobe was collected and submitted to morphological, immunohistochemical and Western Blotting analyses. The results showed that Nintedanib delayed the prostate carcinogenesis progression, with over 20% of reduction in frequency of tissue injuries, particularly in the group treated from 12 to 16 weeks of age. Also, decreased COX-2 and IL-17 levels were observed in both groups treated with Nintedanib in the prostate anterior lobe. Thus, we concluded that Nintedanib was effective in delaying tumor progression and, despite not directly acting on inflammation, Nintedanib may adversely affect inflammatory pathways, favoring prostate cancer delay.

KEYWORDS:

COX-2; IL-17; Inflammation; Nintedanib; Prostate cancer; TRAMP

PMID:
29429524
DOI:
10.1016/j.tice.2017.12.008
[Indexed for MEDLINE]
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9.
Eur J Obstet Gynecol Reprod Biol. 2018 Mar;222:166-170. doi: 10.1016/j.ejogrb.2018.01.034. Epub 2018 Jan 31.

Diurnal rhythm of follicle-stimulating hormone is associated with nonalcoholic fatty liver disease in a Chinese elderly population.

Author information

1
Department of Geriatric Medicine, Fujian Provincial Hospital, Fujian Provincial Institute of Clinical Geriatrics, Fujian Provincial Key Laboratory of Geriatric Diseases, Fujian Medical University, Fuzhou, 350001, China.
2
Department of Pathology, Fujian Provincial Hospital, Fujian Medical University, Fuzhou, 350001, China.
3
Department of Geriatric Medicine, Fujian Provincial Hospital, Fujian Provincial Institute of Clinical Geriatrics, Fujian Provincial Key Laboratory of Geriatric Diseases, Fujian Medical University, Fuzhou, 350001, China. Electronic address: zpl7755@126.com.
4
Department of Endocrinology, Fujian Provincial Hospital Key Laboratory of Endocrinology, Fujian Medical University, Fuzhou, 350001, China. Electronic address: chengangfj@163.com.

Abstract

OBJECTIVE:

Previous studies have found that impairment of the circadian clock appears to contribute to the development of nonalcoholic fatty liver disease (NAFLD) and the circulating follicle-stimulating hormone (FSH) level showed a diurnal cycle. A recent study reported that a lower FSH level was associated with NAFLD. However, the effects of the diurnal rhythm of FSH on NAFLD have not been reported. The aim of this study was to evaluate whether the diurnal rhythm of FSH was associated with NAFLD in an elderly population.

STUDY DESIGN:

We performed a cross-sectional study among 71 elderly patients between August 2015 and November 2015 at Fujian Provincial Hospital. Anthropometrics and tests for laboratory were performed for each patient. FSH was determined by radioimmunoassay. The FSH receptor (FSHR) expression was identified in liver and ovary tissue by immunohistochemical staining. NAFLD was diagnosed by sonographic features.

RESULTS:

Of the 71 patients, 33 (42.9%) had NAFLD on their ultrasound. There were no significant differences between subjects with NAFLD and those without NAFLD in terms of age, sex, body mass index, waist-to-hip ratio, fasting plasma glucose, postload plasma glucose, liver enzyme, triglycerides, total cholesterol, high-density lipoprotein-cholesterol and low-density lipoprotein-cholesterol. Both the serum FSH levels of 8AM and 0AM showed no differences between the groups. The proportion of the 'normal' diurnal rhythm of FSH was higher among the patients with NAFLD (78.1% vs. 52.6%, P = .027). After adjusting for all potential confounders, the fully adjusted odds ratios (OR) of diurnal rhythm of FSH for NAFLD was 3.86 (95%CI: 1.01, 14.81, P = .049). Immunohistochemical staining showed that the FSHR protein was detected in human ovarian and hepatic tissues.

CONCLUSIONS:

These results suggest that the 'normal' diurnal rhythm of FSH was independently associated with NAFLD in an elderly population. This study provides a novel insight into the diurnal rhythm of FSH in the pathogenesis of NAFLD.

