Prolactin does not affect human platelet aggregation or secretion

Anne Q. Reuwer; Rienk Nieuwland; Isabelle Fernandez; Vincent Goffin; Claudia M. van Tiel; Marianne C. L. Schaap; René J. Berckmans; John J. P. Kastelein; Marcel Th. B. Twickler

doi:10.1160/TH08-12-0801

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2009; 101(06): 1119-1127
DOI: 10.1160/TH08-12-0801

Platelets and Blood Cells

Schattauer GmbH

Prolactin does not affect human platelet aggregation or secretion

Anne Q. Reuwer

¹Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands;

,

Rienk Nieuwland

²Department of Clinical Chemistry, Academic Medical Center, Amsterdam, The Netherlands

,

Isabelle Fernandez

³Inserm, U845, Centre de Recherche Croissance et Signalisation, Equipe „Prl, GH et tumeurs“, et Université Paris Descartes, Faculté de Médecine, site Necker, Paris, France

,

Vincent Goffin

³Inserm, U845, Centre de Recherche Croissance et Signalisation, Equipe „Prl, GH et tumeurs“, et Université Paris Descartes, Faculté de Médecine, site Necker, Paris, France

,

Claudia M. van Tiel

⁴Department of Medical Biochemistry of the Academic Medical Center, Amsterdam, The Netherlands

,

Marianne C. L. Schaap

²Department of Clinical Chemistry, Academic Medical Center, Amsterdam, The Netherlands

,

René J. Berckmans

²Department of Clinical Chemistry, Academic Medical Center, Amsterdam, The Netherlands

,

John J. P. Kastelein

¹Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands;

,

Marcel Th. B. Twickler

¹Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands;

› Author Affiliations

Abstract

Summary

Platelets play an important role in the development of plaque formation and in the events after rupture of the atherosclerotic plaque, leading to atherothrombosis. Multiple hormones, either in excess or when deficient, are involved in the development of atherothrombotic disease, but, to which extent such hormones affect platelet function, is still controversial. It was the objective of this study to assess the ability of the pituitary hormone prolactin to affect platelet functions. Venous blood was collected from six healthy males. Platelet activation was studied by (i) flow cytometry in whole blood (exposure of P-selectin as a measure of platelet secretion, and binding of PAC-1 as a measure of ligand-binding conformation of αIIbβ3), and by (ii) optical aggregation and whole blood aggregation. All studies were performed without and with exposure to several concentrations of ADP (0.1, 0.5 and 1.0 μM) and prolactin (50 and 1,000 μg/l). The presence of the prolactin receptor was investigated by Western blot and flow cytometry. In response to either 50 or 1,000 μg/l prolactin, no evidence of platelet activation or aggregation was found. In addition, ADP-induced platelet activation or aggregation was not enhanced by prolactin. Finally, prolactin receptors could not be detected on the surface of platelets. The present data indicate that prolactin does not directly modulate platelet function.

Keywords

Atherothrombosis - prolactin - platelet activation - platelet aggregation - prolactin receptor

