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Biomedical subjects

M F Scanlon

Publications and source records attributed to M F Scanlon.

At least 55 records · Page 3Linked to original sources
PubMed1988

Growth hormone and its modulation.

Our knowledge of the mechanisms involved in the regulation of somatotroph cell growth is scanty and much work is still needed to elucidate the role of different growth factors and the mechanisms involved in oncogene activation in both normal and tumour cell growth. However, there are several recent, important clinical ramifications from our improved understanding of GH neuroregulation. The use of long-acting SS analogues is valuable in the treatment of acromegaly, probably in acute variceal haemorrhage and it also produces symptomatic improvement in patients with vipomas and glucagonomas. GHRH may be of value in the treatment of short stature due to hypothalamic GHRH deficiency but further definitive studies are now required to provide convincing evidence that this line of treatment is of greater benefit than the use of synthetic recombinant human GH. Inhibition of GH release may be of value in prevention of both acute and chronic complications of insulin-dependent diabetes mellitus. The use of cholinergic muscarinic receptor blockade in this context may be particularly useful because of a probably sparing of the counter-regulatory GH response to hypoglycaemia. In view of the relative ease with which nocturnal GH secretion can be abolished, we think it reasonable to consider the possible existence of a permissive or mediating role of GH in other disease states, either directly or by maintaining production of either local tissue or circulating growth factors or both.

Acromegaly↗
PubMed1987

The effects of neonatal hypothyroidism on brain catecholamine turnover in adult rats: assessment by a steady-state method.

The effects of hypothyroidism in utero, and continuing into postnatal life, on the central turnover of catecholamines, noradrenaline and dopamine were studied in rats. Rats were rendered hypothyroid in utero by treating pregnant females with methimazole in the drinking water. In two groups goitrogen treatment continued for 3 or 10 weeks postnatally. Methimazole treatment in utero did not produce significant changes in noradrenaline, dopamine or tyrosine content in either the hypothalamus or striatum. Three weeks' postnatal treatment reduced tyrosine specific radioactivity in the anterior hypothalamus and dopamine specific radioactivity in the striatum. Ten weeks' treatment increased dopamine content and reduced noradrenaline synthesis in the mediobasal hypothalamus and a reduction in tyrosine content in the anterior hypothalamus. These data suggest that hypothyroidism restricted to intrauterine life does not produce permanent changes in adult catecholamine neuronal function. Long term hypothyroidism produced localized changes, suggesting a specific rather than general effect.

Animals↗
PubMed1987

Cholinergic muscarinic receptor blockade with pirenzepine abolishes slow wave sleep-related growth hormone release in young patients with insulin-dependent diabetes mellitus.

Cholinergic receptor blockade has been shown to abolish GH secretion in a variety of physiological and pharmacological situations in normal subjects. We have investigated the effect of pirenzepine on nocturnal GH secretion in young adult patients with Type I insulin-dependent diabetes mellitus. Five patients (three male, two female; aged 20-27 years) were studied in a randomized order on two days separated by at least 1 week. All patients showed episodes of slow wave sleep on each occasion and this was followed by peaks of GH release when placebo alone was administered (range of GH peaks 6-115 mU/l). In contrast, cholinergic muscarinic receptor blockade with pirenzepine (100 mg orally at 2200 and 2400 h) completely abolished nocturnal GH release in each individual without altering the occurrence of slow wave sleep itself. Mean plasma glucose levels at each sampling time between each study did not differ significantly. The ability to abolish nocturnal GH secretion may be important in the field of diabetes, since excess GH secretion is implicated in several acute metabolic and chronic microvascular complications of the disease.

Adult↗
PubMed1987

Effect of oral administration of melatonin on GH responses to GRF 1-44 in normal subjects.

In order to investigate the role of melatonin on the neuroregulation of GH secretion, eight healthy male volunteers each underwent four separate tests in random order separated by at least 1 week. Following oral administration of melatonin (500 mg at -60 min and at -30 min) plasma GH levels were higher than after placebo at 45 min (mean +/- SEM 2.9 +/- 0.8 vs 0.9 +/- 0.4 ng/ml, P less than 0.01) and 60 min (mean +/- SEM 2.9 +/- 0.4 vs 0.8 +/- 0.1 ng/ml, P less than 0.05). Likewise, after prior administration of melatonin, GH responses to GRF 1-44 (1 micrograms/kg i.v. at 0 min) were greater than placebo plus GRF at 15 min (mean +/- SEM 22.4 +/- 6.1 ng/ml vs 11.3 +/- 2.3 ng/ml, P less than 0.05), 45 min (mean +/- SEM 26.2 +/- 5.3 ng/ml vs 13.3 +/- 2.5 ng/ml, P less than 0.01) and 60 min (mean +/- SEM, 24.7 +/- 7.4 ng/ml vs 11.1 +/- 2.5 ng/ml, P less than 0.05). In contrast we did not observe any effect of either 10(-9)M, 10(-7)M melatonin on in-vitro basal GH release and GH responses to 10(-8)M GRF by rat anterior pituitary cells in monolayer culture. These data suggest that melatonin plays a facilitatory role in the neuroregulation of GH secretion, probably by acting at the hypothalamic level.

