Progestins and the Mammary Gland: From Basic Science to by S. J. Han, F. J. DeMayo, B. W. O'Malley (auth.), O.

By S. J. Han, F. J. DeMayo, B. W. O'Malley (auth.), O. Conneely, C. Otto (eds.)

Progestins play a key function in reproductive endocrinology and as pharmaceutical medicines for birth control and in mixed hormone treatment. To additional our figuring out of progestin motion within the mammary gland, a world symposium, attended by way of major researchers from academia and undefined, was once held in Berlin, 21–23 March 2007. Genetic mouse versions helped to explain the function of progestins, either in common breast improvement and in disorder. Mechanistic molecular stories encouraged the layout of latest progestins with more desirable tissue selectivity. moreover, the medical influence of progesterone receptor agonists and antagonists for the prevention and remedy of breast melanoma was once discussed.

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In addition to estrogen, RU486 also triggers specific kinase signaling to regulate PR-mediated cellular process. For example, RU486-induced labor has been associated with an increase in the active phosphorylated form of extracellular signal-regulated kinase ERK2 to increase contractility in vitro (Li et al. 2004). Interestingly, different combinations of MAPKs were activated by RU486, depending upon the tissue examined (Han et al. 2007). For example, ERK1/2 and c-Jun N-terminal kinase (JNK) pathways were activated by chronic RU486 treatment in the uterus.

Progesterone Receptors in Mammary Gland Development . . . . . . . . . . . 3 PR-Dependent Molecular Signaling Pathways in the Mammary Gland . . . . . . . . . . 4 PR Isoform-Selective Contribution to Pregnancy-Associated Mammary Gland Morphogenesis References . . . . . . . . . . . . . . . . . 46 . . 47 . . 48 . . 50 . . 52 Abstract. The mammary gland undergoes extensive epithelial expansion and differentiation during pregnancy, leading ultimately to the development of functional milk-producing alveolar lobules.

J. W. O’Malley Fig. 1. PR BAC clone modification using bacterial recombination system. RPCI-23-422 I 15 PR BAC clone containing 62 kb of genomic DNA flanking 5 to exon 1 and 70 kb of genomic DNA flanking 3 to exon 8 of the PR gene is modified using bacterial recombination. The PR DNA binding domain (DBD) located from exon 2 to exon 3 in the PR gene was replaced with the Gal4 DBD generating the Gal4 version of PR (Gal4-PR). A second modification of this BAC clone included the incorporation of a reporter system consisting of five copies of UASG binding sites, a minimal promoter, and a hrGFP reporter gene.

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