TR has the dual role to silence gene expression in the absence of hormone and activate genes in the presence of the ligand, triiodothyronine (Thormeyer and Baniahmad, 1999) Thyroid hormones have numerous critical effects on development in vertebrates, most notably, they are necessary for normal development of the brain in the fetus (Porterfield and Hendrich, 1993). T3 may also be important for ovarian follicle development, and maturation of the cumulus-oocyte complex. T3 regulates gene expression largely through a family of nuclear thyroid hormone receptors (Zhang et al., 1997).
NCBI Summary:
The protein encoded by this gene is a nuclear hormone receptor for triiodothyronine. It is one of the several receptors for thyroid hormone, and has been shown to mediate the biological activities of thyroid hormone. Knockout studies in mice suggest that the different receptors, while having certain extent of redundancy, may mediate different functions of thyroid hormone. Mutations in this gene are known to be a cause of generalized thyroid hormone resistance (GTHR), a syndrome characterized by goiter and high levels of circulating thyroid hormone (T3-T4), with normal or slightly elevated thyroid stimulating hormone (TSH). Several alternatively spliced transcript variants encoding the same protein have been observed for this gene. [provided by RefSeq, Jul 2008]
Triiodothyronine has been found to enhance gonadotropin- and insulin-stimulated morphologic luteinization and progesterone production by porcine granulosa cells in culture. [(Wakim et al. 1987$ 3799756)] Thyroid hormone has been demonstrated to synergize with FSH to exert stimulatory effects on the differentiation of porcine granulosa cells (Maruo et al., 1992) See also (Zhang et al., 1997).
Expression regulated by
Comment
Ovarian localization
Oocyte, Cumulus, Granulosa, Stromal cells
Comment
Expression of multiple thyroid hormone receptor mRNAs in human oocytes, cumulus cells, and granulosa cells. [Zhang SS et al. (1997)$9268132] Thyroid hormones have diverse effects on ovarian function. We examined the expression of thyroid hormone receptor (TR) mRNAs (including TRalpha-1, TRbeta-1, TRbeta-2, and c-erbAalpha-2 isoforms) in three types of cells from human follicles, and determined the concentration of free tri-iodothyronine (T3) present in human follicular fluid. Human failed-fertilized oocytes, granulosa (GC) and cumulus (CC) cells from patients of the in-vitro fertilization (IVF) programme at Alliant Hospital Fertility Center were used to detect TR mRNA expression using reverse transcription-polymerase chain reaction (RT-PCR) followed by Southern blot analysis. Human spermatozoa were also analysed to determine whether results obtained with CC would be affected by the presence of spermatozoa. beta-Actin mRNA was amplified in each cell type as a positive control for the RT-PCR. Our results show that human oocytes express TRalpha-1, TRbeta-1, TRbeta-2, and c-erbAalpha-2 mRNAs and that these same isoforms are expressed in both human granulosa cells and cumulus cells. No differences were detected in the apparent amounts of RT-PCR products when comparing GC with CC, suggesting a similar pattern of expression of these RNAs. beta-actin mRNA was detected in spermatozoa, but TRalpha-1 expression was not detectable. The concentrations of free T3 measured in follicular fluid were similar to, or slightly below, those in serum of euthyroid patients. These data demonstrated that several isoforms of TR mRNA are expressed in the human oocyte, and hence thyroid hormone may have direct affects on the oocyte, as well as on GC and CC. In addition thyroid hormone may have indirect effects on the oocytes via the CC.//////////////////
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Thyroid hormones have diverse effects on ovarian function. We examined the expression of thyroid hormone receptor (TR) mRNAs (including TR alpha-1, TR beta-1, TR beta-2, and c-erbA alpha-2 isoforms) in three types of cells from human follicles. Human failed-fertilized oocytes, granulosa (GC) and cumulus (CC) cells were used to detect TR mRNA expression. Human oocytes express TR alpha-1, TR beta-1, TR beta-2, and c-erbA alpha-2 mRNAs and that these same isoforms are expressed in both human granulosa cells and cumulus cells. (Zhang et al. 1997) Thyroid hormone receptor messenger ribonucleic acid in human granulosa and ovarian stromal cells: Granulosa cells from the preovulatory antral follicles examined showed positive staining for both the thyroid hormone receptor alpha and beta probes. Positive staining of ovarian stromal cells also was observed for both probes. Thyroid hormone receptor mRNAs are expressed in both granulosa cells and ovarian stromal cells found in nonstimulated ovaries (Wakim et al., 1994).
Follicle stages
Antral, Preovulatory
Comment
Thyroid hormone receptor messenger ribonucleic acid in human granulosa and ovarian stromal cells. Wakim AN et al. (1994) To examine whether mRNA for thyroid hormone receptors alpha and beta is present in human granulosa cells in nonstimulated ovaries. Paraffin-embedded sections of ovaries from normally cycling women were analyzed by in situ hybridization with oligonucleotide probes for thyroid hormone receptors alpha and beta. The sense strand oligonucleotide was used as a control for each of the probes. Granulosa cells from the preovulatory antral follicles examined showed positive staining for both the thyroid hormone receptor alpha and beta probes. Positive staining of ovarian stromal cells also was observed for both probes. Thyroid hormone receptor mRNAs are expressed in both granulosa cells and ovarian stromal cells found in nonstimulated ovaries. It is, therefore, conceivable that thyroid hormone may play a direct role in human ovarian physiology.//////////////////
Phenotypes
Mutations
1 mutations
Species: human
Mutation name: T329N - Resistance to thyroid hormone (RTH)
type: naturally occurring fertility: embryonic lethal Comment: Resistance to thyroid hormone (RTH) is a syndrome of elevated serum thyroxine, inappropriately "normal" serum thyrotropin (TSH) and reduced thyroid hormone responsiveness associated with point mutations in the thyroid hormone receptor-beta (TRbeta) gene. We describe a novel point mutation resulting in a cytosine for adenine substitution at nucleotide 1271 (exon 9) that results in the substitution of threonine for asparagine (T329N). This mutation was identified in a 30-year-old woman who was investigated for recurrent spontaneous abortions and was found to have RTH (Sarkissian et al., 1999).