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Horm Metab Res 2003; 35(4): 228-235
DOI: 10.1055/s-2003-39479
Original Basic
© Georg Thieme Verlag Stuttgart · New York

Prolactin Receptor Signaling during Platelet Activation

H.  Wallaschofski 1 , A.  Kobsar 4 , M.  Koksch 1 , A.  Siegemund 1 , B.  Hentschel 2 , U.  Tuschy 3 , T.  Lohmann 1 , O.  Sokolova 4 , M.  Eigenthaler 4
  • 1 Department of Internal Medicine I, University of Erlangen, Germany
  • 2 Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Germany
  • 3 Department of Internal Medicine II, Hospital of Erfurt, Germany
  • 4 Institute of Clinical Biochemistry and Pathobiochemistry, University of Würzburg, Germany
T. Lohmann, M. Eigenthaler, H. Wallaschofski and A. Kobsar contributed equally.
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Publikationsverlauf

Received 2 July 2002

Accepted after Revision 10 September 2002

Publikationsdatum:
02. Juni 2003 (online)

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Abstract

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.

Key words

Prolactin - Thrombosis - Platelet activation - G proteins - Protein kinase C - Pituitary tumor

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T. Lohmann, MD

University of Erlangen · Department of Internal Medicine I

Krankenhausstraße 12 · 91054 Erlangen · Germany ·

Telefon: +49 (913) 1 8536970

Fax: +49 (913) 1 8533428

eMail: Tobias.Lohmann@med1.imed.uni-erlangen.de