Propylthiouracil (PTU)-induced hypothyroidism in the developing rat impairs synaptic transmission and plasticity in the dentate gyrus of the adult hippocampus

Gilbert, Mary E.; Paczkowski, Christine M.

doi:10.1016/s0165-3806(03)00191-3

Cited by 100 publications

(78 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Neurons are visualized by infrared-differential interference contrast microscopy to allow selection of cells to be recorded (478). Advanced recording procedures can measure hypothyroidism-induced changes in long-term potentiation in hippocampal neuron populations, a cellular mechanism of synaptic plasticity that is thought to be involved in memory (507)(508)(509)(510).…”

Section: And Recommendation 44amentioning

confidence: 99%

American Thyroid Association Guide to Investigating Thyroid Hormone Economy and Action in Rodent and Cell Models

Bianco

Anderson

Forrest

et al. 2014

Thyroid

164

View full text Add to dashboard Cite

Section: And Recommendation 44amentioning

confidence: 99%

American Thyroid Association Guide to Investigating Thyroid Hormone Economy and Action in Rodent and Cell Models

Bianco

Anderson

Forrest

et al. 2014

Thyroid

164

View full text Add to dashboard Cite

“…Works, D-77723 Gengenbach, Germany) daily until postnatal 15-day. Litters were CH rats (Gilbert & Paczkowski 2003). In contrast, from the 15th day of gestation, each rat from the control group was intragastrically administered with 2 .…”

Section: Experimental Animalsmentioning

confidence: 99%

Effects of hyper- and hypothyroid on expression of thyroid hormone receptor mRNA in rat myocardium

Liu

Li²,

Shi³

et al. 2007

Journal of Endocrinology

View full text Add to dashboard Cite

Thyroid dysfunction is classified into hyperthyroidism and congenital hypothyroidism (CH). Both hyperthyroidism and CH can cause heart lesions; however, the mechanisms involved remain unclear. The left ventricle was collected from eu-, hyper-, and hypothyroid rat. RNAwas extracted and reverse-transcripted to cDNA. Real-time fluorescence quantitation-PCR was used to quantify the differential expression of thyroid hormone receptor (TR) subtype mRNA among eu-, hyper-, and hypothyroid rat myocardium. Here, we show that compared with the normal myocardium, TRa1 mRNA expression was upregulated by 51% (P!0 . 01), TRa2 mRNA expression was downregulated by 58% (P!0 . 01), and TRb1 mRNA expression remained unchanged in hyperthyroid rat myocardium (PO0 . 05). TRa1, TRa2, and TRb1 were expressed in normal and hypothyroid rat myocardium throughout the developmental process. In hypothyroid rats, myocardial TRa1 mRNA expression was generally downregulated and the expression peak appeared late. Myocardial TRa2 mRNA expression was generally upregulated and the expression peak appeared late. Myocardial TRb1 mRNA expression was generally downregulated and changed similarly with the control group. In addition, the hypogenetic myocardium can be seen in the hypothyroid rat by pathology study. Taken together, the abnormal expression of TR subtype mRNA may have a close relationship with the pathogenesis of CH and hyperthyroidism heart disease.

show abstract

“…The clinical literature describes numerous cases of fetal goiter secondary to PTU, often reversible upon discontinuation of the drug. 9 The fetus is dependent on the mother for its thyroid hormone supply for the first half of the pregnancy. It is critical to establish whether PTU and MMI can adversely affect brain development.…”

Section: Fetal Safetymentioning

confidence: 99%

Therapeutic Drug Monitoring of Antithyroid Drugs in Pregnancy: The Knowledge Gaps

Koren¹

2006

Therapeutic Drug Monitoring

View full text Add to dashboard Cite

Despite being a common condition in pregnancy, and despite propylthiouracil (PTU) being perceived as safer than methimazole, there are virtually no epidemiological controlled studies on malformation rate an neurobehavioral outcomes with the former. This knowledge gap must be filled to ensure fetal safety. Keywordsantithyroid; therapeutic drug monitoring; malformations; pregnancy; thyrotoxicosis Because the thalidomide era there is a commonly held perception among both patients and physicians that many drugs are a human teratogens. In studies conducted in our institution we have shown that women exposed to non-teratogenic drugs believe they have a 25% risk of major malformations, which is a risk equal in magnitude to that of thalidomide. 1 In reality, the risk for major malformations in the general population ranges between 1-3%. As a result of this misperception, a large number of women refuse to take drugs in pregnancy, even if such refusal may endanger their lives.The Motherisk Program at the Hospital for Sick Children and the University of Toronto counsels women and health professionals on the safety/risk of medicinal drugs, chemicals, radiation and infection during pregnancy and lactation. Presently we deal with up to 200 calls daily from women, their families and health professionals. 2 Over the years we have become painfully aware of large knowledge gaps related to thyroid diseases and their treatments during pregnancy and lactation. In this report we briefly review these issues and identify critical unanswered questions. Hyperthyroidism in PregnancyHyperthyroidism is second only to diabetes as a common endocrinopathy in pregnancy. 3 Large numbers of women need antithyroid drugs to ensure their well being, yet these medications, if they cross the human placenta, may disrupt fetal thyroid development similarly to their disruption of the function of the adult thyroid. This illustrates a potential maternalfetal conflict, because untreated thyrotoxicosis in pregnancy is associated with increased rates of various complications (Table 1).Typically, thyrotoxicosis tends to be aggravated in the first trimester of pregnancy, improve in the second, and recur within one year postpartum. 4 The goals of maternal treatment are to maintain free thyroxine (T 4 ) at the upper level of the normal range with the minimal possible doses of antithyroid drugs. In fact, in about 30% of women antithyroid drugs may be discontinued in the last few weeks of pregnancy. Maternal-Fetal Pharmacokinetics of Antithyroid DrugsThe critical first question that must be addressed is whether the main antithyroid drugs, propylthiouracil (PTU) and methimazole (MMI), cross the human placenta. Experiments with the dually perfused human term placenta documented transfer at both low and high levels of PTU (4 and 40 mcg/gmL and MMI (1.5 and 15 mcg/mL). Both drugs documented relatively similar transfer and placental clearance rates, corresponding to similar clinically documented effects on maternal and fetal thyroid function. 5In studying the p...

show abstract

Propylthiouracil (PTU)-induced hypothyroidism in the developing rat impairs synaptic transmission and plasticity in the dentate gyrus of the adult hippocampus

Cited by 100 publications

References 43 publications

American Thyroid Association Guide to Investigating Thyroid Hormone Economy and Action in Rodent and Cell Models

American Thyroid Association Guide to Investigating Thyroid Hormone Economy and Action in Rodent and Cell Models

Effects of hyper- and hypothyroid on expression of thyroid hormone receptor mRNA in rat myocardium

Therapeutic Drug Monitoring of Antithyroid Drugs in Pregnancy: The Knowledge Gaps

Contact Info

Product

Resources

About