Administration, Oral↗
PubMed1987

Additive effects of growth hormone releasing factor and insulin hypoglycaemia on growth hormone release in man.

We have measured GH and PRL changes following separate and combined administration of insulin and GH releasing factor (GRF) in six normal males. Peak GH responses to separate administration of insulin and GRF were comparable (71.4 +/- 10.2 vs 70.1 +/- 27.7 mU/l; mean +/- SEM). However, the peak GH response following combined administration was significantly higher (120.8 +/- 29.7, P less than 0.05) as was the total GH released as calculated by measuring the area under the curve (P less than 0.05). In contrast the PRL response to hypoglycaemia was not altered by the combined administration of insulin and GRF. This effect was not due to any direct action of hypoglycaemia or insulin at pituitary level since basal and 10(-8) M GRF stimulated GH release from rat anterior pituitary cells in vitro was not influenced by varying glucose and insulin levels. Our findings support the hypothesis that GRF and insulin-induced hypoglycaemia release GH via different pathways which are, at least in part, additive.

Adult↗
PubMed1987

Circulating TSH levels measured with an immunochemiluminometric assay in patients taking drugs interfering with biochemical thyroid status.

Serum TSH was measured using a high sensitivity immunochemiluminometric assay (ICMA) in patients receiving anticonvulsant drugs, heparin or non-steroidal anti-inflammatory agents (NSAIs) and the results compared with those from groups of age- and sex-matched controls. The TSH results have also been compared with those of estimates of free thyroid hormone levels using Amerlex analogue method reagents. All patients were clinically euthyroid and TSH concentrations were in the normal, euthyroid range and did not differ significantly in any group studied. In contrast, Amerlex free T4 levels were significantly reduced in the patients treated with phenytoin (P less than 0.001), carbamazepine (P less than 0.01), sodium valproate (P less than 0.01) and heparin (P less than 0.001). Patients treated with NSAI agents showed no significant change in free T4 levels. Amerlex free T3 levels were also significantly reduced in the patients treated with phenytoin (P less than 0.005), carbamazepine (P less than 0.005) and heparin (P less than 0.001) but not in those treated with sodium valproate or NSAIs. These data support the view that measurement of circulating TSH with an assay of sufficient precision in the relevant range provides a reliable way of assessing thyroid status and could be used to exclude hyperthyroidism in patients taking the medications investigated in this study.

Adolescent↗
PubMed1987

Effect of thyroxine replacement therapy on plasma insulin-like growth factor 1 levels and growth hormone responses to growth hormone releasing factor in hypothyroid patients.

The aim of this study was to evaluate the effect of T4 replacement therapy on plasma insulin-like growth factor 1 (IGF-1) levels in patients with primary hypothyroidism to see whether recovery of pituitary GH responsiveness to GRF was associated with increased plasma IGF-1 levels. IGF-1 levels and GH responses to GRF (1 microgram/kg) were measured in 21 patients with primary hypothyroidism before and after T4 replacement therapy. T4 increased plasma IGF-1 levels (57.2 +/- 4.4 vs 75.9 +/- 8.8 ng/ml, mean +/- SEM, P less than 0.05) and GH responses to GRF as assessed both by peak GH levels (9 +/- 1.5 ng/ml before treatment vs 16.7 +/- 3 ng/ml after treatment, mean +/- SEM, P less than 0.05) and area under curve (496 +/- 92 before treatment vs 896 +/- 161 after treatment, mean- +/- SEM, P less than 0.05). Linear regression analysis showed a positive correlation between free T3 and IGF-1 levels after treatment (r = 0.37, P less than 0.05) and a negative relationship between plasma IGF-1 levels before treatment and delta IGF following T4 replacement therapy (r = 0.45, P less than 0.025). However, no correlation was found between plasma IGF-1 levels and GH responses to GRF, suggesting that GH responses to GRF are of no predictive value in relation to the recovery of plasma IGF-1 levels following T4 replacement therapy in hypothyroid patients.

Adult↗
PubMed1987

Non-adenomatous inappropriate TSH hypersecretion and euthyroidism requires no treatment.

