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 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.

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 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.

The EFEMP1 Gene: A Frequent Target for Epigenetic Silencing in Multiple Human Pituitary Adenoma Subtypes

2013 ◽  
Vol 98 (3) ◽  
pp. 200-211 ◽  
Author(s):  
Cuong V. Duong ◽  
Kiren Yacqub-Usman ◽  
Richard D. Emes ◽  
Richard N. Clayton ◽  
William E. Farrell
Keyword(s):  
Pituitary Adenoma ◽  
Epigenetic Silencing ◽  
Human Pituitary ◽  
Human Pituitary Adenoma

Isolation of large numbers of dispersed human pituitary adenoma cells obtained by aspiration

1984 ◽  
Vol 7 (4) ◽  
pp. 307-311 ◽  
Author(s):  
Robert Oosterom ◽  
G. Blaauw ◽  
R. Singh ◽  
T. Verleun ◽  
S. W. J. Lamberts
Keyword(s):  
Pituitary Adenoma ◽  
Human Pituitary ◽  
Human Pituitary Adenoma ◽  
Large Numbers

scholarly journals Suppression of Tyrosine Kinase Activity Inhibits[ 3H]Thymidine Uptake in Cultured Human Pituitary Tumor Cells1

1997 ◽  
Vol 82 (7) ◽  
pp. 2143-2147
Author(s):  
T. H. Jones ◽  
S. K. Justice ◽  
A. Price
Keyword(s):  
Cell Culture ◽  
Growth Factors ◽  
Tyrosine Kinase ◽  
Pituitary Adenomas ◽  
Kinase Activity ◽  
Gh3 Cells ◽  
Thymidine Uptake ◽  
Tyrosine Kinase Activity ◽  
Human Pituitary ◽  
Human Pituitary Adenoma

Tyrosine kinases are involved in the phosphorylation of proteins that regulate cell growth and proliferation. The mitogenic effect of several growth factors requires tyrosine kinase activity of their receptors. The effect of inhibition of tyrosine kinase activity on thymidine uptake into cultured human pituitary adenoma cells was studied using two inhibitors, genestein and methyl-2,3-dihydroxycinnamate (MDHC). Of 33 pituitary adenomas, 7 incorporated sufficient[ 3H]thymidine to be investigated in the experiments. Genestein and MDHC both potently inhibited thymidine uptake into these tumors, with a mean inhibition by 74 μmol/L genestein of 61.96± 18.96% (±sd inhibition of basal), by 740 μmol/L genestein of 92.65 ± 8.59%, and by 100 μmol/L MDHC of 93.84 ± 3.85%. The 7 pituitary adenomas were all large with suprasellar extension and secreted interleukin-6 in vitro. They included 2 prolactinomas, 1 somatotropinoma, 1 mammosomatropinoma, and 3 clinically nonfunctioning adenomas. Epidermal growth factor stimulated thymidine uptake in 2 of the 3 clinically nonfunctioning adenomas studied, and this stimulation was inhibited by genestein. Both of these tumors released FSH in cell culture and are probably silent gonadotropinomas. The growth stimulatory effect of conditioned medium from human pituitary cell culture on GH3 cells was inhibited by both genestein and MDHC. We conclude that tyrosine kinase activity is crucial for the integrity and growth of pituitary adenomas in culture. Growth factors released by pituitary adenomas potentially may maintain and promote tumor growth by stimulating tyrosine kinase activity.

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