Endocrine Abstracts

Glycoprotein hormone receptors (TSHr, LH/CGr, FSHr)are rhodopsin-like G protein-coupled receptors with a large extracellular N-terminal portion containing leucine rich repeats, responsible for hormone recognition and binding. We have relied on spontaneous gain-of-function mutations in both the serpentine and LRR portions of the receptors to further explore the structure-function relationships of this family of receptors.ECTODOMAIN. From the observation i...

The dichotomy between hormone recognition, by the ectodomain containing leucine-rich repeats (LRR), and activation of the G protein, by the rhodopsin-like serpentine portion, is a well established property of glycoprotein hormone receptors (GpHRs). Extensive site-directed mutagenesis experiments and direct structural data have fully confirmed that high affinity recognition of the hormones by their receptors was built within the structure of the LRRs. It is possible to transfor...

Recent studies suggest TSH inhibits bone remodeling, indicating that TSH deficiency rather than thyroid hormone excess could cause bone loss in thyrotoxicosis. The findings predict that TSH receptor (TSHR) stimulating antibodies (TSHRAb) should inhibit bone turnover, whereas Graves’ disease patients exhibit high bone turnover with increased fracture susceptibility. We characterized TSH-action in primary human and mouse osteoblasts and osteoclasts, and explored whether a p...

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&...