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1.
Exp Clin Endocrinol Diabetes ; 112(1): 18-23, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14758567

ABSTRACT

Estrogens are considered to be critically involved in lactotroph and lactosomatotroph pituitary tumor development. In addition to direct effects, estradiol-induced tumor formation may involve alterations in growth factor and cytokine production. We have studied whether estradiol stimulates the production of the angiogenic vascular endothelial growth factor and the potential tumor progression factor interleukin-6 in 5 lactotroph (LA) and 5 lactosomatotroph (LSA) human pituitary adenoma cell cultures. All tumors secreted heterogenous basal amounts of VEGF (18.0 +/- 1.4 to 425 +/- 26 pg/ml per 24 h) and IL-6 (18.1 +/- 1.5 to 604 +/- 17 pg/ml per 24 h). Estradiol (100 nM) significantly enhanced VEGF release in all LA and LSA cell cultures (47 to 168 % above basal). IL-6 secretion was stimulated in 3 out of 5 LA and in all LSA cell cultures (31 to 287 % above basal). In cell cultures obtained from tumors from which sufficient cells could be isolated, a dose-dependent effect of estradiol (1 to 100 nM) on VEGF and IL-6 production was observed. Stimulation of IL-6 and/or VEGF secretion by estradiol in the majority of human lactotroph and lactosomatotroph adenoma cell cultures studied, suggests that estrogens may contribute to adenoma expansion through the stimulation of these auto-/paracrine-acting adenoma progression factors.


Subject(s)
Estradiol/pharmacology , Interleukin-6/biosynthesis , Pituitary Neoplasms/metabolism , Prolactinoma/metabolism , Vascular Endothelial Growth Factor A/biosynthesis , Adult , Enzyme-Linked Immunosorbent Assay , Female , Humans , Interleukin-6/metabolism , Male , Middle Aged , Tumor Cells, Cultured , Vascular Endothelial Growth Factor A/metabolism
2.
J Endocrinol ; 169(3): 539-47, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11375124

ABSTRACT

Two of the most potent cytokines regulating anterior pituitary cell function are leukemia inhibitory factor (LIF) and interleukin (IL)-6, which belong to the cytokine family using the common gp130 signal transducer. Recently, the expression and action of two other members of this family, IL-11 and ciliary neurotrophic factor (CNTF), on different cell lines has also been demonstrated. We studied the expression of the specific receptor subunits for CNTF in mammotropic, non-functioning and somatotropic tumors and the action of CNTF and IL-11 in the regulation of hormone secretion in these and normal pituitary cells. The mRNA for the alpha chain specific for the CNTF receptor was detected by Northern blot in tumors secreting prolactin (PRL) and GH and in non-functioning tumors. We found that both IL-11 and CNTF exerted a similar stimulatory effect on GH mRNA expression in somatotropic monolayer cell cultures from acromegalic tumors, but these cytokines had no significant influence on GH secretion. CNTF stimulates prolactin secretion in lactotropic monolayer cell cultures from patients with prolactinoma. In monolayer cell cultures from normal rat anterior pituitary, IL-11 and CNTF had no significant effect on the release of either GH or PRL, or on GH mRNA. However, when the cells were cultured in aggregate cultures, in which the three-dimensional structure of the cells is reconstituted, both cytokines, in doses at which they had no effect on monolayer cultures, significantly stimulated both PRL and GH secretion. These data show that IL-11 and CNTF may act as regulatory factors in anterior pituitary cells, in which the three-dimensional structure of the gland is of critical importance.


Subject(s)
Adenoma/metabolism , Ciliary Neurotrophic Factor/pharmacology , Interleukin-11/pharmacology , Pituitary Gland, Anterior/drug effects , Pituitary Neoplasms/metabolism , Animals , Cell Aggregation , Cell Culture Techniques , Gene Expression Regulation, Neoplastic/drug effects , Human Growth Hormone/biosynthesis , Human Growth Hormone/genetics , Humans , Male , Neoplasm Proteins/metabolism , Pituitary Gland, Anterior/cytology , Prolactin/metabolism , RNA, Messenger/genetics , Rats , Rats, Sprague-Dawley , Receptor, Ciliary Neurotrophic Factor/metabolism , Tumor Cells, Cultured
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