KEYWORDS:

Diurnal rhythm; Follicle-stimulating hormone (FSH); Nonalcoholic fatty liver disease (NAFLD)

PMID:
29408750
DOI:
10.1016/j.ejogrb.2018.01.034
[Indexed for MEDLINE]
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10.
Endocrinology. 2018 Feb 1;159(2):1074-1087. doi: 10.1210/en.2017-00638.

Induction of Stress Signaling In Vitro and Suppression of Gonadotropin Secretion by Free Fatty Acids in Female Mouse Gonadotropes.

Author information

1
Department of Reproductive Medicine, University of California, San Diego, La Jolla, California.
2
Neonatal Intensive Care Unit, Dongguan Eighth People's Hospital, Dongguan, People's Republic of China.

Abstract

An emerging body of evidence supports the concept that the pituitary is a site for integration of multiple physiological and metabolic signals that inform and modulate endocrine pathways. Multiple endocrine mediators of energy balance and adiposity are known to impinge on the neuroendocrine axis regulating reproduction. Observations in humans show that obesity is correlated with decreased gonadotropin secretion, and studies have also suggested that pituitary sensitivity to stimulation by gonadotropin-releasing hormone (GnRH) is decreased in obese individuals. Free fatty acids are a potential mediator of adiposity and energy balance, but their impact as an endocrine modulator of pituitary function has not been closely examined. We evaluated the impact of free fatty acids on a pituitary gonadotrope cell line and in primary pituitary cultures of female mice. We show that increasing physiologically relevant doses of the monounsaturated ω-9 fatty acid oleate induces cellular stress and increases production of reactive oxygen species in a mouse gonadotrope cell line. In contrast, the unsaturated ω-3 α-linolenic and ω-6 linoleic fatty acids do not have this effect. Additionally, oleate can activate immediate-early gene expression independent of GnRH stimulation but has a negative impact on GnRH induction and expression of the gonadotropin subunit gene Lhb. Further, oleate suppresses gonadotropin secretion in response to pulsatile stimulation by GnRH. These results indicate that free fatty acids can directly alter gonadotropin gene expression and secretion in response to GnRH and may provide a link between energy sensing and reproduction.

PMID:
29315384
PMCID:
PMC5793794
[Available on 2019-02-01]
DOI:
10.1210/en.2017-00638
[Indexed for MEDLINE]
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11.
Toxicol Lett. 2018 Mar 15;285:104-112. doi: 10.1016/j.toxlet.2018.01.002. Epub 2018 Jan 3.

Differential regulation of tefluthrin and telmisartan on the gating charges of INa activation and inactivation as well as on resurgent and persistent INa in a pituitary cell line (GH3).

Author information

1
Department of Anesthesia, An Nan Hospital, China Medical University, 70965, Tainan City, Taiwan; Department of Anesthesia, China Medical University, 40447 Taichung City, Taiwan. Electronic address: d11320@mail.tmanh.org.tw.
2
Department of Physiology, National Cheng Kung University Medical College, 70101 Tainan City, Taiwan. Electronic address: snwu@mail.ncku.edu.tw.
3
Department of Pharmacology, College of Medicine, Kaohsiung Medical University, 80756 Kaohsiung City, Taiwan. Electronic address: yichlo@kmu.edu.tw.
4
Department of Medicine, Shanghai Medical College, Fudan University, Shanghai City, China. Electronic address: 15301056039@fudan.edu.cn.

