Genetic Dissection of Estrogen Receptor Signaling In Vivo

Wintermantel, Tim; Elzer, Joachim; Herbison, Allan E.; Fritzemeier, Karl Heinrich; Schütz, Günther

doi:10.1007/2789_2006_015

Cited by 6 publications

(9 citation statements)

References 48 publications

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“…These data indicate daily PPT treatments most likely led to restoration of ERα negative feedback of the hypothalamic-pituitary axis and negated hemorrhagic cyst formation in these females [7, 28]. In addition, the αERKO neuron specific knockout does not spontaneously ovulate while the pituitary specific knock mouse does spontaneously form corpora lutea, pointing toward neuronal regulation as critical estrogen targets for permitting spontaneous ovulation [7, 20, 28]. The absence of hemorrhagic cysts in pituitary and neuron specific αERKO animals but present in the ENERKI and αERKO suggests that the presence of a functional estrogen receptor in the ovary may properly regulate vascularization by preventing hemorrhaging when an antral follicle is differentiating into the CL [7, 20, 23, 28].…”

Section: Discussionmentioning

confidence: 98%

“…Therefore, the drastic reduction in preputial gland weights to wild type levels in the daily PPT-treated mice may be due to lowered testosterone levels and lower LH [27]. These data indicate daily PPT treatments most likely led to restoration of ERα negative feedback of the hypothalamic-pituitary axis and negated hemorrhagic cyst formation in these females [7, 28]. In addition, the αERKO neuron specific knockout does not spontaneously ovulate while the pituitary specific knock mouse does spontaneously form corpora lutea, pointing toward neuronal regulation as critical estrogen targets for permitting spontaneous ovulation [7, 20, 28].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the αERKO neuron specific knockout does not spontaneously ovulate while the pituitary specific knock mouse does spontaneously form corpora lutea, pointing toward neuronal regulation as critical estrogen targets for permitting spontaneous ovulation [7, 20, 28]. The absence of hemorrhagic cysts in pituitary and neuron specific αERKO animals but present in the ENERKI and αERKO suggests that the presence of a functional estrogen receptor in the ovary may properly regulate vascularization by preventing hemorrhaging when an antral follicle is differentiating into the CL [7, 20, 23, 28]. Interestingly, NERKI mice have LH levels that are higher than wildtype mice but significantly lower than ERαKO mice, as well as hemorrhagic cysts but significantly fewer than ERαKO.…”

Section: Discussionmentioning

confidence: 99%

“…Although PPT treatments were able to reverse ovarian cysts formed in ENERKI females, the formation of corpora lutea was never detected in these animals. This inability to spontaneously form corpora lutea is likely due to the lack of positive feedback [7, 28]. Regulation of the intra-follicular feedback loop by PPT might have resulted in the reduction of theca cell hypertrophy in the ovary [30], but failed to initiate corpora lutea formation [31].…”

Section: Discussionmentioning

confidence: 99%

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Characterization of the ovarian and reproductive abnormalities in prepubertal and adult estrogen non-responsive estrogen receptor α knock-in (ENERKI) mice

et al. 2009

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Estrogen non-responsive estrogen receptor alpha (ERα) knock-in (ENERKI) mice have a mutation (glycine 525 to leucine, G525L) in the ligand-binding domain of ERα. The mutant ERα protein has a significantly lower affinity and response to endogenous estrogens, while not altering growth factor activated ligand-independent pathways. ENERKI females demonstrated signs of early follicle development as determined by a significant increase in antral follicle formation by 20 days of age. Adult ENERKI females were infertile, had hemorrhagic ovarian follicular cysts, and failed to develop corpora lutea in response to a superovulation regimen. These results illustrate the importance of ERα ligand-induced signaling for ovarian development and for estrogen feedback on the hypothalamus and pituitary. Although ERα ligand-induced signaling by endogenous estrogens is lost in ENERKI females, the ERα selective agonist propyl pyrazole triol (PPT), a synthetic nonsteroidal compound, is still able to activate G525L ERα in vivo to increase uterine weight. To test whether PPT could restore ligand-dependent receptor activation, ENERKI females were treated with PPT and evaluated for spontaneous ovulation, ovarian hemorrhagic cysts, and LH serum levels. Daily PPT treatments beginning on day 4 of life prevented formation of ovarian hemorrhagic cysts in adult ENERKI animals. In accordance with this result, preputial gland weight and LH levels were also lowered in these animals, indicating PPT treatments most likely led to restoration of ERα negative feedback of the hypothalamic-pituitary axis.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Characterization of the ovarian and reproductive abnormalities in prepubertal and adult estrogen non-responsive estrogen receptor α knock-in (ENERKI) mice

