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Biomedical subjects

R A Prysor-Jones

Publications and source records attributed to R A Prysor-Jones.

At least 19 recordsLinked to original sources
PubMed1990

Basic fibroblast growth factor in human pituitary tumours.

Immunoreactive (ir) basic fibroblast growth factor (FGF) has been measured in normal human pituitary glands and in 41 pituitary tumours of various types using a radioimmunoassay. Normal pituitary glands contained ir basic FGF ranging from 29.4 to 355 fmol/mg wet weight whereas 87.5% of pituitary tumours contained amounts of the growth factor which were less than normal. There was no relationship between the type of tumour and the FGF content. Normal and tumorous pituitary FGF had an affinity for heparin which was similar to that of basic FGF. Gel column chromatography revealed that the pituitary ir FGF was present mainly as high molecular weight forms, with only a small proportion as the basic 146 amino-acid peptide. Because of our previous observation that basic FGF inhibits the growth of human pituitary tumour cells, it is suggested that the reduction in basic FGF of many pituitary tumours may favour the stimulation of pituitary growth.

Adenoma↗
PubMed1989

Oestradiol, vasoactive intestinal peptide and fibroblast growth factor in the growth of human pituitary tumour cells in vitro.

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.

Cell Line↗
PubMed1988

Vasoactive intestinal peptide stimulates glycolysis in pituitary tumours; 1H-NMR detection of lactate in vivo.

1H- and 31P-NMR spectroscopy has been applied to rats carrying implanted tumours in vivo, and used to observe simultaneous changes in intracellular pH (pHi) and lactate concentration during the stimulatory action of vasoactive intestinal polypeptide (VIP). A maximal decrease in pHi to a mean of 0.29 units below basal values was recorded. At the same time, 11 min after VIP, a maximal increase in tumour lactate was found, with a mean value of 150% of the basal concentration. The magnitude of these changes was compatible with in vitro measurements of basal lactate concentration and buffering capacity made on the same tumour line. It is concluded that VIP stimulates glycolysis by the tumour cells, resulting in an accumulation of lactate and a consequent fall in pHi.

Adenoma↗
PubMed1988

An analogue of creatine increases TRH-stimulated prolactin secretion and phosphoinositide hydrolysis in rat pituitary tumor cells.

Prolactin (PRL)-secreting GH3 cells were grown, in vitro, with the creatine analogue beta-guanidinopropionic acid (GPA) added to the culture medium. After 5 days there was a small increase in basal and greatly increased thyrotropin-releasing hormone (TRH)-stimulated PRL secretion. The site of action of GPA is at the TRH-induced hydrolysis of phosphoinositides, since increased amounts of mono, bis and tris/tetrakis inositol phosphates were found in treated cells, while the PRL secretion induced by a phorbol ester or a calcium ionophore, treatments which mimic the second messages generated by inositol phospholipid hydrolysis, were not enhanced by GPA. The mechanism by which GPA increases phospholipase C activity has not been fully elucidated but may involve the activity of a controlling G protein.

Aminoquinolines↗
PubMed1988

Vasoactive intestinal peptide and anterior pituitary function.

Vasoactive intestinal peptide (VIP) is a highly basic 28 amino-acid peptide which was first isolated from porcine small intestine (Said & Mutt, 1970). It is related to several other peptides including PHI (peptide with N-terminal histidine and C-terminal isoleucine amide), secretin, glucagon, and has some sequences similar to those of growth hormone releasing hormone (Fig. 1). The amino-acid sequence of human VIP is identical with that of the porcine form (Itoh et al., 1983). It has been shown that human VIP is cosynthesized with PHM (peptide with N-terminal histidine and C-terminal methionine amide, the human analogue of PHI) from the same large precursor protein (Itoh et al., 1983).

Amino Acid Sequence↗
PubMed1988

Vasoactive intestinal peptide and the stimulation of lactotroph growth by oestradiol in rats.

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.

Animals↗
PubMed1987

Hyperprolactinemia reduces vasoactive intestinal peptide in the anterior pituitary glands of rats.

The concentration of vasoactive intestinal polypeptide (VIP) in the anterior pituitary gland of female rats was significantly reduced by pituitary implants, prolactin-secreting tumours or dopamine blockade-induced hyperprolactinemia. Oestradiol implants increased plasma prolactin (PRL) to 12 times and increased pituitary VIP to 3.5 times that of controls after one week. The dopamine agonist bromocriptine significantly reduced pituitary VIP at doses within the clinically used range. These results provide evidence for a suppressive effect of plasma PRL on pituitary VIP, which may be effected by a dopaminergic mechanism, but is over-ridden by oestrogen.

Animals↗
PubMed1987

Increased creatine kinase activity in pituitary tumours of rat and man.