Abstract

Voltage-gated Na+ currents (INa), known to contain many components (e.g., transient, resurgent and persistent INa) with unique gating properties, are involved in the generation and propagation of action potentials in excitable cells. In this study, how tefluthrin (Tef), a synthetic pyrethoid, and telmisartan (TEL), blocker of angiotensin II receptors can perturb those components of INa was investigated. The presence of either Tef or TEL increased the values of the gating charges of INa involved in the activation (za) and inactivation (zi). Tef also increased the amplitude of resurgent INa (INa(R)) or persistent INa (INa(P)) in a pituitary cell line (GH3), while TEL produced minimal effects on them. Subsequent addition of either ranolazine (a blocker of late INa) or d-limonene (a monoterpene), could reverse the changes by TEL or Tef on za or zi. In SCN5A-expressing HEK293T cells, addition of Tef or TEL also increased the peak amplitude and the inactivation time constant of INa which was accompanied by the increased za value of INa. Taken together, the results indicated that Tef- or TEL-mediated changes in the gating kinetics of INa are linked to their actions on functional activity of neurons, neuroendocrine or endocrine cells.

KEYWORDS:

Tefluthrin; Telmisartan; Voltage-gated Na(+) current

PMID:
29306026
DOI:
10.1016/j.toxlet.2018.01.002
[Indexed for MEDLINE]
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12.
Pituitary. 2018 Apr;21(2):194-202. doi: 10.1007/s11102-017-0858-y.

Silent somatotroph pituitary adenomas: an update.

Author information

1
Department of Endocrinology, Centre hospitalier universitaire de Sherbrooke, Sherbrooke, QC, Canada.
2
Department of Medicine, Oregon Health & Science University, Portland, OR, USA.
3
Northwest Pituitary Center, Oregon Health & Science University, Portland, OR, USA.
4
Department of Pathology, Oregon Health & Science University, Portland, OR, USA.
5
Department of Neurological Surgery, Oregon Health & Science University, Portland, OR, USA.
6
Department of Neurological Surgery, Oregon Health & Science University, Portland, OR, USA. fleseriu@ohsu.edu.
7
Department of Medicine, Oregon Health & Science University, Portland, OR, USA. fleseriu@ohsu.edu.
8
Northwest Pituitary Center, Oregon Health & Science University, Portland, OR, USA. fleseriu@ohsu.edu.

Abstract

Silent growth hormone adenomas (SGHA) are a rare entity of non-functioning pituitary neuroendocrine tumors. Diagnosis is invariably made post-operatively of a tumor immunopositive for GH (and Pit-1 in selected cases) but without clinical acromegaly. Mainly young females are affected, and tumors are often uncovered by investigation for headaches or oligoamenorrhea. Integration of clinical, pathological and biochemical data is required for proper diagnosis. Beside normal IGF-1 levels, a third of SGHAs displays elevated GH levels and some will eventually progress to acromegaly. Almost two-thirds will be mixed GH-prolactin tumors and sparsely-granulated monohormonal GH tumors seems the more aggressive subtype. Recurrence and need for radiation is higher than other non-functioning tumors so close follow-up is warranted.

KEYWORDS:

Neuroendocrine tumors; Non-functioning pituitary adenomas; Pituitary; Silent somatotroph; Somatotroph adenomas

PMID:
29305680
DOI:
10.1007/s11102-017-0858-y
[Indexed for MEDLINE]
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13.
Usp Fiziol Nauk. 2017 Jan-Mar;48(1):80-90.

Sensitivity of T-Lymphocytes to Hormones of the Anterior Pituitary Gland.

[Article in Russian]

Abstract

The review provides information about the features of the sensitivity of thymocytes, lymphoid organs' cells and T-lymphocytes of peripheral blood to the hormones secreted by anterior pituitary gland's cells: growth hormone, thyrotropin, adrenocorticotropic hormone, prolactin and β-endorphin. Some aspects of the T-lymphocytes's response to humoral signals from the hypophysis are shown in the article. Also the pituitary hormones' role in the regulation of proliferation, differentiation, and cytokine production of T-lymphocytes in normal and pathological conditions of the organism being discussed.

PMID:
29283520
[Indexed for MEDLINE]
14.
Endocrinology. 2018 Feb 1;159(2):883-894. doi: 10.1210/en.2017-00586.

