Effects of metformin on cell growth and AMPK activity in pituitary adenoma cell cultures, focusing on the interaction with adenylyl cyclase activating signals

2018 ◽  
Vol 470 ◽  
pp. 60-74 ◽  
Author(s):  
Lara Faggi ◽  
Andrea Giustina ◽  
Giovanni Tulipano
1994 ◽  
Vol 130 (1) ◽  
pp. 80-91 ◽  
Author(s):  
Ulrich Renner ◽  
Juri Mojto ◽  
Manfred Lange ◽  
O Albrecht Müller ◽  
Klaus von Werder ◽  
...  

Renner U, Mojto J, Lange M, Albrecht Müller O. von Werder K, Stalla GK. Effect of bromocriptine and SMS 201-995 on growth of human somatotrophic and non-functioning pituitary adenoma cells in vitro. Eur J Endocrinol 1994;130:80–91. ISSN 0804–4643 The effect of the dopamine agonist bromocriptine and the somatostatin analog SMS 201-995 on growth of 12 human somatotrophic and 13 non-functioning adenoma cell cultures was investigated. When adenoma cells were maintained in medium supplemented with 5% fetal calf serum. cell counts of 10 of 12 somatotrophic cultures increased to 145±6 and 171 ±9% (mean±sd) and in 12 of 13 non-functioning cell cultures up to 125±12 and 217±15% after 3 days of incubation. In most cases bromocriptine and SMS 201-995 dose dependently (1 nmol/l to 10 μmol/l) inhibited adenoma cell growth but there was only (1.10 μmol/l) a significant inhibitory effect at high doses of both drugs. A 1 μmol/l concentration of bromocriptine decreased cell counts of 5 of 12 somatotrophic cell cultures (range 84±3 to 76±6% vs control = 100%) and in 5 of 13 non-functioning cell cultures (range 85±4 to 71 ± 7%). A 10 μmol/l concentration of bromocriptine decreased cell counts in all 12 somatotrophic (range 87±1 to 61 ±8%) and in 12 of 13 non-functioning adenoma cultures (range 87±6 to 57±3%). Bromocriptine specifically inhibited growth because its effect could be reversed by the dopamine D2-receptor antagonist haloperidol. Both 1 and 10 μmol/l SMS 201-995 significantly decreased cell counts in three of six somatotrophic (87± 3 to 38 ±3%) cell cultures. In two of five cases growth of non-functioning adenoma cultures was suppressed by 1 μmol/ISMS 201-995, and in four of five cases by 10 μmol/l(86± 3 to 74 ±4%). The growth inhibitory effect of both bromocriptine and SMS 201-995 was not just due to an effect on growth of fibroblasts contaminating the adenoma cell cultures, because it could be observed also when adenoma cells were maintained in a d-valine-supplemented medium that suppresses fibroblast growth. In summary, both bromocriptine and SMS 201-995 at high doses were able to inhibit cell growth of cultured somatotrophic and non-functioning adenomas in vitro. However, the mechanism of this inhibitory effect is not yet well understood. Ulrich Renner, Max-Planck-Institute of Psychiatry, Clinical Institute, Kraepelinstr. 10, D-80804 Munich, Germany


2012 ◽  
Vol 214 (3) ◽  
pp. 389-398 ◽  
Author(s):  
B Shan ◽  
C Schaaf ◽  
A Schmidt ◽  
K Lucia ◽  
M Buchfelder ◽  
...  

Curcumin (diferuloylmethane), a polyphenolic compound derived from the spice plantCurcuma longa, displays multiple actions on solid tumours including anti-angiogenic effects. Here we have studied in rodent and human pituitary tumour cells the influence of curcumin on the production of hypoxia inducible factor 1α (HIF1A) and vascular endothelial growth factor A (VEGFA), two key components involved in tumour neovascularisation through angiogenesis. Curcumin dose-dependently inhibited basal VEGFA secretion in corticotroph AtT20 mouse and lactosomatotroph GH3 rat pituitary tumour cells as well as in all human pituitary adenoma cell cultures (n=32) studied. Under hypoxia-mimicking conditions (CoCl2treatment) in AtT20 and GH3 cells as well as in all human pituitary adenoma cell cultures (n=8) studied, curcumin strongly suppressed the induction of mRNA synthesis and protein production of HIF1A, the regulated subunit of the hypoxia-induced transcription factor HIF1. Curcumin also blocked hypoxia-induced mRNA synthesis and secretion of VEGFA in GH3 cells and in all human pituitary adenoma cell cultures investigated (n=18). Thus, curcumin may inhibit pituitary adenoma progression not only through previously demonstrated anti-proliferative and pro-apoptotic actions but also by its suppressive effects on pituitary tumour neovascularisation.


