PTHLH
Description
The PTHLH (parathyroid hormone like hormone) is a protein-coding gene located on chromosome 12.
PTHLH, also known as parathyroid hormone-related protein (PTHrP), is a proteinaceous hormone and a member of the parathyroid hormone family secreted by mesenchymal stem cells. It is occasionally secreted by cancer cells, such as breast cancer and certain types of lung cancer, including squamous-cell lung carcinoma. However, it also has normal functions in bone, teeth, vascular tissues, and other tissues. PTHLH acts as an endocrine, autocrine, paracrine, and intracrine hormone. It regulates endochondral bone development by maintaining the endochondral growth plate at a constant width. It also regulates epithelial-mesenchymal interactions during the formation of the mammary glands. PTHLH plays a major role in regulating calcium homeostasis in vertebrates, including sea bream, chick, and mammals. In 2005, Australian pathologist and researcher Thomas John Martin found that PTHLH produced by osteoblasts is a physiological regulator of bone formation. Martin and Miao et al. demonstrated that osteoblast-specific ablation of PTHLH in mice results in osteoporosis and impaired bone formation both in vivo and ex vivo, which reiterates the phenotype of mice with haploinsufficiency of PTHLH. These findings demonstrated that PTHLH plays a central role in the physiological regulation of bone formation by promoting the recruitment and survival of osteoblasts.
PTHLH is a critical regulator of cellular and organ growth, development, migration, differentiation, and survival, as well as epithelial calcium ion transport. It regulates endochondral bone development and epithelial-mesenchymal interactions during the formation of the mammary glands and teeth. PTHLH is required for skeletal homeostasis. It promotes mammary mesenchyme differentiation and bud outgrowth by modulating mesenchymal cell responsiveness to BMPs. PTHLH up-regulates BMPR1A expression in the mammary mesenchyme, which increases the sensitivity of these cells to BMPs and allows them to respond to BMP4 in a paracrine and/or autocrine fashion. BMP4 signaling in the mesenchyme, in turn, triggers epithelial outgrowth and augments MSX2 expression, which causes the mammary mesenchyme to inhibit hair follicle formation within the nipple sheath. PTHLH promotes colon cancer cell migration and invasion in an integrin alpha-6/beta-1-dependent manner through activation of Rac1.
PTHLH is also known as BDE2, HHM, PLP, PTHR, PTHRP.
