Hypothalamic Astrocytes and the Role of Neuroprogesterone in Estrogen Positive Feedback

Author(s):  
Paul Micevych ◽  
Margaret Mohr
2021 ◽  
Vol 22 (17) ◽  
pp. 9229
Author(s):  
Yoshihisa Uenoyama ◽  
Naoko Inoue ◽  
Sho Nakamura ◽  
Hiroko Tsukamura

Estrogen produced by ovarian follicles plays a key role in the central mechanisms controlling reproduction via regulation of gonadotropin-releasing hormone (GnRH) release by its negative and positive feedback actions in female mammals. It has been well accepted that estrogen receptor α (ERα) mediates both estrogen feedback actions, but precise targets had remained as a mystery for decades. Ever since the discovery of kisspeptin neurons as afferent ERα-expressing neurons to govern GnRH neurons, the mechanisms mediating estrogen feedback are gradually being unraveled. The present article overviews the role of kisspeptin neurons in the arcuate nucleus (ARC), which are considered to drive pulsatile GnRH/gonadotropin release and folliculogenesis, in mediating the estrogen negative feedback action, and the role of kisspeptin neurons located in the anteroventral periventricular nucleus-periventricular nucleus (AVPV-PeN), which are thought to drive GnRH/luteinizing hormone (LH) surge and consequent ovulation, in mediating the estrogen positive feedback action. This implication has been confirmed by the studies showing that estrogen-bound ERα down- and up-regulates kisspeptin gene (Kiss1) expression in the ARC and AVPV-PeN kisspeptin neurons, respectively. The article also provides the molecular and epigenetic mechanisms regulating Kiss1 expression in kisspeptin neurons by estrogen. Further, afferent ERα-expressing neurons that may regulate kisspeptin release are discussed.


2021 ◽  
Vol 75 (4) ◽  
Author(s):  
Hannah E. A. MacGregor ◽  
Aislinn Cottage ◽  
Christos C. Ioannou

Abstract Consistent inter-individual variation in behaviour within a population, widely referred to as personality variation, can be affected by environmental context. Feedbacks between an individual’s behaviour and state can strengthen (positive feedback) or weaken (negative feedback) individual differences when experiences such as predator encounters or winning contests are dependent on behavioural type. We examined the influence of foraging on individual-level consistency in refuge use (a measure of risk-taking, i.e. boldness) in three-spined sticklebacks, Gasterosteus aculeatus, and particularly whether changes in refuge use depended on boldness measured under control conditions. In the control treatment trials with no food, individuals were repeatable in refuge use across repeated trials, and this behavioural consistency did not differ between the start and end of these trials. In contrast, when food was available, individuals showed a higher degree of consistency in refuge use at the start of the trials versus controls but this consistency significantly reduced by the end of the trials. The effect of the opportunity to forage was dependent on behavioural type, with bolder fish varying more in their refuge use between the start and the end of the feeding trials than shyer fish, and boldness positively predicted the likelihood of feeding at the start but not at the end of the trials. This suggests a state-behaviour feedback, but there was no overall trend in how bolder individuals changed their behaviour. Our study shows that personality variation can be suppressed in foraging contexts and a potential but unpredictable role of feedbacks between state and behaviour. Significance statement In this experimental study, we examined how foraging influences consistency in risk-taking in individual three-spined sticklebacks. We show that bolder individuals become less consistent in their risk-taking behaviour than shyer individuals during foraging. Some bolder individuals reinforce their risk-taking behaviour, suggesting a positive feedback between state and behaviour, while others converge on the behaviour of shyer individuals, suggesting a negative feedback. In support of a role of satiation in driving negative feedback effects, we found that bolder individuals were more likely to feed at the start but not at the end of the trials. Overall, our findings suggest that foraging can influence personality variation in risk-taking behaviour; however, the role of feedbacks may be unpredictable.


