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Endocrine Abstracts (2007) 14 S10.4

1Inserm, Paris, France; 2University René Descartes Paris 5, Paris, France.


Experimental, clinical and/or epidemiological evidence points to a role for prolactin (PRL) in the promotion of benign and malignant tumors of the breast and the prostate. However, therapies reducing PRL levels (dopamine agonists) are currently not considered for the treatment of these pathologies. Dopamine agonists only target PRL secretion from the pituitary, while recent observations suggest that the involvement of autocrine PRL is perhaps even more relevant than circulating PRL in the growth of breast/prostate tumors. Therefore, alternative strategies targeting locally-produced PRL warrant investigation.

For many years, we have been working on the development of PRL receptor antagonists, by introducing mutations into appropriate regions of human PRL. Ideal antagonists should be high-affinity ligands that bind but do not activate the PRL receptor, leading to competitive inhibition of endogenous PRL actions. This presentation will describe the most representative antagonists we have designed, including their structure-function relationships based on cell and animal studies. We will also discuss the pros/cons of our lead compound, the pure antagonist del1-9-G129R-hPRL. Finally, we will address the potential therapeutic indications of this novel class of molecules.

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