Association of Gnrhr mRNA With the Stem Cell Determinant Musashi: A Mechanism for Leptin-Mediated Modulation of GnRHR Expression.

Author information

1
Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas.

Abstract

The cyclic expression of pituitary gonadotropin-releasing hormone receptors (GnRHRs) may be an important checkpoint for leptin regulatory signals. Gonadotrope Lepr-null mice have reduced GnRHR levels, suggesting these receptors may be leptin targets. To determine if leptin stimulated GnRHR directly, primary pituitary cultures or pieces were exposed to 1 to 100 nM leptin. Leptin increased GnRHR protein levels and the percentages of gonadotropes that bound biotinylated analogs of gonadotropin-releasing hormone (bio-GnRH) but had no effect on Gnrhr messenger RNA (mRNA). An in silico analysis revealed three consensus Musashi (MSI) binding elements (MBEs) for this translational control protein in the 3' untranslated region (UTR) of Gnrhr mRNA. Several experiments determined that these Gnrhr mRNA MBE were active: (1) RNA electrophoretic mobility shift assay analyses showed that MSI1 specifically bound Gnrhr mRNA 3'-UTR; (2) RNA immunoprecipitation of pituitary fractions with MSI1 antibody pulled down a complex enriched in endogenous MSI protein and endogenous Gnrhr mRNA; and (3) fluorescence reporter assays showed that MSI1 repressed translation of the reporter coupled to the Gnrhr 3'-UTR. In vitro, leptin stimulation of pituitary pieces reduced Msi1 mRNA in female pituitaries, and leptin stimulation of pituitary cultures reduced MSI1 proteins selectively in gonadotropes identified by binding to bio-GnRH. These findings show that leptin's direct stimulatory actions on gonadotrope GnRHR correlate with a direct inhibition of expression of the posttranscriptional regulator MSI1. We also show MSI1 interaction with the 3'-UTR of Gnrhr mRNA. These findings now open the door to future studies of leptin-modulated posttranscriptional pathways.

PMID:
29228137
PMCID:
PMC5776477
[Available on 2019-02-01]
DOI:
10.1210/en.2017-00586
[Indexed for MEDLINE]
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15.
J Vet Med Sci. 2018 Jan 27;80(1):116-124. doi: 10.1292/jvms.17-0569. Epub 2017 Dec 6.

Annexin A1 is a novel target gene of gonadotropin-releasing hormone in LβT2 gonadotrope cells.

Author information

1
Laboratory of Veterinary Physiology, School of Veterinary Medicine, Kitasato University, Towada, Aomori 034-8628, Japan.

Abstract

Gonadotropin-releasing hormone (GnRH) regulates gonadotropin secretion. We previously demonstrated that the expression of annexin A5 (ANXA5) is stimulated by GnRH in gonadotropes and has a significant role in gonadotropin secretion. It is therefore of interest to know whether other members of the ANXA family, which consists of twelve structurally related members, are also regulated by GnRH. Therefore, the expression of all annexins was examined in LβT2 gonadotrope cells. ANXA4, A5, A6, A7 and A11 were detected in LβT2 cells. The expression of ANXA5 and A1 mRNA was stimulated by a GnRH agonist. An increase in ANXA1 protein by this agonist was demonstrated by western blotting. Immunohistochemistry showed that ANXA1 was present in the nucleus and to a lesser extent in the cytoplasm of some rat pituitary cells. The GnRH agonist induced translocation of ANXA1 to the periphery of LβT2 cells. The presence of ANXA1 in gonadotropes and its increase upon GnRH agonist treatment were confirmed in a primary pituitary cell culture. ANXA1 expression was also demonstrated in the ovary, the testis, the thyroid gland and the pancreas in a different manner to that of ANXA5. These data suggest that ANXA1 is a novel GnRH target gene in gonadotropes. ANXA1 also may be a target of local GnRH in peripheral tissues and may have a different role than that of ANXA5.

