Wallaschofski H, Kobsar A, Koksch M, Siegemund A, Hentschel B, Tuschy U, Lohmann T, Sokolova O, Eigenthaler M
Department of Internal Medicine I, University of Erlangen, Germany.
Horm Metab Res. 2003 Apr;35(4):228-35. doi: 10.1055/s-2003-39479.
Prolactin is a newly recognized platelet coactivator that functions through potentiation of ADP-induced platelet activation. However, the possible association between hyperprolactinemia and venous thromboembolism (VTE) has not been systematically investigated up to now; prolactin signaling mechanisms in platelets still need to be elucidated. In this study, plasma prolactin levels in healthy subjects and patients with VTE were determined, demonstrating that patients with VTE and no other congenital risk factors had significantly increased plasma prolactin levels. Moreover, prolactinoma patients demonstrated a higher incidence of VTE than the general population. To elucidate the molecular mechanisms for the development of venous thrombosis, prolactin receptor signaling during platelet activation was investigated with a focus on ADP-stimulated G-protein-regulated signaling pathways. The short isoform of prolactin receptors was detected on platelets. Signaling through this receptor, although not directly linked to Gq-proteins, substitutes for Gq-protein regulated signaling pathways involved in platelet activation. We identified protein kinase C, a well-established signaling molecule in platelet activation, as a target molecule for prolactin signaling pathways in human platelets. Our findings indicate that hyperprolactinemia may be an important novel risk factor for VTE, suggesting that its thrombogenic effect may be mediated through enhanced platelet reactivity. Revealing the molecular mechanisms of prolactin signaling will allow the design of new antithrombotic therapies.
催乳素是一种新发现的血小板共激活因子，通过增强ADP诱导的血小板激活发挥作用。然而，高催乳素血症与静脉血栓栓塞（VTE）之间的可能关联迄今尚未得到系统研究；血小板中的催乳素信号传导机制仍有待阐明。在本研究中，测定了健康受试者和VTE患者的血浆催乳素水平，结果表明，无其他先天性危险因素的VTE患者血浆催乳素水平显著升高。此外，催乳素瘤患者的VTE发生率高于普通人群。为了阐明静脉血栓形成的分子机制，研究了血小板激活过程中的催乳素受体信号传导，重点是ADP刺激的G蛋白调节信号通路。在血小板上检测到了催乳素受体的短异构体。通过该受体的信号传导虽然不直接与Gq蛋白相关，但可替代参与血小板激活的Gq蛋白调节信号通路。我们确定蛋白激酶C是血小板激活中一个公认的信号分子，是人血小板中催乳素信号通路的靶分子。我们的研究结果表明，高催乳素血症可能是VTE的一个重要新危险因素，提示其血栓形成作用可能通过增强血小板反应性介导。揭示催乳素信号传导的分子机制将有助于设计新的抗血栓治疗方法。
