scholarly journals Obligatory role of hypothalamic neuroestradiol during the estrogen-induced LH surge in female ovariectomized rhesus monkeys

2017 ◽  
Vol 114 (52) ◽  
pp. 13804-13809 ◽  
Author(s):  
Brian P. Kenealy ◽  
Kim L. Keen ◽  
James P. Garcia ◽  
Lucille K. Kohlenberg ◽  
Ei Terasawa
Keyword(s):  
Positive Feedback ◽  
Rhesus Monkeys ◽  
Feedback Loop ◽  
Reproductive Function ◽  
Feedback Mechanism ◽  
Gonadotropin Releasing Hormone ◽  
Feedback Effects ◽  
17Β Estradiol ◽  
Positive Feedback Mechanism

Negative and positive feedback effects of ovarian 17β-estradiol (E2) regulating release of gonadotropin releasing hormone (GnRH) and luteinizing hormone (LH) are pivotal events in female reproductive function. While ovarian feedback on hypothalamo–pituitary function is a well-established concept, the present study shows that neuroestradiol, locally synthesized in the hypothalamus, is a part of estrogen’s positive feedback loop. In experiment 1, E2 benzoate-induced LH surges in ovariectomized female monkeys were severely attenuated by systemic administration of the aromatase inhibitor, letrozole. Aromatase is the enzyme responsible for synthesis of E2 from androgens. In experiment 2, using microdialysis, GnRH and kisspeptin surges induced by E2 benzoate were similarly attenuated by infusion of letrozole into the median eminence of the hypothalamus. Therefore, neuroestradiol is an integral part of the hypothalamic engagement in response to elevated circulating E2. Collectively, we will need to modify the concept of estrogen’s positive feedback mechanism.

scholarly journals Hedgehog signaling activates a positive feedback mechanism involving insulin-like growth factors to induce osteoblast differentiation

2015 ◽  
Vol 112 (15) ◽  
pp. 4678-4683 ◽  
Author(s):  
Yu Shi ◽  
Jianquan Chen ◽  
Courtney M. Karner ◽  
Fanxin Long
Keyword(s):  
Transcriptional Activation ◽  
Positive Feedback ◽  
Hedgehog Signaling ◽  
Osteoblast Differentiation ◽  
Akt Signaling ◽  
Feedback Mechanism ◽  
Genetic Deletion ◽  
Positive Feedback Mechanism ◽  
Igf Signaling

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.

Role of RFRP-3 in the Regulation of Kiss-1 Gene Expression in the AVPV Hypothalamic Cell Model mHypoA-50

2018 ◽  
Vol 26 (9) ◽  
pp. 1249-1255 ◽  
Author(s):  
Haruhiko Kanasaki ◽  
Tuvshintugs Tumurbaatar ◽  
Aki Oride ◽  
Zolzaya Tumurgan ◽  
Hiroe Okada ◽  
...  
Keyword(s):  
Gene Expression ◽  
Positive Feedback ◽  
Messenger Rna ◽  
Cell Model ◽  
Reproductive Function ◽  
Feedback Regulation ◽  
Gonadotropin Releasing Hormone ◽  
Releasing Hormone ◽  
Gonadotropin Inhibitory Hormone

Kisspeptin, encoded by the Kiss-1 gene, plays a crucial role in reproductive function by governing the hypothalamic–pituitary–gonadal axis. The recently established Kiss-1-expressing cell model mHypoA-50 displays characteristics of neuronal cells of the anteroventral periventricular (AVPV) region of the mouse hypothalamus. Because Kiss-1 gene expression in these cells is upregulated by estradiol (E2), mHypoA-50 cells are regarded as a valuable model for the study of Kiss-1-expressing neurons in the AVPV region. These cells also express RFamide-related peptide-3 (RFRP-3), a mammalian homolog of gonadotropin inhibitory hormone. The RFRP-3 expression in mHypoA-50 cells was increased by melatonin stimulation. In addition, E2 stimulation increased RFRP-3 expression in these cells. Treatment of the mHypoA-50 cells with exogenous RFRP-3 resulted in the increase of Kiss-1 messenger RNA expression within the cells; however, RFRP-3 did not modify gonadotropin-releasing hormone or kisspeptin-induced Kiss-1 gene expression in these cells. In addition, we found that RFRP-3 stimulation increased the expression of corticotropin-releasing hormone, which may be involved in E2-induced positive feedback in mHypoA-50 cells. Our observations suggest that RFRP-3 might be involved in positive feedback regulation by directly or indirectly increasing Kiss-1 gene expression.

scholarly journals A positive feedback mechanism ensures proper assembly of the functional inner centromere during mitosis in human cells

