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Biomedical subjects

J M Burrin

Publications and source records attributed to J M Burrin.

At least 127 records · Page 7Linked to original sources
PubMed1987

Growth hormone (GH) release in response to GH-releasing hormone in man is 3-fold enhanced by galanin.

The effect of GHRH in a dose (120 micrograms) thought to produce a maximal GH response was compared with the GH response to insulin-induced hypoglycemia, iv infusion of the hypothalamic neuropeptide galanin (40 pmol/kg.min for 40 min), and a combination of GHRH and galanin in normal men. The median peak serum GH level was 29 mU/L in response to GHRH, 28.9 mU/L in response to insulin hypoglycemia, 17.3 mU/L in response to galanin, and 115.0 mU/L in response to the combination of galanin and GHRH. GH release induced by galanin was completely inhibited by a concomitant somatostatin infusion (50 pmol/kg.min). Thus, galanin increased the peak GH response to GHRH, previously thought to be one of the most powerful stimulants to GH release, more than 3-fold. Since the dose of GHRH used was thought to be maximal and since galanin is reported not to have direct effects on the pituitary, one possible mode of action of galanin would be inhibition of tonic endogenous hypothalamic somatostatin release.

Adult↗
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↗
PubMed1987

Monoclonal and polyclonal antibodies compared for radioimmunoassay of somatomedin-C in patients with acromegaly or hypopituitarism.

We used a synthetic recombinant analog of somatomedin-C (Sm-C) to directly compare the performance of polyclonal and monoclonal antibodies for measuring Sm-C in serum of normal persons and in acromegalic or hypopituitary patients. Mean concentrations of Sm-C in healthy adults were 181 (SD 42) micrograms/L as measured with the monoclonal antibody, 194 (SD 61) micrograms/L with the polyclonal antibody. Both antisera gave excellent discrimination between acromegalics and normals. However, the assay with the polyclonal antibody was more sensitive than that with the monoclonal antibody (lower detection limits: 5 vs 100 micrograms/L) and thus better suited for quantifying Sm-C in samples from hypopituitary patients.

Acromegaly↗
PubMed1986

Effective and lasting growth-hormone suppression in active acromegaly with oral administration of somatostatin analogue SMS 201-995.

Oral administration of the long-acting somatostatin analogue, SMS 201-995 (Sandoz), was assessed in five patients with active acromegaly, four of whom had not responded to pituitary irradiation. Doses of 4-8 mg three times daily lowered mean 24 h growth-hormone concentrations by over 50% in every case, with suppression to below 10 mU/l for several hours after the morning dose. Despite effective suppression of serum insulin levels, deterioration in glucose tolerance was very slight, and the drug had no side-effects. Orally administered SMS 201-995 avoids the need for multiple daily injections and is potentially valuable in the medical treatment of acromegaly.

Acromegaly↗
PubMed1986

Growth hormone release in man induced by galanin, a new hypothalamic peptide.

Galanin, a 29-aminoacid neuropeptide, was infused for 60 min into healthy volunteers at 7.8 pmol/kg/min (n = 4) or 33.2 pmol/kg/min (n = 6). During the infusion there was no change in heart rate or blood pressure and the only symptoms were a transitory bitter taste and slight hypersalivation. Plasma growth hormone levels rose during the high-dose galanin infusion from 2.8 +/- 0.8 mU/l to a mean peak of 48.5 +/- 19.8 mU/l; prolactin levels rose from 176 +/- 33 mU/l to 274 +/- 33 mU/l. A significant rise in growth hormone also occurred with the low-dose infusion (2.5 +/- 1.1 mU/l to a mean peak of 23.5 +/- 6.6 mU/l). There was no change in cortisol, thyroid-stimulating hormone, follicle-stimulating hormone, or luteinising hormone at either dose. 20 min after the start of the infusion a 25 g glucose bolus was given intravenously. Galanin reduced glucose clearance without significantly affecting plasma insulin concentrations. Pancreatic polypeptide levels were suppressed by the galanin infusion but levels of glucagon and gastric inhibitory peptide were unchanged.

Adult↗
PubMed1986

Combined use of vasopressin and synthetic hypothalamic releasing factors as a new test of anterior pituitary function.

