scholarly journals Increase of Anteroventral Periventricular Kisspeptin Neurons and Generation of E2-Induced LH-Surge System in Male Rats Exposed Perinatally to Environmental Dose of Bisphenol-A

Endocrinology ◽  
2011 ◽  
Vol 152 (4) ◽  
pp. 1562-1571 ◽  
Author(s):  
Yinyang Bai ◽  
Fei Chang ◽  
Rong Zhou ◽  
Peng-Peng Jin ◽  
Hirokazu Matsumoto ◽  
...  
Keyword(s):  
Bisphenol A ◽  
G Protein ◽  
Female Rats ◽  
Male Rats ◽  
Perinatal Exposure ◽  
Dependent Manner ◽  
G Protein Coupled Receptor ◽  
Control Male ◽  
Lh Surge ◽  
G Protein Coupled

Abstract Perinatal exposure to environmental levels of bisphenol-A (BPA) impairs sexually dimorphic behaviors in rodents. Kisspeptin neurons in anteroventral periventricular nucleus (AVPV), which plays an important role in the activation of GnRH neurons and the initiation of LH-surge, have been suggested to be sexual dimorphism in rats. This study focused on exploring the influence of a perinatal exposure to an environmental dose of BPA on the development and maturation of male AVPV kisspeptin neurons and hypothalamus-pituitary-gonadal axis. Female rats were injected sc with 2 μg BPA/kg·d from gestation d 10 through lactation d 7. Anatomical and functional changes in AVPV kisspeptin neurons and hypothalamus-pituitary-gonadal axis were examined in prepubertal, pubertal, and adult male rats exposed perinatally to BPA (BPA-rats). Here, we show that in postnatal d (PND)30/50/90 BPA-rats, the number of AVPV kisspeptin-immunoreactive cells was persistently increased in comparison with age-matched control male rats. The number of GnRH-immunoreactive cells in PND30 BPA-rats declined approximately 40% compared with control male rats, whereas that in PND50/90 BPA-rats was increased in a G protein-coupled receptor 54-dependent manner. Estradiol could induce a stable LH-surge in PND90 BPA-rats and control female rats, which was sensitive to the G protein-coupled receptor 54 inhibitor. In PND30/50 BPA-rats, plasma level of LH was higher, but the level of testosterone was lower than control male rats. These findings provide evidence that perinatal exposure to an environmental dose of BPA causes a sustained increase in AVPV kisspeptin neurons in male rats, leading to the generation of estradiol-induced LH-surge system.

scholarly journals Activation of Intracellular Signaling Pathways by the Murine Cytomegalovirus G Protein-Coupled Receptor M33 Occurs via PLC-β/PKC-Dependent and -Independent Mechanisms

2009 ◽  
Vol 83 (16) ◽  
pp. 8141-8152 ◽  
Author(s):  
Joseph D. Sherrill ◽  
Melissa P. Stropes ◽  
Olivia D. Schneider ◽  
Diana E. Koch ◽  
Fabiola M. Bittencourt ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Protein Kinase ◽  
Signaling Pathways ◽  
G Protein ◽  
Intracellular Signaling ◽  
Murine Cytomegalovirus ◽  
Dependent Manner ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

ABSTRACT The presence of numerous G protein-coupled receptor (GPCR) homologs within the herpesvirus genomes suggests an essential role for these genes in viral replication in the infected host. Such is the case for murine cytomegalovirus (MCMV), where deletion of the M33 GPCR or replacement of M33 with a signaling defective mutant has been shown to severely attenuate replication in vivo. In the present study we utilized a genetically altered version of M33 (termed R131A) in combination with pharmacological inhibitors to further characterize the mechanisms by which M33 activates downstream signaling pathways. This R131A mutant of M33 fails to support salivary gland replication in vivo and, as such, is an important tool that can be used to examine the signaling activities of M33. We show that M33 stimulates the transcription factor CREB via heterotrimeric Gq/11 proteins and not through promiscuous coupling of M33 to the Gs pathway. Using inhibitors of signaling molecules downstream of Gq/11, we demonstrate that M33 stimulates CREB transcriptional activity in a phospholipase C-β and protein kinase C (PKC)-dependent manner. Finally, utilizing wild-type and R131A versions of M33, we show that M33-mediated activation of other signaling nodes, including the mitogen-activated protein kinase family member p38α and transcription factor NF-κB, occurs in the absence of Gq/11 and PKC signaling. The results from the present study indicate that M33 utilizes multiple mechanisms to modulate intracellular signaling cascades and suggest that signaling through PLC-β and PKC plays a central role in MCMV pathogenesis in vivo.

scholarly journals Activation of G-protein Coupled Estradiol Receptor 1 in the Dorsolateral Striatum Enhances Motivation for Cocaine and Drug-Induced Reinstatement in Female Rats

