12 Parathyroid hormone and vitamin D receptors

Parathyroid hormone (PTH), an 84-amino-acid polypeptide hormone, interacts with plasma membrane-bound receptors on bone and kidney cells, thereby increasing intracellular cAMP. Although the synthetic amino terminal 1-34 fragment of PTH possesses full biological activity, there is no firm evidence that hormone cleavage is a requisite step in the biological action of PTH. In contrast, vitamin D must undergo hydroxylations in the 1 and 25 positions in order to become fully active on target organs. 1,25(OH)2D, a steroid-like hormone, interacts with cytoplasmic receptors in small intestinal and bone cells. The 1,25(OH)2D-receptor complex (in the same manner as other steroid hormones) directs the synthesis of specific proteins. The integrated actions of PTH and vitamin D maintain serum calcium within narrow limits, thereby permitting normal neuromuscular and secretory function, as well as normal bone mineralization. Abnormalities in hormone secretion (PTH) or metabolic activation (vitamin D) lead to clinical disturbances in hormone action. Abnormalities at the level of the receptor-effector system for PTH and vitamin D also lead to clinical disturbances characterized by resistance to hormone action. Specific examples of the latter include pseudohypoparathyroidism, in which deficient activity of a component (the G unit) of the adenylate cyclase complex may lead to resistance to PTH, and hereditary vitamin D-dependent rickets type II, in which abnormalities in the nuclear uptake of 1,25(OH)2D may lead to impaired response to 1,25(OH)2D.