Horm Metab Res 2004; 36(7): 453-457
DOI: 10.1055/s-2004-825727
Original Basic
© Georg Thieme Verlag Stuttgart · New York

Differences in Platelet Activation by Prolactin and Leptin

H.  Wallaschofski 1 , A.  Kobsar 3 , O.  Sokolova 1 , A.  Siegemund 1 , H.  Stepan 2 , R.  Faber 2 , M.  Eigenthaler 3 , T.  Lohmann 1
  • 1Department of Internal Medicine I, University of Erlangen, Germany
  • 2Department of Obstetrics and Gynecology, University of Leipzig, Germany
  • 3Institute of Clinical Biochemistry and Pathobiochemistry, University of Würzburg, Germany
Further Information

Publication History

Received 16 September 2003

Acceped after Revision 2 March 2004

Publication Date:
11 August 2004 (online)

Abstract

Hormones such as prolactin and leptin have recently been recognized as potent platelet aggregation co-activators, and have therefore been postulated as an additional risk factor for both arterial and venous thrombosis. Clinical situations exist that are known to be associated with higher leptin and/or prolactin levels (obesity, pregnancy, prolactinomas and anti-psychotic therapy respectively) and increased venous thrombosis or atherosclerosis risk. Therefore, we compared the impact of both hormones on platelet activation in vitro and in vivo. First, we investigated platelet aggregation and P-selectin expression after stimulation with 1,000 mU/l prolactin or 100 ng/ml leptin in five healthy volunteers in vitro. Prolactin revealed significant higher levels of P-selectin expression and platelet aggregation than leptin in all subjects. We also compared the correlation of prolactin and leptin values with the P-selection expression on platelets. Previously, we detected a significant correlation between prolactin values and ADP-stimulated P-selectin expression on platelets in pregnant women, patients with pituitary tumours, and patients on anti-psychotic therapy. In contrast, leptin did not correlate with P-selectin expression in all subject groups investigated. However, leptin correlated with body mass index in the subjects investigated. Our data indicate that prolactin has a stronger effect on platelet activation as leptin in vitro and in vivo. Moreover, our data suggest that the stronger effect of prolactin on ADP-stimulated platelet aggregation, compared to leptin, depends on higher stimulation of CD62p expression by prolactin.

