IL-18 expression in clinical human pituitary adenoma

2021 ◽  
pp. 1-6
Author(s):  
Qi Shao ◽  
Ning Liu ◽  
Guo-Fu Li ◽  
Qian-Cheng Meng ◽  
Jia-Hao Yao ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Mrna Expression ◽  
Pituitary Adenomas ◽  
Adrenocorticotropic Hormone ◽  
Pituitary Tumors ◽  
Thyroid Stimulating Hormone ◽  
Mrna Levels ◽  
Human Pituitary ◽  
Human Pituitary Adenoma ◽  
Real Time Quantitative Pcr

BACKGROUND: IL-18 is known as an interferon-inducing factor that belongs to the IL-1 family, and is synthesized as an inactive precursor protein. OBJECTIVE: The present study aims to investigate the expression of IL-18, IL-18R, R and IL-18 binding protein (BP) mRNA in various types of human pituitary tumors, such as adrenocorticotropic hormone (ACTH), growth hormone (GH), prolactin (PRL), thyroid stimulating hormone (TSH)-producing adenomas and non-function adenomas. METHODS: Pituitary adenoma tissues were obtained during the surgery of 41 patients: nine patients had ACTH-producing pituitary adenomas, nine patients had GH-producing pituitary adenomas, five patients had TSH-producing pituitary adenomas, seven patients had PRL-producing pituitary adenomas, and 11 patients had non-functioning adenomas. The mRNA expression levels of IL-18, IL-18BP, IL-18R and IL-18R were quantified using real-time quantitative PCR. RESULTS: The mRNA expression of IL-18 was significantly higher in ACTH-, GH- and PRL-producing adenomas, when compared to non-function tumors. Similarly, a significantly higher mRNA expression of IL-18BP and IL-18R was observed in ACTH-, GH- and PRL-producing adenomas, when compared with non-functional adenomas. In contrast, no upregulation of IL-18R mRNA was observed in any of the pituitary adenomas. CONCLUSIONS: The mRNA levels of IL-18, IL-18BP and IL-18R are significantly elevated in clinical pituitary tumors, such as ACTH-, GH- and PRL-producing adenomas, when compared to non-functional adenomas. These present results suggest the possibility that IL-18 may be involved in the pathogenesis of pituitary adenoma.

scholarly journals miR-26a Plays an Important Role in Cell Cycle Regulation in ACTH-Secreting Pituitary Adenomas by Modulating Protein Kinase Cδ

Endocrinology ◽  
2013 ◽  
Vol 154 (5) ◽  
pp. 1690-1700 ◽  
Author(s):  
Erica Gentilin ◽  
Federico Tagliati ◽  
Carlo Filieri ◽  
Daniela Molè ◽  
Mariella Minoia ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Pituitary Adenoma ◽  
Protein Kinase ◽  
Pituitary Adenomas ◽  
Viable Cell Number ◽  
Pituitary Cells ◽  
Human Pituitary ◽  
Human Pituitary Adenoma ◽  
Acth Secreting ◽  
Protein Kinase Cδ

Abstract The functional aftermath of microRNA (miRNA) dysregulation in ACTH-secreting pituitary adenomas has not been demonstrated. miRNAs represent diagnostic and prognostic biomarkers as well as putative therapeutic targets; their investigation may shed light on the mechanisms that underpin pituitary adenoma development and progression. Drugs interacting with such pathways may help in achieving disease control also in the settings of ACTH-secreting pituitary adenomas. We investigated the expression of 10 miRNAs among those that were found as most dysregulated in human pituitary adenoma tissues in the settings of a murine ACTH-secreting pituitary adenoma cell line, AtT20/D16v-F2. The selected miRNAs to be submitted to further investigation in AtT20/D16v-F2 cells represent an expression panel including 5 up-regulated and 5 down-regulated miRNAs. Among these, we selected the most dysregulated mouse miRNA and searched for miRNA targets and their biological function. We found that AtT20/D16v-F2 cells have a specific miRNA expression profile and that miR-26a is the most dysregulated miRNA. The latter is overexpressed in human pituitary adenomas and can control viable cell number in the in vitro model without involving caspase 3/7-mediated apoptosis. We demonstrated that protein kinase Cδ (PRKCD) is a direct target of miR-26a and that miR26a inhibition delays the cell cycle in G1 phase. This effect involves down-regulation of cyclin E and cyclin A expression via PRKCD modulation. miR-26a and related pathways, such as PRKCD, play an important role in cell cycle control of ACTH pituitary cells, opening new therapeutic possibilities for the treatment of persistent/recurrent Cushing's disease.

