scholarly journals Novel somatic variants involved in biochemical activity of pure growth hormone-secreting pituitary adenoma without GNAS variant

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Cheol Ryong Ku ◽  
Hyeonseob Lim ◽  
Yang Jong Lee ◽  
Sun Ho Kim ◽  
Daham Kim ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Pituitary Adenoma ◽  
Pituitary Adenomas ◽  
Pituitary Tumors ◽  
Genetic Alterations ◽  
Biochemical Activity ◽  
Recurrent Point ◽  
Targeted Resequencing ◽  
Severance Hospital

AbstractWe aimed to identify somatic genetic alterations in pure growth hormone (GH)-secreting pituitary adenomas without GNAS variants. Patients with GH-secreting pituitary adenoma who underwent transsphenoidal adenomectomy at Severance Hospital, Yonsei University College of Medicine were recruited. Somatic genetic alterations were profiled by whole-exome sequencing (WES) and targeted resequencing. WES was performed using DNA from nine GH-secreting pituitary tumors and corresponding blood samples. Absence of GNAS variant was confirmed by Sanger sequencing. For targeted resequencing of 140 fixed tissues, 48 WES-derived candidate genes and 7 GH-secreting pituitary adenoma-associated genes were included. Forty-eight genes with 59 somatic variants were identified by WES. In targeted resequencing, variants in 26 recurrent genes, including MAST4, PRIM2, TNN, STARD9, DNAH11, DOCK4, GPR98, BCHE, DARS, CUBN, NGDN, PLXND1, UNC5B, and COL22A1, were identified, but variants in previously reported genes were not detected. BCHE, DARS, NGDN, and UNC5B variants were associated with increased GH-secreting pituitary tumor biochemical activity, which was confirmed in vitro. Although recurrent point variants were rare, several somatic variants were identified in sporadic pure GH-secreting pituitary adenomas. Several somatic variants may affect pathways involved in the tumorigenesis and biochemical activities of GH-secreting pituitary adenomas.

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.

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.

Prolactin gene expression in human growth hormone-secreting pituitary adenomas

1990 ◽  
Vol 72 (6) ◽  
pp. 879-882 ◽  
Author(s):  
Takashi Nagaya ◽  
Hisao Seo ◽  
Akio Kuwayama ◽  
Tsuyoshi Sakurai ◽  
Nobuhiro Tsukamoto ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Hormone ◽  
Pituitary Adenomas ◽  
Tumor Tissue ◽  
Pituitary Tumors ◽  
Human Growth ◽  
Content Type ◽  
Messenger Ribonucleic Acid ◽  
Prolactin Gene ◽  
Adenoma Tissue

✓ To elucidate the mechanism of hyperprolactinemia often observed in patients with growth hormone (GH)-secreting pituitary adenomas, the presence of immunoreactive prolactin (ir-PRL) and prolactin (PRL) messenger ribonucleic acid (mRNA) in the tumor tissue was examined by immunohistochemistry and cytoplasmic dot hybridization. Hyperprolactinemia was observed in three of 18 patients with GH-secreting adenoma. The tumor tissue was demonstrated to contain ir-PRL in nine patients and PRL mRNA in 13. The presence of ir-PRL in the tumor tissue was always associated with positive PRL mRNA, indicating production of PRL in GH-secreting tumors. Among the three patients with hyperprolactinemia, both ir-PRL and PRL mRNA was revealed in the tumor tissue of one, PRL mRNA but not ir-PRL was detected in the adenoma tissue of another, and neither PRL mRNA nor ir-PRL was found in the tumor tissue of the third. The association of hyperprolactinemia with the presence of both ir-PRL and PRL mRNA or PRL mRNA alone is indicative of PRL production and secretion. However, the absence of ir-PRL and PRL mRNA in the tumor tissue may indicate that hyperprolactinemia is caused by the suppression of PRL inhibitory factor due to hypothalamic dysfunction by the tumor mass. Thus, the study of PRL gene expression and immunohistochemistry in GH-secreting adenomas is valuable to understanding the pathophysiology of pituitary tumors.

scholarly journals Cyclin-dependent kinase inhibitor 1B (CDKN1B) gene variants in AIP mutation-negative familial isolated pituitary adenoma kindreds

