Receptors of Calciotropic Hormones

The recent cloning of receptors for calcitonin (CT) and parathyroid hormone (PTH)/parathyroid hormone-related peptide (PTHrP) has enabled very rapid progress in understanding the molecular and cell biology of these receptors. In particular, much has been learnt about the tissue distribution of these receptors, as well as their mode of interaction with ligands, signal transduction and regulation of expression. The conventional view of these hormone-receptors systems as "calciotropic" has been broadened by recent work showing important developmental roles. Isoforms of the CT receptor (CTR), with interesting functional differences, have been identified and a new form of the PTH receptor, highly specific for PTH, has been cloned. Investigation of the homologous regulation of the CTR in osteoclasts by CT treatment of mouse marrow cultures, has shown that continuous exposure to CT results in formation of resorption competent, CTR-deficient osteoclasts. Treatment of mature osteoclasts causes a rapid and prolonged decrease in CTR mRNA levels, reflected in a loss of cell surface CTR. Since these cells regain resorption competence, the data support the concept that the clinical phenomenon of "escape" from the hypocalcemic action of CT results from a loss of CT sensitivity by osteoclasts to the hormone