Advances in Our Understanding of Pituitary Adenoma

2008 ◽  
Vol 04 (01) ◽  
pp. 88
Author(s):  
Sandra Pekic ◽  
Vera Popovic-Brkic
Keyword(s):  
Pituitary Adenoma ◽  
Pituitary Adenomas ◽  
Pituitary Tumors ◽  
Pituitary Hormones ◽  
Current Treatment ◽  
Thyroid Stimulating Hormone ◽  
Treatment Modalities ◽  
High Resolution Computed Tomography ◽  
New Therapeutic Approaches ◽  
Asymptomatic Patients

Pituitary adenomas are common benign monoclonal neoplasms— accounting for 15% of intracranial neoplasms—that may be clinically silent or secrete anterior pituitary hormones such as prolactin, growth hormone (GH), adrenocorticotrophic hormone (ACTH), or, rarely, thyroid-stimulating hormone (TSH) or gonadotrophins. Radiological studies for other reasons using high-resolution computed tomography (CT) or magnetic resonance imaging (MRI) detect incidental pituitary adenomas in approximately 20% of asymptomatic patients.1The incidence of the various types of adenoma varies;2prolactinomas are the most common pituitary adenomas. Clinically non-functioning pituitary adenomas (NFPAs), which do not secrete hormones, often cause local mass symptoms and represent one-third of pituitary adenomas. GH- and ACTH-producing adenomas each account for 10–15% of pituitary adenomas, while TSH-producing adenomas are rare. Pituitary adenomas are infrequent in childhood: fewer than 10% of pituitary adenomas are diagnosed before 20 years of age.3These adenomas can be either microor macroadenomas. The natural course of microadenomas is that a few tumors enlarge over a period of more than eight years.Although several genes and signaling pathways have been identified as important factors in the development of pituitary tumors, our understanding of pituitary tumorigenesis remains incomplete and is the focus of current research. The reason for this is that current treatment modalities fail to completely control this disorder and prevent the associated morbidity and mortality. This article reviews the advances in our understanding of pituitary adenoma, especially in the field of pathogenesis of pituitary tumors, and the possibility of new therapeutic approaches.

scholarly journals Identification of Adrenocorticotropin Receptor Messenger Ribonucleic Acid in the Human Pituitary and Its Loss of Expression in Pituitary Adenomas

2003 ◽  
Vol 88 (12) ◽  
pp. 6080-6087 ◽  
Author(s):  
Damian G. Morris ◽  
Blerina Kola ◽  
Ninetta Borboli ◽  
Gregory A. Kaltsas ◽  
Maria Gueorguiev ◽  
...  
Keyword(s):  
Pituitary Adenomas ◽  
Direct Sequencing ◽  
Mrna Levels ◽  
Coding Region ◽  
Human Pituitary ◽  
Messenger Ribonucleic Acid ◽  
Human Pituitary Gland ◽  
Real Time Quantitative Pcr ◽  
Acth Secreting ◽  
Corticotroph Adenomas

Abstract The ACTH receptor (ACTH-R) is the second member of the melanocortin (MC-2) receptor family that includes five seven-transmembrane G protein-coupled receptors and has been shown to be predominantly expressed in the adrenal cortex. It has been postulated that ACTH may regulate its own secretion through ultra-short-loop feedback within the pituitary. ACTH-secreting adenomas are characterized by resistance to glucocorticoid feedback, and they may have dysregulated ACTH feedback. We therefore investigated the ACTH-R in normal and adenomatous human pituitary tissue. We report here the identification of ACTH-R mRNA in the human pituitary gland, which was confirmed by direct sequencing. We studied the expression of the ACTH-R in 23 normal pituitary specimens and 53 pituitary adenomas (22 ACTH-secreting, nine GH-secreting, eight prolactin-secreting, one TSH-secreting, one FSH-secreting, 10 nonfunctioning, and two silent corticotroph adenomas), using the sensitive technique of real-time quantitative PCR. Contamination of ACTH-secreting adenomas and nonfunctioning pituitary adenomas with nonadenomatous tissue was excluded by lack of Pit-1 expression. ACTH-R mRNA was detected in all normal pituitary specimens, and in situ hybridization colocalized expression to ACTH staining cells only. However, ACTH-R mRNA levels were undetectable in 16 of 22 ACTH-secreting tumors and in both silent corticotroph tumors. Diagnostic preoperative plasma ACTH levels were significantly lower in the ACTH-R positive ACTH-secreting tumors, compared with those who were ACTH-R negative (P = 0.0006). Direct sequencing of the coding region of the ACTH-R in cDNA from three ACTH-secreting tumors positively expressing the receptor showed no mutations, as did sequencing of genomic DNA in three receptor negative ACTH-secreting tumors and the two silent corticotrophs. These results provide further evidence compatible with an ACTH feedback loop in the pituitary and suggest that loss of expression of the ACTH-R in corticotroph adenomas of patients with Cushing’s disease may play a role in the resistance to feedback of the pituitary-adrenal axis seen in these patients.

