Oncocytomas and null cell adenomas of the human pituitary: Morphometric and in vitro functional comparison

1988 ◽  
Vol 413 (4) ◽  
pp. 333-339 ◽  
Author(s):  
Shozo Yamada ◽  
Sylvia L. Asa ◽  
Kalman Kovacs
Keyword(s):  
Null Cell ◽  
Human Pituitary ◽  
Null Cell Adenomas

Gonadotropin Secretion in Vitro by Human Pituitary Null Cell Adenomas and Oncocytomas**

1986 ◽  
Vol 62 (5) ◽  
pp. 1011-1019 ◽  
Author(s):  
SYLVIA L. ASA ◽  
BLAIR M. GERRIE ◽  
WILLIAM SINGER ◽  
EVA HORVATH ◽  
KALMAN KOVACS ◽  
...  
Keyword(s):  
Null Cell ◽  
Human Pituitary ◽  
Gonadotropin Secretion ◽  
Null Cell Adenomas

scholarly journals Clinically Non-Functioning Human Pituitary Adenomas

1992 ◽  
Vol 19 (2) ◽  
pp. 228-235 ◽  
Author(s):  
Sylvia L. Asa ◽  
Kalman Kovacs
Keyword(s):  
Pituitary Adenomas ◽  
Cell Types ◽  
Null Cell ◽  
Human Pituitary ◽  
Endocrine Activity ◽  
Hormone Synthesis ◽  
A Subunit ◽  
Null Cell Adenomas

ABSTRACT:Clinically non-functioning pituitary adenomas are morphologically classified into two groups, those which have hormone immunoreactivity and ultrastructural features of known adenohypophysial cell types but are clinically silent, and those composed of cells that do not resemble nontumorous adenohypophysial cell types. Among the fomer are the silent somatotroph adenomas, silent corticotroph adenomas and silent gonadotroph adenomas; the latter include the silent type III adenomas, null cell adenomas and oncocytomas. We review their histological, immunohistochemical and ultrastructural features, the results of in situ hybridization to determine hormone synthesis by these tumors and data obtained from tissue culture characterizing their hormone release in vitro. Non-functioning adenomas represent a heterogeneous group. The discrepancies between morphology, immunoreactivity and lack of endocrine activity of silent adenomas are not clear. Oncocytomas are variants of null cell adenomas. We suggest that null cell adenomas and oncocytomas originate in uncommitted pluripotent precursor cells capable of undergoing multidirectional differentiation. The progenitor cells differentiate most frequently toward FSH / a-subunit producing cells; the mechanism of preferential differentiation is obscure.

Null cell adenomas, oncocytomas, and gonadotroph adenomas of the human pituitary: An immunocytochemical and ultrastructural anafysis of 300 cases

1993 ◽  
Vol 4 (1) ◽  
pp. 20-27 ◽  
Author(s):  
George Kontogeorgos ◽  
Kalman Kovacs ◽  
Eva Horvath ◽  
Bernd W. Scheithauer
Keyword(s):  
Null Cell ◽  
Human Pituitary ◽  
Null Cell Adenomas

scholarly journals PTTG’s C-terminal PXXP motifs modulate critical cellular processes in vitro

2004 ◽  
Vol 33 (3) ◽  
pp. 663-677 ◽  
Author(s):  
K Boelaert ◽  
R Yu ◽  
L A Tannahill ◽  
A L Stratford ◽  
F L Khanim ◽  
...  
Keyword(s):  
Cell Transformation ◽  
Phosphorylation Site ◽  
Null Cell ◽  
Human Pituitary ◽  
Multifunctional Protein ◽  
Cellular Processes ◽  
Proliferation Assays ◽  
Nih 3T3