Much has been said at the symposium about the pre-eminent role of the brain in the continuing emergence of man. Tobias has spoken of its explosive enlargement during the last 1 Ma, and how much of its enlargement in individual ontogeny is postnatal. We are born before our brains are fully grown and ‘wired up ’. During our long adolescence we build up internal models of the outside world and of the relations of parts of our bodies to it and to one another. Neurons that are present at birth spread their dendrites and project axons which acquire their myelin sheaths, and establish innumerable contacts with other neurons, over the years. New connections are formed; genetically endowed ones are stamped in or blanked off. People born without arms may grow up to use their toes in skills that are normally manual. Tobias, Darlington and others have stressed the enormous survival value of adaptive behaviour and the ‘positive feedback’ relation between biological and cultural evolution. The latter, the unique product of the unprecedentedly rapid biological evolution of big brains, advances on a time scale unknown to biological evolution.


2018 ◽  
Vol 115 (47) ◽  
pp. E11168-E11177 ◽  
Author(s):  
Iksung Jin ◽  
Hiroshi Udo ◽  
Russell Nicholls ◽  
Huixiang Zhu ◽  
Eric R. Kandel ◽  
...  

Whereas short-term plasticity is often initiated on one side of the synapse, long-term plasticity involves coordinated changes on both sides, implying extracellular signaling. We have investigated the possible signaling role of an Aplysia neurotrophin (ApNT) in facilitation induced by serotonin (5HT) at sensory-to-motor neuron synapses in culture. ApNT is an ortholog of mammalian BDNF, which has been reported to act as either an anterograde, retrograde, or autocrine signal, so that its pre- and postsynaptic sources and targets remain unclear. We now report that ApNT acts as a presynaptic autocrine signal that forms part of a positive feedback loop with ApTrk and PKA. That loop stimulates spontaneous transmitter release, which recruits postsynaptic mechanisms, and presynaptic protein synthesis during the transition from short- to intermediate-term facilitation and may also initiate gene regulation to trigger the transition to long-term facilitation. These results suggest that a presynaptic ApNT feedback loop plays several key roles during consolidation of learning-related synaptic plasticity.


2015 ◽  
Vol 112 (15) ◽  
pp. 4678-4683 ◽  
Author(s):  
Yu Shi ◽  
Jianquan Chen ◽  
Courtney M. Karner ◽  
Fanxin Long

Hedgehog (Hh) signaling is essential for osteoblast differentiation in the endochondral skeleton during embryogenesis. However, the molecular mechanism underlying the osteoblastogenic role of Hh is not completely understood. Here, we report that Hh markedly induces the expression of insulin-like growth factor 2 (Igf2) that activates the mTORC2-Akt signaling cascade during osteoblast differentiation. Igf2-Akt signaling, in turn, stabilizes full-length Gli2 through Serine 230, thus enhancing the output of transcriptional activation by Hh. Importantly, genetic deletion of the Igf signaling receptor Igf1r specifically in Hh-responding cells diminishes bone formation in the mouse embryo. Thus, Hh engages Igf signaling in a positive feedback mechanism to activate the osteogenic program.


2021 ◽  
pp. 002204262110414
Author(s):  
Robyn Vanherle ◽  
Kathleen Beullens ◽  
Hanneke Hendriks

Go-along interviews among adolescents ( N = 26, M age = 16.31, SD = .83) were conducted to examine how adolescents interpret alcohol posts in terms of appropriateness and how this, in turn, plays a role in adolescents’ reactions toward alcohol posts on public and private social media entries. The findings of this study, first, indicate that alcohol posts were classified as appropriate or inappropriate based on the amount of alcohol and the displayed behavior in the post. Second, most posts, including inappropriate ones, received positive or no feedback. Moreover, adolescents deliberately seemed to withhold negative feedback out of fear of being misjudged by peers. Still, negative reactions were expressed more quickly in safer off- and online environments (i.e., face-to-face conversation and online chat messages) because they were visible to close friends only. This is important in view of prevention as it unravels the interesting role of private environments in stimulating negative interpersonal communication.


Endocrinology ◽  
2013 ◽  
Vol 154 (1) ◽  
pp. 363-374 ◽  
Author(s):  
Raphael E. Szawka ◽  
Maristela O. Poletini ◽  
Cristiane M. Leite ◽  
Marcelo P. Bernuci ◽  
Bruna Kalil ◽  
...  

