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Key Event Title
|Level of Biological Organization|
|steroid hormone secreting cell|
Key Event Components
Key Event Overview
AOPs Including This Key Event
|AOP Name||Role of event in AOP||Point of Contact||Author Status||OECD Status|
|Hypothalamic estrogen receptors inhibition leading to ovarian cancer||KeyEvent||Cataia Ives (send email)||Under development: Not open for comment. Do not cite|
|Adult, reproductively mature||High|
Key Event Description
Biological state: The most predominant form of estrogens is 17β-estradiol (E2) which is sex hormone. In women having premenopausal it is mainly produced in the ovaries. For postmenopausal women, it E2 primarily is sythesized from testosterone by aromatase enzyme in extragonadal tissues(Simpson, 2003). Estradiol stimulates both cell growth and cholesterogenesis in the MCF-7 line (breast cancer cell line) (Cypriani et al., 1988). Cholesterol increases neuronal estradiol release into the medium through synapse formation(Fester et al., 2009).
Biological compartments: Estrogen is considered as the risk of developing cholesterol gallstones by enhancing the hepatic secretion of biliary cholesterol leading to an increase in cholesterol(Wang et al., 2009).
General role in biology: When estrogen levels decline, levels of low-density lipoprotein, the harmful kind of cholesterol increases, and levels of high-density lipoprotein, the positive kind of cholesterol decrease, due to which fat build up in the body and cholesterol in the arteries that causes heart attack and stroke(Fåhraeus, 1988; Wahl et al., 1983). Granulosa cells are the primary cell which provides the support and microenvironment required for the developing oocyte in the ovary(Sen and Hammes, 2010; Sterneck et al., 1997).
How It Is Measured or Detected
Radioimmunoassay (RIA) and analytical method based on mass spectroscopic are used for estrogen measurement present in serum (Smy and Straseski, 2018; Giese, 2003).
Domain of Applicability
It is applicable in reproduction system, cell growth and cell function
Adashi, E., & Hsueh, A. (1982). Estrogens augment the stimulation of ovarian aromatase activity by follicle-stimulating hormone in cultured rat granulosa cells. Journal of Biological Chemistry, 257(11), 6077-6083.
Cypriani, B., Tabacik, C., & Descomps, B. (1988). Effect of estradiol and antiestrogens on cholesterol biosynthesis in hormone-dependent and-independent breast cancer cell lines. Biochimica et Biophysica Acta (BBA)-Bioenergetics, 972(2), 167-178.
Darabi, M., Rabbani, M., Ani, M., Zarean, E., Panjehpour, M., & Movahedian, A. (2011). Increased leukocyte ABCA1 gene expression in post-menopausal women on hormone replacement therapy. Gynecological Endocrinology, 27(9), 701-705.
Fåhraeus, L. (1988). The effects of estradiol on blood lipids and lipoproteins in postmenopausal women. Obstetrics and gynecology, 72(5 Suppl), 18S-22S.
Fester, L., Zhou, L., Bütow, A., Huber, C., Von Lossow, R., Prange‐Kiel, J., et al. (2009). Cholesterol‐promoted synaptogenesis requires the conversion of cholesterol to estradiol in the hippocampus. Hippocampus, 19(8), 692-705.
Giese, R. W. (2003). Measurement of endogenous estrogens: analytical challenges and recent advances. Journal of Chromatography A, 1000(1), 401-412. doi:https://doi.org/10.1016/S0021-9673(03)00306-6.
Mao, Z., Li, J., & Zhang, W. (2018). Hormonal regulation of cholesterol homeostasis. Cholesterol-Good, Bad and the Heart.
Park, Y., Maizels, E. T., Feiger, Z. J., Alam, H., Peters, C. A., Woodruff, T. K., et al. (2005). Induction of cyclin D2 in rat granulosa cells requires FSH-dependent relief from FOXO1 repression coupled with positive signals from Smad. Journal of Biological Chemistry, 280(10), 9135-9148.
Sen, A., & Hammes, S. R. (2010). Granulosa cell-specific androgen receptors are critical regulators of ovarian development and function. Molecular endocrinology, 24(7), 1393-1403.
Simpson, E. R. (2003). Sources of estrogen and their importance. The Journal of steroid biochemistry and molecular biology, 86(3-5), 225-230.
Smy, L., & Straseski, J. A. (2018). Measuring estrogens in women, men, and children: Recent advances 2012-2017. Clin Biochem, 62, 11-23.
Sterneck, E., Tessarollo, L., & Johnson, P. F. (1997). An essential role for C/EBPβ in female reproduction. Genes & development, 11(17), 2153-2162.
Wahl, P., Walden, C., Knopp, R., Hoover, J., Wallace, R., Heiss, G., et al. (1983). Effect of estrogen/progestin potency on lipid/lipoprotein cholesterol. New England Journal of Medicine, 308(15), 862-867.
Wang, H. H., Liu, M., Clegg, D. J., Portincasa, P., & Wang, D. Q.-H. (2009). New insights into the molecular mechanisms underlying effects of estrogen on cholesterol gallstone formation. Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids, 1791(11), 1037-1047.