scholarly journals Glutamatergic Transmission to Hypothalamic Kisspeptin Neurons Is Differentially Regulated by Estradiol through Estrogen Receptor α in Adult Female Mice

2017 ◽  
Vol 38 (5) ◽  
pp. 1061-1072 ◽  
Author(s):  
Luhong Wang ◽  
Laura L. Burger ◽  
Megan L. Greenwald-Yarnell ◽  
Martin G. Myers ◽  
Suzanne M. Moenter
Endocrinology ◽  
2015 ◽  
Vol 156 (3) ◽  
pp. 1111-1120 ◽  
Author(s):  
Sharon L. Dubois ◽  
Maricedes Acosta-Martínez ◽  
Mary R. DeJoseph ◽  
Andrew Wolfe ◽  
Sally Radovick ◽  
...  

Abstract Hypothalamic kisspeptin (Kiss1) neurons express estrogen receptor α (ERα) and exert control over GnRH/LH secretion in female rodents. It has been proposed that estradiol (E2) activation of ERα in kisspeptin neurons in the arcuate nucleus (ARC) suppresses GnRH/LH secretion (negative feedback), whereas E2 activation of ERα in kisspeptin neurons in the anteroventral periventricular nucleus (AVPV) mediates the release of preovulatory GnRH/LH surges (positive feedback). To test these hypotheses, we generated mice bearing kisspeptin cell–specific deletion of ERα (KERαKO) and treated them with E2 regimens that evoke either negative or positive feedback actions on GnRH/LH secretion. Using negative feedback regimens, as expected, E2 effectively suppressed LH levels in ovariectomized (OVX) wild-type (WT) mice to the levels seen in ovary-intact mice. Surprisingly, however, despite the fact that E2 regulation of Kiss1 mRNA expression was abrogated in both the ARC and AVPV of KERαKO mice, E2 also effectively decreased LH levels in OVX KERαKO mice to the levels seen in ovary-intact mice. Conversely, using a positive feedback regimen, E2 stimulated LH surges in WT mice, but had no effect in KERαKO mice. These experiments clearly demonstrate that ERα in kisspeptin neurons is required for the positive, but not negative feedback actions of E2 on GnRH/LH secretion in adult female mice. It remains to be determined whether the failure of KERαKO mice to exhibit GnRH/LH surges reflects the role of ERα in the development of kisspeptin neurons, in the active signaling processes leading to the release of GnRH/LH surges, or both.


Author(s):  
Emmanuel Guivarc'h ◽  
Julie Favre ◽  
Anne‐Laure Guihot ◽  
Emilie Vessières ◽  
Linda Grimaud ◽  
...  

Background The cardiovascular protective effects of estrogens in premenopausal women depend mainly on estrogen receptor α (ERα). ERα activates nuclear gene transcription regulation and membrane‐initiated signaling. The latter plays a key role in estrogen‐dependent activation of endothelial NO synthase. The goal of the present work was to determine the respective roles of the 2 ERα activities in endothelial function and cardiac and kidney damage in young and old female mice with hypertension, which is a major risk factor in postmenopausal women. Methods and Results Five‐ and 18‐month‐old female mice lacking either ERα (ERα −/− ), the nuclear activating function AF2 of ERα (AF2°), or membrane‐located ERα (C451A) were treated with angiotensin II (0.5 mg/kg per day) for 1 month. Systolic blood pressure, left ventricle weight, vascular reactivity, and kidney function were then assessed. Angiotensin II increased systolic blood pressure, ventricle weight, and vascular contractility in ERα −/− and AF2° mice more than in wild‐type and C451A mice, independent of age. In both the aorta and mesenteric resistance arteries, angiotensin II and aging reduced endothelium‐dependent relaxation in all groups, but this effect was more pronounced in ERα −/− and AF2° than in the wild‐type and C451A mice. Kidney inflammation and oxidative stress, as well as blood urea and creatinine levels, were also more pronounced in old hypertensive ERα −/− and AF2° than in old hypertensive wild‐type and C451A mice. Conclusions The nuclear ERα‐AF2 dependent function attenuates angiotensin II–dependent hypertension and protects target organs in aging mice, whereas membrane ERα signaling does not seem to play a role.


1997 ◽  
Vol 32 (3) ◽  
pp. 176-183 ◽  
Author(s):  
Scott R Wersinger ◽  
Koen Sannen ◽  
Constanza Villalba ◽  
Dennis B Lubahn ◽  
Emilie F Rissman ◽  
...  

2021 ◽  
Vol 3 ◽  
Author(s):  
Igor Ferraz da Silva ◽  
Eduardo Merlo ◽  
Charles S. Costa ◽  
Jones B. Graceli ◽  
Lívia C. M. Rodrigues

Tributyltin (TBT) is a persistent organometallic pollutant widely used in several agricultural and industrial processes. TBT exposure is associated with various metabolic, reproductive, immune, and cardiovascular abnormalities. However, few studies have evaluated the effects of TBT on behavior. In the present study, we aimed to investigate whether TBT exposure results in oxidative, neuroendocrine, and behavioral alterations. TBT was administered to adult female mice (250, 500, or 750 ng/kg/day or veh for 14 days), and their recognition memory was assessed. We have also evaluated estrogen receptor (ER)α protein expression and oxidative stress (OS) in brain areas related to memory, as well as the correlation between them. A reduction in short- and long-term recognition memory (STM and LTM) performance, as well as in total exploration time was observed in TBT mice. Reduced ERα protein expression was observed in the prefrontal cortex (PFC) and hippocampus of TBT mice, while an increase in TBARS concentration was observed in the PFC of treated animals. Collectively, these data suggest that TBT exposure impairs recognition memory in female mice as a result of, at least in part, its toxicological effects on ERα expression and OS in specific brain areas related to memory.


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