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Truncated growth hormone receptor (GHR) mutations that lack the majority of the cytoplasmic domain have been identified in familial short stature and same truncated GHR isoforms generated by alternative splicing in a number of normal human tissues. The binding affinity of the truncated GHR was similar to that seen for the full-length receptor and the truncated GHR showed a much greater expression on the cell surface, which is consistent with lack of internalization. These truncated receptors function as dominant-negative inhibitors of the growth hormone (GH) signal and generate large amounts of GH binding protein (GHBP). Thus, truncated GHR isoform may be important as a physiological regulator of GH signaling in addition to providing a mechanism for the production of GHBP.

Laron syndrome, characterized by a short stature with raised serum levels of growth hormone but extremely low levels of insulin-like growth factor I, is caused by genetic defects of growth hormone receptor, including loss of functions of growth hormone receptor and abnormal growth hormone receptor acting in a dominant negative manner. This chapter focused on loss of functions of growth hormone receptor causing disruption of growth hormone binding and intracellular signalling. Most mutations and deletions have been found in extracellular domains of growth hormone receptor. Serum levels of growth hormone binding protein, cleaved from the extracellular portion of the growth hormone receptor, are typically decreased in most patients but are normal or high in some patients.

The diagnostic criteria of GH deficiency and acromegaly have been revised in 1990 by the Ministry of Health and Welfare in Japan. According to this criteria, not only the classical type of severe GH deficiency but also partial GH deficiency can be diagnosed and treated. With development of technology, anatomical abnormalities could be seen by MRI and genetic abnormality analysed. For the treatment of patients with GH deficiency, the pen-system has becomes available, which makes the daily injection of GH painless and easy. For the treatment of GH producing pituitary tumor (acromegaly), a long acting analog of somatostatin is now available to reduce the size of the tumor.