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Title: Thyroid hormone receptor and albumin gene expression in Xenopus laevis ovary and liver
Author: Brooks, Alan R.
ISNI:       0000 0001 3481 6313
Awarding Body: University of Warwick
Current Institution: University of Warwick
Date of Award: 1989
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I have isolated a full length cDNA clone encoding a thyroid hormone receptor from a Xenopus laevis mature oocyte cDNA library. This receptor binds thyroid hormone with high affinity when expressed in COS cells. Expression from the thymidine kinase promoter containing an artificial thyroid hormone response element could be induced by thyroid hormone in the presence (but not in the absence) of this receptor. Thyroid hormone receptors isolated from other organisms are known to act directly upon gene expression at the level of transcription by binding to regulatory sequences within thyroid hormone responsive genes. My results with the Xenopus thyroid hormone receptor are consistent with this mode of action. There appear to be several rare transcripts in X. laevis ovary which hybridised to the thyroid hormone receptor cDNA clone. These transcripts could not be detected in eggs, suggesting that they are located in the follicle cells rather than the oocyte itself. Several rare transcripts which hybridised to the cDNA clone are also present in early embryonic stages. These differently sized but clearly related transcripts are suggestive of differential splicing. Synthetic RNA prepared from the entire cDNA translates very poorly in vitro and this is almost certainly due to the presence of several AUG codons upstream of the long open reading frame. Thyroid hormone is known to play a vital role in inducing the many biochemical and physiological changes that occur during amphibian metamorphosis. It is almost certain that some of these changes are the result of the activation and repression of specific genes at a transcriptional level. I have demonstrated that transcription of the Xenopus albumin genes is activated at the onset of metamorphosis. The albumin genes are therefore candidates for genes whose expression is activated by thyroid hormone. I have tested the response of a cloned X. laevis 68Kda albumin gene to thyroid hormone in a transient transfection assay. From this experiment I tentatively conclude that thyroid hormone does increase expression of the 68Kda albumin gene, at the level of the messenger RNA, and that this increase requires the presence of the co-transfected (Xenopus) thyroid hormone receptor. The liver-specific expression of albumin genes from Xenopus and other organisms is known to be controlled at the level of transcription by liver-specific trans-acting factors which interact with regulatory sequences upstream of these genes. In vivo, in the developing liver, transcription of the Xenopus albumin genes might require the presence of both tissue-specific trans-acting factors and the thyroid hormone receptor complex.
Supervisor: Not available Sponsor: Medical Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QP Physiology