The mammary gland response to estradiol: Monotonic at the cellular level, non-monotonic at the tissue-level of organization?

The mammary gland response to estradiol: Monotonic at the cellular level, non-monotonic at the... The role of hormones in mammary gland development has been studied in detail using surgical and genetic models. These studies have indicated roles for estrogen in ductal elongation and terminal end bud formation. However, no comprehensive study has quantified how different doses of estrogen affect morphological parameters of mammary gland development. Additionally, comparisons between the estrogen-responsiveness of the mammary gland and uterus, the model organ for estrogen action are incomplete. In this study, immature mice were ovariectomized and implanted with osmotic pumps releasing one of eight doses of 17β-estradiol for 10 days. As expected from the classical uterotrophic assay, the uterus showed a monotonic dose–response curve for all measured endpoints. In contrast, the mammary gland showed a non-monotonic, inverted-U shaped response to estrogen with regard to morphometric parameters, and a monotonic response with regard to gene expression parameters. These results indicate that estrogen has opposing effects in mammary gland morphogenesis depending on estrogen dose, i.e. low to moderate doses induce terminal end bud formation and ductal elongation while higher doses inhibit these processes. This non-monotonic dose–response in the mammary gland may reflect complex interactions, where estrogen can act on multiple targets either as an agonist or antagonist. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Steroid Biochemistry and Molecular Biology Elsevier

The mammary gland response to estradiol: Monotonic at the cellular level, non-monotonic at the tissue-level of organization?

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Publisher
Elsevier
Copyright
Copyright © 2006 Elsevier Ltd
ISSN
0960-0760
eISSN
1879-1220
D.O.I.
10.1016/j.jsbmb.2006.06.028
Publisher site
See Article on Publisher Site

Abstract

The role of hormones in mammary gland development has been studied in detail using surgical and genetic models. These studies have indicated roles for estrogen in ductal elongation and terminal end bud formation. However, no comprehensive study has quantified how different doses of estrogen affect morphological parameters of mammary gland development. Additionally, comparisons between the estrogen-responsiveness of the mammary gland and uterus, the model organ for estrogen action are incomplete. In this study, immature mice were ovariectomized and implanted with osmotic pumps releasing one of eight doses of 17β-estradiol for 10 days. As expected from the classical uterotrophic assay, the uterus showed a monotonic dose–response curve for all measured endpoints. In contrast, the mammary gland showed a non-monotonic, inverted-U shaped response to estrogen with regard to morphometric parameters, and a monotonic response with regard to gene expression parameters. These results indicate that estrogen has opposing effects in mammary gland morphogenesis depending on estrogen dose, i.e. low to moderate doses induce terminal end bud formation and ductal elongation while higher doses inhibit these processes. This non-monotonic dose–response in the mammary gland may reflect complex interactions, where estrogen can act on multiple targets either as an agonist or antagonist.

Journal

The Journal of Steroid Biochemistry and Molecular BiologyElsevier

Published: Nov 1, 2006

References

  • Prolactin and mammary gland development
    Horseman, N.D.
  • Mammary gland development in prolactin receptor knockout mice
    Ormandy, C.J.; Binart, N.; Kelly, P.A.
  • Expression of progesterone receptor isoforms A and B is differentially regulated by estrogen in different breast cancer cell lines
    Vienonen, A.; Syvala, H.; Miettinen, S.; Tuohimaa, P.; Ylikomi, T.
  • Mammalian development in a changing environment: exposure to endocrine disruptors reveals the developmental plasticity of steroid-hormone target organs
    Markey, C.M.; Coombs, M.A.; Sonnenschein, C.; Soto, A.M.
  • Mammary gland development and tumorigenesis in estrogen receptor knockout mice
    Bocchinfuso, W.P.; Korach, K.S.
  • Identification of human estrogen-inducible transcripts that potentially mediate the apoptotic response in breast cancer
    Szelei, J.; Soto, A.M.; Geck, P.; Desronvil, M.; Prechtl, N.V.; Weill, B.C.; Sonnenschein, C.
  • Expression of novel genes linked to the androgen-induced, proliferative shutoff in prostate cancer cells
    Geck, P.; Szelei, J.; Jimenez, J.; Lin, T.M.; Sonnenschein, C.; Soto, A.M.
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    Friedmann, Y.; Daniel, C.W.

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