Author(s):  
Dean A. Handley ◽  
Jack T. Alexander ◽  
Shu Chien

In situ preparation of cell cultures for ultrastructural investigations is a convenient method by which fixation, dehydration and embedment are carried out in the culture petri dish. The in situ method offers the advantage of preserving the native orientation of cell-cell interactions, junctional regions and overlapping configurations. In order to section after embedment, the petri dish is usually separated from the polymerized resin by either differential cryo-contraction or solvation in organic fluids. The remaining resin block must be re-embedded before sectioning. Although removal of the petri dish may not disrupt the native cellular geometry, it does sacrifice what is now recognized as an important characteristic of cell growth: cell-substratum molecular interactions. To preserve the topographic cell-substratum relationship, we developed a simple method of tapered rotary beveling to reduce the petri dish thickness to a dimension suitable for direct thin sectioning.


2011 ◽  
Vol 89 (9) ◽  
pp. 1363-1374 ◽  
Author(s):  
Megumi Hirose ◽  
Pawel Niewiadomski ◽  
Gary Tse ◽  
Gloria C. Chi ◽  
Hongmei Dong ◽  
...  

1994 ◽  
Vol 130 (2) ◽  
pp. 125-131 ◽  
Author(s):  
Günter K Stalla ◽  
Steffi J Brockmeier ◽  
Ulrich Renner ◽  
Chris Newton ◽  
Michael Buchfelder ◽  
...  

Stalla GK, Brockmeier SJ, Renner U, Newton C, Buchfelder M, Stalla J, Müller OA. Octreotide exerts different effects in vivo and in vitro in Cushing's disease. Eur J Endocrinol 1994;130:125–31. ISSN 0804–4643 The effect of the long-acting somatostatin analog octreotide (SMS 201-995) on adrenocorticotropin (ACTH) secretion was studied in five patients with untreated Cushing's disease in vivo and in six human corticotropic adenoma cell cultures in vitro. For the in vivo study, 100 μg of octreotide sc was given 30 and 180 min after cannulation of the cubital vein and 100 μg of corticotropin-releasing hormone (CRH) was injected iv at 210 min. Serum ACTH and cortisol levels were measured for 390 min. In vivo, octreotide had no significant effect either on basal or CRH-stimulated ACTH levels and did not influence cortisol levels. The in vitro studies were conducted with corticotropic adenoma cell cultures derived from adenoma tissue obtained from six patients with Cushing's disease. In four of six cell cultures, octreotide (1 nmol/l–1 μmol/l) inhibited basal ACTH secretion in a dose-dependent manner. The inhibition ranged from 70 to 92% for 1 nmol/l octreotide to 14–46% for 1 μmol/l octreotide as compared to controls (100%). In three of three octreotide-responsive adenoma cell cultures investigated, CRH-stimulated ACTH secretion was suppressed by octreotide. Hydrocortisone pretreatment in vitro abolished the inhibitory effect of octreotide on ACTH secretion in one octreotide-responsive corticotropic adenoma cell culture. In conclusion, we showed that octreotide in most cases could inhibit the ACTH release from human corticotropic adenoma cells in vitro but had no suppressive effect on ACTH levels of patients with Cushing's disease in vivo. This discrepancy could be due to a somatostatin receptor down-regulation by cortisol at the hypercortisolemic state in vivo. Günter K Stalla, Max-Planck-Institute of Psychiatry, Clinical Institute, Kraepelinstr. 10, D-80804 Munich, Germany


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