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D R Weightman

Publications and source records attributed to D R Weightman.

33 records · Page 2Linked to original sources
PubMed1984

Differential TSH and PRL responses to dopamine receptor blockade in acromegaly.

The serum TSH and prolactin responses to dopamine receptor blockade (domperidone 10 mg i.v.) were measured in eight acromegalic subjects and seven normal controls. The serum TSH response was exaggerated in acromegalics when compared to controls (sum of the increments 12.2 +/- 2.8 mU/l and 4.0 +/- 1.2 mU/l respectively P less than 0.05), whereas the serum prolactin response was blunted (sum of the increments 5029 +/- 1377 mU/l and 14 673 +/- 2889 mU/l respectively P less than 0.01). Dopamine receptor blockade did not significantly alter basal growth hormone levels in either group. To ascertain whether this response was merely a reflection of high circulating growth hormone levels six normal controls were pretreated for 24 h with either intramuscular growth hormone (three injections of 4 IU) or an equivalent volume of saline before the administration of domperidone (10 mg i.v.). The serum TSH and prolactin responses were not affected by prior growth hormone treatment. The opposite TSH and prolactin responses to dopamine blockade do not allow any firm conclusions to be made about the level of hypothalamic dopamine activity in acromegaly.

Acromegaly↗
PubMed1982

Reduced dopaminergic inhibition of thyrotrophin release in states of physiological hyperprolactinaemia.

We have tested the hypothesis that physiological puerperal hyperprolactinaemia may be secondary to reduced hypothalamic dopaminergic inhibition of prolactin (PRL) release. Nine post-partum females with physiological hyperprolactinaemia (aged 19-40 years; mean basal PRL +/- SE, 2099 +/- 257 mU/1, range 1002-3762 mU/1) were studied and results compared with fourteen normoprolactinaemic females (basal PRL less than 400 mU/1; aged 18-36 years). Puerperal hyperprolactinaemic females showed a reduced TSH response to dopamine (DA) receptor blockade with metoclopramide (10 mg i.v.) compared with normal females over a 60-min period following drug administration (total incremental TSH change, mean +/- SE, mU/1; 0.5 +/- 0.3 v. 3.1 +/- 1.0 P less than 0.005). This finding of reduced dopaminergic inhibition of TSH release in females with physiological puerperal hyperprolactinaemia supports the view that an overall reduction in hypothalamic dopaminergic tone may contribute towards hyperprolactinaemia in post-partum women.

Adult↗
PubMed1981

A rapid radioassay for human IgG produced in lymphocyte in vitro culture systems.

Protein A bearing Staphylococcus aureus was used to develop a solid-phase radioassay for IgG immunoglobulins. The assay was specifically optimised for use with in vitro human lymphocyte culture work. Compared with a solid-phase radioimmunoassay for IgG produced in lymphocyte culture, this assay had similar performance profile and the advantages of rapidly and technical ease.

Binding Sites↗
PubMed1981

Impaired dopaminergic control of thyroid stimulating hormone secretion in chronic renal failure.

After administration of intravenous metoclopramide, a dopaminergic receptor blocking agent, no rise in thyroid stimulating hormone (TSH) could be found in patients with chronic renal failure, in contrast to non-uraemic controls. Basal TSH values were normal in the uraemic patients but the TSH response to thyrotrophin-releasing hormone (TRH) was significantly reduced. These results suggest that a discrete abnormality in the hypothalamo-pituitary axis exists in uraemia which may in part be due to interference with central dopaminergic control by a uraemic toxin.

Adult↗
PubMed1980

Domperidone: a novel agent for the investigation of anterior pituitary function and control in man.

Administration of the novel agent domperidone (10 mg iv), which combines the properties of specific dopamine receptor blockade and inability to cross the blood-brain barrier, leads to acute and significant TSH and PRL release in man. This suggests that the in vivo site of action of endogenous dopamine in the inhibitory control of these two hormones is either the anterior pituitary or median eminence, since these tissues lie outside the blood-brain barrier. This class of drug is of potential value both clinically and experimentally in the investigation of anterior pituitary control mechanisms.

