Secretion and metabolism of PTH

Secretion of intact PTH by the parathyroid glands is accompanied by release of a family of CPTH fragments (stippled shading), the amount of which, relative to intact PTH, increases at higher serum calcium concentrations. Intact PTH acts directly on PTH1Rs via its amino-terminal sequence (black shading) in target tissues (ie, bone) or is directly cleared by liver or kidney. Hepatic clearance of PTH involves rapid proteolysis by Kupffer cells to amino-terminal fragments (degraded in situ) and a series of carboxyl-terminal fragments, some of which reappear in the circulation (refer to UpToDate topic on parathyroid hormone secretion and action). CPTH fragments produced by the parathyroids and the liver are chemically similar or identical and include minimally amino-truncated, long forms and some midregion fragments truncated at both ends. Like intact PTH, CPTH fragments can exert direct effects on bone cells via a novel class of CPTH receptors. CPTH fragments normally circulate at fivefold higher concentrations than intact PTH but are cleared predominantly by the kidney and, thus, accumulate disproportionately during kidney failure.