KEYWORDS:

GnRH; annexin A1; annexin A5; cell biology; gonadotrope

PMID:
29213013
PMCID:
PMC5797869
DOI:
10.1292/jvms.17-0569
[Indexed for MEDLINE]
Free PMC Article
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16.
Gen Comp Endocrinol. 2018 Apr 1;259:104-114. doi: 10.1016/j.ygcen.2017.11.009. Epub 2017 Nov 23.

miRNAome, mRNAome and degradome analysis of Tibetan minipigs anterior pituitary.

Author information

1
Chinese National Engineering Research Center for Breeding Swine Industry, SCAU-Alltech Research Joint Alliance, Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou 510642, China.
2
Chinese National Engineering Research Center for Breeding Swine Industry, SCAU-Alltech Research Joint Alliance, Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou 510642, China. Electronic address: xqy0228@163.com.
3
Chinese National Engineering Research Center for Breeding Swine Industry, SCAU-Alltech Research Joint Alliance, Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou 510642, China. Electronic address: Zhangyl@scau.edu.cn.

Abstract

Tibetan minipig is an important animal model for human diseases. The anterior pituitary is the master gland responsible for growth, reproduction, and metabolism and is regulated by thousands of miRNAs/mRNAs molecules. However, little is known about miRNAs and their relationships with mRNAs in Tibetan minipig anterior pituitary. Using microarray and mRNA-Sequencing, we identified 203 miRNAs and 12,040 mRNA transcripts from the anterior pituitary of Tibetan minipigs. These miRNAs were corresponding to 194 hairpin precursors, 25 miRNA clusters and 24 miRNA families. In addition, 64 intragenic miRNAs were annotated. Using three bioinformatic algorithms (TargetScan, miRanda and RNAhybrid), 359,184 possible miRNA-mRNA interactions were predicted, and an integrated network of miRNAs and pituitary-specific mRNA transcripts was established. To validate the predicted results, the degradome sequencing was employed to confirm miRNA-mRNA interactions, totally, 30 miRNA-mRNA pairs were identified. The present study provided a general overview of miRNA and mRNA annotation in Tibetan minipig anterior pituitary and established a miRNA-mRNA interactions database at the whole genome scale, which helps shed light on the molecular mechanisms in the anterior pituitary of pigs even other mammals.

KEYWORDS:

Anterior pituitary; Pig; Targets; miRNA

PMID:
29174487
DOI:
10.1016/j.ygcen.2017.11.009
[Indexed for MEDLINE]
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17.
Exp Clin Endocrinol Diabetes. 2018 Jun;126(6):342-348. doi: 10.1055/s-0043-122224. Epub 2017 Nov 23.

Sex-Dependent Effect of Metformin on Serum Prolactin Levels In Hyperprolactinemic Patients With Type 2 Diabetes: A Pilot Study.

Author information

1
Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Katowice, Poland.
#
Contributed equally

Abstract

BACKGROUND:

Metformin was found to reduce circulating levels of pituitary hormones.

OBJECTIVE:

The purpose of this study was to assess whether sex determines the effect of metformin on lactotroph secretory function.

METHODS:

The study population included 25 women and 12 men with mildly elevated serum prolactin levels (25-75 ng/mL). Because of concomitant type 2 diabetes, all participants were treated with metformin (3 g daily). Plasma levels of glucose and lipids, HOMA1-IR, serum levels of prolactin, thyrotropin and free thyroid hormones, as well as Jostel's, SPINA-GT and SPINA-GD indices were assessed at baseline and at the end of metformin treatment.

RESULTS:

The study completed 24 women and 11 men. At baseline, there were no significant differences in circulating levels of glucose and lipids, insulin sensitivity, hormones, Jostel's, SPINA-GT and SPINA-GD indices between women and men. In both men and women, metformin reduced fasting glucose levels and HOMA1-IR. However, only in women metformin decreased elevated prolactin levels and this effect correlated with an improvement insulin sensitivity, as well as with the impact on SPINA-GT.

