Tissue Specific and Developmentally Regulated Human TRb1 5' UTR Splice Variants

Dr Sarah Frankton, under the supervision of Dr. Graham Williams, Consultant Endocrinologist and Senior Lecturer at The Hammersmith Hospital and Imperial College School of Medicine. The research is jointly funded by the Medical Research Council

FINAL REPORT

Thyroid disease is common and may result in thyrotoxicosis due to excessive thyroid hormone secretion, hypothyroidism due to thyroid hormone deficiency or mental retardation and growth delay in thyroid hormone deficient children. Although the features of these diseases are well recognised, the way in which thyroid hormone acts in individual tissues and at different stages of development is poorly understood. The British Thyroid Foundation (BTF) Research Award 1999 has helped us continue our research in this area.

These diseases illustrate the essential role of thyroid hormone in regulating metabolic activity in adults and in promoting normal development of the nervous system and skeleton in children. More recent studies, highlighted in both medical journals and the press, have demonstrated an association between hypothyroidism in pregnant women and a subsequent reduction in I.Q. of the child, suggesting that thyroid hormone is essential for normal brain development from the very first weeks of life.

The actions of thyroid hormone are facilitated by proteins known as thyroid hormone receptors. Recent studies in which various thyroid hormone receptors have been deleted by genetic methods (thyroid hormone receptor knockouts) have confirmed the essential requirements of thyroid hormones during the development and growth of individual tissues, and thus emphasize the central importance of the thyroid hormone receptor for mammalian development. Funding from the BTF award has resulted directly in our current identification of new variations in the way in which the human thyroid hormone receptor beta gene is expressed.

Since our last update, part of the research has resulted in a Lancet publication, 'Pituitary-thyroid feedback hypersensitivity as a novel cause of hypothyroidism in children' (Frankton et al., October 2000 356: 1238-1240). This work was also funded by the BTF and may result in increased awareness of possibly under-recognised phenotype.

We wish to thank the British Thyroid Foundation and its members for their support in funding our research, which we anticipate will contribute to a better understanding of thyroid hormone action, mechanisms of thyroid disease and ultimately, improved treatment for patients.