Polyribosome and ribonucleoprotein complex redistribution of mRNA induced by GnRH involves both EIF2AK3 and MAPK signaling

Minh‐Ha, T.; Kim, Taeshin; He, Feng; Dave, Hiral; Intriago, Rachel E.; Astorga, Uriah A.; Jain, Sonia; Lawson, Mark A.

doi:10.1016/j.mce.2013.10.007

Cited by 11 publications

(8 citation statements)

References 54 publications

(70 reference statements)

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“…LβT2 cells were pretreated (30 min) with vehicle (0), RAPA (10nM), or PP242 (50μM) followed by a 15 min treatment of either vehicle (0) or GnRHa (10nM). Selective inhibition of mTORC1 using RAPA had no effect on ERK activation (Figure 3), consistent with previous work (Do, Kim, He et al, 2014). However, PP242 treatment significantly decreased GnRHa-stimulated ERK activation (Figure 3).…”

Section: Resultssupporting

confidence: 92%

Gonadotropin releasing hormone activation of the mTORC2/Rictor complex regulates actin remodeling and ERK activity in LβT2 cells

Edwards

Isom

Navratil

2017

Molecular and Cellular Endocrinology

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The mammalian target of rapamycin (mTOR) assembles into two different multi-protein complexes, mTORC1 and mTORC2. The mTORC2 complex is distinct due to the unique expression of the specific core regulatory protein Rictor (rapamycin-insensitive companion of mTOR). mTORC2 has been implicated in regulating actin cytoskeletal reorganization but its role in gonadotrope function is unknown. Using the gonadotrope-derived LβT2 cell line, we find that the GnRH agonist buserelin (GnRHa) phosphorylates both mTOR and Rictor. Interestingly, inhibition of mTORC2 blunts GnRHa-induced cyto-architectural rearrangements. Coincident with blunting of actin reorganization, inhibition of mTORC2 also attenuates GnRHa-mediated activation of both protein kinase C (PKC) and extracellular signal regulated kinase (ERK). Collectively, our data suggests that GnRHa-mediated mTORC2 activation is important in facilitating actin reorganization events critical for initiating PKC activity and subsequent ERK phosphorylation in the gonadotrope-derived LβT2 cell line.

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Section: Resultssupporting

confidence: 92%

Gonadotropin releasing hormone activation of the mTORC2/Rictor complex regulates actin remodeling and ERK activity in LβT2 cells

Edwards

Isom

Navratil

2017

Molecular and Cellular Endocrinology

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“…Transcriptional regulation of gonadotropin subunit genes is modest overall but exhibits integrative interpretation ( 22 ). GnRH also regulates protein synthesis and the distribution of mRNA in polyribosomes ( 23 – 26 ). Each of these may utilize different interpretative mechanisms.…”

Section: The Challenge Of Pulsatile Gonadotropin-releasing Hormone (Gmentioning

confidence: 99%

“…In LβT2 cells, GnRH stimulation causes transient activation of the unfolded protein response (UPR) ( 24 ). Translation is largely inhibited by the UPR but Dusp1 and Dusp8 mRNA escape translation inhibition and DUSP1 is increased during the time the UPR is active ( 23 , 35 ). Translational control of Dusp1 mRNA is MAPK1/3 dependent and is attributed to the 3′UTR ELAVL1 binding site known to contribute to mRNA stability ( 23 , 70 ).…”

Section: Resolution Of Gnrh-stimulated Mapk Signalingmentioning

confidence: 99%

“…Translation is largely inhibited by the UPR but Dusp1 and Dusp8 mRNA escape translation inhibition and DUSP1 is increased during the time the UPR is active ( 23 , 35 ). Translational control of Dusp1 mRNA is MAPK1/3 dependent and is attributed to the 3′UTR ELAVL1 binding site known to contribute to mRNA stability ( 23 , 70 ). Pulsatile GnRH increases Dusp1, Dusp8 , and Dusp16 expression, all of which target MAP kinases ( 17 ).…”

Section: Resolution Of Gnrh-stimulated Mapk Signalingmentioning

confidence: 99%

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Reactive Oxygen Species Link Gonadotropin-Releasing Hormone Receptor Signaling Cascades in the Gonadotrope

Terasaka

Adakama

et al. 2017

Front. Endocrinol.

