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Rational Design of Competitive Prolactin/Growth Hormone Receptor Antagonists

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Journal of Mammary Gland Biology and Neoplasia Aims and scope Submit manuscript

Abstract

There is increasing evidence that prolactin (PRL) and growth hormone (GH) act as growth-promoters of breast tumors. Recent arguments have accumulated to suggest that when they are locally-produced within the mammary tissue, these hormones, acting by an autocrine-paracrine mechanism may have enhanced, or even specific functions compared to endocrine PRL and GH. Classical drugs blocking pituitary hormone production (dopamine and somatostatin analogs) are ineffective on extrapituitary expression of PRL/GH genes, therefore the undesirable effects of these locally-produced hormones remain a target of interest for alternative strategies. This has encouraged the development of competitive PRL and/or GH receptor antagonists, which involve engineered variants of natural receptor ligands (PRL or GH) aimed at blocking receptor activation rather than hormone production in peripheral tissues. This article overviews the rational design of this new class of molecules, their specific molecular features (receptor specificity, biological properties, etc.) and whenever available, the data that have been obtained in cell or animal models of breast cancer.

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Abbreviations

PRL:

prolactin

GH:

growth hormone

PRLR:

PRL receptor

GHR:

GH receptor

bp:

binding protein

h:

human

r:

rat

o:

ovine

PEG:

polyethylene glycol

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Acknowledgment

The authors are grateful to The Journal of Biological Chemistry and Endocrinology for the permission to insert some panels from two earlier publications by our group in Fig. 4 [54, 60].

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Authors and Affiliations

  1. Inserm, U845, Centre de Recherche “Croissance et signalisation”, Equipe “PRL, GH et tumeurs”, Paris, 75015, France

    Estelle Tallet, Vincent Rouet, Jean-Baptiste Jomain, Paul A. Kelly, Sophie Bernichtein & Vincent Goffin

  2. Faculté de Médecine, Université Paris Descartes, Paris, 75015, France

    Estelle Tallet, Vincent Rouet, Jean-Baptiste Jomain, Paul A. Kelly, Sophie Bernichtein & Vincent Goffin

  3. Faculté de Médecine Necker, INSERM U845, 156 rue de Vaugirard,, Paris, 75015, France

    Vincent Goffin

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  1. Estelle Tallet
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  2. Vincent Rouet
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Correspondence to Vincent Goffin.

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Tallet, E., Rouet, V., Jomain, JB. et al. Rational Design of Competitive Prolactin/Growth Hormone Receptor Antagonists. J Mammary Gland Biol Neoplasia 13, 105–117 (2008). https://doi.org/10.1007/s10911-008-9066-8

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