Gonadotropin-releasing hormone increases the release of extracellular vesicles from gonadotropes

AbstractWhile extracellular vesicles play a role in intercellular communication, it is not known how their release is regulated. We show here that hypothalamic gonadotropin-releasing hormone (GnRH) stimulates extracellular vesicle (EV) formation associated with annexin A5 (ANXA5) from pituitary gonadotropes. The results show that 1) membrane blebs containing ANXA5 are produced after GnRH agonist (GnRHa) stimulation of gonadotropes and that this is observed in situ as a loss of distinction at cell-cell boundaries, 2) EV containing ANXA5 are increased by GnRHa, 3) a gonadotrope-derived EV fraction stimulates LH release from other gonadotropes, and 4) an increase in ANXA5-loaded EV occurs in the plasma of ovariectomized rats. Finally, we also showed that 5) GnRHa stimulation of blebbing and EV-ANXA5 were suppressed by a protein kinase A inhibitor. These present results demonstrate a novel autocrine/paracrine mechanism mediated through the production of EV containing ANXA5. A hormonal regulation mechanism of cell-cell communication by means of EV is suggested.

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Extracellular vesicle-mediated cell–cell communication in haematological neoplasms

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2016.0484 ◽

2017 ◽

Vol 373 (1737) ◽

pp. 20160484 ◽

Cited By ~ 13

Author(s):

Junko H. Ohyashiki ◽

Tomohiro Umezu ◽

Kazuma Ohyashiki

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Extracellular Vesicles ◽

Stromal Cells ◽

Cell Communication ◽

Tumour Microenvironment ◽

Extracellular Vesicle ◽

Emerging Issues ◽

Haematological Neoplasms ◽

Cell Cell

Crosstalk between bone marrow tumour cells and surrounding cells, including bone marrow mesenchymal stromal cells (BM-MSCs), endothelial cells and immune cells, is important for tumour growth in haematological neoplasms. In addition to conventional signalling pathways, extracellular vesicles (EVs), which are endosome-derived vesicles containing proteins, mRNAs, lipids and miRNAs, can facilitate modulation of the bone marrow microenvironment without directly contacting non-tumourous cells. In this review, we discuss the current understanding of EV-mediated cell–cell communication in haematological neoplasms, particularly leukaemia and multiple myeloma. We highlight the actions of tumour and BM-MSC EVs in multiple myeloma. The origin of EVs, their tropism and mechanism of EV transfer are emerging issues that need to be addressed in EV-mediated cell–cell communication in haematological neoplasms. This article is part of the discussion meeting issue ‘Extracellular vesicles and the tumour microenvironment’.

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CSF extracellular vesicles and risk of disease activity after a first demyelinating event

Multiple Sclerosis Journal ◽

10.1177/1352458520987542 ◽

2021 ◽

pp. 135245852098754

Author(s):

Gloria Dalla Costa ◽

Tommaso Croese ◽

Marco Pisa ◽

Annamaria Finardi ◽

Lorena Fabbella ◽

...

Keyword(s):

Disease Activity ◽

Extracellular Vesicles ◽

Prognostic Markers ◽

Cell Communication ◽

Extracellular Vesicle ◽

Intervention Strategies ◽

Targeted Intervention ◽

Improve Risk Stratification ◽

Risk Of Disease ◽

In Cis

Background: Extracellular vesicles (EVs), a recently described mechanism of cell communication, are released from activated microglial cells and macrophages and are a candidate biomarker in diseases characterized by chronic inflammatory process such as multiple sclerosis (MS). Methods: We explored cerebrospinal fluid extracellular vesicle (CSF EV) of myeloid origin (MEVs), cytokine and chemokine levels in patients with clinically isolated syndrome (CIS). Results: We found that CSF MEVs were significantly higher in CIS patients than in controls and were inversely correlated to CSF CCL2 levels. MEVs level were significantly associated with an shorter time to evidence of disease activity (hazard ratio: 1.01, 95% confidence interval: 1.00–1.02, p < 0.01) independently from other known prognostic markers. Conclusion: After a first demyelinating event, CSF EVs may improve risk stratification of these patients and allow more targeted intervention strategies.

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