Full Text

References

References
1 Raaz D, Wallaschofski H, Stumpf C. et al. Increased prolactin in acute coronary syndromes as putative Co-activator of ADP-stimulated P-selectin expression. Horm Metab Res 2006; 11: 767-772.
2 Wallaschofski H, Lohmann T, Hild E. et al. Enhanced platelet activation by prolactin in patients with ischemic stroke. Thromb Haemost 2006; 1: 38-44.
3 Yavuz D, Deyneli O, Akpinar I. et al. Endothelial function, insulin sensitivity and inflammatory markers in hyperprolactinemic pre-menopausal women. Eur J Endocrinol 2003; 3: 187-193.
4 Chavez-Rueda K, Hernandez J, Zenteno E. et al. Identification of prolactin as a novel immunomodulator on the expression of co-stimulatory molecules and cytokine secretions on T and B human lymphocytes. Clin Immunol 2005; 2: 182-191.
5 Montes de Oca P, Macotela Y, Nava G. et al. Prolactin stimulates integrin-mediated adhesion of circulating mononuclear cells to endothelial cells. Lab Invest 2005; 5: 633-642.
6 Pellegrini I, Lebrun JJ, Ali S. et al. Expression of prolactin and its receptor in human lymphoid cells. Mol Endocrinol 1992; 7: 1023-1031.
7 Ricken AM, Traenkner A, Merkwitz C. et al. The short prolactin receptor predominates in endothelial cells of micro- and macrovascular origin. J Vasc Res 2007; 1: 19-30.
8 Aziz MM, Ishihara S, Rumi MA. et al. Prolactin induces MFG-E8 production in macrophages via transcription factor C/EBPbeta-dependent pathway. Apoptosis 2008; 5: 609-620.
9 Sauro MD, Buckley AR, Russell DH. et al. Prolactin stimulation of protein kinase C activity in rat aortic smooth muscle. Life Sci 1989; 23: 1787-1792.
10 Davi G, Patrono C. Platelet activation and atherothrombosis. N Engl J Med 2007; 24: 2482-2494.
11 Falcinelli E, Giannini S, Boschetti E. et al. Platelets release active matrix metalloproteinase-2 in vivo in humans at a site of vascular injury: lack of inhibition by aspirin. Br J Haematol 2007; 2: 221-230.
12 Wallaschofski H, Kobsar A, Koksch M. et al. Prolactin receptor signaling during platelet activation. Horm Metab Res 2003; 4: 228-235.
13 Wallaschofski H, Donne M, Eigenthaler M. et al. PRL as a novel potent cofactor for platelet aggregation. J Clin Endocrinol Metab 2001; 12: 5912-5919.
14 Atmaca A, Gurlek A, Dagdelen S. et al. Hyperprolactinemia of pregnancy is not associated with increased in vivo platelet activity and shortened in vitro bleeding times. Exp Clin Endocrinol Diabetes 2006; 4: 188-191.
15 Paris N, Rentier-Delrue F, Defontaine A. et al. Bacterial production and purification of recombinant human prolactin. Biotechnol Appl Biochem 1990; 4: 436-449.
16 Gutzman JH, Miller KK, Schuler LA. Endogenous human prolactin and not exogenous human prolactin induces estrogen receptor alpha and prolactin receptor expression and increases estrogen responsiveness in breast cancer cells. J Steroid Biochem Mol Biol 2004; 1: 69-77.
17 Kinet S, Bernichtein S, Kelly PA. et al. Biological properties of human prolactin analogs depend not only on global hormone affinity, but also on the relative affinities of both receptor binding sites. J Biol Chem 1999; 37: 26033-26043.
18 Bernichtein S, Jeay S, Vaudry R. et al. New homo-logous bioassays for human lactogens show that agonism or antagonism of various analogs is a function of assay sensitivity. Endocrine 2003; 1–2: 177-190.
19 Kawaguchi R, Shimokawa T, Umehara N. et al. Priming of peripheral monocytes with prolactin (PRL) sensitizes IFN-gamma-mediated indoleamine 2,3-dioxygenase (IDO) expression without affecting IFN-gamma signaling. J Reprod Immunol 2008; 2: 117-125.
20 Galsgaard ED, Rasmussen BB, Folkesson CG. et al. Re-evaluation of the prolactin receptor expression in human breast cancer. J Endocrinol 2009; 201: 115-128.
21 Libby P. Inflammatory mechanisms: the molecular basis of inflammation and disease. Nutr Rev 2007; 12: S140-S146.
22 Carvalho-Freitas MI, Rodrigues-Costa EC, Nasello AG. et al. In vitro macrophage activity: biphasic effect of prolactin and indirect evidence of dopaminergic modulation. Neuroimmunomodulation 2008; 2: 131-139.
23 Lindemann S, Kramer B, Daub K. et al. Molecular pathways used by platelets to initiate and accelerate atherogenesis. Curr Opin Lipidol 2007; 5: 566-573.
24 Schmidt R, Bultmann A, Fischel S. et al. Extracellular matrix metalloproteinase inducer (CD147) is a novel receptor on platelets, activates platelets, and augments nuclear factor kappaB-dependent inflammation in monocytes. Circ Res 2008; 3: 302-309.