Targeting mediators of Wnt signalling pathways by GnRH in gonadotropes

Gardner, Samantha; Stavrou, Emmanouil; Rischitor, Patricia E; Faccenda, Elena; Pawson, Adam J.

doi:10.1677/jme-09-0168

Cited by 13 publications

(4 citation statements)

References 69 publications

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“…The transcription of GnRH target genes is modulated by several factors, such as β-catenin [24], which activation, in turn, is itself dependent on a number of molecules including intracellular Ca 2+ and CREB. Although β-catenin activation acts as an enhancer of the Lhb gene transcription [55], and immunostaining has revealed its weak inhibition by Teverelix, all three antagonists had similar effects on GnRH-induced Lhb expression. These data highlight the potential of GnRH antagonists in exerting LiSS behavior at the early signaling level, in spite of the similar inhibition of gonadotropin production.…”

Section: Discussionmentioning

confidence: 99%

GnRH Antagonists Produce Differential Modulation of the Signaling Pathways Mediated by GnRH Receptors

Sperduti

Limoncella

Lazzaretti

et al. 2019

IJMS

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Commercial gonadotropin-releasing hormone (GnRH) antagonists differ by 1–2 amino acids and are used to inhibit gonadotropin production during assisted reproduction technologies (ART). In this study, potencies of three GnRH antagonists, Cetrorelix, Ganirelix and Teverelix, in inhibiting GnRH-mediated intracellular signaling, were compared in vitro. GnRH receptor (GnRHR)-transfected HEK293 and neuroblastoma-derived SH-SY5Y cell lines, as well as mouse pituitary LβT2 cells endogenously expressing the murine GnRHR, were treated with GnRH in the presence or absence of the antagonist. We evaluated intracellular calcium (Ca2+) and cAMP increases, cAMP-responsive element binding-protein (CREB) and extracellular-regulated kinase 1 and 2 (ERK1/2) phosphorylation, β-catenin activation and mouse luteinizing-hormone β-encoding gene (Lhb) transcription by bioluminescence resonance energy transfer (BRET), Western blotting, immunostaining and real-time PCR as appropriate. The kinetics of GnRH-induced Ca2+ rapid increase revealed dose-response accumulation with potency (EC50) of 23 nM in transfected HEK293 cells, transfected SH-SY5Y and LβT2 cells. Cetrorelix inhibited the 3 × EC50 GnRH-activated calcium signaling at concentrations of 1 nM–1 µM, demonstrating higher potency than Ganirelix and Teverelix, whose inhibitory doses fell within the 100 nM–1 µM range in both transfected HEK293 and SH-SY5Y cells in vitro. In transfected SH-SY5Y, Cetrorelix was also significantly more potent than other antagonists in reducing GnRH-mediated cAMP accumulation. All antagonists inhibited pERK1/2 and pCREB activation at similar doses, in LβT2 and transfected HEK293 cells treated with 100 nM GnRH. Although immunostainings suggested that Teverelix could be less effective than Cetrorelix and Ganirelix in inhibiting 1 µM GnRH-induced β-catenin activation, Lhb gene expression increase occurring upon LβT2 cell treatment by 1 µM GnRH was similarly inhibited by all antagonists. To conclude, this study has demonstrated Cetrorelix-, Ganirelix- and Teverelix-specific biased effects at the intracellular level, not affecting the efficacy of antagonists in inhibiting Lhb gene transcription.

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Section: Discussionmentioning

confidence: 99%

GnRH Antagonists Produce Differential Modulation of the Signaling Pathways Mediated by GnRH Receptors

Sperduti

Limoncella

Lazzaretti

et al. 2019

IJMS

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“…Undernutrition and malnutrition lead to an increase in CRH levels, which can lead to a decrease in the release of GnRH and LH [18][19]. Decrease in GnRH and LH release lead to a decrease in reproductive function, including a decrease in fertility and an increase in the risk of miscarriage [20]. Leptin produced primarily in adipose tissue, acts on the hypothalamus to regulate appetite and energy balance.…”

Section: Nutrition and Its Effects On Reproductionmentioning

confidence: 99%

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2023

ARVS

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The concept of "stress" refers to a complex set of physiological and behavioural responses that occur in response to aversive stimuli. In 1929, Cannon aptly described stress as the body's attempt to maintain homeostasis when faced with a range of stressors, activating the sympatho-adrenomedullary (SAM) system. Meanwhile, Selye coined stress as the "non-specific response of the body to any demand for change". The stress response in animals is a finely tuned, integrated

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“…β-Catenin acts as a coactivator of SF-1 when it transduces Wnt signals to Dax1 [71], StarD1 [72], aromatase [73]; GnRH receptor [74], Müllerian inhibiting substance type II receptor [75], LHB/Lhb [76], and inhibin [77] target genes. Consistent with this, ChIP and site-directed mutagenesis assays have shown that activation of StarD7 expression requires the binding of β-catenin to the TCF4 transcription factor, suggesting that β-catenin functions as a bridge between SF-1 and TCF4 to form a ternary complex, which in turn activates StarD7 expression [66].…”

Section: Transcriptional Regulation Of Stard7mentioning

confidence: 99%

The Lipid Transfer Protein StarD7: Structure, Function, and Regulation

Flores-Martín

Rena

Angeletti

et al. 2013

IJMS

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The steroidogenic acute regulatory (StAR) protein-related lipid transfer (START) domain proteins constitute a family of evolutionarily conserved and widely expressed proteins that have been implicated in lipid transport, metabolism, and signaling. The 15 well-characterized mammalian START domain-containing proteins are grouped into six subfamilies. The START domain containing 7 mRNA encodes StarD7, a member of the StarD2/phosphatidylcholine transfer protein (PCTP) subfamily, which was first identified as a gene overexpressed in a choriocarcinoma cell line. Recent studies show that the StarD7 protein facilitates the delivery of phosphatidylcholine to the mitochondria. This review summarizes the latest advances in StarD7 research, focusing on the structural and biochemical features, protein-lipid interactions, and mechanisms that regulate StarD7 expression. The implications of the role of StarD7 in cell proliferation, migration, and differentiation are also discussed.

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Targeting mediators of Wnt signalling pathways by GnRH in gonadotropes

Cited by 13 publications

References 69 publications

GnRH Antagonists Produce Differential Modulation of the Signaling Pathways Mediated by GnRH Receptors

GnRH Antagonists Produce Differential Modulation of the Signaling Pathways Mediated by GnRH Receptors

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The Lipid Transfer Protein StarD7: Structure, Function, and Regulation

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