CONCLUSIONS:

The results of the study suggest that the effect of metformin on serum prolactin levels is sex-dependent.

PMID:
29169197
DOI:
10.1055/s-0043-122224
[Indexed for MEDLINE]
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18.
Ann Endocrinol (Paris). 2017 Oct;78 Suppl 1:S31-S40. doi: 10.1016/S0003-4266(17)30923-X.

Contrôle de l’axe gonadotrope : nouveaux aspects physiologiques et thérapeutiques: Control of the gonadotrope axis: new physiologic and therapeutic aspects.

[Article in French]

Author information

1
Université Paris-Sud, Orsay 91400, France; Service d'endocrinologie et des maladies de la reproduction, hôpital Bicêtre, Assistance publique-Hôpitaux de Paris, 94275 Le Kremlin-Bicêtre, France; Service de génétique moléculaire, pharmacogénétique et hormonologie, hôpital Bicêtre, Assistance publique-Hôpitaux de Paris, 94275 Le Kremlin-Bicêtre, France. Electronic address: luigi.maione@aphp.fr.
2
Service d'endocrinologie, hôpital Saint-Antoine, Assistance publique-Hôpitaux de Paris, 75012 Paris, France; Université Pierre-et-Marie-Curie, 75006, Paris, France.
3
Université Paris-Sud, Orsay 91400, France; Service d'endocrinologie et des maladies de la reproduction, hôpital Bicêtre, Assistance publique-Hôpitaux de Paris, 94275 Le Kremlin-Bicêtre, France; INSERM UMR-1185, faculté de médecine Paris-Sud, 94276 Le Kremlin-Bicêtre, France.

Abstract

The endocrine and exocrine functions of the gonads are controlled by the gonadotrope axis, whose master regulator is the hypothalamic decapeptide GnRH. The Kisspeptin/Neurokinin B (Kp/NkB) neuronendocrine system is the main physiologic regulator of GnRH neurons. The Kp/NkB system is currently considered the key mediator for the hypothalamic negative feedback exerted by sex steroids and prolactin, as well as by various metabolic signals. Intrinsic alterations or regulatory abnormalities of Kp/NkB system lead to various gonadotrope axis puberty and fertility dysfunctions. Molecular inactivations of Kp/NkB system actors are associated with some forms of congenital hypogonadotropic hypogonadism without anosmia. The Kp/NkB System is also involved in a few forms of precocious puberty. Finally, the Kp/NKB system is also implicated in gonadotrope axis alterations leading to functional hypothalamic amenorrhea or hyperprolactinemia. NkB is particularly and directly involved in vasomotor menopausal hot flushes mechanism. Various Kp/NkB agonist/antagonist compounds have been developed during the last ten years, and are currently being evaluated in humans. These molecules have potential applications not only in rare genetic diseases with Kp/NkB alterations, but also in various gonadotrope axis-related diseases or in vitro fertilization. The administration of NkB antagonists in menopausal women represents a real therapeutic advance because of their impressive effect in controlling vasomotor menopausal hot flushes.

KEYWORDS:

Bouffées de chaleur de la ménopause; Congenital hypogonadotropic hypogonadism; GnRH; Hypogonadisme hypogonadotrophique congénital; Kisspeptin; Kisspeptine; Neurokinin B; Neurokinine B; Post-menopausal hot flushes; climatére

PMID:
29157487
DOI:
10.1016/S0003-4266(17)30923-X
[Indexed for MEDLINE]
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19.
Brain Res. 2018 Jan 1;1678:278-287. doi: 10.1016/j.brainres.2017.10.036. Epub 2017 Nov 6.

Obestatin stimulates the somatotrophic axis activity in sheep.

Author information

1
Department of Animal Physiology, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, 05-110 Jabłonna, Poland.
2
Department of Animal Physiology, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, 05-110 Jabłonna, Poland. Electronic address: m.szlis@ifzz.pl.

