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Event: 1973

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Increased, estrogens

Short name
The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help
Increased, estrogens
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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help
Level of Biological Organization
Cellular

Cell term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help
Cell term
steroid hormone secreting cell

Organ term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help
Organ term
reproductive organ

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling).  The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor).  Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description.  To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons.  If a desired term does not exist, a new term request may be made via Term Requests.  Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help
Process Object Action
estrogen secretion Estrogen increased

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE. Clicking on the name of the AOP will bring you to the individual page for that AOP. More help
AOP Name Role of event in AOP Point of Contact Author Status OECD Status
Hypothalamic estrogen receptors inhibition leading to ovarian cancer KeyEvent Kalyan Gayen (send email) Under development: Not open for comment. Do not cite Under Development

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help
Term Scientific Term Evidence Link
human Homo sapiens High NCBI
rat Rattus norvegicus High NCBI
mice Mus sp. High NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help
Life stage Evidence
Adult, reproductively mature High

Sex Applicability

An indication of the the relevant sex for this KE. More help
Term Evidence
Female High
Male Moderate

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

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

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

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

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided).  More help

It is applicable in reproduction system, cell growth and cell function

References

List of the literature that was cited for this KE description. More help

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.