scholarly journals Synthetic gene network restoring endogenous pituitary–thyroid feedback control in experimental Graves’ disease

2016 ◽  
Vol 113 (5) ◽  
pp. 1244-1249 ◽  
Author(s):  
Pratik Saxena ◽  
Ghislaine Charpin-El Hamri ◽  
Marc Folcher ◽  
Henryk Zulewski ◽  
Martin Fussenegger
Keyword(s):  
Thyroid Hormone ◽  
Feedback Control ◽  
Thyroid Stimulating Hormone ◽  
Graves Disease ◽  
Hormone Levels ◽  
Pituitary Thyroid Axis ◽  
Thyroid Axis ◽  
Thyroid Hormone Levels ◽  
Hormone Homeostasis ◽  
Stimulating Hormone

Graves’ disease is an autoimmune disorder that causes hyperthyroidism because of autoantibodies that bind to the thyroid-stimulating hormone receptor (TSHR) on the thyroid gland, triggering thyroid hormone release. The physiological control of thyroid hormone homeostasis by the feedback loops involving the hypothalamus–pituitary–thyroid axis is disrupted by these stimulating autoantibodies. To reset the endogenous thyrotrophic feedback control, we designed a synthetic mammalian gene circuit that maintains thyroid hormone homeostasis by monitoring thyroid hormone levels and coordinating the expression of a thyroid-stimulating hormone receptor antagonist (TSHAntag), which competitively inhibits the binding of thyroid-stimulating hormone or the human autoantibody to TSHR. This synthetic control device consists of a synthetic thyroid-sensing receptor (TSR), a yeast Gal4 protein/human thyroid receptor-α fusion, which reversibly triggers expression of the TSHAntag gene from TSR-dependent promoters. In hyperthyroid mice, this synthetic circuit sensed pathological thyroid hormone levels and restored the thyrotrophic feedback control of the hypothalamus–pituitary–thyroid axis to euthyroid hormone levels. Therapeutic plug and play gene circuits that restore physiological feedback control in metabolic disorders foster advanced gene- and cell-based therapies.

EFFECTS OF TRIMETHOPRIM AND SULPHONAMIDE PREPARATIONS ON THE PITUITARY–THYROID AXIS OF RODENTS

1981 ◽  
Vol 91 (2) ◽  
pp. 299-303 ◽  
Author(s):  
H. N. COHEN ◽  
J. A. FYFFE ◽  
W. A. RATCLIFFE ◽  
A. M. McNICOL ◽  
H. McINTYRE ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Stimulating Hormone ◽  
Histological Evidence ◽  
Hormone Levels ◽  
Gland Weight ◽  
Pituitary Thyroid Axis ◽  
Thyroid Axis ◽  
Thyroid Hormone Levels ◽  
Bacterial Preparations ◽  
Thyroid Gland Weight

The effects on pituitary–thyroid function of the commonly prescribed anti-bacterial preparations co-trimoxazole and co-trifamole, and their component drugs, have been studied in the rat and compared to the changes caused by propylthiouracil. Co-trimoxazole and co-trifamole, in doses 20-fold in excess of a pharmacological dose administered for 10 days, produced marked changes in hormone levels consistent with blocking of thyroidal activity. Significant increases in thyroid gland weight, with histological evidence of hyperplastic goitre formation, were also demonstrated. Propylthiouracil produced less marked changes of thyroid hormone levels but higher levels of thyroid-stimulating hormone. Pharmacological doses of co-trimoxazole and co-trifamole and sulphamoxole, the sulphonamide component of co-trifamole, caused significant changes in thyroid hormone levels consistent with anti-thyroidal activity. In contrast, there was no evidence that trimethoprim, which is common to both preparations, or sulphamethoxazole, the sulphonamide component of co-trimoxazole, had an anti-thyroidal action, indeed, serum thyroxine levels were significantly increased at pharmacological dosage. We have concluded that the new commonly prescribed combination preparations retain the goitrogenic properties of the earlier sulphonamides.

scholarly journals Specific Reference Intervals of Serum Triiodothyronine, Thyroxine, and Thyroid-stimulating Hormone in Normal Pregnant Indian Women as per Trimester

2017 ◽  
Vol 21 (1) ◽  
pp. 17-21
Author(s):  
Nandita Hazra ◽  
Binay Mitra ◽  
Reetika Pal
Keyword(s):  
Thyroid Hormone ◽  
Pregnant Women ◽  
Reference Intervals ◽  
Thyroid Stimulating Hormone ◽  
Specific Reference ◽  
Indian Women ◽  
Hormone Levels ◽  
Thyroid Hormone Levels ◽  
Maternal Thyroid ◽  
Stimulating Hormone