Abstract

The effects of obestatin (an anorexigenic peripheral peptide) on somatotrophic axis activity in ruminants have not yet been determined. The aim of this study was to investigate the consequence of intracerebroventricular infusions of obestatin on the activity of the somatotrophic axis in peripubertal female sheep. Animals were randomly divided into two groups: control group received intracerebroventricular infusions of the vehicle, and the obestatin group was infused with obestatin (25 µg/120 µL h-1). The series of four hourly infusions on three consecutive days were performed. The blood samples were collected on day 0 and on day 3. Immediately after the end of experiment sheep were slaughtered. Parts of the brains were fixed in situ for further immunohistochemical analysis, while the remaining brains were frozen for Real Time RT-qPCR analysis. Substantial changes in the activity of the somatotrophic axis were observed in obestatin-infused sheep. In those animals obestatin evoked an increase in growth hormone-releasing hormone (GHRH) mRNA expression and a decrease in somatostatin mRNA expression in the anterior hypothalamic area. Moreover, a decrease in somatostatin immunoreactivity in the periventricular nucleus and an increase in somatostatin immunopositive fibers in the median eminence were noted. Changes in the GHRH and somatostatin activity are associated with an increase in growth hormone (GH) gene expression and in the amount of GH immunoreactive material stored in the somatotrophic pituitary cells. Consequently, an increase in GH concentration in the peripheral blood, due to an increase in the number of pulses was observed. It was revealed that obestatin affects the somatostatin/GHRH/GH system at the level of protein synthesis, accumulation and release. It is suggested that obestatin participates in the mechanism modulating somatotrophic axis activity at the central level by stimulating GH release through suppression of somatostatin output. Thereby, it can be concluded that obestatin may be involved in the modulation of growth processes in sheep.

KEYWORDS:

Growth hormone; Hypothalamus; Obestatin; Pituitary; Sheep; Somatostatin

PMID:
29108816
DOI:
10.1016/j.brainres.2017.10.036
[Indexed for MEDLINE]
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20.
Biomed Res. 2017;38(5):285-296. doi: 10.2220/biomedres.38.285.

Integrative method for three-dimensional imaging of the entire Golgi apparatus by combining thiamine pyrophosphatase cytochemistry and array tomography using backscattered electron-mode scanning electron microscopy.

Author information

1
Department of Microscopic Anatomy and Cell Biology, Asahikawa Medical University.
2
Division of Morphological Sciences, Kagoshima University Graduate School of Medical and Dental Sciences.
3
Division of Microscopic Anatomy and Bio-imaging, Niigata University Graduate School of Medical and Dental Sciences.

Abstract

Thiamine pyrophosphatase (TPPase) cytochemistry is an established method for specific labeling of the trans-Golgi cisterns in tissue sections. Herein, we combined this enzyme cytochemical method with array tomography using scanning electron microscopy (SEM), a new imaging technique based on collection of backscattered electron (BSE) images of consecutive resin-embedded sections on glass slides, to detect the entire three-dimensional (3D) organization of the Golgi apparatus with sufficient spatial resolution. As the signal intensity of BSE depends on the atomic number of the materials, lead precipitates confined to the trans-Golgi cisterns after TPPase cytochemistry were clearly observed by BSE-mode SEM. The mild fixative used for TPPase cytochemistry also enabled accurate identification of target gonadotropes in the composite pituitary tissue by immunocytochemical staining. By 3D reconstruction of the entire trans-Golgi cisterns based on serial ultrathin section images of tissues after TPPase cytochemistry, we detected ultrastructural differences in the 3D configuration of the Golgi apparatus between cerebellar Purkinje cells and pituitary gonadotropes. The appropriate combination of enzyme cytochemistry and/or immunostaining with array tomography will further clarify the relationship between the organization and functional states of the Golgi apparatus.

PMID:
29070778
DOI:
10.2220/biomedres.38.285
[Indexed for MEDLINE]
Free full text
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