Endocrine Abstracts

There is increasing evidence that cytokines may play an important role in the pathogenesis of human pituitary adenomas. We have measured the production of interleukin-1 alpha from 30 cultured human pituitary adenomas and looked at the relationship of its secretion to interleukin-6 and soluble gp130. Tumours were also analysed for interleukin-2 secretion. We also used the HP75 cell line to look at the effects of varying levels of interleukin-1 on interleukin-6 secretion.<p...

Vascular smooth muscle cells (VSMC) form a major constituent of the atherosclerotic plaque providing structural stability. However, increased cell number due to high proliferation rates can lead to greater artery occlusion. Testosterone replacement therapy improves exercise capacity and reduces symptoms of angina in men with coronary artery disease, although its effect upon VSMC growth is currently unknown. Testosterone deficiency is associated with increased atheroma burden a...

Several studies have demonstrated that atherosclerosis is associated with low serum levels of testosterone and replacement therapy reduces myocardial ischaemia in men. Vascular smooth muscle cell (VSMC) apoptosis reduces plaque stability. The role of testosterone if any, in this process is unknown. Testosterone has been demonstrated act via both the classic androgen receptor and by calcium channel antagonism. Calcium channel blockers have been shown to induce VSMC apoptosis. W...

Low testosterone levels in men are associated with increased atherosclerosis, and testosterone replacement therapy has been shown to reduce myocardial ischemia in men with coronary artery disease. Vascular smooth muscle cell (VSMC) apoptosis is proposed to reduce plaque stability, but the role of testosterone in this process is unknown. Testosterone causes vasodilatation via calcium channel antagonism and the calcium channel antagonist nifedipine induces VSMC apoptosis. We hav...

Atherosclerotic plaque smooth muscle cells (SMCs) are sensitive to apoptotic stimuli, increasing plaque instability. Testosterone replacement therapy is beneficial in men with coronary artery disease, although its effect upon plaque stability is unknown. We have utilised the rat A7r5 vascular SMC line to investigate the effects of testosterone on apoptosis induced by serum deprivation or the calcium channel antagonist nifedipine.Cells were plated at 1500...

Leptin is known to be produced by human pituitary adenomas, and inhibits the proliferation of HP75 cells in vitro. The HP75 cell line is derived from gonadotroph tumour cells from a clinically non-functioning human pituitary adenoma transfected with SV40. The aim of this study was to examine the effects of interleukins (IL) IL1-alpha and IL-6 on growth of HP75 cells and their effects on the growth inhibitory actions of leptin.HP75 cells were plated in 2...

Tyrosine kinase inhibitors have previously been shown to inhibit DNA synthesis in human pituitary adenomas (Jones et al JCEM 1997; 82: 2143-7). ZD1839 ('Iressa'), a selective inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, is currently undergoing clinical trials in human cancers. We have investigated the effects of ZD1839 and EGF in the human pituitary cell line HP75 (derived by SV40 transfection of a human pituitary silent gonadotrophinoma) and in s...

The cytokine IL-6 is synthesed and released by over half of surgically removed human pituitary adenomas and by the HP75 human pituitary tumour cell line. We have previously shown that IL6 is associated with tumour invasiveness but not with Ki67, a marker of cell proliferation. Membrane IL6R (mIL6R) has been demonstrated in some pituitary adenomas, however, we have shown that sIL6R is not shed by the majority (92%) of human pituitary adenomas in culture nor by HP75 cells(super)...