scholarly journals RSUME is implicated in HIF-1-induced VEGF-A production in pituitary tumour cells

2011 ◽  
Vol 19 (1) ◽  
pp. 13-27 ◽  
Author(s):  
B Shan ◽  
J Gerez ◽  
M Haedo ◽  
M Fuertes ◽  
M Theodoropoulou ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Hypoxia Inducible Factor ◽  
Pituitary Tumour ◽  
Mrna Levels ◽  
Human Pituitary ◽  
Human Pituitary Adenoma ◽  
Protein Levels ◽  
Hypoxic Conditions ◽  
Adaptive Processes ◽  
Endothelial Growth Factor

The recently cloned small RWD-domain containing protein RSUME was shown to increase protein levels of hypoxia-inducible factor-1α (HIF-1α). The latter is the oxygen-regulated subunit of HIF-1, the most important transcription factor of the cellular adaptive processes to hypoxic conditions. It is also a major regulator of vascular endothelial growth factor-A (VEGF-A), which is critically involved in the complex process of tumour neovascularisation. In this study, the expression and role of RSUME in pituitary tumours was studied. We found that RSUME mRNA was up-regulated in pituitary adenomas and significantly correlated with HIF-1α mRNA levels. Hypoxia (1% O2) or treatment with hypoxia-mimicking CoCl2enhanced RSUME and HIF-1α expression, induced translocation of HIF-1α to the nuclei and stimulated VEGF-A production both in pituitary tumour cell lines and primary human pituitary adenoma cell cultures. When RSUME expression was specifically down-regulated by siRNA, the CoCl2-induced increase VEGF-A secretion was strongly reduced which was shown to be a consequence of the RSUME knockdown-associated reduction of HIF-1α synthesis. Thus, RSUME plays an important role in initiating pituitary tumour neovascularisation through regulating HIF-1α levels and subsequent VEGF-A production and may therefore be critically involved in pituitary adenoma progression.

scholarly journals Pituitary adenoma in aged rats. A case report

2018 ◽  
Vol 59 (1) ◽  
pp. 58
Author(s):  
M KATSIMPOULAS ◽  
M FOTEINOU ◽  
E PARONIS ◽  
P ALEXAKOS ◽  
N KOSTOMITSOPOULOS
Keyword(s):  
Pituitary Adenoma ◽  
Pituitary Adenomas ◽  
Large Scale ◽  
Laboratory Animals ◽  
Neoplastic Disease ◽  
Aged Rats ◽  
Human Pituitary ◽  
Human Pituitary Adenoma ◽  
Neoplastic Lesion ◽  
Toxicological Studies

The prevalence of neoplastic disease in the rat is well defined, because this species has been routinely used for decades in large-scale carcinogenic, aging and toxicological studies. Stock and strain-specific differences in the prevalence of some types of tumors are well documented. Pituitary adenoma is a neoplastic lesion which can be observed in older or aged rats of both sexes. In addition to sex, strain, diet, genetic factor, breeding history and accommodation may also play a role. Pituitary adenoma can also affect hamster, guinea pig and mice. The aim of this article is to report an incidence of pituitary adenomas, which was observed in a rat breeding colony of the Center for Experimental Surgery of the Biomedical Research Foundation of the Academy of Athens. During the clinical examination five female Wistar rats, at the age of 18 to 24 months old, expressed anorexia, weight loss, ataxia and bilateral blindness. At necropsy, the pituitary gland was enlarged with lobulations, often dark red to brown and hemorrhagic in appearance. In some cases there was a marked compression of the overlying mesencephalon. Histological examination with haematoxylin-eosin were observed cords and nests of glandular cells bound by strands of connective tissue, with an abundant capillary network. On immunohistochemical examination were observed strong positive reaction of synaptophysin. Findings were similar to pituitary adenoma. Pituitary adenoma is a serious non-reversible disease leading to the death of the animal. Laboratory animals with pituitary adenomas can be used as models in research of human pituitary adenoma.

scholarly journals Cushing Disease Due to Ectopic Pituitary Adenoma.

