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Impaired mouse mammary gland growth and development is mediated by melatonin and its MT1 G protein‐coupled receptor via repression of ERα, Akt1, and Stat5
Author(s) -
Xiang Shulin,
Mao Lulu,
Yuan Lin,
Duplessis Tamika,
Jones Frank,
Hoyle Gary W.,
Frasch Tripp,
Dauchy Robert,
Blask David E.,
Chakravarty Geetika,
Hill Steven M.
Publication year - 2012
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2012.01000.x
Subject(s) - mammary gland , medicine , endocrinology , biology , lactation , melatonin , estrogen receptor , genetically modified mouse , transgene , receptor , progesterone receptor , pregnancy , breast cancer , biochemistry , genetics , cancer , gene
To determine whether melatonin, via its MT 1 G protein‐coupled receptor, impacts mouse mammary gland development, we generated a mouse mammary tumor virus (MMTV)‐MT1‐Flag‐mammary gland over‐expressing (MT1‐mOE) transgenic mouse. Increased expression of the MT 1 ‐Flag transgene was observed in the mammary glands of pubescent MT1‐mOE transgenic female mice, with further significant increases during pregnancy and lactation. Mammary gland whole mounts from MT1‐mOE mice showed significant reductions in ductal growth, ductal branching, and terminal end bud formation. Elevated MT 1 receptor expression in pregnant and lactating female MT1‐mOE mice was associated with reduced lobulo‐alveolar development, inhibition of mammary epithelial cell proliferation, and significant reductions in body weights of suckling pups. Elevated MT 1 expression in pregnant and lactating MT1‐mOE mice correlated with reduced mammary gland expression of Akt1, phospho‐Stat5, Wnt4, estrogen receptor alpha, progesterone receptors A and B, and milk proteins β‐casein and whey acidic protein. Estrogen‐ and progesterone‐stimulated mammary gland development was repressed by elevated MT 1 receptor expression and exogenous melatonin administration. These studies demonstrate that the MT 1 melatonin receptor and its ligand melatonin play an important regulatory role in mammary gland development and lactation in mice through both growth suppression and alteration of developmental paradigms.