ThrombopoietinRezeptorAgonisten

Thrombopoietin (TPO) is a glycoprotein hormone and the primary regulator of platelet production. It is produced mainly by the liver, with additional contributions from the kidneys and bone marrow stromal cells. TPO acts on the c-Mpl receptor (CD110) on megakaryocyte progenitors and platelets, stimulating their proliferation, differentiation, and maturation into megakaryocytes and promoting thrombopoiesis.

Regulation of TPO circulating levels occurs through receptor-mediated clearance. Platelets and other MPL-expressing cells bind TPO and internalize it for degradation, creating a feedback loop: higher platelet mass lowers TPO availability, whereas thrombocytopenia raises circulating TPO.

Clinically, thrombopoietin receptor agonists such as romiplostim and eltrombopag mimic TPO signaling and are used to treat thrombocytopenia, notably chronic immune thrombocytopenia (ITP) and thrombocytopenia associated with liver disease or chemotherapy. These agents activate the MPL pathway to increase platelet production.

Genetics and pathology involve the THPO gene, which encodes thrombopoietin. Deficiency or disruption of THPO signaling can cause inherited thrombocytopenias, and abnormal MPL signaling can contribute to certain myeloproliferative disorders.

Overview of signaling shows that TPO activates downstream pathways such as JAK-STAT, MAPK, and PI3K, promoting progenitor survival and megakaryocyte maturation. Through these mechanisms, TPO coordinates the production of platelets to maintain hemostasis and respond to physiological demand.