2018 ◽  
Vol 294 (5) ◽  
pp. 1437-1450 ◽  
Author(s):  
Cai Liang ◽  
Zhenlei Zhang ◽  
Qinfu Chen ◽  
Haiyan Yan ◽  
Miao Zhang ◽  
...  
Keyword(s):  
Positive Feedback ◽  
Histone H3 ◽  
Causal Link ◽  
Feedback Mechanism ◽  
Histone H2a ◽  
Defective Mutant ◽  
Chromosomal Passenger ◽  
Phosphatase 2A ◽  
Elevated Rate ◽  
Positive Feedback Mechanism

The inner centromere region of a mitotic chromosome critically regulates sister chromatid cohesion and kinetochore–microtubule attachments. However, the molecular mechanism underlying inner centromere assembly remains elusive. Here, using CRISPR/Cas9-based gene editing in HeLa cells, we disrupted the interaction of Shugoshin 1 (Sgo1) with histone H2A phosphorylated on Thr-120 (H2ApT120) to selectively release Sgo1 from mitotic centromeres. Interestingly, cells expressing the H2ApT120-binding defective mutant of Sgo1 have an elevated rate of chromosome missegregation accompanied by weakened centromeric cohesion and decreased centromere accumulation of the chromosomal passenger complex (CPC), an integral part of the inner centromere and a key player in the correction of erroneous kinetochore–microtubule attachments. When artificially tethered to centromeres, a Sgo1 mutant defective in binding protein phosphatase 2A (PP2A) is not able to support proper centromeric cohesion and CPC accumulation, indicating that the Sgo1–PP2A interaction is essential for the integrity of mitotic centromeres. We further provide evidence indicating that Sgo1 protects centromeric cohesin to create a binding site for the histone H3–associated protein kinase Haspin, which not only inhibits the cohesin release factor Wapl and thereby strengthens centromeric cohesion but also phosphorylates histone H3 at Thr-3 to position CPC at inner centromeres. Taken together, our findings reveal a positive feedback–based mechanism that ensures proper assembly of the functional inner centromere during mitosis. They further suggest a causal link between centromeric cohesion defects and chromosomal instability in cancer cells.

scholarly journals Autocrine signaling by an Aplysia neurotrophin forms a presynaptic positive feedback loop

2018 ◽  
Vol 115 (47) ◽  
pp. E11168-E11177 ◽  
Author(s):  
Iksung Jin ◽  
Hiroshi Udo ◽  
Russell Nicholls ◽  
Huixiang Zhu ◽  
Eric R. Kandel ◽  
...  
Keyword(s):  
Positive Feedback ◽  
Feedback Loop ◽  
Autocrine Signaling ◽  
Positive Feedback Loop ◽  
Short Term Plasticity ◽  
Extracellular Signaling ◽  
Presynaptic Protein ◽  
Long Term Facilitation

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.

scholarly journals Survival and Proliferation of Neural Progenitor–Derived Glioblastomas Under Hypoxic Stress is Controlled by a CXCL12/CXCR4 Autocrine-Positive Feedback Mechanism

2016 ◽  
Vol 23 (5) ◽  
pp. 1250-1262 ◽  
Author(s):  
Anda-Alexandra Calinescu ◽  
Viveka Nand Yadav ◽  
Erica Carballo ◽  
Padma Kadiyala ◽  
Dustin Tran ◽  
...  
Keyword(s):  
Positive Feedback ◽  
Neural Progenitor ◽  
Feedback Mechanism ◽  
Hypoxic Stress ◽  
Positive Feedback Mechanism

Inverter design with positive feedback field-effect transistors

2021 ◽  
Author(s):  
Changhoon Lee ◽  
Changwoo Han ◽  
Changhwan Shin
Keyword(s):  
Positive Feedback ◽  
Computer Aided Design ◽  
Field Effect ◽  
Field Effect Transistors ◽  
Feedback Mechanism ◽  
Silicon On Insulator ◽  
Logic Device ◽  
Device Applications ◽  
Positive Feedback Mechanism ◽  
Switching Devices

Abstract As the physical size of semiconductor devices continues to be aggressively scaled down, feedback field-effect transistors (FBFET) with a positive feedback mechanism among a few promising steep switching devices have received attention as next-generation switching devices. Conventional FBFETs have been studied to explore their device performance. However, this has been restricted to the case of single FBFET; basic circuit designs with FBFETs have not been investigated extensively. In this work, we propose an inverter circuit design with silicon-on-insulator (SOI) FBFETs; we verified this inverter design with mixed-mode technology computer-aided design simulation. The basic principles and mechanisms for designing FBFET inverter circuits are explained because their configuration is different from conventional inverters. In addition, the device parameters necessary to optimize circuit construction are introduced for logic device applications.

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