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Biological rhythms lie at the center of regulatory schemes that control many aspects of living systems. At the cellular level, meaningful responses to external stimuli depend on propagation and quenching of a signal to maintain vigilance for subsequent stimulation or changes that serve to shape and modulate the response. The hypothalamus–pituitary–gonad endocrine axis that controls reproductive development and function relies on control through rhythmic stimulation. Central to this axis is the pulsatile stimulation of the gonadotropes by hypothalamic neurons through episodic release of the neuropeptide gonadotropin-releasing hormone. Alterations in pulsatile stimulation of the gonadotropes result in differential synthesis and secretion of the gonadotropins LH and FSH and changes in the expression of their respective hormone subunit genes. The requirement to amplify signals arising from activation of the gonadotropin-releasing hormone (GnRH) receptor and to rapidly quench the resultant signal to preserve an adaptive response suggests the need for rapid activation and feedback control operating at the level of intracellular signaling. Emerging data suggest that reactive oxygen species (ROS) can fulfill this role in the GnRH receptor signaling through activation of MAP kinase signaling cascades, control of negative feedback, and participation in the secretory process. Results obtained in gonadotrope cell lines or other cell models indicate that ROS can participate in each of these regulatory cascades. We discuss the potential advantage of reactive oxygen signaling for modulating the gonadotrope response to GnRH stimulation and the potential mechanisms for this action. These observations suggest further targets of study for regulation in the gonadotrope.

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“…Thus, GnRHR signaling also engages translational regulation. Interestingly, GnRHR signaling induces remodeling of ribosome content in LβT-2 cells ( 67 ).…”

Section: Basal and Gnrh-regulated Gnrhr Expressionmentioning

confidence: 99%

Intrinsic and Regulated Gonadotropin-Releasing Hormone Receptor Gene Transcription in Mammalian Pituitary Gonadotrophs

2017

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The hypothalamic decapeptide gonadotropin-releasing hormone (GnRH), acting via its receptors (GnRHRs) expressed in pituitary gonadotrophs, represents a critical molecule in control of reproductive functions in all vertebrate species. GnRH-activated receptors regulate synthesis of gonadotropins in a frequency-dependent manner. The number of GnRHRs on the plasma membrane determines the responsiveness of gonadotrophs to GnRH and varies in relation to age, sex, and physiological status. This is achieved by a complex control that operates at transcriptional, translational, and posttranslational levels. This review aims to overview the mechanisms of GnRHR gene (Gnrhr) transcription in mammalian gonadotrophs. In general, Gnrhr exhibits basal and regulated transcription activities. Basal Gnrhr transcription appears to be an intrinsic property of native and immortalized gonadotrophs that secures the presence of a sufficient number GnRHRs to preserve their functionality independently of the status of regulated transcription. On the other hand, regulated transcription modulates GnRHR expression during development, reproductive cycle, and aging. GnRH is crucial for regulated Gnrhr transcription in native gonadotrophs but is ineffective in immortalized gonadotrophs. In rat and mouse, both basal and GnRH-induced Gnrhr transcription rely primarily on the protein kinase C signaling pathway, with subsequent activation of mitogen-activated protein kinases. Continuous GnRH application, after a transient stimulation, shuts off regulated but not basal transcription, suggesting that different branches of this signaling pathway control transcription. Pituitary adenylate cyclase-activating polypeptide, but not activins, contributes to the regulated transcription utilizing the protein kinase A signaling pathway, whereas a mechanisms by which steroid hormones modulate Gnrhr transcription has not been well characterized.

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Polyribosome and ribonucleoprotein complex redistribution of mRNA induced by GnRH involves both EIF2AK3 and MAPK signaling

Cited by 11 publications

References 54 publications

Gonadotropin releasing hormone activation of the mTORC2/Rictor complex regulates actin remodeling and ERK activity in LβT2 cells

Gonadotropin releasing hormone activation of the mTORC2/Rictor complex regulates actin remodeling and ERK activity in LβT2 cells

Reactive Oxygen Species Link Gonadotropin-Releasing Hormone Receptor Signaling Cascades in the Gonadotrope

Intrinsic and Regulated Gonadotropin-Releasing Hormone Receptor Gene Transcription in Mammalian Pituitary Gonadotrophs

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