Endocrine Abstracts

Resistance to thyroid hormone due to THRA mutations (RTHα) is a recently discovered genetic disease with high variability in its clinical presentation. This variability may result from the fact that patients bear different types of mutations, which may impact in different ways the functionality of thyroid hormone receptor α1 (TRα1). Our aim was to understand the relationship between specific THRA mutations and symptoms, using mouse models. CRISPR/Cas9 genome edi...

Thyroid hormone (T3) has been known for a long time to be required for brain development which activate TRα and TRβ nuclear receptors. In rodent models, histological defects are mainly observed in cerebellum. Whether T3 action during cerebellum development is due to direct regulation of gene transcription by liganded thyroid hormone receptors (mainly TRα) or also the indirect consequences of other defects and systemic disorders is currently unknown.<p class=...

Context: Cyproterone acetate (CPA) is an androgen receptor blocker often used for testosterone suppression as a part of gender-affirming hormonal treatment (GAHT) in transgender women. In recent years, more concerns have been raised towards an increased risk of meningioma development, linked to CPA use in higher doses (25 mg or more per day).Objectives: To determine if lower doses of CPA are equally effective in maintain...

Objectives: Acute liver failure (ALF) is a rare but life-threatening condition with severe liver dysfunction. In ALF liver regeneration capacity is exceeded due to loss of hepatocyte function. A well-known trigger of ALF is paracetamol (acetaminophen, APAP) intoxication. Unfortunately, based on the poor prognosis and rapidly increasing mortality rate liver transplantation offers the so far only effective therapeutic strategy. Even if the underlying mechanisms of ALF are not ye...

Studies of TSHR−/− mice suggest that TSH inhibits bone turnover, but these mice have congenital hypothyroidism and the actions of TSH cannot be separated from effects of thyroid hormone deficiency. We characterised skeletal development in hyt/hyt mice, which have a point mutation in the Tshr gene, and Pax8−/− mice with thyroid gland agenesis. Hyt/hyt mice have a 100-fold increase in TSH but inactive TSHRs, whereas Pax8&...

Thyroid hormones (TH) reduce liver steatosis. As steatosis is the initial step of alcoholic liver disease (ALD), we hypothesized that TH treatment could ameliorate ALD. Wildtype (WT) mice were treated with either ethanol (EtOH) or liquid control diet for 10 days followed by a single EtOH or maltose binge on day 11. In both groups, diet was supplemented with either T3 or solvent. Serum triglycerides (TG) were increased by EtOH and, surprisingly, further elevated by T3. Liver we...