References

  • 1 Ross R. Atherosclerosis - an inflammatory disease.  N Engl J Med. 1999;  340 115-126
  • 2 Ruggeri Z M. Platelets in atherothrombosis.  Nat Med. 2002;  8 1227-1234
  • 3 Merten M, Thiagarajan P. P-selectin expression on platelets determines size and stability of platelet aggregates.  Circulation. 2000;  102 1931-1936
  • 4 Prandoni P, Bilora F, Marchiori A, Bernardi E, Petrobelli F, Lensing A W, Prins M H, Girolami A. An association between atherosclerosis and venous thrombosis.  N Engl J Med.. 2003;  348 1435-1441
  • 5 Li N, Hu H, Lindqvist M, Wikstrom-Jonsson E, Goodall A H, Hjemdahl P. Platelet-leukocyte cross talk in whole blood.  Arterioscler Thromb Vasc Biol. 2000;  20 2702-2708
  • 6 Celi A, Lorenzet R, Furie B, Furie B C. Platelet-leukocyte-endothelial cell interaction on the blood vessel wall.  Semin Hematol. 1997;  34 327-335
  • 7 Pulmonary Embolism Prevention trial . Prevention of pulmonary embolism and deep vein thrombosis with low dose aspirin: Pulmonary Embolism Prevention (PEP) trial.  Lancet. 2000;  355 1295-1302
  • 8 Wallaschofski H, Donne M, Eigenthaler M, Hentschel B, Faber R, Stepan H, Koksch M, Lohmann T. PRL as a novel potent cofactor for platelet aggregation.  J Clin Endocrinol Metab. 2001;  86 5912-5919
  • 9 Wallaschofski H, Kobsar A, Koksch M, Siegemund A, Hentschel B, Tuschy U, Lohmann T, Sokolova O, Eigenthaler M. Prolactin Receptor Signaling during Platelet Activation.  Horm Metab Res. 2003;  35 228-235
  • 10 Zornberg G I, Jick H. Antipsychotic drug use and risk of first-time idiopathic venous thromboembolism: a case-control study.  Lancet. 1999;  356 1219-1223
  • 11 Wallaschofski . et al . Hyperprolactinemia in patients on antipsychotic drugs causes ADP stimulated platelet activation that might explain the increased risk for venous thrombembolism - pilot study.  J Clin Psychopharmacology. in press; 
  • 12 Nakata M, Yada T, Soejima N, Maruyama I. Leptin promotes aggregation of human platelets via the long form of its receptor.  Diabetes. 1999;  48 426-429
  • 13 Konstantinidis S, Schäfer K, Koschnick S, Loskutoff D J. Leptin-dependent platelet aggregation and arterial thrombosis suggest a mechanism for atherothrombotic disease in obesity.  J Clin Invest. 2001;  108 1533-1540
  • 14 Konstantinides S, Schafer K, Loskutoff D J. The prothrombotic effects of leptin possible implications for the risk of cardiovascular disease in obesity.  Ann N Y Acad Sci. 2001;  947 134-141
  • 15 Bodary P F, Westrick R J, Wickenheiser K J, Shen Y, Eitzman D T. Effect of leptin on arterial thrombosis following vascular injury in mice.  JAMA. 2002;  287 1706-1709
  • 16 Pirisi A. Leptin linked to blood clots in obesity.  Lancet. 2002;  359 1215
  • 17 Greenman Y, Tordjman K, Stern N. Increased body weight associated with prolactin secreting pituitary adenomas: weight loss with normalization of prolactin levels.  Clin Endocrinol (Oxf). 1998;  48 547-553
  • 18 Considine R V, Sinha M K, Heiman M L, Kriaciunas A, Stephens T W, Nyce M R, Ohanessian J P, Marco C C, McKee L J, Bauer T R, Caro T R. Serum immunoreactive-leptin concentrations in normal-weight and obese humans.  N Engl J Med. 1996;  334 292-295
  • 19 Maffei M. et al . Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects.  Nat Med. 1995;  1 1155-1161
  • 20 Friedman J M, Halaas J L. Leptin and the regulation of body weight in mammals.  Nature. 1998;  395 763-770
  • 21 Boyar R M, Finkelstein J W, Kapen S, Hellman L. Twenty-four hour prolactin (PRL) secretory patterns during pregnancy.  J Clin Endocrinol Metab. 1975;  40 1117-1120
  • 22 Sagawa N, Yura S, Itoh H, Mise H, Kakui K, Korita D, Takemura M, Nuamah M A, Ogawa Y, Masuzaki H, Nakao K, Fujii S. Role of leptin in pregnancy a review.  Placenta. 2002;  23 Suppl A S80-S86
  • 23 Wauters M, Considine R V, van Gaal L F. Human leptin: from an adipocyte hormone to an endocrine mediator.  Eur J Endocrinol. 2000;  143 293-311
  • 24 Wieck A, Haddad P M. Antipsychotic-induced hyperprolactinaemia in women: pathophysiology, severity and consequences. Selective literature review.  Br J Psychiatry. 2003;  182 199-204
  • 25 Herran A, Garcia-Unzueta M T, Amado J A, de la Maza M T, Alvarez C, Vazquez-Barquero J L. Effects of long-term treatment with antipsychotics on serum leptin levels.  Br J Psychiatry. 2001;  179 59-62
  • 26 Libby P, Simon D I. Thrombosis and atherosclerosis. In: Colman RW, Hirsh J, Marder VJ, Clowes AW, George JN (eds) Hemostasis and thrombosis: basic principles & clinical practice. 4th ed. Philadelphia; Lippincott Williams Wilkins 2000: 743-752
  • 27 Libby P. Multiple mechanisms of thrombosis complicating atherosclerotic plaques.  Clin Cardiol. 2000;  23 Suppl 6 VI-3
  • 28 Sueishi K, Ichikawa K, Kato K, Nakagawa K, Chen Y X. Atherosclerosis: coagulation and fibrinolysis.  Semin Thromb Hemost. 1998;  24 255-260
  • 29 Holvoet P, Collen D. Thrombosis and atherosclerosis.  Curr Opin Lipidol. 1997;  8 320-328
  • 30 Fitzgerald G A, Tigges J, Barry P, Lawson J A. Markers of platelet activation and oxidant stress in atherothrombotic disease.  Thromb Haemost. 1997;  78 280-284
  • 31 Drouet L, Mazoyer E, Bal dit Sollier C, Hainaud P, Ripoll L. Participation des mécanismes de la thrombose et de l’hémostase aux étapes initiales de l’athérosclérose.  Arch Mal Coeur Vaiss. 1998;  91 41-51
  • 32 Koenig W, Rothenbacher D, Hoffmeister A, Griesshammer M, Brenner H. Plasma fibrin D-dimer levels and risk of stable coronary artery disease: results of a large case-control study.  Arterioscler Thromb Vasc Biol. 2001;  21 1701-1705
  • 33 Collins R, Baigent C, Sandercock P, Peto R. Antiplatelet therapy for thromboprophylaxis: the need for careful consideration of the evidence from randomised trials. Antiplatelet Trialists’ Collaboration.  BMJ. 1994;  309 1215-1217
  • 34 Antiplatelet Trialists’ Collaboration. . Collaborative overview of randomised trials of antiplatelet therapy-III: Reduction in venous thrombosis and pulmonary embolism by antiplatelet prophylaxis among surgical and medical patients. Antiplatelet Trialists’ Collaboration.  BMJ. 1994;  308 235-246
  • 35 Holmsen H, Walsh P N, Koike K, Murphy S, Holme S, Johnson M M, Dangelmaier C A, Egan J J, Benzel J E, Tuszynski G P. Familial bleeding disorder associated with deficiencies in platelet signal processing and glycoproteins.  Br J Haematol. 1987;  67 335-344
  • 36 Harrison P, Cramer E M. Platelet alpha-granules.  Blood Rev. 1993;  7 52-62
  • 37 Ozata M, Avcu F, Durmus O, Yilmaz I, Ozdemir I C, Yalcin A. Leptin does not play a major role in platelet aggregation in obesity and leptin deficiency.  Obesity Research. 2001;  9 627-630
  • 38 Corsonello A, Malara A, Ientile R, Corica F. Leptin enhances adenosine diphosphate-induced platelet aggregation in healthy subjects.  Obes Res. 2002;  10 306
  • 39 Nakahashi T K, Kambayashi J, Nakamura T, Le S N, Yoshitake M, Tandon N N, Sun B. Platelets in nonresponders to epinephrine stimulation showed reduced response to ADP.  Thromb Res. 2001;  104 127-135

H. Wallaschofski, M. D.

University of Erlangen · Department of Internal Medicine I

Ulmenweg 18 · 91054 Erlangen · Germany

Phone: + 49/9131/85-35230

Fax: + 49/9131/85-35231 ·

Email: Henri.Wallaschofski@med1.imed.uni-erlangen.de

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