scholarly journals Gonadotropin-Releasing Hormone in Regulation of Thymic Development in Rats: Profile of Thymic Cytokines

2019 ◽  
Vol 20 (16) ◽  
pp. 4033 ◽  
Author(s):  
Victoria I. Melnikova ◽  
Nadezhda V. Lifantseva ◽  
Svetlana N. Voronova ◽  
Liudmila A. Zakharova
Keyword(s):  
Ex Vivo ◽  
Interferon Γ ◽  
Gonadotropin Releasing Hormone ◽  
Recent Experimental Data ◽  
Mrna Levels ◽  
Fetal Thymus ◽  
Releasing Hormone ◽  
Thymus Development ◽  
Ex Vivo Culture ◽  
The Impact

An increasing body of recent experimental data confirms the impact of neurohormones on fetal development and function of different body systems. The synthesis of many neurohormones starts in fetal tissues before the hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal systems are formed, and their high levels are detected in the bloodstream. Here, we studied the role of gonadotropin-releasing hormone (GnRH) in rat thymus development and tried to reveal possible mechanisms underlying the GnRH effects in early development. Western blotting and reverse transcription-polymerase chain reaction allowed us to identify receptor for GnRH in the fetal thymus with peak expression on embryonic days 17–18 (ED17–18). Blocking the receptors in utero on ED17 by a GnRH antagonist suppressed the concanavalin A-induced proliferative response of T cells in adults. GnRH (10−7 M) increased mRNA expression of interleukin (IL)-4, IL-10, IL-1β, interferon γ (IFNγ), and tumor necrosis factor α (TNFα) in the thymus of 18-day fetuses after an ex vivo culture for 24 h. The increased mRNA levels of the cytokines in the thymus were accompanied by increased numbers of CD4+ T helpers. Overall, the data obtained confirm the regulatory or morphogenetic effect of GnRH on fetal thymus development mediated by synthesis of thymic cytokines.

scholarly journals Ex vivo culture of Fancc-/- stem/progenitor cells predisposes cells to undergo apoptosis, and surviving stem/progenitor cells display cytogenetic abnormalities and an increased risk of malignancy

Blood ◽  
2005 ◽  
Vol 105 (9) ◽  
pp. 3465-3471 ◽  
Author(s):  
Xiaxin Li ◽  
Michelle M. Le Beau ◽  
Samantha Ciccone ◽  
Feng-Chun Yang ◽  
Brian Freie ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Genome Stability ◽  
Bone Marrow Cells ◽  
Ex Vivo ◽  
Acquired Resistance ◽  
Intrinsic Defects ◽  
Cytogenetic Abnormalities ◽  
Increased Risk ◽  
Ex Vivo Culture ◽  
The Impact

AbstractCurrent strategies for genetic therapy using Moloney retroviruses require ex vivo manipulation of hematopoietic cells to facilitate stable integration of the transgene. While many studies have evaluated the impact of ex vivo culture on normal murine and human stem/progenitor cells, the cellular consequences of ex vivo manipulation of stem cells with intrinsic defects in genome stability are incompletely understood. Here we show that ex vivo culture of Fancc-/- bone marrow cells results in a time-dependent increase in apoptosis of primitive Fancc-/- progenitor cells in conditions that promote the proliferation of wild-type stem/progenitor cells. Further, recipients reconstituted with the surviving Fancc-/- cells have a high incidence of cytogenetic abnormalities and myeloid malignancies that are associated with an acquired resistance to tumor necrosis factor α (TNF-α). Collectively, these data indicate that the intrinsic defects in the genomic stability of Fancc-/- stem/progenitor cells provide a selective pressure for cells that are resistant to apoptosis and have a propensity for the evolution to clonal hematopoiesis and malignancy. These studies could have implications for the design of genetic therapies for treatment of Fanconi anemia and potentially other genetic diseases with intrinsic defects in genome stability.

scholarly journals Effect of Inflammation on Female Gonadotropin-Releasing Hormone (GnRH) Neurons: Mechanisms and Consequences

2020 ◽  
Vol 21 (2) ◽  
pp. 529 ◽  
Author(s):  
Klaudia Barabás ◽  
Edina Szabó-Meleg ◽  
István M. Ábrahám
Keyword(s):  
Suppressive Effect ◽  
Gonadotropin Releasing Hormone ◽  
Releasing Hormone ◽  
Inflammatory Signals ◽  
Cholinergic Pathway ◽  
Gnrh Neurons ◽  
Functional Consequences ◽  
Anti Inflammatory ◽  
The Impact

Inflammation has a well-known suppressive effect on fertility. The function of gonadotropin-releasing hormone (GnRH) neurons, the central regulator of fertility is substantially altered during inflammation in females. In our review we discuss the latest results on how the function of GnRH neurons is modified by inflammation in females. We first address the various effects of inflammation on GnRH neurons and their functional consequences. Second, we survey the possible mechanisms underlying the inflammation-induced actions on GnRH neurons. The role of several factors will be discerned in transmitting inflammatory signals to the GnRH neurons: cytokines, kisspeptin, RFamide-related peptides, estradiol and the anti-inflammatory cholinergic pathway. Since aging and obesity are both characterized by reproductive decline our review also focuses on the mechanisms and pathophysiological consequences of the impact of inflammation on GnRH neurons in aging and obesity.