2019 ◽  
pp. 1-5
Keyword(s):  
Pituitary Adenoma ◽  
Pituitary Adenomas ◽  
Adrenocorticotropic Hormone ◽  
Pituitary Tumors ◽  
Pituitary Stalk ◽  
Cushing Disease ◽  
Ectopic Acth ◽  
Common Cause ◽  
Ectopic Pituitary Adenoma ◽  
Acth Secreting

Abstract Adrenocorticotropic hormone (ACTH) - secreting pituitary adenomas are the most common cause of Cushing disease. A pituitary adenoma is rarely ectopic and suprasellar dependent (ectopic) ACTH -secreting pituitary tumors are extremely rare, with few cases described in the literature. Therefore, this study aimed to report the case of a patient with a diagnosis of Cushing disease because of a suprasellar ACTH-secreting tumor attached to the pituitary stalk, requiring a craniotomy.

scholarly journals Characterization of SNARE Proteins in Human Pituitary Adenomas: Targeted Secretion Inhibitors as a New Strategy for the Treatment of Acromegaly?

2013 ◽  
Vol 98 (12) ◽  
pp. E1918-E1926 ◽  
Author(s):  
Edwin A. Garcia ◽  
Giampaolo Trivellin ◽  
Elena D. Aflorei ◽  
Michael Powell ◽  
Joana Grieve ◽  
...  
Keyword(s):  
Catalytic Activity ◽  
Pituitary Adenoma ◽  
Pituitary Adenomas ◽  
Hormone Secretion ◽  
Snare Proteins ◽  
University Hospitals ◽  
Human Pituitary ◽  
Human Pituitary Adenoma ◽  
Gh Secretion ◽  
Ghrh Receptor

Context: Targeted secretion inhibitors (TSIs), a new class of recombinant biotherapeutic proteins engineered from botulinum toxin, represent a novel approach for treating diseases with excess secretion. They inhibit hormone secretion from targeted cell types through cleavage of SNARE (soluble N-ethylmaleimide-sensitive factor-activating protein receptor) proteins. qGHRH-LHN/D is a TSI targeting pituitary somatotroph through binding to the GHRH-receptor and cleavage of the vesicle-associated membrane protein (VAMP) family of SNARE proteins. Objective: Our objective was to study SNARE protein expression in pituitary adenomas and to inhibit GH secretion from somatotropinomas using qGHRH-LHN/D. Design: We analyzed human pituitary adenoma analysis for SNARE expression and response to qGHRH-LHN/D treatment. Setting: The study was conducted in University Hospitals. Patients: We used pituitary adenoma samples from 25 acromegaly and 47 nonfunctioning pituitary adenoma patients. Outcome: Vesicle-SNARE (VAMP1–3), target-SNARE (syntaxin1, SNAP-23, and SNAP-25), and GHRH-receptor detection with RT-qPCR, immunocytochemistry, and immunoblotting. Assessment of TSI catalytic activity on VAMPs and release of GH from adenoma cells. Results: SNARE proteins were variably expressed in pituitary samples. In vitro evidence using recombinant GFP-VAMP2&3 or pituitary adenoma lysates suggested sufficient catalytic activity of qGHRH-LHN/D to degrade VAMPs, but was unable to inhibit GH secretion in somatotropinoma cell cultures. Conclusions: SNARE proteins are present in human pituitary somatotroph adenomas that can be targeted by TSIs to inhibit GH secretion. qGHRH-LHN/D was unable to inhibit GH secretion from human somatotroph adenoma cells. Further studies are required to understand how the SNARE proteins drive GH secretion in human somatotrophs to allow the development of novel TSIs with a potential therapeutic benefit.

MICROSURGICAL ANATOMY OF THE DIAPHRAGMA SELLAE AND ITS ROLE IN DIRECTING THE PATTERN OF GROWTH OF PITUITARY ADENOMAS

Neurosurgery ◽  
2008 ◽  
Vol 62 (3) ◽  
pp. 717-723 ◽  
Author(s):  
Alvaro Campero ◽  
Carolina Martins ◽  
Alexandre Yasuda ◽  
Albert L. Rhoton
Keyword(s):  
Pituitary Adenoma ◽  
Cavernous Sinus ◽  
Dura Mater ◽  
Pituitary Adenomas ◽  
Potential Role ◽  
Pituitary Tumors ◽  
Microsurgical Anatomy ◽  
Suprasellar Region ◽  
Lateral Distance ◽  
Diaphragma Sellae

Abstract OBJECTIVE To evaluate the anatomic aspects of the diaphragma sellae and its potential role in directing the growth of a pituitary adenoma. METHODS Twenty cadaveric heads were dissected and measurements were taken at the level of the diaphragma sellae. RESULTS The diaphragma sellae is composed of two layers of dura mater. There is a remarkable variation in the morphology of the diaphragm opening. The average anteroposterior distance of the opening was 7.26 mm (range, 3.4–10.7 mm) and the average lateral-to-lateral distance was 7.33 mm (range, 2.8–14.1 mm). CONCLUSION The variability in the diameter of the opening of the diaphragma sellae could explain the growth of pituitary tumors toward the cavernous sinus or toward the suprasellar region.

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