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The effects of angiotensin peptides and angiotensin receptor antagonists on the cell growth and angiogenic activity of GH3 lactosomatotroph cells in vitro

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Abstract

The local renin–angiotensin system (RAS) is present in the pituitary gland, and inhibitory effects of angiotensins on the lactosomatotroph (GH3) cell growth have been revealed. The aim of this study was to examine the influence of various angiotensin peptides and angiotensin AT1, AT2, and AT4 receptors antagonists on the cell proliferation, viability, and VEGF secretion in pituitary lactosomatotroph GH3 cell culture in order to identify receptors involved in antiproliferative effects of angiotensins on GH3 tumor cells. Cell viability and proliferation using Mosmann method and BrdU incorporation during DNA synthesis, and VEGF secretion using ELISA assay were estimated. The inhibitory effects of ang II, ang IV, and ang 5–8 on the cell viability and BrdU incorporation in GH3 culture were not abolished by AT1, AT2, and AT4 receptors antagonists. Ang II, as well as ang III and ang IV at lower concentrations stimulated the secretion of VEGF in GH3 cell culture. The secretion of VEGF was inhibited by ang III and ang IV at higher concentrations. AT1 and AT2 receptors antagonists prevented the proangiogenic effects of ang II. Ang II, ang IV, and ang 5–8 decrease the cell number and proliferation in GH3 cell culture independently of the AT1, AT2, and AT4 receptors. These peptides affect also secretion of VEGF in culture examined. Both the AT1 and AT2 receptors appear to mediate the proangiogenic effects of ang II.

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Acknowledgments

This study has been supported with the contribution of European Cooperation in the field of Scientific and Technical Research—COST ACTION, Grant No. CM0602 and by Polish Ministry of Science and Higher Education, Grant No. 505-04-001. The authors are grateful to Professor John W Wright from Department of Physiology of Washington State University for providing Divalinal.

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Authors and Affiliations

  1. Department of Endocrinology, The County Hospital of Kutno, 52 Kosciuszki Street, 99-300, Kutno, Poland

    Dorota Ptasinska-Wnuk

  2. Clinic of Endocrinology, Medical University of Lodz, Dr Sterling 3 Street, 91-425, Lodz, Poland

    Slawomir A. Mucha & Jolanta Kunert-Radek

  3. Department of Immunoendocrinology, Medical University of Lodz, Dr Sterling 3 Street, 91-425, Lodz, Poland

    Hanna Lawnicka, Jolanta Fryczak, Marek Pawlikowski & Henryk Stepien

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  1. Dorota Ptasinska-Wnuk
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  2. Slawomir A. Mucha
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Correspondence to Henryk Stepien.

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Dorota Ptasinska-Wnuk and Slawomir A. Mucha have contributed equally to this study.

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Ptasinska-Wnuk, D., Mucha, S.A., Lawnicka, H. et al. The effects of angiotensin peptides and angiotensin receptor antagonists on the cell growth and angiogenic activity of GH3 lactosomatotroph cells in vitro. Endocrine 42, 88–96 (2012). https://doi.org/10.1007/s12020-012-9659-2

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