scholarly journals Stimulation by Urocortin of Growth Hormone (GH) Secretion in GH-Producing Human Pituitary Adenoma Cells.

1997 ◽  
Vol 44 (4) ◽  
pp. 627-629 ◽  
Author(s):  
YOSHIO MURAKAMI ◽  
TOSHIAKI MORI ◽  
KUNIO KOSHIMURA ◽  
MASAMICHI KUROSAKI ◽  
TOMOKATSU HORI ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Pituitary Adenoma ◽  
Human Pituitary ◽  
Human Pituitary Adenoma ◽  
Gh Secretion

Human growth hormone-secreting pituitary adenoma cells in long-term culture: effects of dexamethasone and growth hormone releasing factor

1984 ◽  
Vol 100 (3) ◽  
pp. 353-360 ◽  
Author(s):  
R. Oosterom ◽  
T. Verleun ◽  
S. W. J. Lamberts
Keyword(s):  
Growth Hormone ◽  
Pituitary Adenoma ◽  
Human Growth ◽  
Prostaglandin E ◽  
Human Pituitary ◽  
Human Pituitary Adenoma ◽  
Thyrotrophin Releasing Hormone ◽  
Long Term Culture ◽  
Gh Secretion

ABSTRACT Growth hormone-secreting human pituitary adenoma cells in long-term culture show a decline in GH secretion. We investigated the effects of dexamethasone on GH production and on the responsiveness of the adenoma cells to various drugs. Twenty-four-hour GH secretion by cultures from seven acromegalics was consistently stimulated by 100 nM-dexamethasone. In four out of seven cultures the effect of dexamethasone occurred within 24 h. After 3 weeks in culture the decline in GH secretion by control cultures was over 90%, while in dexamethasone-treated cultures this was limited to less than 50%. The effect of dexamethasone was dose-dependent over a range of 1 nmol/l to 10 μmol/l. Dexamethasone stimulated not only GH secretion (fivefold), but also GH content (twofold). Cycloheximide and actinomycin D blocked the stimulatory effect of dexamethasone on GH secretion, the latter irreversibly. After 4 days of treatment with 100 nm-dexamethasone, the relative effects of somatostatin, prostaglandin E1, bromocriptine and thyrotrophin releasing hormone were the same in treated and untreated cultures. However, the response to synthetic GH releasing factor (GRF) was greatly enhanced by pretreatment of adenoma cells with dexamethasone (100 and 5 nmol/l). Cells unresponsive to small concentrations of GRF could be stimulated effectively by GRF after pretreatment with dexamethasone. In conclusion, dexamethasone prevents the decline in GH production as seen in control cultures, possibly by stimulation of DNA transcription. Furthermore, the response to GRF is greatly enhanced in the presence of dexamethasone, while the relative effects of other direct GH stimulatory and inhibitory compounds seem to be unchanged. J. Endocr. (1984) 100, 353–360

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 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.

Localization of concanavalin A binding sites in human pituitary adenoma cells as revealed by HRP-labelling method

1983 ◽  
Vol 62 (1-2) ◽  
pp. 59-66 ◽  
Author(s):  
T. Hori ◽  
F. Nishiyama ◽  
A. Teramoto ◽  
M. Matsutani ◽  
K. Takakura ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Concanavalin A ◽  
Binding Sites ◽  
Human Pituitary ◽  
Human Pituitary Adenoma ◽  
Labelling Method
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