Selective Estrogen Receptor Modulators and the Tissue-Selective Estrogen Complex: Analysis of Cell Type-Specific Effects Using In Vivo Imaging of a Reporter Mouse Model

Part of the Methods in Molecular Biology book series (MIMB, volume 1366)

Abstract

Selective estrogen receptor modulators (SERMs) are a class of compounds that act differentially on the estrogen receptor (ER) in various tissues with a mixed agonist/antagonistic activity (agonistic in some tissues while antagonist in others). This peculiarity represents a challenge for developing new hormone replacement therapies (HRTs) and highlights the need of new tools to evaluate the specific effects of a given SERM in different organs/tissues of an entire organism and with time.

Reporter mice represent invaluable tools in pharmacology to analyze specific signaling in physiological conditions and monitor the effects of drugs acting on these signals in a spatio-temporal dimension. Here, we describe an in vivo protocol to examine the effects of different SERMs on estrogen receptor activity by using the ERE-Luc reporter model, a mouse that reports ER transcriptional activity.

Key words

Reporter mice Estrogenreceptors Luciferase In vivo imaging Selective estrogen receptor modulators (SERMs) Longitudinal studies Clustering analysis 

Notes

Acknowledgements

To Prof. Adriana Maggi for helpful discussion. This work was supported by ERC-Advanced Grant 322977.

References

  1. 1.
    Dahlman-Wright K, Cavailles V, Fuqua SA et al (2004) International Union of Pharmacology. LXIV. Estrogen receptors. Pharmacol Rev 58(4):773–781CrossRefGoogle Scholar
  2. 2.
    Prossnitz ER, Barton M (2014) Estrogen biology: new insights into GPER function and clinical opportunities. Mol Cell Endocrinol 389(1-2):71–83CrossRefPubMedCentralGoogle Scholar
  3. 3.
    Ciana P, Di Luccio G, Belcridito S et al (2001) Engineering of a mouse for the in vivo profiling of estrogen receptor activity. Mol Endocrinol 15(7):1104–1113CrossRefGoogle Scholar
  4. 4.
    Mirkin S, Komm BS (2013) Tissue-selective estrogen complexes for postmenopausal women. Maturitas 76(3):213–220CrossRefGoogle Scholar
  5. 5.
    Della Torre S, Rando G, Meda C et al (2011) Amino acid-dependent activation of liver estrogen receptor alpha integrates metabolic and reproductive functions via IGF-1. Cell Metab 13(2):205–214CrossRefGoogle Scholar
  6. 6.
    Turgeon JL, McDonnell DP, Martin KA, Wise PM (2004) Hormone therapy: physiological complexity belies therapeutic simplicity. Science 304(5675):1269–1273CrossRefGoogle Scholar
  7. 7.
    Johnson KA (2006) Editorial: The SERM of my dreams. J Clin Endocrinol Metab 91(10):3754–3756CrossRefGoogle Scholar
  8. 8.
    Klotz DM, Hewitt SC, Ciana P et al (2002) Requirement of estrogen receptor-alpha in insulin-like growth factor-1 (IGF-1)-induced uterine responses and in vivo evidence for IGF-1/estrogen receptor cross-talk. J Biol Chem 277(10):8531–8537CrossRefGoogle Scholar
  9. 9.
    Peano BJ, Crabtree JS, Komm BS, Winneker RC, Harris HA (2009) Effects of various selective estrogen receptor modulators with or without conjugated estrogens on mouse mammary gland. Endocrinology 150(4):1897–1903CrossRefGoogle Scholar
  10. 10.
    Rando G, Horner D, Biserni A et al (2010) An innovative method to classify SERMs based on the dynamics of estrogen receptor transcriptional activity in living animals. Mol Endocrinol 24(4):735–744CrossRefPubMedCentralGoogle Scholar
  11. 11.
    Ciana P, Brena A, Sparaciari P, Bonetti E, Di Lorenzo D, Maggi A (2003) Estrogenic activities in rodent estrogen-free diets. Endocrinology 146(12):5144–5150CrossRefGoogle Scholar
  12. 12.
    Biserni A, Giannessi F, Sciarroni AF, Milazzo FM, Maggi A, Ciana P (2008) In vivo imaging reveals selective peroxisome proliferator activated receptor modulator activity of the synthetic ligand 3-(1-(4-chlorobenzyl)-3-t-butylthio-5-isopropylindol-2-yl)-2,2-dimethylpropanoic acid (MK-886). Mol Pharmacol 73(5):1434–1443CrossRefGoogle Scholar
  13. 13.
    Della Torre S, Biserni A, Rando G et al (2011) The conundrum of estrogen receptor oscillatory activity in the search for an appropriate hormone replacement therapy. Endocrinology 152(6):2256–2265CrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Center of Excellence on Neurodegenerative Diseases and Department of Pharmacological and Biomolecular SciencesUniversity of MilanMilanItaly

Personalised recommendations