et al. 2009

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“…Oestrogen receptor (ER)α-expressing neurones mediate the positive [11] and negative [12] feedback effects of oestrogen onto the GnRH neurones. Given that the latter express ERβ rather than ERα [13], the neurotransmitter phenotype and anatomical location of the ERα-expressing neurones that communicate oestrogen-induced signals to GnRH neurones have been the subject of intense investigation over the past three decades [14,15].…”

Section: Introductionmentioning

confidence: 99%

Gonadotropin-Releasing Hormone Neurones Innervate Kisspeptin Neurones in the Female Mouse Brain

Kalló

Vida²,

Bardóczi³

et al. 2013

Neuroendocrinology

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Kisspeptin (KP) neurones in the rostral periventricular area of the third ventricle (RP3V) and arcuate nucleus (Arc) are important elements in the neuronal circuitry regulating gonadotropin-releasing hormone (GnRH) secretion. KP and co-synthesised neuropeptides/neurotransmitters act directly on GnRH perikarya and processes. GnRH neurones not only form the final output pathway regulating the reproductive functions of the anterior pituitary gland, but also provide neuronal input to sites within the hypothalamus. The current double-label immunohistochemical studies investigated whether GnRH-immunoreactive (IR) projections to the RP3V and/or Arc establish morphological connections with KP-IR neurones at these sites. To optimise visualisation of KP immunoreactivity in, respectively, the RP3V and Arc, ovariectomised (OVX) oestrogen-treated and OVX oil-treated female mice were studied. Confocal laser microscopic analysis of immunofluorescent specimens revealed GnRH-IR axon varicosities in apposition to approximately 25% of the KP-IR neurones in the RP3V and 50% of the KP-IR neurones in the Arc. At the ultrastructural level, GnRH-IR neurones were seen to establish asymmetric synaptic contacts, which usually reflect excitatory neurotransmission, with KP-IR neurones in both the RP3V and Arc. Together with previous data, these findings indicate reciprocal connectivity between both of the KP cell populations and the GnRH neuronal system. The functional significance of the GnRH-IR input to the two separate KP cell populations requires electrophysiological investigation.

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Proximate mechanisms driving circadian control of neuroendocrine function: Lessons from the young and old

Williams

Gibson

Wang

et al. 2009

Integrative and Comparative Biology

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Circadian rhythms impact a variety of behavioral and physiological functions contributing to longevity and successful reproduction. In their natural environments, individuals of a species are faced with a multitude of challenges and the coordination of internal processes and behavior with external pressures has been hypothesized to be an important target of natural selection. Several lines of evidence from cyanobacteria, Drosophila, and plants provide strong support for an important role of the circadian clock in survival and reproductive success. Similarly in mammals, disruptions in circadian function markedly impact reproduction and lifespan. The present review discusses research outlining the proximate and ultimate mechanisms responsible for the central and peripheral control of the reproductive axis. Because precise temporal coordination of the endocrine system is particularly crucial for reproduction by females, the present overview focuses on the role of circadian timing in this sex.

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Genetic Dissection of Estrogen Receptor Signaling In Vivo

Cited by 6 publications

References 48 publications

Characterization of the ovarian and reproductive abnormalities in prepubertal and adult estrogen non-responsive estrogen receptor α knock-in (ENERKI) mice

Characterization of the ovarian and reproductive abnormalities in prepubertal and adult estrogen non-responsive estrogen receptor α knock-in (ENERKI) mice

Gonadotropin-Releasing Hormone Neurones Innervate Kisspeptin Neurones in the Female Mouse Brain

Proximate mechanisms driving circadian control of neuroendocrine function: Lessons from the young and old

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