The demonstration that phosphocreatine is used as an energy source by rat PRL-secreting pituitary tumours prompted the study of the enzyme creatine kinase in both rat and human pituitary tumours. Rats treated with diethylstilbestrol developed greatly enlarged pituitaries and hyperprolactinaemia. Total creatine kinase was significantly increased and fractionation on diethylaminoethyl Sephadex showed that the 'brain' form was increased, whereas the 'muscle' and mitochondrial forms showed no change. Exposure to large concentrations of oestradiol caused similar changes in creatine kinase which increased over a period of 25 weeks. The total creatine kinase content of a series of human pituitary tumours was highly variable, but the mean value of 183 +/- 46 (SEM) units per gram protein was significantly higher than the mean for normal pituitary tissues (28.4 +/- 2.9). The brain:muscle isozyme ratio was measured in six human PRL-secreting tumours with a mean of 3.47 +/- 0.73, significantly higher than in 'non-functional' tumours (1.57 +/- 0.29) or normal tissue (1.77 +/- 0.28). Three of four GH-secreting tumours had a ratio below 0.6. The highest ratio found (8.66) was in an ACTH-secreting tumour. Previous reports have shown that oestradiol rapidly induces brain creatine kinase in oestrogen responsive tissues. This is not the case with the rat pituitary gland or oestrogen responsive human tumour cells in culture. Chronic oestrogen treatment, however, does increase creatine kinase in the proliferating gland and many human pituitary tumours have increased enzyme activity. These results suggest that the phosphocreatine/ATP system and in particular the brain isozyme of creatine kinase are of particular importance in lactotropes.

Adenoma↗
PubMed1987

Vasoactive intestinal polypeptide and dopamine in the hypothalamus and pituitary of ageing rats with prolactinomas.

Vasoactive intestinal peptide (VIP), an dopamine have been measured in the hypothalamus and anterior pituitaries of female rats at three different ages. Rats aged 19 months had a high incidence (35%) of prolactin-secreting tumours of the pituitary and these animals had increased hypothalamic and pituitary VIP compared with three-month-old rats or rats without tumours. VIP in old animals without tumours was similar to that in young animals. The third group, with an even more advanced age of 22-28 months, had a lower incidence of PRL-secreting tumours, and pituitary and hypothalamic VIP concentrations similar to those in young animals. Dopamine was significantly increased in the pituitaries of 22-28-month-old nontumorous rats and slightly raised in 19-month-old rats. We conclude that the increased pituitary and hypothalamic VIP content of 19-month-old rats could be a factor in the development of tumours seen at this age, and the differences seen in the two groups of old rats may be related to changes in the steroid environment.

Age Factors↗
PubMed1987

Vasoactive intestinal peptide increases intracellular free calcium in rat and human pituitary tumour cells in vitro.

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 secretagogues, VIP and probably EGF, increase Ca2+ i through an effect on plasma membrane calcium channels and that this effect differs from that of TRH.

Animals↗
PubMed1987

Arginine vasopressin and oxytocin in the bovine adrenal gland.

The concentrations of immunoreactive oxytocin and arginine vasopressin (AVP) and their respective neurophysins (NpI and NpII) were compared in bovine adrenal cortex and medulla. While the concentration of AVP was similar in both tissues there was more NpII in the medulla. The medulla also contained much more oxytocin and NpI than the cortex. The extracted AVP and oxytocin had identical retention times to those of the synthetic peptides on high-performance liquid chromatography (HPLC) and were biologically active in assays for antidiuretic and milk-ejection activity (with potencies of 310 units/mg and 340 units/mg respectively). Adrenal NpI and NpII behaved identically to commercially available neurohypophysial proteins on HPLC. Oxytocin, NpI and AVP were assayed in five subcellular fractions of bovine adrenal medulla prepared on discontinuous sucrose gradients. A high proportion of each co-localized with noradrenaline and adrenaline in the chromaffin granule fraction. Binding of [3H]AVP and [3H]oxytocin to crude bovine adrenal medulla membranes was dependent upon both time and temperature. The binding sites were specific and saturable: studies with the V1 AVP antagonist d(CH2)5Tyr(Me)AVP and the V2 agonist 1-deamino-8-D-AVP indicated that the AVP receptor was V1 in specificity. Scatchard plots showed that each ligand interacted with a single high-affinity, low-capacity binding site: oxytocin dissociation constant (Kd) 3.1 +/- 0.29 nmol/l, maximum binding capacity (Bmax) 89.6 +/- 18.4 fmol/mg protein (n = 3); AVP Kd 0.73 +/- 0.02 nmol/l, Bmax 26.5 +/- 8.3 fmol/mg protein (n = 3).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗
PubMed1986

Energy metabolism in rat pituitary tumors during stimulation of prolactin by vasoactive intestinal polypeptide and thyrotropin-releasing hormone: a study with nuclear magnetic resonance spectroscopy.

