Abstract
Estrogens are the subject of intensive researches aiming to elucidate their mechanism of action on the various tissues they target and especially on mammary gland and breast cancer. The use of ready-to-use slow releasing devices to administer steroids, especially estrogens, to small experimental animals remains the method of choice in terms of animal well-being and of safety for both the researcher and the animal. In this study, we evaluated and compared, in vitro and in vivo, the release kinetic of estradiol (E2) over sixty days from two different slow-releasing systems: the matrix pellet (MP) and the reservoir implant (RI). We compared the impact of these systems in three E2-sensitive mouse models : mammary gland development, human MCF7 adenocarcinoma xenograft and mouse melanoma progression. The real amount of E2 that is released from both types of devices could differ from manufacturer specifications due to inadequate release for MP and initial burst effect for RI. Compared to MP, the interindividual variability was reduced with RI thanks to a superior control of the E2 release. Depending on the dose-dependent sensitivity of the physiological or pathological readout studied, this could lead to an improvement of the statistical power of in vivo experiments and thus to a reduction of the required animal number. Altogether, our data draw attention on the importance to adequately select the slow-releasing device that is the most appropriated to a specific experiment to better fulfill the 3Rs rule (Replacement, Reduction, Refinement) related to animal welfare and protection.
Highlights
Estrogens play a key role in sexual development and reproduction
The use of ready-to-use commercial slow releasing devices to administer steroids, especially estrogens, to small experimental animals remains the method of choice in terms of animal well-being and of safety for both the researcher and the animal
We evaluated and compared the release kinetic of E2 over sixty days from two different slowreleasing systems matrix pellet (MP) and reservoir implant (RI)
Summary
Estrogens play a key role in sexual development and reproduction. They are implicated in a large number of other physiological and pathological events including cancer progression [1,2,3,4,5,6,7,8]. The elucidation of the molecular mechanisms sustaining steroid action on the various tissues they target and especially on mammary gland and breast cancer is the subject of intensive researches. The use of animal models, especially rodents, is crucial for elucidating the biological effects and molecular mechanisms of 17β-estradiol (E2) and SERMs. A substantial part of the experimental animal studies have been conducted in ovariectomized rodents receiving exogenous E2, to avoid the cyclic influence of ovarian hormones [11,12,13,14,15,16]. There is a lack of consensus about the optimal means to reach appropriate E2 plasma concentrations and maintain long-term steady state E2 plasma level
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