Nine normal volunteers and 15 patients with pituitary disorders were given a combined test of anterior pituitary function using four hypothalamic releasing factors and arginine vasopressin. Rapid sequential intravenous infusions of human corticotrophin releasing factor 100 micrograms, growth hormone releasing factor 100 micrograms, luteinising hormone releasing hormone 100 micrograms, and thyrotrophin releasing hormone 200 micrograms were administered. Arginine vasopressin (10 pressor units) was given intramuscularly at the same time. Plasma or serum samples were assayed for concentrations of cortisol, growth hormone, luteinising hormone, follicle stimulating hormone, prolactin, and thyroid stimulating hormone at multiple times for 120 minutes. No troublesome side effects occurred. The results of the releasing factor combined test with arginine vasopressin were compared in the same subjects with a conventional combined test using insulin together with thyrotrophin releasing hormone and luteinising hormone releasing hormone. No difference was observed in the basal and peak concentrations of luteinising hormone, follicle stimulating hormone, thyroid stimulating hormone, and prolactin. Both cortisol and growth hormone responses to the releasing factors with arginine vasopressin were much greater than those seen with insulin induced hypoglycaemia or the combined releasing factors without arginine vasopressin. Patients with pituitary hypo-function were similarly recognised in both studies. There was a rapid increase in all hormone values with a peak usually by 60 minutes. In most people adequate assessment of individual hormone reserves may be achieved using basal, 30 minute, and 60 minute samples. This new combined releasing factor test appears to be a safe, rapid, and useful test of anterior pituitary function.

Adult↗
PubMed1986

Serum immunoreactive insulin responses to a glucose load in Asian Indian and European type 2 (non-insulin-dependent) diabetic patients and control subjects.

The serum immunoreactive insulin response to an oral glucose load was estimated in 15 Asian Indian and 29 European non-diabetic subjects, and in 45 Asian Indian and 72 European Type 2 (non-insulin-dependent) diabetic patients. In the non-diabetic group, basal insulin values were higher in the Asian Indians than the Europeans (16.7 +/- 3.0 vs. 6.9 +/- 0.7 mU/l, p less than 0.001), and remained higher throughout the glucose tolerance test. Total insulin response was also higher in the Asian Indians (p less than 0.001), and linear regression analysis revealed basal insulin, body mass index and race to be important predictors of insulin response. Amongst the diabetic patients, basal insulin values were again higher in the Asian Indians compared with the Europeans (18.0 +/- 5.0 vs. 11.5 +/- 0.9 mU/l, p less than 0.05). Total insulin response was also greater (p less than 0.01). Linear regression analysis revealed the basal insulin value to be the only significant predictor of insulin response. The results demonstrate higher insulin levels in Asian Indians than Europeans in both normal subjects and Type 2 diabetic subjects. The insulin response to a glucose load is also greater in the Asian Indians. In the control subjects, ethnic differences contribute to this response, whereas in the diabetic patients this is a function of the elevated basal insulin values of the Asian Indians.

Adult↗
PubMed1986

Low serum thyroxine concentrations and neural maturation in preterm infants.

The effect of hypothyroxinaemia on postnatal progression of the motor nerve conduction velocity was studied in 33 very low birthweight infants. Serum concentrations of thyroid stimulating hormone, triiodothyronine, and thyroxine were determined at birth and at ages 3, 7, and 21 days. Nerve conduction velocity was measured in the first week of life, on day 21, and at 40 weeks' postmenstrual age. Seven infants maintained their thyroxine concentration above 60 nmol/l (4.67 micrograms/100 ml) throughout the study. Three of these infants needed mechanical ventilation and one had an intraventricular haemorrhage. Twenty six infants developed hypothyroxinaemia (thyroxine less than 60 nmol/l). The nerve conduction velocity was delayed in 13 infants, two on day 21 and 11 at 40 weeks' postmenstrual age. The delay was equivalent to 1.9-4.4 weeks. All these infants belonged to the group with depressed thyroxine concentrations. The delay in progression in nerve conduction velocity was associated with prolonged hypothyroxinaemia, especially in those infants who also required ventilation. Further studies are in progress to study the effect of thyroid hormone on the nerve conduction velocity in preterm infants.

Aging↗
PubMed1986

Exercise-induced increases in plasma catecholamines and growth hormone are augmented by selective alpha 2-adrenoceptor blockade in man.