The effect of the peptides TRH and vasoactive intestinal polypeptide (VIP) on phosphate-bound energy of GH3 tumor cells in vivo was investigated using the noninvasive technique of topical 31P-nuclear magnetic resonance spectroscopy. VIP (4.0 micrograms/100 g BW) caused a reduction in the high energy metabolite phosphocreatine and an increase in inorganic phosphate. In the same experiments (n = 9), VIP stimulated PRL secretion to a value of 146% +/- 13 of basal concentrations. The change in the inorganic phosphate-phosphocreatinine ratio had a positive correlation with the increase in PRL secretion (P less than 0.001), indicating a VIP-induced energy consumption for a process related to PRL secretion. In separate experiments, in vitro, it was confirmed that VIP increased energy consumption by demonstrating an increase in glycogenolysis by the pituitary tumor cells. TRH also increased PRL secretion to 145% +/- 23 of basal values but, in contrast, did not induce changes in energy metabolites detectable by nuclear magnetic resonance. It is concluded that VIP and TRH promote PRL release through different stages in the secretion process.

Adenine Nucleotides↗
PubMed1985

Growth hormone in normal female rat plasma appears on gel filtration as a large molecular weight form.

Gel filtration of female rat plasma with normal growth hormone (GH) concentrations (less than 100 ng/m1) showed that nearly all the immuno-reactivity was centred on a peak with an apparent molecular weight in the region of 82,000. In contrast, pituitary GH was almost entirely monomeric. The majority of plasma prolactin (PRL) in the same samples had a molecular weight of 23,000 (i.e. monomeric), and was similar in profile to pituitary PRL. Samples from male rats showed some GH immunoreactivity at the 82,000 molecular weight position but more than 65% coeluted with monomeric PRL. In female plasma with GH concentration between 300 and 1,000 ng/ml, immuno-reactivity resolved into peaks at the void volume, the monomeric position, and a peak at 82,000 that decreased, as a percentage of the total, with increasing GH concentration. These results indicate the possible presence of a GH binding factor, with greater activity in female than male rat plasma.

Animals↗
PubMed1985

Differential effects of extracellular matrix on secretion of prolactin and growth hormone by rat pituitary tumour cells in vitro.

Two types of rat pituitary tumour cells secreting both prolactin (Prl) and growth hormone (GH) were cultured in vitro either on plastic dishes or on surfaces coated with an extracellular matrix (ECM) derived from bovine corneal endothelium. The presence of ECM caused an increase in Prl but a decrease in GH. On one cell line the Prl response to thyrotrophin releasing hormone (TRH) was increased by ECM. There was an increase in the rate of spread of the cultures, an increase in cell protein, and DNA synthesis and a change in cell morphology when ECM was used. It is suggested that these observations can be explained by a sensitizing action of ECM to growth factors present in serum.

Animals↗
PubMed1985

Effect of prolonged dopamine receptor blockade on lactotroph activity in the rat pituitary gland.

The dopamine antagonist fluphenazine was administered to young rats in the presence or absence of physiological concentrations of oestradiol for periods of 230 days. An important observation arising from the investigation was that no pituitary tumours were produced by the combination of prolonged dopamine receptor blockade and small amounts of oestradiol. Prolactin (Prl) secretion increased rapidly with fluphenazine but in the absence of oestrogen lactotroph activity subsequently declined after 20 days and this decrease in hormone secretion was accompanied by a greatly increased dopamine turnover in the medio-basal hypothalamus. In contrast, small amounts of oestradiol modified the effect of fluphenazine alone causing a greatly increased secretion of Prl for a much larger period and a reduction in the dopamine content of the hypothalamus. This combination also doubled the synthesis of DNA by the pituitary compared with controls, and electron microscopy revealed evidence of increased secretory activity of the lactotrophs in the presence of both fluphenazine and oestrogen but not in those animals treated with fluphenazine only. Towards the end of the experiment Prl values declined even in the presence of oestrogen and increasing the dose of fluphenazine had no significant effect. It was suggested that eventually there may be a direct inhibitory action of the dopamine antagonist on the lactotrophs.

Animals↗
PubMed1985

31P-Nuclear magnetic resonance spectroscopy of rat pituitary tumours in vivo.

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 greater than 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.

Animals↗
PubMed1984

VIP enhances TRH-stimulated prolactin secretion of pituitary tumours. Studies with 31P NMR.

Intravenous thyrotrophin releasing hormone (TRH) caused a 6.5-fold increase in plasma prolactin (PRL) in rats carrying implanted pituitary tumours. Vasoactive intestinal polypeptide (VIP) had no effect, but TRH given after VIP raised TRH stimulated secretion 13-fold above basal. 31P NMR spectroscopy showed that VIP caused a decrease in high energy metabolites (depleted phosphocreatine, elevated inorganic phosphate and lowered intracellular pH). TRH alone caused a similar but smaller effect; given after VIP, it caused no detectable depletion. We suggest that the changes in high energy metabolite concentrations reflect increased cellular energy consumption consistent with a priming process (stage 1) in PRL secretion, followed by hormone release (stage 2). VIP induces stage 1 whereas RTH induced both stages.

Animals↗