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R. A. Prysor-Jones
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J. J. Silverlight
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J. S. Jenkins
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ABSTRACT

Prolactin secretion by a human pituitary tumour cell line produced in our laboratory was stimulated by TRH, vasoactive intestinal peptide (VIP) and epithelial growth factor (EGF). All raised the intracellular concentration of free calcium (Ca2+ i) of cells loaded with a fluorescent quinoline Ca2+ indicator in suspension, but the effect of TRH was much more rapid and less prolonged than that of VIP and EGF. Both TRH and VIP also increased Ca2+ i in GH3 rat pituitary tumour cells, but in this cell line the effect of VIP was only found in attached cells grown on cover-slips. In both human and rat cell lines, the increase in Ca2+ i produced by TRH was independent of extracellular calcium, whereas this was a requirement for the action of VIP and EGF. It is concluded that the prolactin secretogogues, VIP and probably EGF, increase Ca2+ i through an effect on plasma membrane calcium channels and that this effect differs from that of TRH.

J. Endocr. (1987) 114, 119–123

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R. A. Prysor-Jones
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J. J. Silverlight
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J. S. Jenkins
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ABSTRACT

The growth of two human prolactin-secreting cell lines developed in our laboratory has been investigated in response to a number of factors. Oestrogen stimulated the synthesis of DNA and protein and increased prolactin secretion. Dexamethasone had the opposite effect to oestrogen. In the presence of serum, epidermal growth factor (EGF) inhibited cell growth at concentrations of 5 ng/ml. Known secretagogues of prolactin (vasoactive intestinal peptide (VIP), TRH, bombesin and neurotensin) were investigated for their action on cell growth but only VIP had a stimulatory effect. Two preparations of fibroblast growth factor (FGF) were studied. One form, derived from bovine pituitary glands, stimulated human pituitary cell growth. In contrast, another FGF, of the basic type (rFGF), was inhibitory to cell growth, increasing the time for cell doubling from 30 to 72 h. This inhibitory effect of rFGF was modified but not abolished by serum, oestradiol, platelet-derived growth factor or EGF. We conclude that bovine pituitary contains at least two fibroblast growth factors, both of which stimulate fibroblast cell growth, but one stimulates and the other inhibits human pituitary tumour cell growth.

Journal of Endocrinology (1989) 120, 171–177

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R. A. Prysor-Jones
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J. J. Silverlight
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J. S. Jenkins
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Dopamine concentration within the hypothalamus and its depletion after the administration of α-methyl-para-tyrosine were measured in young rats and compared with values obtained in aged animals with and without spontaneously occurring pituitary tumours. Old rats had significantly reduced hypothalamic dopamine concentrations and there was less depletion of dopamine compared with young animals but there were no differences between tumorous and non-tumorous animals. Hyperprolactinaemia induced in young animals caused a much greater depletion of hypothalamic dopamine than in old tumorous rats with comparable plasma prolactin concentrations. The catechol oestrogen 2-hydroxyoestradiol inhibited the release of prolactin from normal rat pituitary glands in vitro but measurement of catechol oestrogens in the hypothalamus showed no differences between young and old tumorous or non-tumorous rats. It is concluded that reduced dopamine concentration and an impaired response to hyperprolactinaemia in old rats may facilitate the growth of prolactin-secreting tumours arising in the pituitary gland.

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R. A. Prysor-Jones
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J. J. Silverlight
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J. S. Jenkins
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The antioestrogenic drug tamoxifen was administered to rats bearing transplanted prolactin-secreting tumours derived from spontaneously occurring pituitary adenomas in Wistar–Furth rats. Some inhibition of tumour growth was observed but this was accompanied by an increase in plasma prolactin concentrations. Bromocriptine, however, consistently inhibited both growth and prolactin secretion of these tumours. The addition of tamoxifen to bromocriptine treatment produced no increased response to the dopamine agonist. Tamoxifen increased prolactin secretion by tumour cells in vitro but did not affect DNA synthesis. Normal rats responded to tamoxifen with a moderate increase in plasma prolactin concentrations and there was no change in pituitary DNA synthesis.

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R. A. Prysor-Jones
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J. J. Silverlight
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S. J. Kennedy
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J. S. Jenkins
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ABSTRACT

Treatment with a high dose of oestradiol for 6 months caused hyperprolactinaemia and pituitary hyperplasia in female Wistar–Furth rats. Changes in the vasoactive intestinal peptide (VIP) and dopamine content of the hypothalamus and pituitary were also found. The hypothalamic dopamine concentration was only slightly reduced and, although the concentration of dopamine in the pituitary was less in treated animals, the total pituitary content was increased. The concentration of VIP in the pituitary was increased by oestradiol treatment but decreased in the non-median eminence hypothalamus. In the median eminence the VIP content was increased by oestradiol treatment and the amount present correlated positively and significantly with pituitary wet weight in animals treated with both oestradiol and fluphenazine. In Fischer 344 rats, oestradiol produced greater incremental changes in pituitary wet weight and plasma concentrations of prolactin than in Wistar controls and the increase in the pituitary concentration of VIP was five times greater. Although peptide turnover has not been measured, these results suggest that oestradiol, as well as having a direct action, stimulates pituitary lactotrophs by increasing pituitary concentrations of VIP.

J. Endocr. (1988) 116, 259–265

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R. A. Prysor-Jones
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J. J. Silverlight
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J. S. Jenkins
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A. N. Stevens
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J. L. Rodrigues
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J. R. Griffiths
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ABSTRACT

31P-Nuclear magnetic resonance (NMR) spectra were obtained in the living rat from 19 implanted prolactin-secreted pituitary tumours. Seven major peaks were found including those arising from the high energy phosphorus metabolites ATP and phosphocreatine. Intracellular pH of the tumours was measured and a relationship with prolactin secretion was observed, the highest plasma prolactin concentrations being associated with an intracellular pH >7·18. Repeated NMR measurements in three tumours over periods of up to 21 days revealed progressive changes with age, shown by an increase in inorganic phosphate, a decrease in high energy phosphorus metabolites and a decrease in prolactin secretion. It is concluded that NMR spectroscopy provides a useful method of studying intracellular events which accompany hormone secretion in vivo.

J. Endocr. (1985) 106, 349–353

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