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Biomedical subjects

E F Adams

Publications and source records attributed to E F Adams.

At least 73 records · Page 4Linked to original sources
PubMed1987

Neuropeptide Y directly inhibits growth hormone secretion by human pituitary somatotropic tumours.

Neuropeptide Y (NPY) is a 36 amino acid peptide, widely distributed throughout the brain and is found in hypothalamic neurones. This latter finding suggests that NPY may possess a hypophysiotropic function. A number of studies have demonstrated effects of NPY on LH and GH secretion by rat pituitary cells. We report here the results of experiments investigating the effects of NPY on GH secretion by tumorous human somatotropic pituitary cells in culture. NPY (0.25-25 nmol/l) inhibited GH secretion by 20-53%, the maximal effect depending upon the tumour studied. The potency of NPY was less than that of somatostatin (SRIH). The stimulatory effects of growth hormone releasing factor (GHRH) and theophylline were reduced by NPY, but NPY did not modify the inhibitory effect of SRIH on GH secretion. It is concluded that NPY may be involved in the control of GH secretion, at least by tumorous human pituitary somatotropes.

Cells, Cultured↗
PubMed1987

Effects of two novel dopaminergic drugs, CV 205-502 and CQP 201-403, on prolactin and growth hormone secretion by human pituitary tumours in vitro.

Two novel dopaminergic drugs, designated CV 205-502 and CQP 201-403 have recently been developed by Sandoz Pharmaceuticals Ltd (Basle, Switzerland). The effects of these drugs on PRL and GH secretion by normal rat and tumorous human pituitary cells in vitro have been investigated. Low doses of both CV 205-502 and CQP 201-403 immediately and profoundly suppressed PRL secretion, which failed to recover up to 7 h after removal of the drugs. Similarly, CQP 201-403 significantly suppressed basal GH secretion by human pituitary somatotropic tumours in culture, and both drugs significantly reduced the stimulatory effect of GHRH. These effects are more potent and longer acting than the previously described in vitro effects of bromocriptine. It is concluded that CV 205-502 and CQP 201-403 hold potential for the treatment of patients with hyperprolactinaemia and, possibly, also in patients with acromegaly.

Aminoquinolines↗
PubMed1986

Localization of human pituitary hormones by multiple immunoenzyme staining procedures using monoclonal and polyclonal antibodies.

Mouse monoclonal and rabbit polyclonal antibodies to human pituitary hormones were applied together to sections of normal and neoplastic human pituitary tissue. Binding sites were revealed with species-specific immune reagents combined with various enzymes (peroxidase, alkaline phosphatase, and beta-D-galactosidase). The enzymes were developed separately to give differently colored end-products. Where two hormones were present in the same cell, a mixed color was produced. Up to four hormones could be immunostained in a single section. Multiple immunoenzymatic staining has great potential for the analysis of plural antigen production by single cells and relationships between cells producing different antigens.

Animals↗
PubMed1985

Role of cell and explant culture in the diagnosis and characterization of human pituitary tumours.

The pattern of hormone secretion by human pituitary tumours in cell or explant culture has been shown to be of value in establishing the nature of the tissue. There was complete agreement between the diagnosis reached by conventional immunocytochemical techniques and by examining the secretion of hormones in culture. Culture techniques, however, have some advantages over immunocytochemical analysis. In particular, immunocytochemical techniques can only be used to examine a small, possibly unrepresentative, portion of the pituitary tissue, whereas the in vitro culture systems make use of the whole tissue. In addition, in vitro culture is simpler to employ and can be carried out relatively rapidly. Cell and explant culture was therefore used to examine the nature of human pituitary tumours. To determine the incidence of mixed GH-PRL secreting pituitary tumours in acromegaly, the pattern of hormone secretion in vitro by 98 somatotrophic tumours was examined. Thirty-seven per cent were found to be pure somatotrophic tumours and 59.2% secreted both GH and PRL, but no other hormone, indicating that these tumours were of mixed nature. This latter group could be divided into those removed from patients with hyperprolactinaemia (35.7% of all tumours) and those from patients with normal pre-operative serum PRL levels (23.5%). A further small group (3.1%) of tumours secreted only GH in culture, despite elevated pre-operative serum PRL levels, indicating that the hyperprolactinaemia in these patients was due to pituitary stalk compression by the somatotrophic tumour, thereby preventing prolactin release inhibiting factor reaching the lactotrophs and allowing uncontrolled PRL secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Culture Techniques↗
PubMed1985

The plasma noradrenaline and growth hormone response to alpha-methyldopa and clonidine in hypertensive subjects.

