PTH-related peptide (PTHrP) produced by many cancers causes hypercalcemia by binding to which receptor?

• A. Calcitonin receptor
• B. PTH receptor
• C. Vitamin D receptor
• D. Growth hormone receptor

Answer: (B)

PTH-related peptide from cancers raises calcium by acting on the same receptor as parathyroid hormone, the PTH/PTHrP receptor on bone and kidney. When PTHrP binds this receptor (PTH1R), it triggers signaling that increases calcium release from bone and enhances calcium reabsorption in the kidney, leading to hypercalcemia. In tumors, PTHrP mimics PTH’s actions, driving these effects even though PTH itself may be suppressed by high calcium levels.

Other receptors listed don’t mediate this effect: the calcitonin receptor responds to calcitonin (which tends to lower calcium), the vitamin D receptor is a nuclear receptor for 1,25-dihydroxy vitamin D, and the growth hormone receptor mediates GH actions rather than calcium homeostasis via PTHrP.