Autoimmune Diseases↗
PubMed1980

Dopaminergic modulation of circadian thyrotropin rhythms and thyroid hormone levels in euthyroid subjects.

Basal TSH levels are known to rise during the evening, but the mechanism by which this rise occurs is poorly understood. The rise in TSH in response to dopamine (DA) receptor blockade with metoclopramide in the morning in normal subjects and hypothyroid patients has provided evidence for a tonic inhibitory role for DA in the control of TSH secretion. We have tested the hypothesis in normal, euthyroid volunteers (14 females, aged 20--40 yr; 12 males, aged 22--45 yr) that the nocturnal elevation of serum TSH levels might result from a reduction in DA action on the thyrotroph, in which case a reduced TSH response to metoclopramide would be expected. We found, however, that the TSH response to DA receptor blockade with metoclopramide (10 mg, iv) was significantly greater at 2300 h than at 1100 h [net incremental response over 120 min, 14.9 +/- 2.5 vs. 6.7 +/- 1.6 mU/liter (mean +/- SE); P < 0.001], indicating greater DA inhibition of TSH release at night. Thus, the nocturnal elevation of TSH is not due to decreased DA action on the thyrotroph; rather, increased DA tone is present and may limit the TSH response to other as yet unknown factors. Thyroid hormone levels also rose significantly after metoclopramide at both 1100 and 2300 h compared with control values after placebo [incremental difference (in nanomoles per liter) between 0 and 120 min values (mean +/- SE): 1100 h, T3, 0.24 +/- 0.09 vs. -0.05 +/- 0.08 (P < 0.02); T4, 19.4 +/- 6.1 vs. -1.8 +/- 2.5 (P < 0.01); 2300 h, T3 +/- 0.53 +/-0.07 vs. 0.04 +/- 0.07 (P < 0.01); T4 20.9 +/- 5.6 vs. 2.8 +/- 3.2 (P < 0.01)]. Incremental thyroid hormone and TSH responses to metoclopramide were directly related (T3 vs. TSH, r = 0.59 and P < 0.001; T4 vs. TSH, r = 0.41 and P < 0.01), suggesting that the thyroid hormone responses were mediated by TSH and illustrating the sensitivity of the thyroid gland to even small increases in endogenous TSH levels.

Adult↗
PubMed1979

Dopamine is a physiological regulator of thyrotrophin (TSH) secretion in normal man.

Using a sensitive and precise radioimmunoassay for human TSH we have demonstrated significant elevations in serum TSH levels in euthyroid volunteers following administration of the dopamine receptor blocking drug metoclopramide when compared with placebo. The degree of TSH response is significantly greater in females than in males and is sustained over a 3-hour period after a single oral 10 mg dose of metoclopramide. The degree of TSH release after metoclopramide is inversely related to the basal TSH level suggesting that dopamine is a determinant of low daytime TSH levels and is thus implicated in the circadian rhythm of TSH secretion. Pretreatment with 10 mg of metoclopramide orally, one hour before TRH administration leads to significant enhancement of the TSH response to TRH. Our findings provide further evidence for the physiological inhibitory role of dopamine in the contol of TSH secretion in normal man. The possible mode of action of dopamine and the clinical implications of this neuroregulatory pathway are discussed.

Adult↗
PubMed1977

Evidence for dopaminergic control of thyrotrophin secretion in man.

After administration of the dopamine-receptor-blocking drug, metoclopramide (10 mg orally), there is significant release of thyrotrophin (T.S.H.) in hypothyroid patients which is not evident in euthyroid subjects. This is not due to spontaneous fluctuation in basal T.S.H. levels, and it indicates inhibitory dopaminergic control of T.S.H. release in man. The lack of significant T.S.H. release in euthyroid subjects may be due to the inhibitory effects of normal circulating levels of T3 and T4 on T.S.H. release. The T.S.H. response in hypothyroidism is significantly correlated with both T3 and T4 levels, suggesting suppression of this inhibitory pathway in increasingly severe hypothyroidism.