The mechanism of the antihypertensive effect of alpha-methyldopa was compared with clonidine by administering equipotent single doses of clonidine (0.2 mg) and alpha-methyldopa (750 mg) to nine hypertensive patients. Plasma noradrenaline was followed for 8 h thereafter as an index of peripheral sympathetic activity. alpha-Methyldopa and clonidine produced the same hypotensive response at 6 and 8 h after dosing with a similar fall in plasma noradrenaline levels at these times. Linear regression analysis between the systolic blood pressure fall and the corresponding plasma noradrenaline fall, showed that the slopes of the two regression lines were similar for alpha-methyldopa as for clonidine. Equipotent doses of alpha-methyldopa and clonidine produce the same fall in plasma noradrenaline. This supports the current hypothesis that an alpha-methyldopa metabolite acts centrally, like clonidine, to reduce peripheral sympathetic activity.

Adult↗
PubMed1985

Ovine corticotrophin releasing factor stimulates ACTH release from human corticotrophinoma cells in culture; interaction with hydrocortisone and arginine vasopressin.

We have investigated the effects of ovine corticotrophin releasing factor (oCRF) and its interaction with hydrocortisone (HC), and arginine vasopressin (AVP) on ACTH release from human corticotrophinoma cells in culture. Tumour tissue was obtained from six patients (three with active Cushing's disease and three with Nelson's syndrome). Cultures were maintained for periods of up to six months. Ovine CRF (21 nmol) significantly (P less than 0.01) stimulated ACTH release from all tumours. Dose response (21 pmol-21 nmol) effects were observed for the three tumours investigated over 2 and 4 h. Cortisol (20 mumol) significantly (P less than 0.01) inhibited basal ACTH release from one tumour (Nelson's syndrome) by 75% over 4 h, and completely prevented the stimulatory effects of oCRF. AVP directly stimulated ACTH release from two tumours (Nelson's syndrome), and also potentiated the stimulatory action of oCRF during 30 min incubations. These data show corticotrophinoma cells from subjects with Cushing's disease and Nelson's syndrome can be directly stimulated by hypothalamic oCRF and may be potentiated by AVP. Cortisol and oCRF have been shown in one tumour to have antagonistic actions at the pituitary level.

Adrenocorticotropic Hormone↗
PubMed1985

Effect of nivazol on ACTH secretion by human pituitary corticotrophic tumours in cell culture.

The effects of nivazol, a novel steroid which lacks glucocorticoid activity, on ACTH secretion by cell cultures of human pituitary corticotrophic tumours has been investigated. Nivazol (0.002-20 mumol/l) inhibited ACTH secretion by 50-80%, after 4 and 24 h of incubation. (Trilostane (0.3-30 mumol/l) did not affect basal or stimulated ACTH secretion.) The potency of nivazol was comparable with that of hydrocortisone, and less than dexamethasone. The stimulatory effects of oCRF and AVP were reduced or completely blocked by nivazol in a similar manner to that previously described for hydrocortisone. It is concluded that nivazol may be of benefit in the direct treatment of Cushing's disease, particularly since it lacks glucocorticoid activity.

Adrenocorticotropic Hormone↗
PubMed1984

Effect of pancreatic growth hormone releasing factors on GH secretion by human somatotrophic pituitary tumours in cell culture.

Human pancreatic growth hormone releasing factors (hpGRF(1-40) and hpGRF(1-44) significantly stimulated GH secretion when added to cell cultures of human somatotrophic pituitary tumours for 2 h. There was little difference in potency between the two peptides, and the response of different tumours varied, ranging from 30% to 500% increases in GH secretion over control levels. This stimulatory effect was blocked by somatostatin (SRIF) and bromocriptine. The suppressive effect of bromocriptine, but not of SRIF, was overcome by high doses of hpGRF(1-44). TRH stimulated GH secretion by one of three somatotrophic tumours in cell culture, and it was found to potentiate the stimulatory effects of hpGRF(1-44). These results demonstrate that hpGRFs increase serum GH levels in man by a direct action at the pituitary somatotroph level.