The syndrome of inappropriate TSH secretion is described in a euthyroid girl and her father. Based on nuclear T3 binding studies in fibroblasts, generalized tissue resistance was associated with a lower binding affinity for T3 in nuclear extracts suggestive of a structurally abnormal receptor for T3. Early recognition of the syndrome and observation of the short-term response to thyroid medication prevented unnecessary trials of antithyroid medication and later radical ablative thyroid treatment.

Child, Preschool↗
PubMed1987

Thyroid status in senile dementia of the Alzheimer type (SDAT).

Thyroid function was investigated in a group of 21 patients with severe senile dementia of the Alzheimer type (SDAT) and in a group of 17 age and sex matched normal controls. Free thyroid hormone levels (triiodothyronine (T3) and thyroxine (T4) were measured, as were also the thyrotrophin (TSH), prolactin (PRL) and growth hormone (GH) responses to thyrotrophin releasing hormone (TRH)). When compared to controls, patients demonstrated a significantly lower free T3 value (but not free T4), a blunted TSH response to TRH, slightly elevated basal PRL and GH values and a small GH response to TRH. However, all differences were small in biological terms and were within the laboratory's normal range. This emphasizes the relative normality of neuroendocrine function, particularly thyroid status, in SDAT.

Aged↗
PubMed1987

Free fatty acids block growth hormone (GH) releasing hormone-stimulated GH secretion in man directly at the pituitary.

Increases in plasma FFA levels inhibit GH responses to a variety of pharmacological and physiological stimuli. To gain further insight into the mechanism by which FFA exert their effect, we studied the plasma GH responses to GHRH-(1-44) (1 microgram/kg, iv) in normal subjects in whom plasma FFA levels were raised by a lipid-heparin infusion (250 mL 10% Intralipid plus 2500 U heparin). Paired tests were performed in 10 normal subjects, with and without lipid-heparin pretreatment. Lipid-heparin infusion from -30 to 120 min increased mean FFA levels from 0.41 +/- 0.03 (+/- SEM) to 3.12 +/- 0.40 mmol/L at 120 min. The mean plasma GH levels after GHRH administration were lower at all times; however, the values were significantly different (P less than 0.05) only at the later times (45, 60, and 90 min). When considered individually, an all or none pattern was observed; 5 subjects had no plasma GH response to GHRH, and 5 had no reduction. To investigate the time relationships between the FFA peak and subsequent GH blockade, a different protocol of paired tests was performed with GHRH with or without a different lipid-heparin infusion protocol. Lipid-heparin was infused from -90 to 0 min, with an additional heparin pulse at -15 min, to obtain a higher and earlier (0 min) FFA increase. FFA increased from 1.06 +/- 0.19 to 11.61 +/- 0.83 mmol/L at zero time. The GHRH-induced GH secretory peak (15.8 +/- 3.5 ng/ml) at 15 min was completely blocked (0.9 +/- 0.2 ng/ml), and the mean plasma GH levels were also lower at 30, 45, and 60 min. To determine whether the FFA-induced blockade of GH secretion was exerted in the pituitary, a series of in vitro studies was conducted using monolayer cultures of rat anterior pituitary glands, with GHRH concentrations of both 10(-10) and 10(-8) M and 10(-5) M forskolin to stimulate GH release. Both caprylic and oleic acid inhibited basal GH release and GHRH- or forskolin-induced GH release. PRL release was not altered, nor were toxic actions noted on the cells. In conclusion, FFA are able to block GH secretion directly at the pituitary level.

Adult↗
PubMed1987

Alpha-adrenoreceptor blockade with thymoxamine reduces basal thyrotrophin levels but does not influence circadian thyrotrophin changes in man.

We have tested the hypothesis that alpha-adrenergic drive is involved in the nocturnal increase in TSH in man. Seven mildly hypothyroid women (basal TSH levels 5.0-11.0 mU/l), aged 38-60 years, and nine euthyroid women, aged 27-60 years, were studied. Subjects underwent alpha-adrenergic blockade by infusion of thymoxamine (210 micrograms/min from 19.00 to 24.00 h); the same women were used as controls, with saline infused on different nights. Subjects were not allowed to sleep during the study period. A clear evening rise in basal TSH levels was apparent in both normal subjects and patients. Although overall secretion of TSH was slightly decreased in normal subjects (mean +/- S.E.M. area under the curve, 29.93 +/- 0.96 vs 30.71 +/- 0.80 mU/l per h; P less than 0.05), thymoxamine infusion did not produce any major alteration in the gradual rise in TSH levels during the evening (incremental change above baseline +0.96 +/- 0.21 during control infusion and +0.97 +/- 0.27 mU/l during thymoxamine infusion). In mildly hypothyroid patients the TSH changes were exaggerated and alpha-adrenergic blockade caused a reduction in basal TSH levels and a delayed rise in TSH (incremental change above baseline +2.93 +/- 1.42 during control infusion and +2.26 +/- 0.73 mU/l during thymoxamine infusion; P less than 0.02). Overall TSH secretion was significantly decreased by thymoxamine (mean +/- S.E.M. area 106 +/- 2.45 mU/l per h vs 123.32 +/- 3.68 in the control study; P less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

The role of calcium and calmodulin in mediating release of thyrotrophin-releasing hormone by cultured hypothalamic cells.