A specific alpha 2-adrenoceptor antagonist (idazoxan) was used in man to examine the neuroregulation of growth hormone (GH) release and the effect of alpha 2-adrenoceptors on noradrenaline release. In the first study, GH-releasing factor (GRF)-induced GH release was unaffected in 6 normal volunteers by the prior administration of idazoxan, suggesting that the alpha 2-receptors involved in GH release are not operative at pituitary level. In the second study, 6 normal volunteers performed a bicycle exercise test with and without prior treatment with idazoxan. The exercise-induced GH response (to 13 +/- 5 mU/l) was significantly augmented by idazoxan (to 20 +/- 7 mU/l) which contrasts with the current view of GH release being regulated by stimulatory hypothalamic alpha 2-adrenoceptors and suggests that these alpha 2-adrenoceptors are capable of exerting a dual effect on GH release. The exercise-induced increase in plasma noradrenaline (to 1.45 +/- 0.19 micrograms/l) and in heart rate (to 142 +/- 5 beats/min) were also augmented by idazoxan (to 2.24 +/- 0.23 micrograms/l and 152 +/- 6 beats/min). A similar augmentation of the plasma adrenaline response to exercise was also found, whereas the blood glucose, plasma insulin and potassium response to exercise was unaffected by idazoxan. These results suggest that during exercise in man, alpha 2-adrenoceptors exert a tonic inhibitory influence on noradrenaline release which also serves to limit the exercise-induced tachycardia.

Adult↗
PubMed1986

Effect of ketoconazole on adrenocorticotrophic hormone secretion in vitro and in vivo.

The direct effects of ketoconazole on ACTH secretion have been investigated using a rat pituitary cell culture system. Ketoconazole had no significant effects on basal ACTH secretion, corticotrophin-releasing factor- or arginine vasopressin-stimulated ACTH secretion, nor did it affect dexamethasone inhibition of ACTH secretion. In-vivo studies demonstrated an increased ACTH level (168 vs 76 ng/l) accompanied by a fall in plasma corticosterone (193 vs 307 micrograms/l) in normal rats given ketoconazole (24 mg/kg, five oral doses given 8 hourly). No effects were seen in adrenalectomized rats or at lower doses (6 mg/kg) in normal or adrenalectomized rats. A high dose of ketoconazole (24 mg/kg, twice daily oral doses) also caused increased ACTH levels in normal rats (129 vs 86 ng/l) when given for 7 days. No effects were seen in adrenalectomized rats or on plasma corticosterone levels in normal rats. Our data suggest that ketoconazole at these doses has no direct effects on pituitary ACTH secretion but causes an increase in plasma ACTH due to its inhibition of adrenal steroid synthesis.

Adrenalectomy↗
PubMed1985

Growth hormone secretion dynamics in a patient with ectopic growth hormone-releasing factor production.

A female patient with acromegaly, hypercalcemia, and Zollinger-Ellison syndrome was found to have a very high plasma concentration (average 2,300 pmol/liter; normal less than 50 pmol/liter) of growth hormone-releasing factor as measured by a radioimmunoassay to human pituitary growth hormone-releasing factor-1-44. The plasma concentration of growth hormone averaged 25 mIU/liter (normal less than 5 mIU/liter) and there was no rise following an intravenous 100 micrograms bolus of human pituitary growth hormone-releasing factor-1-44. Plasma growth hormone and growth hormone-releasing factor levels were unaffected by bromocriptine, insulin-induced hypoglycemia, and sleep. A long-acting somatostatin analogue lowered both the growth hormone-releasing factor and the growth hormone levels. Thyrotropin-releasing hormone stimulation and oral glucose tolerance tests produced significant increases in plasma growth hormone levels whereas the growth hormone-releasing factor level remained unchanged, suggesting that when normal somatotrophs are exposed to maximal growth hormone-releasing factor stimulation, thyrotropin-releasing hormone becomes a secretagogue of growth hormone from the pituitary. It is proposed that in the absence of a radioimmunoassay for growth hormone-releasing factor, a lack of growth hormone response to growth hormone-releasing factor in a patient with acromegaly is compatible with a source of ectopic growth hormone-releasing factor production.

Apudoma↗
PubMed1985

Metabolic and haemodynamic effects of alpha 2-adrenoceptor stimulation and antagonism in man.

Six healthy volunteers received a 60 min infusion of guanfacine (alpha 2-agonist) on two occasions, preceded by either idazoxan (alpha 2-antagonist) or vehicle. Idazoxan elevated blood pressure by 8/7 mmHg, but there was no change on either day during guanfacine infusion. Guanfacine reduced plasma noradrenaline by approximately 30%, and this was not antagonized by idazoxan. By contrast, the 30-fold increase in plasma growth hormone caused by guanfacine was almost completely blocked by idazoxan. Guanfacine caused a two- to three-fold increase in plasma glucagon and a similar reduction in plasma insulin. Only the latter was antagonized by idazoxan. No consistent changes in plasma ACTH were observed after either idazoxan or guanfacine. Idazoxan itself elevated plasma noradrenaline up to twice baseline values, but did not affect the other metabolic measurements. alpha 2-Adrenoceptor stimulation plays a minor role in control of hormone release but has a greater physiological role in regulating release of the neurotransmitter, noradrenaline.

Adrenergic alpha-Agonists↗