Biomedical subjects
Publications and source records attributed to D J Shale.
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.
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.
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.
From the differences in radiation profiles between 131I and 125I isotopes of iodine it would be expected that they would show different effects on thyroid function. The differences should lead to lower rates of thyroid gland destruction with 125I and hence less post-irradiation hypothyroidism. This difference in biological effect has been demonstrated in rats by indirect assessment of thyroid function. In this report the long-term effects of a range of similar doses of 131I and 125I were compared, in male and female rats, by direct assessment of thyroid function. Seventeen months after receiving 25 and 125 muCi of 131I, male and female rats showed significant elevation of serum TSH concentration and a reduction in 3 h radioiodine uptake. Rats receiving 1 and 5 muCi of 131I and all doses of 125I showed no significant changes in thyroid function. These findings confirm the previously reported differences in effect between the 131I and 125I isotopes of iodine in the rat.
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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.
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