Joseph D Fondell 1 Introduction

Thyroid hormone receptors (TRs) are capable of both activating and repressing transcription from genes bearing TR-binding elements (TREs). In general, TRs function as activators in the presence of thyroid hormone (T3) and repressors in the absence of T3 (1). The ability of TRs to regulate transcription has been linked to their ability to recruit distinct types of transcriptional coregulatory factors, termed coactivators and corepressors, to target gene promoters (2,3). Remarkably, yeast...

Expression of TR and RXR in Xenopus laevis and Its Implications in Frog Development

Four TR genes, two TRa, and two TRfi genes, are present in Xenopus laevis (25). The total dependence of anuran metamorphosis on T3 offers an opportunity to study TR RXR function during development. As expected, both TRa and TRfi genes are highly expressed during metamorphosis (Fig. 1) (25,26). In addition, RXR genes are also expressed during metamorphosis. More importantly, the expression of both TR and RXR genes correlates temporally with metamorphosis of individual organs (26). Thus, high...

Wolfgang H Dillmann and Bernd R Gloss 1 Introduction

Thyroid hormone (T3) is an important signaling molecule for cardiac function. Chronic exposure of the heart to either elevated levels of thyroid hormone (hyperthyroidism) or lower thyroid hormone levels (hypothyroidism) have profound effects on cardiac output. Hyperthyroidism increases the risk of cardiac failure dramatically, and hypothyroidism is associated with a diminished contractile performance of the heart, which is frequently compensated by cardiac hypertrophy. The molecular mechanisms...

Generation of Hypothyroid Hyperthyroid and Euthyroid Mice

Hypothyroid mice are generated by feeding them with a low iodine (loI) diet supplemented with 0.15 propylthiouracil (PTU) purchased from Harlan Teklad Co. (Madison, WI) for 4 wk. 2. Serum thyroid-stimulating hormone (TSH) measurements (kindly measured by Dr. Samuel Refetoff, University of Chicago, Chicago, IL) show that mice littermate control and transgenic mice treated with PTU were profoundly hypothyroid. 3. Hyperthyroid mice are generated by injecting hypothyroid mice intraperitoneally with...

NCoRi Animal Model to Study Biological Function of NCoR in Liver

Biochemistry

Hollenberg et al. (37) have reported that a variant form of NCoR, NCoRi, lacks the repression domains in the amino terminus, but retains the nuclear receptor interaction domains. NCoRi is derived from a 3.1 kb cDNA that was originally isolated from a human placental library. NCoRi protein contains the TR interaction domains and surrounding amino acids (AA 1539-2453), but lacks the repressor domains (AA 1-1120) present in full-length murine NCoR. It also has been shown that NCoRi has dominant...

Generation of Hypothyroid Rats and Mice

The induction of severe hypothyroidism is essential to observe changes in gene expression by thyroid hormone. Moderate hypothyroidism leads to physiological changes aimed at maintaining T3 concentrations in neural tissue within normal levels. The most important mechanism concerns deiodinase type 2 (D2). D2 is a selenoenzyme that catalyzes the removal of the iodine atom in the 5' position of T4 to generate the active hormone, T3. D2 activity is inhibited by T4 through a mechanism involving...