Inclusion of 17β-estradiol into liposome prevent the activation of membrane initiated signaling of ERalpha

Estrogens are implicated in many physiological and pathological processes thanks to their interaction with estrogen receptors (ERs). The estrogen receptor alpha (ERα) controls reproduction, normal mammary gland development and breast cancer progression. The activation of ERα by estrogens, especially by 17β-estradiol (E2), leads to two major pathways: (1) the genomic effects associated to the transcriptional activity of the ERα and (2) the MISS (Membrane Initiated Steroid Signaling) effects related to the induction of fast signaling pathways occurring when ERα is anchored to the plasma membrane.
Liposome are small non-toxic and biodegradable vectors widely studied for treatment of pathologies, like multiple sclerosis, Parkinson and Alzheimer disease and cancer. The encapsulation of several types of molecules (proteins, DNA and steroids), the protection of the activity and the improvement of the pharmacokinetic properties of these compounds represent the main advantages of liposome’s use. However, the impact of the encapsulation on molecular mechanisms is not yet established. As a proof of concept, we evaluate the impact of E2 inclusion into liposome (named POPC E2) in vitro and in vivo on ERα signaling pathway activation.