Human pituitary tumor-transforming gene (PTTG), known also as securin, is a multifunctional protein implicated in the control of mitosis and the pathogenesis of thyroid, colon, oesophageal and other tumour types. Critical to PTTG function is a C-terminal double PXXP motif, forming a putative SH3-interacting domain and housing the gene’s sole reported phosphorylation site. The exact role of phosphorylation and PXXP structure in the modulation of PTTG action in vitro remains poorly understood. We therefore examined the mitotic, transformation, proliferation and transactivation function of the C-terminal PXXP motifs of human PTTG. Live-cell imaging studies using an EGFP-PTTG construct indicated that PTTG’s regulation of mitosis is retained regardless of phosphorylation status. Colony-formation assays demonstrated that phosphorylation of PTTG may act as a potent inhibitor of cell transformation. In proliferation assays, NIH-3T3 cells stable transfected and overexpressing mutations preventing PTTG phosphorylation (Phos-) showed significantly increased [3H]thymidine incorporation compared with WT, whereas mutants mimicking constitutive phosphorylation of PTTG (Phos+) exhibited reduced cell proliferation. We demonstrated that PTTG transactivation of FGF-2 in primary thyroid and PTTG-null cell lines was not affected by PTTG phosphorylation but was prevented by a mutant disrupting the PXXP motifs (SH3-). Taken together, our data suggest that PXXP structure and phosphorylation are likely to exert independent and critical influences upon PTTG’s diverse actions in vitro.

Inactivation of the p16 Gene in Human Pituitary Nonfunctioning Tumors by Hypermethylation Is More Common in Null Cell Adenomas

2001 ◽  
Vol 12 (3) ◽  
pp. 281-290 ◽  
Author(s):  
Katharina H Ruebel ◽  
Long Jin ◽  
Shuya Zhang ◽  
Bernd W Scheithauer ◽  
Ricardo V Lloyd
Keyword(s):  
Null Cell ◽  
Human Pituitary ◽  
P16 Gene ◽  
Null Cell Adenomas

scholarly journals Non-secreting pituitary tumours characterised by enhanced expression of YAP/TAZ

2019 ◽  
Vol 26 (1) ◽  
pp. 215-225 ◽  
Author(s):  
Paraskevi Xekouki ◽  
Emily J Lodge ◽  
Jakob Matschke ◽  
Alice Santambrogio ◽  
John R Apps ◽  
...  
Keyword(s):  
Cell Fate ◽  
Cell Types ◽  
Pituitary Tumours ◽  
Null Cell ◽  
Human Pituitary ◽  
Enhanced Expression ◽  
Kinase Cascade ◽  
Mouse Pituitary

Tumours of the anterior pituitary can manifest from all endocrine cell types but the mechanisms for determining their specification are not known. The Hippo kinase cascade is a crucial signalling pathway regulating growth and cell fate in numerous organs. There is mounting evidence implicating this in tumour formation, where it is emerging as an anti-cancer target. We previously demonstrated activity of the Hippo kinase cascade in the mouse pituitary and nuclear association of its effectors YAP/TAZ with SOX2-expressing pituitary stem cells. Here, we sought to investigate whether these components are expressed in the human pituitary and if they are deregulated in human pituitary tumours. Analysis of pathway components by immunofluorescence reveals pathway activity during normal human pituitary development and in the adult gland. Poorly differentiated pituitary tumours (null-cell adenomas, adamantinomatous craniopharyngiomas (ACPs) and papillary craniopharyngiomas (PCPs)), displayed enhanced expression of pathway effectors YAP/TAZ. In contrast, differentiated adenomas displayed lower or absent levels. Knockdown of the kinase-encoding Lats1 in GH3 rat mammosomatotropinoma cells suppressed Prl and Gh promoter activity following an increase in YAP/TAZ levels. In conclusion, we have demonstrated activity of the Hippo kinase cascade in the human pituitary and association of high YAP/TAZ with repression of the differentiated state both in vitro and in vivo. Characterisation of this pathway in pituitary tumours is of potential prognostic value, opening up putative avenues for treatments.

scholarly journals Reduced expression levels of the cell-cycle inhibitor p27Kip1 in human pituitary adenomas