2021 ◽  
Author(s):  
Jacqueline Quigley ◽  
Molly K. Logsdon ◽  
Brianna C. Graham ◽  
Kendra G. Beaudoin ◽  
Jill B Becker
Keyword(s):  
G Protein ◽  
Progressive Ratio ◽  
Female Rats ◽  
Male Rats ◽  
Ratio Schedule ◽  
Drug Induced ◽  
Drug Seeking ◽  
Schedule Of Reinforcement ◽  
Estradiol Receptor ◽  
G Protein Coupled

Abstract BackgroundEstradiol potentiates drug-taking behaviors, including motivation to self-administer cocaine and reinstatement of drug-seeking after extinction in females, but not males. The dorsolateral stratum (DLS) is a region of the brain implicated in mediating drug-seeking behaviors and more specifically, is a target brain area to study how estradiol regulates these behaviors. The estradiol receptors α, β, and G-protein coupled estradiol receptor 1 (GPER1) are all present in the DLS. In this study the effects of activating GPER1 in the DLS on drug-seeking are investigated. MethodsGonad-intact male and female rats were trained to self-administer cocaine (0.4 mg/kg/inf) on an fixed-ratio 1 schedule of reinforcement. For four weeks, animals underwent testing on a progressive ratio schedule of reinforcement to determine their motivation to attain cocaine. Halfway through progressive ratio testing, a selective agonist targeting GPER1 (G1) was administered intra-DLS to determine the contribution of GPER1 activation on motivation for cocaine. The effects of intra-GPER1 activation on drug-induced reinstatement after extinction was subsequently determined. ResultsActivation of GPER1, via G1 administration intra-DLS potentiated females’ motivation to self-administer cocaine. There was no effect of prior G1 treatment on extinction of cocaine-taking in females, however, G1 treatment resulted in greater drug-induced reinstatement (10 mg/kg cocaine, i.p.). There were no effects of intra-DLS GPER1 activation observed on motivation for cocaine or cocaine-induced reinstatement of responding in males. Conclusions These results support the conclusion that activation of GPER1 in the DLS enhances cocaine seeking behaviors for female, but not male rats.

scholarly journals Activation of GPR39 With TC-G 1008 Attenuates Neuroinflammation Via SIRT1/PGC-1α/Nrf2 Pathway Post Neonatal Hypoxic-ischemic Injury in Rats

2021 ◽  
Author(s):  
Shucai Xie ◽  
Xili Jiang ◽  
Desislava Met Doycheva ◽  
Hui Shi ◽  
Peng Jin ◽  
...  
Keyword(s):  
G Protein ◽  
Sirtuin 1 ◽  
Neonatal Rat ◽  
Neurological Deficits ◽  
Dependent Manner ◽  
G Protein Coupled Receptor ◽  
Short Term ◽  
Nrf2 Pathway ◽  
G Protein Coupled

Abstract Background: Hypoxic-ischemic encephalopathy (HIE) is a severe anoxic brain injury that leads to premature mortality or long-term disabilities in infants. Neuroinflammation is a vital contributor to the pathogenic cascade post HIE and a mediator to secondary neuronal death. As a plasma membrane G-protein coupled receptor, GPR39, exhibits anti-inflammatory activity in several diseases. This study aimed to explore the neuroprotective function of GPR39 through inhibition of inflammation post hypoxic-ischemic (HI) injury and to elaborate the contribution of sirtuin 1(SIRT1)/ peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α)/ nuclear factor, erythroid 2 like 2(Nrf2) in G protein-coupled receptor 39 (GPR39)-mediated protection.Methods: A total of 206 10-day old Sprague Dawley rat pups were subjected to HIE or sham surgery. TC-G 1008 was administered intranasally at 1h, 25h, 49h, and 73h post HIE induction. SIRT1 inhibitor EX527, GPR39 CRISPR, and PGC-1α CRISPR were administered to elucidate the underlying mechanisms. Brain infarct area, short-term and long-term neurobehavioral tests, Nissl staining, western blot, and immunofluorescence staining were performed post HIE.Results: The expression of GPR39 and pathway-related proteins, SIRT1、PGC-1α and Nrf2 were increased in a time-dependent manner, peaking at 24 h or 48h post HIE. Intranasal administration of TC-G 1008 reduced the percent infarcted area and improved short-term and long-term neurological deficits. Moreover, TC-G 1008 treatment significantly increased the expression of SIRT1, PGC-1α, Nrf2, IL-6, IL-1β, and TNF-α. GPR39 CRISPR EX527 and PGC-1α CRISPR abolished GPR39’s neuroprotective effects post HIE.Conclusions:TC-G 1008 attenuated neuroinflammation in part via the SIRT1/PGC-1α/Nrf2 pathway in a neonatal rat model of HIE. TC-G 1008 may be a novel therapeutic target for treatment post neonatal HIE injury.

scholarly journals Gpr1, a Putative G-Protein-Coupled Receptor, Regulates Morphogenesis and Hypha Formation in the Pathogenic Fungus Candida albicans