Adult↗
PubMed1983

Abnormalities of growth hormone release in response to human pancreatic growth hormone releasing factor (GRF (1-44) ) in acromegaly and hypopituitarism.

Human pancreatic growth hormone releasing factor (GRF (1-44)) is the parent molecule of several peptides recently extracted from pancreatic tumours associated with acromegaly. A study was conducted to examine its effects on the release of growth hormone in normal volunteers and in patients with hypopituitarism and acromegaly. GRF (1-44) dose dependently stimulated the release of growth hormone in normal people and produced no appreciable side effect. This response was grossly impaired in patients with hypopituitarism and, although similar to the growth hormone response to hypoglycaemia, was of quicker onset and a more sensitive test of residual growth hormone function. Patients with acromegaly appeared to fall into (a) those with a normal response to GRF, whose growth hormone suppressed significantly with oral glucose, and (b) those who had an exaggerated response to GRF (1-44), whose growth hormone had not suppressed previously after oral glucose. Present methods for testing growth hormone deficiency entail using the insulin stress test, which is time consuming, unpleasant, and sometimes dangerous. A single intravenous injection of GRF now offers the possibility of an easier, safer, and more reliable routine test for growth hormone deficiency. It has the further advantage of being free of side effects and readily performed in outpatients. Hence it seems likely to become the standard test and take the place of the insulin stress test.

Acromegaly↗
PubMed1983

Gonadotrophin and alpha subunit secretion by human 'functionless' pituitary adenomas in cell culture: long term effects of luteinizing hormone releasing hormone and thyrotrophin releasing hormone.

The long-term effects of LHRH and TRH on gonadotrophin alpha subunit, FSH and LH secretion by cell cultures of four human chromophobic pituitary tumours have been examined. The tumours derived from one male and three female patients who presented because of visual disturbance but had no evident endocrine symptoms. Subsequent serum hormone analysis showed the FSH to be high in the male but low or normal in the post-menopausal females whereas LH levels were low in all patients. In culture, basal hormone secretion could be maintained for periods up to 63 d. All tumours secreted alpha subunit and FSH, but much lower amounts of LH. Addition of LHRH or TRH for a period of 12 to 41 d showed that alpha subunit, FSH and LH secretion were stimulated by LHRH from one tumour, by LHRH and TRH from two tumours. There was always a rapid decline in the LH secretion. The tumour which secreted FSH predominantly was stimulated by TRH. We conclude that human pituitary 'functionless' adenomas can secrete gonadotrophin alpha subunit and FSH in vitro and that secretion can be stimulated during long term releasing hormone experiments. LH secretion, however, cannot be maintained.

Adenoma, Chromophobe↗
PubMed1982

Vasoactive intestinal peptide stimulates adrenocorticotropin release from human corticotropinoma cells in culture: interaction with arginine vasopressin and hydrocortisone.

The effect of vasoactive intestinal peptide (VIP), cholecystokinin octapeptide (CCK), bombesin, arginine vasopressin (AVP), and hydrocortisone (HC) on ACTH release from human corticotropinoma cells in culture has been studied. Tumor tissue was obtained from 6 patients with pituitary corticotropinomas. Eleven to 21 cultures yielding 0.7-2.0 X 10(6) cells/culture, were obtained from each tumor and maintained for periods of 4 weeks to longer than 6 months. VIP (500 ng/ml) significantly (P less than 0.005) stimulated ACTH release from all tumors studied, and a dose (5-500 ng/ml)-response effect was observed in 3 of 5 tumors. Stimulation by VIP was seen at 2,4, and 24 h and was maximal at 4 h. CCK and bombesin were without effect on ACTH release from 4 tumors studies at 4 h. AVP (1-10 mU/ml) stimulated ACTH from 4 tumors studied at 60 min or 4 h. Coincubation of cultures with VIP (50-500 ng/ml) and AVP (1-10 mU/ml) resulted in at least an additive effect. HC (100 ng/ml) significantly (P less than 0.025) inhibited basal ACTH secretion from 2 of 4 tumors at 4 h and from 3 of 4 (P less than 0.005) at 24 h. Simultaneous coincubation of cultures with VIP (50 ng/ml) and HC (100 ng/ml) resulted in an attenuation or blockade of the VIP-stimulated ACTH release, whereas prior incubation of cultures with HC for 28 h before exposure to VIP did not. The results demonstrate that VIP is a potent ACTH secretagogue from human corticotropinoma cells in culture; its effects are additive to those of AVP and modulated by HC.