ABSTRACT Aim Maternal thyroid hormone levels during pregnancy are vital for the health of the mother as well as the developing child. Fetal growth is affected by maternal thyroid levels. Various physiological changes like alterations of thyroxine-binding globulins, human chorionic gonadotropin level, and changes in iodide metabolism affect maternal thyroid hormone levels. Therefore, reference intervals (RIs) for thyroid hormones in pregnant population require to be established separately from the general population. Materials and methods The RIs of serum triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) were determined in healthy pregnant women by enzyme-linked immunosorbent assay (ELISA) technique after segregating them into three trimesters. This study was conducted in a 492-bedded zonal-level hospital. The reference population was chosen from a study population of pregnant women by strict inclusion and exclusion criteria. The assays were done by the most-commonly used, economical ELISA method employing standard kits. Tests were done using accurate and precise methods with proper quality control measures. Results The RIs were calculated from the central 95% of distribution of total T3, total T4, and TSH values located between 2.5 and 97.5 percentile values. The 0.90 confidence intervals for the upper and lower reference limits were calculated. The values thus obtained were different from those provided by the manufacturer kit literature. Conclusion It is recommended to determine one's own laboratory-specific, method-specific, trimester-wise RIs for maternal thyroid hormone status and use them for screening of pregnant women. How to cite this article Chakrabarty BK, Mitra B, Pal R, Hazra N. Specific Reference Intervals of Serum Triiodothyronine, Thyroxine, and Thyroid-stimulating Hormone in Normal Pregnant Indian Women as per Trimester. Indian J Med Biochem 2017;21(1):17-21.

The effect of benziodarone on the thyroid hormone levels and the pituitary-thyroid axis

1986 ◽  
Vol 9 (4) ◽  
pp. 337-339 ◽  
Author(s):  
B. Xanthopoulos ◽  
D. A. Koutras ◽  
M. A. Boukis ◽  
G. D. Piperingos ◽  
J. Kitsopanides ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Hormone Levels ◽  
Pituitary Thyroid Axis ◽  
Thyroid Axis ◽  
Thyroid Hormone Levels

scholarly journals Differential Effects of Central Leptin, Insulin, or Glucose Administration during Fasting on the Hypothalamic-Pituitary-Thyroid Axis and Feeding-Related Neurons in the Arcuate Nucleus

Endocrinology ◽  
2006 ◽  
Vol 147 (1) ◽  
pp. 520-529 ◽  
Author(s):  
Csaba Fekete ◽  
Praful S. Singru ◽  
Edith Sanchez ◽  
Sumit Sarkar ◽  
Marcelo A. Christoffolete ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Arcuate Nucleus ◽  
Mrna Levels ◽  
Central Administration ◽  
Hormone Levels ◽  
Intracerebroventricular Infusion ◽  
Essential Components ◽  
Pituitary Thyroid Axis ◽  
Thyroid Axis ◽  
Thyroid Hormone Levels

The reductions in circulating levels of leptin, insulin, and glucose with fasting serve as important homeostasis signals to neurons of the hypothalamic arcuate nucleus that synthesize neuropeptide Y (NPY)/agouti-related protein (AGRP) and α-MSH/cocaine and amphetamine-regulated transcript. Because the central administration of leptin is capable of preventing the inhibitory effects of fasting on TRH mRNA in hypophysiotropic neurons primarily through effects on the arcuate nucleus, we determined whether the continuous administration of 30 mU/d insulin or 648 μg/d glucose into the cerebrospinal fluid by osmotic minipump might also have similar effects on the hypothalamic-pituitary-thyroid axis. As anticipated, the intracerebroventricular infusion of leptin reduced fasting-induced elevations in NPY and AGRP mRNA and increased proopiomelanocortin and cocaine and amphetamine-regulated transcript mRNA in the arcuate nucleus. In addition, leptin prevented fasting-induced reduction in pro-TRH mRNA levels in the paraventricular nucleus and in circulating thyroid hormone levels. In contrast, whereas insulin increased proopiomelanocortin mRNA and both insulin and glucose reduced NPY mRNA in arcuate nucleus neurons, neither prevented the fasting-induced suppression in hypophysiotropic TRH mRNA or circulating thyroid hormone levels. We conclude that insulin and glucose only partially replicate the central effects of leptin and may not be essential components of the hypothalamic-pituitary-thyroid regulatory system during fasting.

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