217 PRODUCTION OF A GONADOTROPIN-RELEASING HORMONE II RECEPTOR KNOCKDOWN SWINE LINE

2014 ◽  
Vol 26 (1) ◽  
pp. 222
Author(s):  
A. T. Desaulniers ◽  
R. A. Cederberg ◽  
G. A. Mills ◽  
B. R. White
Keyword(s):  
Integration Site ◽  
Gonadotropin Releasing Hormone ◽  
Injection System ◽  
Multiple Cloning Site ◽  
Sequencing Analysis ◽  
Mrna Levels ◽  
Green Fluorescence ◽  
Releasing Hormone ◽  
Transgene Integration ◽  
Shrna Sequence

Unlike the native form of gonadotropin-releasing hormone (GnRH-I), the second isoform of GnRH (GnRH-II) is highly conserved throughout evolution and is ubiquitously expressed. The pig represents one of the few species possessing coding sequence for a functional receptor specific to GnRH-II (GnRHR-II). Binding of GnRH-II to its receptor has been linked to regulation of cell proliferation, feed intake, and the interaction between energy balance and reproductive behaviour. The objective of this study was to develop a porcine model with reduced levels of endogenous GnRHR-II to examine the biological role of this G-protein coupled receptor. Previously, we produced lentiviral particles from a vector overexpressing both small hairpin RNA (shRNA) sequence specific to the porcine GnRHR-II and cDNA encoding the fluorescent ZsGreen1 protein (pLVX-shRNA2; Clontech). Transduction of swine testis cells with these particles (1.44 × 107 viral particles) reduced porcine GnRHR-II mRNA levels by 99% compared with control particles (P < 0.05). In the current study, pronuclear zygotes (n = 50) surgically collected from 1 white crossbred donor sow were microinjected into the perivitelline space with lentiviral particles containing the shRNA2 sequence (3.3 × 108 IU mL–1) using a Nikon diaphot inverted microscrope equipped with Eppendorf micromanipulators and FemtoJet injection system. A total of 40 microinjected zygotes were immediately transferred into the oviduct of 1 synchronized recipient female, resulting in the production of 5 healthy, live piglets (20% efficiency rate). Interestingly, 1 female exhibited green fluorescence, indicative of successful transgene integration and expression. Transgene integration was confirmed via conventional PCR using primers designed to amplify portions of the human U6 promoter driving the shRNA, the CMV promoter driving ZsGreen1 expression, and the multiple cloning site for incorporation of the shRNA sequence. Next, inverse PCR was performed to determine the location and number of integration sites. Sequencing analysis of PCR products revealed that a single integration site was present on chromosome 14, aligning with clone NW_003612067.1 with 99% identity and matching identities 448,946–448,37. The GnRHR-II knockdown (KD) female along with 2 female littermates were maintained and monitored during development. Attainment of puberty occurred at 149 days for the transgenic female and 145 and 151 days for littermate control gilts (P > 0.05). Upon exhibition of their third behavioural oestrus, females were bred and allowed to gestate to term. Litter size was similar between the GnRHR-II KD female (15 live piglets) and control littermates (15 and 16 live piglets). Of the 15 piglets produced, 5 (3 males and 2 females) were positive for green fluorescence, confirming germline transmission of the transgene and further evidence for a single integration site. The swine produced from this study represent the first animal model to examine the physiological implications of reduced GnRH-II receptor levels.

scholarly journals The influence of sGnRH-A and antidopaminergic drug – pimozide – on prolactin mRNA synthesis in female Prussian carp (Carassius gibelio Bloch) in vivo

2013 ◽  
Vol 58 (No. 1) ◽  
pp. 31-36
Author(s):  
J. Chyb ◽  
M. Socha ◽  
P. Szczerbik ◽  
M. Sokolowska-Mikolajczyk ◽  
T. Mikołajczyk ◽  
...  
Keyword(s):  
Gonadotropin Releasing Hormone ◽  
Inhibitory Influence ◽  
Mrna Levels ◽  
Mrna Synthesis ◽  
Releasing Hormone ◽  
Prussian Carp ◽  
Carassius Gibelio ◽  
Prolactin Synthesis ◽  
Prolactin Mrna

