Disease relevance of Tshb

• The TRH effect on the TSH beta gene was specific; no increase in CAT activity was detected for TKCAT (thymidine kinase of herpes simplex virus promoter), pBRCAT (no promoter), or TSH beta CAT (3'-5'-orientation) [1].
• A more marked effect of hypothyroidism on TSH beta mRNA than on alpha mRNA was evident, suggesting differential control of regulation of the TSH genes [2].
• Body weight and temperature, food and water intake, and plasma TSH, T4, free T4 (FT4), T3, and corticosterone levels were measured daily, and hypothalamic pro-TRH messenger RNA (mRNA) and hypophysial TSH beta mRNA were determined after termination of the experiments [3].

Psychiatry related information on Tshb

• Although plasma levels of thyroid hormones remained reduced, food deprivation no longer had negative effects on hypothalamic proTRH mRNA, pituitary TSH beta mRNA and plasma TSH in starved adrenalectomized rats [4].

High impact information on Tshb

• This pattern of gene expression corresponds temporally and spatially to the onset of thyroid-stimulating hormone (TSH beta) gene expression, which defines the thyrotroph phenotype [5].
• Moreover, perinatal hypothyroid animals demonstrated a dramatic increase in the ratio of sialylated to sulfated species within oligosaccharides of the same negative charge (2.9- to 7.4-fold increase for TSH-alpha; 15.1- to 25.5-fold increase for TSH-beta) [6].
• In addition, sequence homologies with the glucocorticoid receptor binding site, the GC box hexanucleotide, and a portion of the flanking region of the thyroid stimulating hormone beta-subunit gene were also identified [7].
• Using S1 nuclease mapping and oligonucleotide-primed reverse transcription of normal and thyroidectomized rat pituitary mRNA, two transcriptional start sites were identified in the rat TSH beta gene that are 28 and 71 nucleotides upstream from the translational start site [8].
• TSH and its two subunits, TSH beta and alpha-subunit, are in turn regulated by the thyroid hormones and several stimulatory and inhibitory factors produced by the hypothalamus [9].

Chemical compound and disease context of Tshb

• We have studied the influence of hypothyroidism and thyroid hormone replacement in vivo on rat pituitary cytoplasmic concentrations of TSH beta and alpha-subunit mRNA, measured by cytoplasmic dot hybridization, as well as circulating TSH and pituitary TSH content [2].

Biological context of Tshb

• Isolation and characterization of the gene encoding the TSH beta gene will facilitate the study of the molecular mechanisms by which hormones regulate TSH beta gene expression [8].
• After transfection, specific TSH beta promoter activity was evident in both TRH-responsive pituitary-derived GH3 and primary pituitary cell cultures [1].
• To study the structure-function relation of TRH stimulation of the activity of the single rat TSH beta gene, chimaeric plasmids were constructed [1].
• We compared binding of native T3 receptor to the TSH beta gene sequences and to the rat GH (rGH) gene T3 response element (TRE), and examined the ability of two different forms of in vitro synthesized T3 receptor to bind to the TSH beta gene [10].
• Deletion mutation analysis indicated that TRH sensitivity was detected in a 1.1 kilobase, but not in a 0.38 kilobase TSH beta gene fragment suggesting that the TRH responsive element(s) resides at least in part within the 700 base pairs of the 5'-flanking sequence.(ABSTRACT TRUNCATED AT 250 WORDS)[1]

Anatomical context of Tshb

• Two TRH-responsive elements have been identified in the rat TSH beta gene by deletion/mutation analysis of the 5'-flanking region of the gene and transfection of TSH beta-luciferase constructs into the GH3 pituitary cell line [11].
• After that time, the thyrotropes enlarged and partially degranulated, and TSH beta was stored in some of the large pleomorphic saccules in the cytoplasm [12].
• We have applied a gel retardation method to examine the binding of nuclear proteins from the rat pituitary gland to regulatory sequences of the rat TSH beta-subunit gene [13].
• Food deprivation for 3 days reduced the hypothalamic content of prothyrotrophin-releasing hormone (proTRH) mRNA, the amount of proTRH-derived peptides (TRH and proTRH160-169) in the paraventricular nucleus, the release of proTRH-derived peptides into hypophysial portal blood and the pituitary levels of TSH beta mRNA [4].
• Previous studies have demonstrated immunocytochemical staining for beta chains of thyroid stimulating hormone (TSH-beta) in rough endoplasmic reticulum of pituitary cells hypertrophied after thyroidectomy ("thyroidectomy cells") (Moriarty CG(1976): J Histochem Cytochem (24:846; Moriarty GC, Tobin RB (1976): J Histochem Cytochem 24:1140) [14].

Associations of Tshb with chemical compounds

• Treatment with 10(-5) M dopamine, an inhibitor of TSH secretion, decreased both alpha-subunit and TSH beta mRNA synthesis within 15 min, and maximal decreases of approximately 75% for both subunits were obtained after 30 min [9].
• Thyroid hormone treatment specifically suppressed alpha-subunit (38% of control) and TSH beta (17% of control) mRNA synthesis, indicating that the culture system is responding in an appropriate physiological manner and that decreases in transcription can be easily and accurately measured with this system [15].
• Using nuclear runoff and transient expression assays, we have analyzed the interactions among TRH, the phorbol ester 12-myristate 13-acetate (PMA), and the adenylate cyclase activator forskolin on TSH beta gene transcription [16].
• The apparent half-life of the TSH beta-subunit mRNA was determined by adding actinomycin-D (2 microM) to dispersed rat pituitary cultures in hypothyroid medium or medium containing 10(-7) M T3 and analyzing the decline in subunit mRNA levels with time [17].
• Vitamin A deficiency had no effect on TSH beta mRNA levels in hypothyroid rats [18].

Regulatory relationships of Tshb

• Cotransfection with RAR alpha and retinoid X receptor-beta induced TSH beta expression by 3.5-fold, and treatment with RA suppressed this induction by 46% [18].

Other interactions of Tshb

• Together, these facts point to a central role of the IB1/JIP-1 protein in the control of TRH-mediated TSH-beta stimulation [19].
• Hypophysial TSH beta mRNA was significantly decreased after 2 (-62%) and 7 (-62%) days, but not after 1 day, of IL-1 infusion and was unaffected by IL-6 infusion [3].
• It is demonstrated for the first time that both leptin and NPY exert a direct action at rat pituitary affecting steady-state levels of mRNA of TSHbeta and PGHalpha subunits [20].
• Furthermore, in the anterior pituitary, TSH beta mRNA decreased significantly in food-deprived animals, while PRL mRNA was unaltered [21].
• In contrast, leptin was localized most frequently in FSH beta/LH beta- and less frequently in TSH beta-positive cells [22].

Analytical, diagnostic and therapeutic context of Tshb

• Our previous studies demonstrated TRH stimulation of TSH beta gene transcription in rat pituitary cell cultures and in transient expression assays, with the TRH-sensitive region located between -1.3 kilobases and -204 basepairs (bp) relative to the major transcriptional start site [16].
• Northern blot analysis of total RNA from the above cultures revealed that T3 treatment reduces the size of the TSH beta-subunit mRNA [17].
• In additional experiments rats were treated with T4 or TRH, and subsequent in situ hybridization studies showed that TSH beta messenger RNA (mRNA) formation was not altered in the PT [23].
• Thyroidectomy increased, by 27 and 75 times, the normal levels of mRNAs for alpha and TSH beta, respectively [24].
• Two hours after treatment, neither TSHbeta mRNA nor TSH protein levels were altered by LG100268 [25].

References