Administration, Oral↗
PubMed1977

Effects of nomifensine, an inhibitor of endogenous catecholamine re-uptake, in acromegaly, in hyperprolactinaemia, and against stimulated prolactin release in man.

1. Nomifensine, an inhibitor of endogenous catecholamine re-uptake, did not affect the growth hormone (GH) or prolactin levels in patients with acromegaly or hyperprolactinaemia. It does not, therefore, have any therapeutic role in these conditions at the dosage used in this study. 2. It had no effect on thyrotrophin-releasing hormone (TRH)-induced thyrotrophin (TSH) or prolactin release in males, yet caused marked suppression of monoiodotyrosine (MIT)-induced prolactin release in males but not in females. 3. The significant suppression of MIT-induced prolactin release in males is likely to reflect the dopamine (DA) agonist activity of the drug and its lack of effect in the other situations tested could be dose related. 4. It is proposed that the difference in male and female patterns of prolactin response to MIT after nomifensine, could be due to a "damping" effect of oestrogen on the hypothalamic dopaminergic system.

Acromegaly↗
PubMed1975

Bromocriptine therapy in acromegaly.

Bromocriptine (CB-154, Sandoz) has been given to 21 acromegalic patients (11 female, 10 male) for a period of 6-10 months. The mean serum growth-hormone (G.H.) levels ranged from 10 mug/1 to 512 mug/1 before therapy. Bromocriptine suppressed G.H. values to 5 mug/1 or less in 4 patients and to less than 10 mug/1 in a further 8 patients, but in 2 patients G.H. levels did not show any significant reduction. Bromocriptine did not block stress-induced G.H. secretion. It did not distrub pituitary function other than secretion of prolactin and had negligible side-effects. Its effect on tumour size is uncertain and it is therefore unsuitable for patients with suprasellar extension of the tumour. Otherwise it seems reasonable to offer a trial of bromocriptine to all patients with acromegaly where therapy is deemed necessary. In those who show a full response of G.H. levels with a dose of 20-40 mg of bromocriptine per day, external radiation to the pituitary can be used to prevent tumour expansion and bromocriptine withdrawn at intervals to assess the effect of the radiation. In patients with a partial response to bromocriptine, the decision to offer alternative therapy depends on the extent of the response and on the age and medical condition of the patient. In patients who fail to respond to bromocriptine, particularly those younger patients with active disease, more definitive local treatment (e.g., trans-sphenoidal removal of the tumour or yttrium-90 implantation) would be indicated. Bromocriptine may also be used with benefit in the large number of patients who have shown a partial response to other forms of therapy.

11-Hydroxycorticosteroids↗
PubMed1975

Growth hormone release inhibiting hormone: actions on thyrotrophin and prolactin secretion after thyrotrophinreleasing hormone.

The hypothalamic tetradecapeptide growth hormone release inhibiting hormone (GH-RIH) blocked the thyrotrophin response to thyrotrophin-releasing hormone (TRH) in normal people and in patients with primary hypothyroidism. This inhibition was dose related. The TRH-induced prolactin release was not affected by GH-RIH. This dissociation of the thyrotrophin and prolactin responses to TRH by GH-RIH suggests that there are different mechanisms for release of thyrotrophin and prolactin and that only the former is affected by GH-RIH.

Adult↗
PubMedDate not supplied

Catecholaminergic interactions in the regulation of thyrotropin (TSH) secretion in man.

The TSH responses to the catecholamine depleting agent monoiodotyrosine (1 g po) and the dopamine receptor blocking drug metoclopramide (10 mg po) have been compared in euthyroid and hypothyroid subjects. Both drugs lead to a prompt and significant rise in TSH levels (peak values at 60-75 min) which is very much greater in hypothyroid than euthyroid subjects. The findings lend further support to the inhibitory role of dopamine in the control of TSH release in man, since TSH release follows either dopamine depletion with monoiodotyrosine or dopamine receptor blockade with metoclopramide.

Adolescent↗