Adenoma↗
PubMed1981

Bromocriptine suppresses ACTH secretion from human pituitary tumour cells in culture by a dopaminergic mechanism.

Bromocriptine (0.13-13 microM) significantly inhibited ACTH secretion in a dose-dependent manner when added to cell cultures of a human corticotrophic adenoma for 24 h. Haloperidol (13 microM), but not serotonin (13 microM), blocked this inhibition but had no significant effect when added alone. In addition, dopamine (10 microM) reduced ACTH secretion during a 4-h incubation, whereas serotonin (0.01-10 microM) was ineffective. An ectopic ACTH secreting lung carcinoid was non-responsive to doses of bromocriptine up to 13 microM. These results demonstrate a direct suppressive action of bromocriptine on a human pituitary corticotrophic adenoma through dopaminergic rather than serotoninergic mechanisms.

Adenoma↗
PubMed1981

Growth hormone and prolactin secretion by dispersed cell cultures of a normal human pituitary: effects of thyrotrophin releasing hormone, theophylline, somatostatin, and 2-bromo-alpha-ergocryptine.

Growth hormone (GH) and prolactin (Prl) secretion by a normal human pituitary in dispersed cell culture has been investigated. Prl secretion was significantly stimulated after 0.5, 1, 2 and 4 h exposure to 1, 10, 100 and 1000 ng/ml thyrotrophin releasing hormone (TRH). Maximal effects were obtained with 10 ng/ml TRH at 2 h, higher doses being less effective. GH secretion was unchanged with the exception that 1 ng/ml TRH produced a small decrease at 4 h. GH and Prl secretion was significantly inhibited by incubation with 0.01, 0.1, 1 or 10 micrograms/ml 2-bromo-alpha-ergocryptine (bromocriptine). The inhibition persisted for a further 24 h after removal of bromocriptine. Theophylline (10(-2) M) significantly increased GH and Prl secretion during a 4 h incubation and this effect was blocked by co-incubation with 10 ng/ml somatostatin (SRIF). SRIF also inhibited basal GH and Prl secretion during 4 h and removal of SRIF and incubation for at further 4 h led to a rebound in GH and Prl secretion to levels greater than control. It is concluded that cell culture techniques previously applied to the study of hormone secretion by pituitary adenomas can be equally applied to the normal human pituitary.

Bromocriptine↗
PubMed1980

Adrenocorticotropin and lipotropin secretion by dispersed cell cultures of a human corticotropic adenoma: effect of hypothalamic extract, arginine vasopressin, hydrocortisone, and serotonin.

Basal and modulated secretion of ACTH and lipotropin (LPH) by cultures of trypsin-dispersed cells of a biopsy of a human corticotropic adenoma have been examined. ACTH secretion was detectable throughout the period of culture (13 days) but declined steadily from an initial production rate of 238 +/- 124 ng/3 X 10(5) cells/12 h. The time course of secretion showed a slower phase over the first 4 h, with increases up to 12 h. An extract of rat stalk median eminence caused a significant (P less than 0.005) dose-dependent increase in both ACTH and LPH secretion during 30 min. The patterns of response for ACTH and LPH were very similar; both exhibited a decline in the basal release of peptide subsequent to the period of stimulation. The addition of hydrocortisone (0.2 micrograms/ml) did not suppress basal ACTH secretion during 30 min but significantly (P less than 0.05) inhibited stimulation produced by rat stalk median eminence extract. Arginine vasopressin (dose range, 1-9 ng/ml) significantly (P less than 0.025) stimulated both ACTH and LPH secretion during 30 min. The patterns of response were again very similar. Serotonin (dose range, 0.01-10 micrograms/ml) did not affect ACTH secretion during incubations of 30 min to 4 h. The results obtained with the cell cultures of a human corticotropic cell adenoma concur with in vivo findings of incomplete autonomy of secretion, parallel secretion of ACTH and LPH in response to provocative stimuli, and suppression by corticosteroids. The technique has potential for exploring the cellular mechanisms controlling secretion by human corticotropic adenomas as well as the nature of the hormones produced.

Adrenocorticotropic Hormone↗