Growth Factors and Cytokines: Function and Molecular Regulation in Pituitary Adenomas

2004 ◽  
pp. 96-109 ◽  
Author(s):  
U. Renner ◽  
M. Paez-Pereda ◽  
E. Arzt ◽  
G.K. Stalla
Keyword(s):  
Growth Factors ◽  
Pituitary Adenomas ◽  
Molecular Regulation

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.

scholarly journals Expression of p53, Ki-67 and c-erb B2 in growth hormone-and/or prolactin-secreting pituitary adenomas

2006 ◽  
Vol 64 (1) ◽  
pp. 60-66 ◽  
Author(s):  
Carlos Henrique A. Botelho ◽  
Albino Verçosa de Magalhães ◽  
Paulo Andrade de Mello ◽  
Fernando C. Schmitt ◽  
Luiz Augusto Casulari
Keyword(s):  
Growth Hormone ◽  
Growth Factors ◽  
Tumor Growth ◽  
Pituitary Adenomas ◽  
Membrane Receptor ◽  
Ki 67 ◽  
Definite Effect ◽  
And Behavior

The subcellular events implicated on the formation and behavior of pituitary adenomas are not fully understood. In this study we investigated the presence of p53, Ki-67 and c-erb B2 in 38 pituitary adenomas with immunohistochemical positivity for GH and prolactin (n=26; 68.4%), for prolactin (n=9; 23.7%) and for GH (n=3. 7.8%). The analyses revealed the following results: 24 (63.2%) tumors expressed variable positivity for c-erb B2, 11 (28.9%) expressed p53 positivity and 11 (28.9%) tumors were variably positive for Ki-67. Our results demonstrated a high percentage of GH/prolactin-, prolactin- and GH-secreting tumors with immunohistochemical positivity for c-erb B2. Once this membrane receptor is related to growth factors EGF and TGFalpha and both have a definite effect on tumor growth, our data suggest a possible role for c-erb B2 on the evolution of these tumors.

Transcripts of PTTG and Growth Factors bFGF and IGF-1 are Correlated in Pituitary Adenomas

2009 ◽  
Vol 118 (02) ◽  
pp. 121-126 ◽  
Author(s):  
K. Chamaon ◽  
D. Kanakis ◽  
C. Mawrin ◽  
K. Dietzmann ◽  
E. Kirches
Keyword(s):  
Growth Factors ◽  
Pituitary Adenomas

Autocrine and paracrine roles of polypeptide growth factors, cytokines and vasogenic substances in normal and tumorous pituitary function and growth: a review

1996 ◽  
Vol 135 (5) ◽  
pp. 515-532 ◽  
Author(s):  
Ulrich Renner ◽  
Uberto Pagotto ◽  
Eduardo Arzt ◽  
Günter Karl Stalla
Keyword(s):  
Growth Factors ◽  
Pituitary Adenomas ◽  
Cell Communication ◽  
Pituitary Function ◽  
Pituitary Cells ◽  
Max Planck ◽  
Endocrine Control ◽  
Polypeptide Growth Factors ◽  
Postnatal Differentiation ◽  
And Function

Renner U, Pagotto U, Arzt E, Stalla GK. Autocrine and paracrine roles of polypeptide growth factors, cytokines and vasogenic substances in normal and tumorous pituitary function and growth: a review. Eur J Endocrinol 1996;135:515–32. ISSN 0804–4643 In addition to the classical hormones, the production of numerous polypeptide growth factors, cytokines, vasogenic substances and neuropeptides by pituitary cells has been demonstrated. Expression of the corresponding receptors on pituitary cells enables these factors to influence growth and function of the pituitary by auto- or paracrine mechanisms. Thus, in addition to the external endocrine control of pituitary growth and function, an intrinsic intercellular communication network seems to be involved in the control of pituitary homeostasis. The cell-to-cell communication may be of importance for the pre- and postnatal differentiation of the pituitary, for the regulation of the cellular composition of the gland (by balancing mitosis and apoptosis and controlling angiogenesis) and for the adaption of pituitary function to altered physiological conditions (i.e. stress, pregnancy and diseases). Differences in the expression of or the response to the above-mentioned factors in pituitary adenomas indicate that these substances are of importance for pituitary tumorigenesis. Disturbances of auto-/paracrine mechanisms may not necessarily be involved in the tumor initiation processes, but they may play a crucial role in tumor progression. After the initial transformation, the clonal expansion of the tumor cell is dependent on its ability to escape either from the inhibitory action of growth suppressing factors or to develop an autocrine mechanism that allows autonomous growth. In summary, therefore, this review outlines the potential role of polypeptide growth factors, cytokines and vasogenic peptides as auto-/paracrine-acting substances in normal pituitary and pituitary adenomas. Ulrich Renner, Max-Planck-Institute of Psychiatry, Clinical Institute, Department of Endocrinology, Kraepelinstr. 10, D-80804 Munich, Germany

Ultrastructural Investigation of Spontaneous Pituitary Adenomas in Aging Sprague-Dawley Rats

1982 ◽  
Vol 40 ◽  
pp. 216-217
Author(s):  
D. J. McComb ◽  
J. Beri ◽  
F. Zak ◽  
K. Kovacs
Keyword(s):  
Microscopic Study ◽  
Pituitary Adenomas ◽  
Wistar Rats ◽  
Microscopic Level ◽  
Sprague Dawley ◽  
Prolactin Cells ◽  
Light Microscopic Level ◽  
Ultrastructural Investigation ◽  
Sprague Dawley Rats ◽  
Long Evans

Investigation of the spontaneous pituitary adenomas in rat have been limited mainly to light microscopic study. Furth et al. (1973) described them as chromophobic, secreting prolactin. Kovacs et al. (1977) in an ul trastructural investigation of adenomas of old female Long-Evans rats, found that they were composed of prolactin cells. Berkvens et al. (1980) using immunocytochemistry at the light microscopic level, demonstrated that some spontaneous tumors of old Wistar rats could contain GH, TSH or ACTH as well as PRL.

Ultrastructural comparison of prolactin adenomas of pituitary in men and women

1988 ◽  
Vol 46 ◽  
pp. 346-347
Author(s):  
R.C. Caughey ◽  
U.P. Kalyan-Raman
Keyword(s):  
Endoplasmic Reticulum ◽  
Electron Microscope ◽  
Phosphate Buffer ◽  
Pituitary Adenomas ◽  
Osmium Tetroxide ◽  
Secretory Granules ◽  
Uranyl Acetate ◽  
En Bloc ◽  
Men And Women ◽  
Transmission Electron

Prolactin producing pituitary adenomas are ultrastructurally characterized by secretory granules varying in size (150-300nm), abundance of endoplasmic reticulum, and misplaced exocytosis. They are also subclassified as sparsely or densely granulated according to the amount of granules present. The hormone levels in men and women vary, being higher in men; so also the symptoms vary between both sexes. In order to understand this variation, we studied 21 prolactin producing pituitary adenomas by transmission electron microscope. This was out of a total of 80 pituitary adenomas. There were 6 men and 15 women in this group of 21 prolactinomas.All of the pituitary adenomas were fixed in 2.5% glutaraldehyde, rinsed in Millonig's phosphate buffer, and post fixed with 1% osmium tetroxide. They were then en bloc stained with 0.5% uranyl acetate, rinsed with Walpole's non-phosphate buffer, dehydrated with graded series of ethanols and embedded with Epon 812 epoxy resin.

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