PTHLH

PTHLH stands for parathyroid hormone-like hormone, a protein encoded by the human PTHLH gene. The gene product is also known as parathyroid hormone-related peptide (PTHrP). PTHrP is synthesized as a prepropeptide and processed to a mature peptide that acts primarily in a paracrine or autocrine manner rather than as an endocrine hormone.

PTHrP shares functional similarities with parathyroid hormone (PTH) and can bind to the same PTH1R receptor, activating signaling pathways such as cAMP. However, its physiological actions are largely local and context-dependent, rather than serving as a circulating regulator of calcium homeostasis. In development, PTHrP is essential for normal endochondral ossification and growth plate regulation, influencing chondrocyte proliferation and maturation. It also plays roles in mammary gland development and placental calcium transport, among other processes.

In adults, PTHrP continues to participate in local control of calcium and bone remodeling in certain tissues, though it does not typically function as a systemic calcium regulator like PTH. Pathologically, ectopic expression of PTHrP by tumors can cause humoral hypercalcemia of malignancy, a paraneoplastic syndrome characterized by elevated calcium levels. Genetic alterations in PTHLH can lead to brachydactyly type E, a skeletal disorder involving shortening of the bones in the hands and feet and, in some cases, additional skeletal anomalies.

PTHLH/PTHrP thus has important roles in development, local tissue signaling, and certain disease states, serving as a critical autocrine/paracrine regulator in multiple tissues.