Thyroid hormone receptor alpha sumoylation modulates white adipose tissue stores.

Thyroid hormone (TH) and thyroid hormone receptor (THR) regulate stem cell proliferation and differentiation during development, as well as during tissue renewal and repair in the adult. THR undergoes posttranslational modification by small ubiquitin-like modifier (SUMO). We generated the THRA (K283Q/K288R) mouse model for in vivo studies and used human primary preadipocytes expressing the THRA sumoylation mutant (K283R/K288R) and isolated preadipocytes from mutant mice for in vitro studies.

Persistent COUP-TFII expression underlies the myopathy and impaired muscle regeneration observed in resistance to thyroid hormone-alpha.

Thyroid hormone signaling plays an essential role in muscle development and function, in the maintenance of muscle mass, and in regeneration after injury, via activation of thyroid nuclear receptor alpha (THRA). A mouse model of resistance to thyroid hormone carrying a frame-shift mutation in the THRA gene (THRA-PV) is associated with accelerated skeletal muscle loss with aging and impaired regeneration after injury. The expression of nuclear orphan receptor chicken ovalbumin upstream promoter-factor II (COUP-TFII, or Nr2f2) persists during myogenic differentiation in THRA-PV myoblasts and skeletal muscle of aged THRA-PV mice and it is known to negatively regulate myogenesis.

Thyroid Hormone Protects Primary Cortical Neurons Exposed to Hypoxia by Reducing DNA Methylation and Apoptosis.

Traumatic brain injury (TBI) is associated with disruption of cerebral blood flow leading to localized brain hypoxia. Thyroid hormone (TH) treatment, administered shortly after injury, has been shown to promote neural protection in rodent TBI models. The mechanism of TH protection, however, is not established.

Acute Hyperglycemia Due to Topical Corticosteroid Administration.

We present the case of a 71-year-old man with longstanding, previously well-controlled type 1 diabetes who developed acute hyperglycemia. His insulin requirements, via his insulin pump, increased to nearly five times his typical daily dose. The patient was admitted for evaluation and treatment and started on an insulin infusion.

Thyroid Hormone Receptor Alpha is Essential to Maintain the Satellite Cell Niche During Skeletal Muscle Injury and Sarcopenia of Aging.

Background: Myopathic changes are commonly described in hypothyroid and hyperthyroid patients, including muscular atrophy and weakness. Satellite cells (SCs) play a major role in skeletal muscle maintenance and regeneration after injury. A mouse model of resistance to thyroid hormone-TRα1PV demonstrated impaired skeletal muscle regeneration after injury with significant reduction of SCs, suggesting that exhaustion of the SC pool contributes to the impaired regeneration.

Thyroid hormone treatment activates protective pathways in both in vivo and in vitro models of neuronal injury.

Thyroid hormone plays an important role in brain development and adult brain function, and may influence neuronal recovery after Traumatic Brain Injury (TBI). We utilized both animal and cell culture models to determine the effects of thyroid hormone treatment, post TBI or during hypoxia, on genes important for neuronal survival and neurogenesis. We show that TBI in rats is associated with a reduction in serum thyroxine (T4) and triiodothyronine (T3).

Thyroid Hormone Receptor α Plays an Essential Role in Male Skeletal Muscle Myoblast Proliferation, Differentiation, and Response to Injury.

Thyroid hormone plays an essential role in myogenesis, the process required for skeletal muscle development and repair, although the mechanisms have not been established. Skeletal muscle develops from the fusion of precursor myoblasts into myofibers. We have used the C2C12 skeletal muscle myoblast cell line, primary myoblasts, and mouse models of resistance to thyroid hormone (RTH) α and β, to determine the role of thyroid hormone in the regulation of myoblast differentiation.

Thyroid Hormone Signaling in Muscle Development, Repair and Metabolism.

Skeletal muscle is a plastic organ made by highly specialize fibers with specific and different structure, function and metabolism. Skeletal muscle fibers can adapt, change, recover/regenerate after injury in response to various stimulators including hormones. Thyroid hormones are important players in the homeostasis of several tissue including skeletal muscle and their genomic action mostly depend on the tissue T3 bioavailability and on the distribution of the thyroid receptor isoforms which act as transcription factors and are modulated by T3.

Thyroid hormone receptor sumoylation is required for preadipocyte differentiation and proliferation.

Thyroid hormone and thyroid hormone receptor (TR) play an essential role in metabolic regulation. However, the role of TR in adipogenesis has not been established. We reported previously that TR sumoylation is essential for TR-mediated gene regulation and that mutation of either of the two sites in TRα or any of the three sites in TRβ reduces TR sumoylation.

Amniotic fluid stem cells prevent β-cell injury.

Background Aims: The contribution of amniotic fluid stem cells (AFSC) to tissue protection and regeneration in models of acute and chronic kidney injuries and lung failure has been shown in recent years. In the present study, we used a chemically induced mouse model of type 1 diabetes to determine whether AFSC could play a role in modulating β-cell injury and restoring β-cell function.

Methods: Streptozotocin-induced diabetic mice were given intracardial injection of AFSC; morphological and physiological parameters and gene expression profile for the insulin pathway were evaluated after cell transplantation.

Humoral hypercalcemia of malignancy caused by parathyroid hormone-related peptide-secreting neuroendocrine tumors. Report of six cases.

We report the clinical characteristics and management of six patients with metastatic gastroentero-pancreatic neuroendocrine tumor (NET) presenting with severe hypercalcemia due to elevation of parathyroid hormone-related protein (PTHrP). All patients had histological confirmation of NET, five well-differentiated and one poorly differentiated. In 5 patients, hypercalcemia developed after years after the initial diagnosis of NET.

β-Cell regeneration mediated by human bone marrow mesenchymal stem cells.

Bone marrow mesenchymal stem cells (BMSCs) have been shown to ameliorate diabetes in animal models. The mechanism, however, remains largely unknown. An unanswered question is whether BMSCs are able to differentiate into β-cells in vivo, or whether BMSCs are able to mediate recovery and/or regeneration of endogenous β-cells.

Injection of amniotic fluid stem cells delays progression of renal fibrosis.

Injection of amniotic fluid stem cells ameliorates the acute phase of acute tubular necrosis in animals by promoting proliferation of injured tubular cells and decreasing apoptosis, but whether these stem cells could be of benefit in CKD is unknown. Here, we used a mouse model of Alport syndrome, Col4a5(-/-) mice, to determine whether amniotic fluid stem cells could modify the course of progressive renal fibrosis. Intracardiac administration of amniotic fluid stem cells before the onset of proteinuria delayed interstitial fibrosis and progression of glomerular sclerosis, prolonged animal survival, and ameliorated the decline in kidney function.

Management of hypothyroidism in pregnancy.

Purpose Of Review: Examine recent studies on the assessment of thyroid status in pregnancy, approach to thyroid testing, the spectrum of hypothyroidism in pregnancy, and strategies for thyroid replacement in women with known hypothyroidism.

Recent Findings: Trimester-specific references range for thyroid-stimulating hormone (TSH) and free thyroxine in pregnancy must take into account iodine and thyroid autoantibody status, race, BMI, as well as other factors. Thyroid testing of only those pregnant women at increased risk for thyroid disease, case finding, will miss 30-80% of women with thyroid disease.