2004 ◽  
Vol 3 (4) ◽  
pp. 919-931 ◽  
Author(s):  
Takuya Miwa ◽  
Yukinobu Takagi ◽  
Makiko Shinozaki ◽  
Cheol-Won Yun ◽  
Wiley A. Schell ◽  
...  
Keyword(s):  
Candida Albicans ◽  
G Protein ◽  
Pathogenic Fungus ◽  
Glucose Sensing ◽  
Dependent Manner ◽  
G Protein Coupled Receptor ◽  
Epistasis Analysis ◽  
Hypha Formation ◽  
Mutant Strains ◽  
G Protein Coupled

ABSTRACT In response to various extracellular signals, the morphology of the human fungal pathogen Candida albicans switches from yeast to hypha form. Here, we report that GPR1 encoding a putative G-protein-coupled receptor and GPA2 encoding a Gα subunit are required for hypha formation and morphogenesis in C. albicans. Mutants lacking Gpr1 (gpr1/gpr1) or Gpa2 (gpa2/gpa2) are defective in hypha formation and morphogenesis on solid hypha-inducing media. These phenotypic defects in solid cultures are suppressed by exogenously added dibutyryl-cyclic AMP (dibutyryl-cAMP). Biochemical studies also reveal that GPR1 and GPA2 are required for a glucose-dependent increase in cellular cAMP. An epistasis analysis indicates that Gpr1 functions upstream of Gpa2 in the same signaling pathway, and a two-hybrid assay reveals that the carboxyl-terminal tail of Gpr1 interacts with Gpa2. Moreover, expression levels of HWP1 and ECE1, which are cAMP-dependent hypha-specific genes, are reduced in both mutant strains. These findings support a model that Gpr1, as well as Gpa2, regulates hypha formation and morphogenesis in a cAMP-dependent manner. In contrast, GPR1 and GPA2 are not required for hypha formation in liquid fetal bovine serum (FBS) medium. Furthermore, the gpr1 and the gpa2 mutant strains are fully virulent in a mouse infection. These findings suggest that Gpr1 and Gpa2 are involved in the glucose-sensing machinery that regulates morphogenesis and hypha formation in solid media via a cAMP-dependent mechanism, but they are not required for hypha formation in liquid medium or during invasive candidiasis.

scholarly journals Hypothalamic action of phoenixin to control reproductive hormone secretion in females: importance of the orphan G protein-coupled receptor Gpr173

2016 ◽  
Vol 311 (3) ◽  
pp. R489-R496 ◽  
Author(s):  
Lauren M. Stein ◽  
Chloe W. Tullock ◽  
Stacy K. Mathews ◽  
David Garcia-Galiano ◽  
Carol F. Elias ◽  
...  
Keyword(s):  
G Protein ◽  
Hormone Secretion ◽  
Reproductive Function ◽  
Female Rats ◽  
Pituitary Cells ◽  
G Protein Coupled Receptor ◽  
Hpg Axis ◽  
Ovarian Cyclicity ◽  
Lh Secretion ◽  
G Protein Coupled

Sexual maturation and maintenance of reproductive function are regulated by neurohormonal communication between the hypothalamus, pituitary, and gonads (referred to as the HPG axis). Phoenixin (PNX) is a newly identified, endogenous peptide abundantly produced in the hypothalamus and shown to be an important mediator of ovarian cyclicity. However, the underlying mechanisms by which phoenixin functions within the HPG axis are unknown. Previous in vitro studies demonstrated a direct action of PNX on gonadotrophs to potentiate gonadotrophin-releasing hormone (GnRH) induced luteinizing hormone (LH) secretion. Therefore, we hypothesized that centrally derived phoenixin regulates the preovulatory LH surge required for ovarian cyclicity. We observed a significant dose-related increase in the level of plasma LH in diestrous, female rats that were given an intracerebroventricular injection of PNX compared with vehicle-treated controls. While this suggests that even under low-estrogen conditions, PNX acts centrally to stimulate the HPG axis, further characterization is contingent on the elucidation of its cognate receptor. Using the “deductive ligand receptor matching strategy,” we identified the orphan G protein-coupled receptor, Gpr173, as our top candidate. In cultured pituitary cells, siRNA-targeted compromise of Gpr173 abrogated PNX's action to potentiate GnRH-stimulated LH secretion. In addition, siRNA-mediated knockdown of endogenous Gpr173, which localized to several hypothalamic sites related to reproductive function, not only significantly extended the estrous cycle but also prevented the PNX-induced LH secretion in diestrous, female rats. These studies are the first to demonstrate a functional relationship between PNX and Gpr173 in reproductive physiology and identify a potential therapeutic target for ovulatory dysfunction.

Involvement of activating ERK1/2 through G protein coupled receptor 30 and estrogen receptor α/β in low doses of bisphenol A promoting growth of Sertoli TM4 cells

2014 ◽  
Vol 226 (1) ◽  
pp. 81-89 ◽  
Author(s):  
Li-Chen Ge ◽  
Zhuo-Jia Chen ◽  
Han-Yan Liu ◽  
Kun-Shui Zhang ◽  
Hao Liu ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Bisphenol A ◽  
G Protein ◽  
Estrogen Receptor Α ◽  
Low Doses ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled
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