The role of norepinephrine (NE) in regulation of LH is still controversial. We investigated the role played by NE in the positive feedback of estradiol and progesterone. Ovarian-steroid control over NE release in the preoptic area (POA) was determined using microdialysis. Compared with ovariectomized (OVX) rats, estradiol-treated OVX (OVX+E) rats displayed lower release of NE in the morning but increased release coincident with the afternoon surge of LH. OVX rats treated with estradiol and progesterone (OVX+EP) exhibited markedly greater NE release than OVX+E rats, and amplification of the LH surge. The effect of NE on LH secretion was confirmed using reverse microdialysis. The LH surge and c-Fos expression in anteroventral periventricular nucleus neurons were significantly increased in OVX+E rats dialyzed with 100 nm NE in the POA. After Fluoro-Gold injection in the POA, c-Fos expression in Fluoro-Gold/tyrosine hydroxylase-immunoreactive neurons increased during the afternoon in the A2 of both OVX+E and OVX+EP rats, in the locus coeruleus (LC) of OVX+EP rats, but was unchanged in the A1. The selective lesion of LC terminals, by intracerebroventricular N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine, reduced the surge of LH in OVX+EP but not in OVX+E rats. Thus, estradiol and progesterone activate A2 and LC neurons, respectively, and this is associated with the increased release of NE in the POA and the magnitude of the LH surge. NE stimulates LH secretion, at least in part, through activation of anteroventral periventricular neurons. These findings contribute to elucidation of the role played by NE during the positive feedback of ovarian steroids.


2014 ◽  
Vol 4 (1) ◽  
Author(s):  
Andreea Munteanu ◽  
James Cotterell ◽  
Ricard V. Solé ◽  
James Sharpe

2014 ◽  
Vol 306 (11) ◽  
pp. C1089-C1100 ◽  
Author(s):  
Amit Bera ◽  
Falguni Das ◽  
Nandini Ghosh-Choudhury ◽  
Xiaonan Li ◽  
Sanjay Pal ◽  
...  

Platelet-derived growth factor BB and its receptor (PDGFRβ) play a pivotal role in the development of renal glomerular mesangial cells. Their roles in increased mesangial cell proliferation during mesangioproliferative glomerulonephritis have long been noted, but the operating logic of signaling mechanisms regulating these changes remains poorly understood. We examined the role of a recently identified MAPK, Erk5, in this process. PDGF increased the activating phosphorylation of Erk5 and tyrosine phosphorylation of proteins in a time-dependent manner. A pharmacologic inhibitor of Erk5, XMD8-92, abrogated PDGF-induced DNA synthesis and mesangial cell proliferation. Similarly, expression of dominant negative Erk5 or siRNAs against Erk5 blocked PDGF-stimulated DNA synthesis and proliferation. Inhibition of Erk5 attenuated expression of cyclin D1 mRNA and protein, resulting in suppression of CDK4-mediated phosphorylation of the tumor suppressor protein pRb. Expression of cyclin D1 or CDK4 prevented the dominant negative Erk5- or siErk5-mediated inhibition of DNA synthesis and mesangial cell proliferation induced by PDGF. We have previously shown that phosphatidylinositol 3-kinase (PI3-kinase) contributes to PDGF-induced proliferation of mesangial cells. Inhibition of PI3-kinase blocked PDGF-induced phosphorylation of Erk5. Since PI3-kinase acts through Akt, we determined the role of Erk5 on Akt phosphorylation. XMD8-92, dominant negative Erk5, and siErk5 inhibited phosphorylation of Akt by PDGF. Interestingly, we found inhibition of PDGF-induced Erk5 phosphorylation by a pharmacological inhibitor of Akt kinase and kinase dead Akt in mesangial cells. Thus our data unfold the presence of a positive feedback microcircuit between Erk5 and Akt downstream of PI3-kinase nodal point for PDGF-induced mesangial cell proliferation.


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