2012 ◽  
Vol 19 (3) ◽  
pp. 233-241 ◽  
Author(s):  
Maria A Tichomirowa ◽  
Misu Lee ◽  
Anne Barlier ◽  
Adrian F Daly ◽  
Ilaria Marinoni ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Pituitary Adenomas ◽  
Kinase Inhibitor ◽  
Carney Complex ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Pituitary Tumorigenesis ◽  
Sds Page ◽  
Clinicopathological Profile ◽  
Low Incidence

Familial isolated pituitary adenoma (FIPA) occurs in families and is unrelated to multiple endocrine neoplasia type 1 and Carney complex. Mutations inAIPaccount only for 15–25% of FIPA families.CDKN1Bmutations cause MEN4 in which affected patients can suffer from pituitary adenomas. With this study, we wanted to assess whether mutations inCDKN1Boccur among a large cohort ofAIPmutation-negative FIPA kindreds. Eighty-eightAIPmutation-negative FIPA families were studied and 124 affected subjects underwent sequencing ofCDKN1B. Functional analysis of putativeCDKN1Bmutations was performed usingin silicoandin vitroapproaches. GermlineCDKN1Banalysis revealed two nucleotide changes: c.286A>C (p.K96Q) and c.356T>C (p.I119T).In vitro, the K96Q change decreased p27 affinity for Grb2 but did not segregate with pituitary adenoma in the FIPA kindred. The I119T substitution occurred in a female patient with acromegaly. p27I119Tshows an abnormal migration pattern by SDS–PAGE. Three variants (p.S56T, p.T142T, and c.605+36C>T) are likely nonpathogenic becauseIn vitroeffects were not seen. In conclusion, two patients had germline sequence changes inCDKN1B, which led to functional alterations in the encoded p27 proteinsin vitro. Such rareCDKN1Bvariants may contribute to the development of pituitary adenomas, but their low incidence and lack of clear segregation with affected patients makeCDKN1Bsequencing unlikely to be of use in routine genetic investigation of FIPA kindreds. However, further characterization of the role ofCDKN1Bin pituitary tumorigenesis in these and other cases could help clarify the clinicopathological profile of MEN4.

scholarly journals A Rare Corticotroph-Secreting Tumor with Coexisting Prolactin and Growth Hormone Staining Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Subramanian Kannan ◽  
Susan M. Staugaitis ◽  
Robert J. Weil ◽  
Betul Hatipoglu
Keyword(s):  
Growth Hormone ◽  
Transcription Factors ◽  
Pituitary Adenoma ◽  
Pituitary Adenomas ◽  
Rare Case ◽  
Pituitary Hormones ◽  
Review Literature ◽  
Pituitary Cells ◽  
Biological Mechanisms

Pituitary adenomas can express and secrete different hormones. Expression of pituitary hormones in nonneoplastic pituitary cells is regulated by different transcription factors. Some pituitary adenomas show plurihormonal expression. The most commonly reported plurihormonal adenomas are composed of somatotrophs, lactotrophs, thyrotrophs and gonadotrophs. Pituitary adenomas composed of both corticotroph and somatolactotroph secreting cells are not common because transcription factors regulating the expression of these hormones are different. We report a rare case of pituitary adenoma with concomitant corticotroph, prolactin, and growth hormone staining cells, review literature on similar cases, and discuss possible biological mechanisms underlying these plurihormonal tumors.

MicroRNA miR-107 is overexpressed in pituitary adenomas and inhibits the expression of aryl hydrocarbon receptor-interacting protein in vitro

2012 ◽  
Vol 303 (6) ◽  
pp. E708-E719 ◽  
Author(s):  
Giampaolo Trivellin ◽  
Henriett Butz ◽  
Juliette Delhove ◽  
Susana Igreja ◽  
Harvinder S. Chahal ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Tumor Suppressor ◽  
Aryl Hydrocarbon Receptor ◽  
Pituitary Adenomas ◽  
Expression Profiles ◽  
Luciferase Assay ◽  
Human Neuroblastoma ◽  
Interacting Protein ◽  
Aryl Hydrocarbon

