A transcriptomics model of estrogen action in the ovine fetal hypothalamus: evidence for estrogenic effects of ICI 182,780

Feedback controls of estrogen in LHRH-1 neurons play a pivotal role in reproductive function. However, the mechanism of estrogen action in LHRH-1 neurons is still unclear. In the present study, the effect of estrogens on intracellular calcium ([Ca2+]i) oscillations in primate LHRH-1 neurons was examined. Application of 17β-estradiol (E2, 1 nm) for 10 min increased the frequency of [Ca2+]i oscillations within a few minutes. E2 also increased the frequency of [Ca2+]i synchronization among LHRH-1 neurons. Similar E2 effects on the frequency of [Ca2+]i oscillations were observed under the presence of tetrodotoxin, indicating that estrogen appears to cause direct action on LHRH-1 neurons. Moreover, application of a nuclear membrane-impermeable estrogen dendrimer conjugate, not control dendrimer, resulted in a robust increase in the frequencies of [Ca2+]i oscillations and synchronizations, indicating that effects estrogens on [Ca2+]i oscillations and their synchronizations do not require their entry into the cell nucleus. Exposure of cells to E2 in the presence of the estrogen receptor antagonist ICI 182,780 did not change the E2-induced increase in the frequency of [Ca2+]i oscillations or the E2-induced increase in the synchronization frequency. Collectively, estrogens induce rapid, direct stimulatory actions through receptors located in the cell membrane/cytoplasm of primate LHRH-1 neurons, and this action of estrogens is mediated by an ICI 182,780-insensitive mechanism yet to be identified.

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Elucidation of Underlying Mechanisms by Which Millettia macrophylla Benth Induces Its Estrogenic Activity

International Scholarly Research Notices ◽

10.1155/2014/763781 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 2

Author(s):

Stéphane Zingue ◽

Chantal Beatrice Magne Nde ◽

Colin Clyne ◽

Dieudonné Njamen

Keyword(s):

Estrogenic Activity ◽

Receptor Expression ◽

Ovariectomized Rats ◽

Human Embryonic Kidney Cells ◽

Ici 182,780 ◽

Beneficial Effects ◽

Estrogenic Effects ◽

Underlying Mechanisms

Millettia macrophylla is used traditionally to treat menopause related symptoms. This plant was shown to exhibit estrogenic effects in vitro on human embryonic kidney cells and in vivo on ovariectomized rats. The present study aimed at elucidating underlying mechanisms by which M. macrophylla induced its estrogenic effects. To accomplish our goal, kidney Hek293T cells transiently transfected with estrogen alpha or beta receptor expression plasmids were cotreated with a pure antiestrogen ICI 182,780 and the dichloromethane or methanol soluble fractions of M. macrophylla. To follow up, we cotreated ovariectomized rats with both extracts and ICI 182,780 for 3 days in the classical uterotrophic assay. Animals were then sacrificed and the uterine wet weight, total protein levels in uteri, uterine, and vaginal epithelial heights, and mammary gland were assessed. In vitro, the results suggested that the induction of the estrogenic activity by M. macrophylla is due to the binding of its secondary metabolites to ERα and ERβ. In vivo, the cotreatment of extracts and ICI 182,780 significantly abrogated the biological responses induced by the extracts alone. Taken together, these results indicate that the active principles of M. macrophylla induce their beneficial effects on menopausal symptoms by activating the ERs.

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83 The blockade of estrogen action by fulvestrant (ICI 182,780) prevents cholesterol gallstone formation in the mouse

Hepatology ◽

10.1016/s0270-9139(03)80126-x ◽

2003 ◽

Vol 38 ◽

pp. 195-195 ◽

Cited By ~ 2

Author(s):

H WANG ◽

N AFDHAL ◽

D WANG

Keyword(s):

Cholesterol Gallstone ◽

Gallstone Formation ◽

Estrogen Action ◽

Ici 182,780

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Mitochondria: Target organelles for estrogen action

Postępy Higieny i Medycyny Doświadczalnej ◽

10.5604/01.3001.0010.3828 ◽

2017 ◽

Vol 71 (1) ◽

pp. 0-0

Author(s):

Małgorzata Chmielewska ◽

Izabela Skibińska ◽

Małgorzata Kotwicka

Keyword(s):

Estrogen Receptor ◽

Biological Effects ◽

Mitochondrial Gene ◽

Estrogen Action ◽

Cell Organelles ◽

Exogenous Estrogen ◽

Estrogenic Effects ◽

Ligand Type ◽

Nongenomic Effects ◽

Membrane Signaling

Estrogens belong to a group of sex hormones, which have been shown to act in multidirectional way. Estrogenic effects are mediated by two types of intracellular receptors: estrogen receptor 1 (ESR1) and estrogen receptor 2 (ESR2). There are two basic mechanisms of estrogen action: 1) classical-genomic, in which the ligand-receptor complex acts as a transcriptional factor and 2) a nongenomic one, which is still not fully understood, but has been seen to lead to distinct biological effects, depending on tissue and ligand type. It is postulated that nongenomic effects may be associated with membrane signaling and the presence of classical nuclear receptors within the cell membrane. Estrogens act in a multidirectional way also within cell organelles. It is assumed that there is a mechanism which manages the migration of ESR into the mitochondrial membrane, wherein the exogenous estrogen affect the morphology of mitochondria. Estrogen, through its receptor, can directly modulate mitochondrial gene expression. Moreover, by regulating the level of reactive oxygen species, estrogens affect the biology of mitochondria. The considerations presented in this paper indicate the pleiotropic effects of estrogens, which represent a multidirectional pathway of signal transduction.

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