there is no gyno from estradiol, cos there is very low estradiol, not gyno from nandro alone cycle.
3 options:
1.-progestogenic action,2.-prolactin action or 3.-direct binding of nor-derivatives to the estrogen receptor.
1.-Science. 2006 Dec 1;314(5804):1467-70.
Prevention of Brca1-mediated mammary tumorigenesis in mice by a progesterone antagonist.
Poole AJ, Li Y, Kim Y, Lin SC, Lee WH, Lee EY.
Department of Biological Chemistry, University of California, Irvine, CA 92697-4037, USA.
Women with mutations in the breast cancer susceptibility gene BRCA1 are predisposed to breast and ovarian cancers. Why the BRCA1 protein suppresses tumor development specifically in ovarian hormone-sensitive tissues remains unclear. We demonstrate that mammary glands of nulliparous Brca1/p53-deficient mice accumulate lateral branches and undergo extensive alveologenesis, a phenotype that occurs only during pregnancy in wild-type mice. Progesterone receptors, but not estrogen receptors, are overexpressed in the mutant mammary epithelial cells because of a defect in their degradation by the proteasome pathway. Treatment of Brca1/p53-deficient mice with the progesterone antagonist mifepristone (RU 486) prevented mammary tumorigenesis. These findings reveal a tissue-specific function for the BRCA1 protein and raise the possibility that antiprogesterone treatment may be useful for breast cancer prevention in individuals with BRCA1 mutations.
http://cuttingedgemuscle.com/Forum/...=&threadid=1642
2.-Oncogene. 2003 Jul 24;22(30):4664-74.
Prolactin induces ERalpha-positive and ERalpha-negative mammary cancer in transgenic mice.
Rose-Hellekant TA, Arendt LM, Schroeder MD, Gilchrist K, Sandgren EP, Schuler LA.
Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, 2015 Linden Dr., Madison, WI 53706, USA.
The role of prolactin in human breast cancer has been controversial. However, it is now apparent that human mammary epithelial cells can synthesize prolactin endogenously, permitting autocrine/paracrine actions within the mammary gland that are independent of pituitary prolactin. To model this local mammary production of prolactin (PRL), we have generated mice that overexpress prolactin within mammary epithelial cells under the control of a hormonally nonresponsive promoter, neu-related lipocalin (NRL). In each of the two examined NRL-PRL transgenic mouse lineages, female virgin mice display mammary developmental abnormalities, mammary intraepithelial neoplasias, and invasive neoplasms. Prolactin increases proliferation in morphologically normal alveoli and ducts, as well as in lesions. The tumors are of varied histotype, but papillary adenocarcinomas and adenosquamous neoplasms predominate. Neoplasms can be separated into two populations: one is estrogen receptor alpha (ERalpha) positive (greater than 15% of the cells stain for ERalpha), and the other is ERalpha- (<3%). ERalpha expression does not correlate with tumor histotype, or proliferative or apoptotic indices. These studies provide a mouse model of hormonally dependent breast cancer, and, perhaps most strikingly, a model in which some neoplasms retain ERalpha, as occurs in the human disease.
http://cuttingedgemuscle.com/Forum/...&threadid=19119
3.-J Steroid Biochem Mol Biol. 2006 May;99(2-3):108-14.
Synthetic 19-nortestosterone derivatives as estrogen receptor alpha subtype-selective ligands induce similar receptor conformational changes and steroid receptor coactivator recruitment than natural estrogens.
García-Becerra R, Borja-Cacho E, Cooney AJ, Smith CL, Lemus AE, Pérez-Palacios G, Larrea F.
Department of Reproductive Biology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga No. 15, Mexico City 14000, Mexico.
The binding of estradiol (E(2)) to estrogen receptors (ER) is followed by conformational changes resulting in coactivator or corepressor recruitment that influences gene transcription. A series of synthetic A-ring reduced 19-nortestosterone-derived progestins has the capacity to selectively bind and activate transcription through the ERalpha. Herein, the molecular mechanisms involved in ER subtype-selective interactions of these compounds as assessed by their effects upon both ERalpha and ERbeta structural conformation and their ability to induce recruitment of steroid receptor coactivator-1 (SRC-1) to ERalpha were investigated. The results demonstrated that all synthetic A-ring 3beta,5alpha-tetrahydro-reduced derivatives of 19-nortestosterone induced an ERalpha trypsin digestion pattern similar to that seen with E(2), without effects upon ERbeta. In addition, these compounds had the ability to recruit SRC-1 to the ligand-binding domain of ERalpha similar to E(2). Our data indicate that A-ring 3beta,5alpha-tetrahydro-reduced 19-nortestosterone-derived progestins behave as selective ERalpha agonists with ligand-receptor structural and functional responses similar to those induced with natural E(2).
http://cuttingedgemuscle.com/Forum/...&threadid=17140
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Originally Posted by mooseman33