Abnormal microRNA (miRNA) expression profiles have recently been associated with sporadic pituitary adenomas, suggesting that miRNAs can contribute to tumor formation; miRNAs are small noncoding RNAs that inhibit posttranscriptional expression of target mRNAs by binding to target sequences usually located in the 3′-UTR. In this study, we investigated the role played by miR-107, a miRNA associated with different human cancers, in sporadic pituitary adenomas and its interaction with the pituitary tumor suppressor gene aryl hydrocarbon receptor-interacting protein ( AIP). miR-107 expression was evaluated in pituitary adenoma and normal pituitary samples using microRNA screen TLDA (TaqMan Low-Density Array) and RT-qPCR assays. We show that miR-107 expression was significantly upregulated in GH-secreting and nonfunctioning pituitary adenomas. We found that human AIP-3′-UTR is a target of miR-107 since miR-107 inhibited in vitro AIP expression to 53.9 ± 2% of the miRNA control in a luciferase assay and reduced endogenous AIP mRNA expression to 53 ± 22% of the miRNA control in human cells. However, we did not observe a negative correlation between AIP and miR-107 expression in the human tumor samples. Furthermore, we show that miR-107 overexpression inhibited cell proliferation in human neuroblastoma and rat pituitary adenoma cells. In conclusion, miR-107 is overexpressed in pituitary adenomas and may act as a tumor suppressor. We have identified and confirmed AIP as a miR-107 target gene. Expression data in human samples suggest that the expression of AIP and miR-107 could be influenced by a combination of tumorigenic factors as well as compensatory mechanisms stimulated by the tumorigenic process.

In Vitro Effect of Dopamine on Growth Hormone (GH)Release from Human GH-Secreting Pituitary Adenomas

1982 ◽  
Vol 55 (4) ◽  
pp. 734-740 ◽  
Author(s):  
A. SPADA ◽  
A. SARTORIO ◽  
M. BASSETTI ◽  
G. PEZZO ◽  
G. GIANNATTASIO
Keyword(s):  
Growth Hormone ◽  
Pituitary Adenomas ◽  
Vitro Effect

scholarly journals Dopamine receptor subtype 2 and somatostatin receptor subtype 5 expression influences somatostatin analogs effects on human somatotroph pituitary adenomas in vitro

2005 ◽  
Vol 35 (2) ◽  
pp. 333-341 ◽  
Author(s):  
M C Zatelli ◽  
D Piccin ◽  
F Tagliati ◽  
A Bottoni ◽  
M R Ambrosio ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Primary Culture ◽  
Pituitary Adenomas ◽  
Somatostatin Receptor ◽  
Somatostatin Analogs ◽  
Receptor Subtype ◽  
Inhibitory Effects ◽  
Gh Secretion ◽  
Secretion Inhibition

Dopamine (DA) and somatostatin (SRIF) receptor agonists inhibit growth hormone (GH) secretion by pituitary adenomas. We investigated DA subtype 2 receptor (DR2) and SRIF receptor (sst) subtypes 2 and 5 expression in 25 GH-secreting pituitary adenomas and tested in primary culture the effects on GH and prolactin (PRL) secretion of sst agonists selectively interacting with sst2 (BIM-23120), sst5 (BIM-23206), and sst2 and sst5 (BIM-23244). All adenomas expressed sst2; eight adenomas expressed both sst5 and DR2, eight sst5 but not DR2, and eight DR2 but not sst5. One tissue lacked expression of DR2 and sst5. GH secretion was inhibited by BIM-23120 in all samples, while it was reduced by BIM-23206 only in adenomas not expressing DR2. BIM-23120’s inhibitory effects correlated with sst2 and DR2 expression, whereas DR2 expression correlated inversely with BIM-23206 inhibitory effects on GH secretion. In seven mixed GH-/PRL-secreting pituitary adenomas, PRL secretion was inhibited in sst5-expressing tumors by BIM-23206, but not by BIM-23120. BIM-23244 reduced PRL secretion only in adenomas expressing sst2, sst5 and DR2. sst5 and DR2 expression correlated directly with BIM23206 inhibitory effects on PRL secretion. Our results suggest that adenomas expressing DR2 are less likely to respond to clinically available SRIF analogs in terms of GH secretion inhibition. Therefore, drugs interacting also with DR2 might better control secretion of pituitary adenomas.

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