1999 ◽  
pp. 250-255 ◽  
Author(s):  
CM Bamberger ◽  
M Fehn ◽  
AM Bamberger ◽  
DK Ludecke ◽  
FU Beil ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Pituitary Adenomas ◽  
Anterior Pituitary ◽  
Cellular Proliferation ◽  
Cell Types ◽  
Null Cell ◽  
Human Pituitary ◽  
Expression Levels ◽  
Cell Cycle Inhibitor ◽  
Null Cell Adenomas

The molecular mechanisms leading to increased cellular proliferation rates and, thus, tumor formation in the anterior pituitary gland are poorly understood. The cyclin-dependent kinase inhibitor p27Kip1 is a key molecule regulating the G1 phase of the cell cycle in many cell types. Furthermore, it was shown that p27 knock-out mice develop pro-opiomelanocortin-positive pituitary tumors. In an effort to clarify the role of p27 in the normal and tumorous human pituitary, we studied the expression of p27 by immunohistochemistry, using a highly specific mouse monoclonal anti-human p27 antibody. Normal pituitaries and 54 pituitary adenomas (twelve somatotrope adenomas, nine prolactinomas, twelve corticotrope adenomas, three TSH-producing tumors, six gonadotrope adenomas, six null cell adenomas, and six oncocytomas) were analyzed. p27 expression was determined semiquantitatively with regard to both the percentage of positive cells and the intensity of the staining. Normal human pituitaries showed strong expression of p27 in most nuclei. In contrast, the levels of p27 were reduced in the majority of the tumors analyzed. Twenty-two tumors (six somatotrope adenomas, five prolactinomas, four corticotrope adenomas, two TSH-producing tumors, two gonadotrope adenomas, and three null cell adenomas) were completely p27-negative. In 18 tumors, p27 expression was found in < or = 10% of the cells. In the other ten tumors, 11-80% of the cells were p27-positive. In summary, we were able to demonstrate reduced expression levels of the cell-cycle inhibitor p27 in tumors derived from all pituitary cell types. Our data indicate that p27 may be an important regulator of cellular proliferation in the anterior pituitary, the underexpression of which could play a role in pituitary tumorigenesis.

scholarly journals A Coiled-Coil Domain of Melanophilin Is Essential for Myosin Va Recruitment and Melanosome Transport in Melanocytes

2006 ◽  
Vol 17 (11) ◽  
pp. 4720-4735 ◽  
Author(s):  
Alistair N. Hume ◽  
Abul K. Tarafder ◽  
José S. Ramalho ◽  
Elena V. Sviderskaya ◽  
Miguel C. Seabra
Keyword(s):  
Coiled Coil ◽  
Binding Domain ◽  
Actin Binding ◽  
Binding Studies ◽  
Null Cell ◽  
Coiled Coil Region ◽  
Actin Binding Domain ◽  
Transport Assay ◽  
Myosin Va

Melanophilin (Mlph) regulates retention of melanosomes at the peripheral actin cytoskeleton of melanocytes, a process essential for normal mammalian pigmentation. Mlph is proposed to be a modular protein binding the melanosome-associated protein Rab27a, Myosin Va (MyoVa), actin, and microtubule end-binding protein (EB1), via distinct N-terminal Rab27a-binding domain (R27BD), medial MyoVa-binding domain (MBD), and C-terminal actin-binding domain (ABD), respectively. We developed a novel melanosome transport assay using a Mlph-null cell line to study formation of the active Rab27a:Mlph:MyoVa complex. Recruitment of MyoVa to melanosomes correlated with rescue of melanosome transport and required intact R27BD together with MBD exon F–binding region (EFBD) and unexpectedly a potential coiled-coil forming sequence within ABD. In vitro binding studies indicate that the coiled-coil region enhances binding of MyoVa by Mlph MBD. Other regions of Mlph reported to interact with MyoVa globular tail, actin, or EB1 are not essential for melanosome transport rescue. The strict correlation between melanosomal MyoVa recruitment and rescue of melanosome distribution suggests that stable interaction with Mlph and MyoVa activation are nondissociable events. Our results highlight the importance of the coiled-coil region together with R27BD and EFBD regions of Mlph in the formation of the active melanosomal Rab27a-Mlph-MyoVa complex.

Sign in / Sign up

Export Citation Format

Share Document