Effects of salmon gonadotropin releasing hormone analogue (sGnRH-A) and antidopaminergic drug, pimozide, on the synthesis of prolactin mRNA in vivo in female Prussian carp (Carassius gibelio Bloch) during two different stages of the reproductive cycle were evaluated. The results showed that the lowest dose of sGnRH-A (5 &mu;g/kg body weight) significantly stimulated the mRNA synthesis in fish during the recrudescence as well as during the preovulatory period, higher doses of this compound having no significant effect on prolactin mRNA synthesis. The blocker of dopamine receptors, pimozide, also potentiated prolactin mRNA synthesis &ndash; in recrudescent females it increased mRNA levels at the dose of 1 mg/kg, while in the preovulatory period all of the used pimozide doses (1, 5, and 10 mg/kg) were responsible for the increase of prolactin mRNA levels. Taken together, the above results suggest that gonadotropin releasing hormone (GnRH) is the factor responsible for the stimulation of prolactin synthesis, while dopamine has an inhibitory influence on the prolactin production. &nbsp;

scholarly journals Angiotensin II AT2 receptor regulates ureteric bud morphogenesis

2010 ◽  
Vol 298 (3) ◽  
pp. F807-F817 ◽  
Author(s):  
Renfang Song ◽  
Melissa Spera ◽  
Colleen Garrett ◽  
Samir S. El-Dahr ◽  
Ihor V. Yosypiv
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Ex Vivo ◽  
Branching Morphogenesis ◽  
Mrna Levels ◽  
Ureteric Bud ◽  
Embryonic Mouse ◽  
Genetic Inactivation ◽  
The Impact

ANG II AT2 receptor (AT2R)-deficient mice exhibit abnormal ureteric bud (UB) budding, increased incidence of double ureters, and vesicoureteral reflux. However, the role of the AT2R during UB morphogenesis and the mechanisms by which aberrant AT2R signaling disrupts renal collecting system development have not been fully defined. In this study, we mapped the expression of the AT2R during mouse metanephric development, examined the impact of disrupted AT2R signaling on UB branching, cell proliferation, and survival, and investigated the cross talk of the AT2R with the glial-derived neurotrophic factor ( GDNF)/ c-Ret/Wnt11 signaling pathway. Embryonic mouse kidneys express AT2R in the branching UB and the mesenchyme. Treatment of embryonic day 12.5 ( E12.5) metanephroi with the AT2R antagonist PD123319 or genetic inactivation of the AT2R in mice inhibits UB branching, decreasing the number of UB tips compared with control (34 ± 1.0 vs. 43 ± 0.6, P < 0.01; 36 ± 1.8 vs. 48 ± 1.3, P < 0.01, respectively). In contrast, treatment of metanephroi with the AT2R agonist CGP42112 increases the number of UB tips compared with control (48 ± 1.8 vs. 39 ± 12.3, P < 0.05). Using real-time quantitative RT-PCR and whole mount in situ hybridization, we demonstrate that PD123319 downregulates the expression of GDNF, c-Ret, Wnt11, and Spry1 mRNA levels in E12.5 metanephroi grown ex vivo. AT2R blockade or genetic inactivation of AT2R stimulates apoptosis and inhibits proliferation of the UB cells in vivo. We conclude that AT2R performs essential functions during UB branching morphogenesis via control of the GDNF/c-Ret/Wnt11 signaling pathway, UB cell proliferation, and survival.

PKC and ERK are differentially involved in gonadotropin-releasing hormone-induced growth hormone gene expression in the goldfish pituitary

2005 ◽  
Vol 289 (6) ◽  
pp. R1625-R1633 ◽  
Author(s):  
Christian Klausen ◽  
Takeshi Tsuchiya ◽  
John P. Chang ◽  
Hamid R. Habibi
Keyword(s):  
Gene Expression ◽  
Growth Hormone ◽  
Primary Cultures ◽  
Gonadotropin Releasing Hormone ◽  
Growth Hormone Gene ◽  
Pituitary Cells ◽  
Mrna Levels ◽  
Releasing Hormone ◽  
Gh Secretion ◽  
Gh Gene

Gonadotropin-releasing hormone (GnRH) is produced by the hypothalamus and stimulates the synthesis and secretion of gonadotropin hormones. In addition, GnRH also stimulates the production and secretion of growth hormone (GH) in some fish species and in humans with certain clinical disorders. In the goldfish pituitary, GH secretion and gene expression are regulated by two endogenous forms of GnRH known as salmon GnRH and chicken GnRH-II. It is well established that PKC mediates GnRH-stimulated GH secretion in the goldfish pituitary. In contrast, the signal transduction of GnRH-induced GH gene expression has not been elucidated in any model system. In this study, we demonstrate, for the first time, the presence of novel and atypical PKC isoforms in the pituitary of a fish. Moreover, our results indicate that conventional PKCα is present selectively in GH-producing cells. Treatment of primary cultures of dispersed goldfish pituitary cells with PKC activators (phorbol ester or diacylglycerol analog) did not affect basal or GnRH-induced GH mRNA levels, and two different inhibitors of PKC (calphostin C and GF109203X) did not reduce the effects of GnRH on GH gene expression. Together, these results suggest that, in contrast to secretion, conventional and novel PKCs are not involved in GnRH-stimulated increases in GH mRNA levels in the goldfish pituitary. Instead, PD98059 inhibited GnRH-induced GH gene expression, suggesting that the ERK signaling pathway is involved. The results presented here provide novel insights into the functional specificity of GnRH-induced signaling and the regulation of GH gene expression.

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