Endocrine Abstracts

The glycoprotein hormone, TSH, is synthesized and secreted by thyrotrophs in the anterior pituitary gland. It acts at the TSH receptor (TSHR), a 7-transmembrane G-protein coupled cell membrane receptor expressed in thyroid follicular cells. The TSHR, thus, plays a key role in the regulation of thyroid status and growth of the thyroid gland. In recent years TSHR expression has also been identified in a wide variety of extra-thyroidal tissues including: anterior pituitary; hypothalamus; ovary; testis; skin; kidney; immune system; bone marrow and peripheral blood cells; white and brown adipose tissue; orbital preadipocyte fibroblasts and bone. Considerable data are emerging that describe possible functional roles of TSHR at these various sites, but their physiological importance in many cases remains a subject of controversy and much interest. In particular, expression of TSHR in bone and the possible role of TSH in the skeleton have attracted considerable controversy. Thus, TSH has been proposed to act as a negative regulator of bone remodeling, acting directly via effects on the TSHR expressed in bone-forming osteoblasts and bone-resorbing osteoclasts. This hypothesis has challenged the conventional view that that skeletal responses to abnormal thyroid status result from altered thyroid hormone action in bone. Thus, in thyrotoxicosis, high bone turnover and osteoporosis are considered to result from thyroid hormone excess. By contrast, in the TSH model, these consequences are proposed to result from TSH deficiency. Unfortunately, because of the reciprocal physiological relationship between thyroid hormones and TSH it has been difficult to distinguish the actions of thyroid hormones from those proposed to result from TSH deficiency. This presentation will address these issues in particular as well as considering the wider actions of TSH in other extra-thyroidal tissues.