We have developed a fetal rat hypothalamic cell culture system for the study of factors controlling the acute release of TRH. Release of TRH by the cells has been characterized by reversed-phase high pressure liquid chromatography and about 86% of the total immunoreactivity in the medium co-eluted with synthetic TRH. Release of TRH by the cells in response to 56 mmol K+/l increased between days 5 and 9 of culture but reached a plateau thereafter. Cell contents of TRH did not change significantly between days 5 and 14 of culture. Release of TRH from the cells was stimulated by K+ (56 mmol/l), veratridine (100 mumol/l) and ouabain (100 mumol/l) to 550, 480 and 335% of basal release respectively over a 1-h period. Release of TRH was dependent upon calcium in that it was absent when calcium-free medium was used and could be blocked by verapamil (20 mumol/l); however it could not be blocked by nifedipine (50 mumol/l). The calcium ionophore blocked by nifedipine (50 mumol/l). The calcium ionophore A23187 (1 mumol/l) stimulated TRH release to 340% of basal release. Tetrodotoxin (1 mumol/l) completely abolished the release in response to veratridine but had no effect on the release stimulated by K+ (56 mmol/l). The calmodulin antagonists trifluoperazine and triflupromazine (50 mumol/l) inhibited veratridine-stimulated TRH release. This was at a site after calcium influx as they also inhibited A23187-stimulated TRH release. The highly specific calmodulin antagonist W7 (10 mumol/l) also inhibited both veratridine and A23187-stimulated TRH release whereas, at the same concentration, its inactive analogue W5 did not significantly inhibit TRH release in response to either stimulus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Dopamine stimulates release of thyrotrophin-releasing hormone from perfused intact rat hypothalamus via hypothalamic D2-receptors.

We have studied the effect of dopamine together with agonist and antagonist drugs of different specificities on the release of TRH from the perfused, intact hypothalamus of the adult rat in vitro. Dopamine produced a dose-related stimulatory effect on TRH release with maximal effect being achieved at 1 mumol/l (increase over basal, 118 +/- 16.5 (S.E.M.) fmol TRH; P less than 0.001 vs basal). This effect was mimicked by the specific D2-agonist drugs bromocriptine (0.1 mumol/l) and LY 171555 (0.1 mumol/l) (increase over basal values, 137.5 +/- 13.75 fmol and 158.6 +/- 10.7 fmol respectively; P less than 0.001 vs basal), but not by the D1-agonist SKF 38393A. The stimulatory effect of dopamine (1 mumol/l) was blocked in a stereospecific manner by the active (D) but not by the inactive (L) isomers of the dopamine antagonist butaclamol. Similar blockade was achieved with the specific D2-antagonist domperidone (0.01 mumol/l) whereas the D1-antagonist SCH 23390 was only effective when used at a concentration 100 times greater. Lower concentrations (0.01 mumol/l) of this D1-antagonist did not block the stimulatory effect of dopamine. High-performance liquid chromatography characterization of the material secreted within the hypothalamus showed one single peak of immunoreactive material which coeluted with synthetic TRH. These data suggest that dopamine exerts a stimulatory role in the control of hypothalamic TRH release by acting at specific D2-receptors.

Animals↗
PubMed1987

Clinical value of immunoradiometric assay of thyrotropin for patients with nonthyroidal illness and taking various drugs.

Using a two-site immunoradiometric assay, we measured concentrations of thyrotropin (TSH) in serum of 134 clinically euthyroid subjects, 93 patients with nonthyroidal illness, and 80 patients who were being treated with various drugs. Abnormal concentrations of TSH, free thyroxin, and free triiodothyronine, respectively, were recorded in serum of three (3.2%), 19 (20.4%), and 37 (39.8%) of the patients with nonthyroidal illness and in three (3.8%), five (6.3%), and 10 (12.5%) of the patients taking drugs. TSH could be detected in all patients' serum samples. We conclude that, for most patients without thyroid disease, a basal (i.e., unstimulated) measurement of their TSH concentration in serum will indicate their thyroid status more reliably than will assay of free thyroxin or free triiodothyronine.

Adolescent↗