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Pituitary

, Volume 17, Issue 5, pp 464–469 | Cite as

AZA-Deoxycytidine stimulates proopiomelanocortin gene expression and ACTH secretion in human pituitary ACTH-secreting tumors

  • Maria Francesca Cassarino
  • Antonella Sesta
  • Luca Pagliardini
  • Marco Losa
  • Giovanni Lasio
  • Francesco Cavagnini
  • Francesca Pecori GiraldiEmail author
Article

Abstract

Purpose

It is well known that methylation plays an important role in regulating tissue expression of proopiomelanocortin (POMC) and recent studies have shown that demethylation can occur also in vitro in neuroendocrine tumors. Aim of the present study was to evaluate whether inhibition of methylation modulates POMC expression and ACTH secretion by human corticotrope tumors.

Methods

Twenty two ACTH-secreting pituitary tumors were incubated with 5-AZA-2′-deoxycytidine (AZA), an inhibitor of DNA-methyltransferases, with or without 10 nM corticotropin-releasing hormone (CRH). Both dose response (100 nM–10 μM AZA) and time course (4–96 h) experiments were carried out for measurement of ACTH secretion and POMC gene expression.

Results

Incubation with AZA increased constitutive POMC expression and ACTH secretion by human corticotrope adenomas. The effect appeared most notable at 24 and 48 h with 1 μM AZA. Incubation with AZA did not exert an additional stimulatory effect on CRH-stimulated POMC and ACTH.

Conclusions

The present study shows that AZA increases POMC gene expression and ACTH secretion in human pituitary ACTH-secreting tumors. This can be taken to indicate that mechanisms set into motion by AZA play a role in the regulation of ACTH secretion/POMC expression in tumoral corticotropes and paves the way to further studies in Cushing’s disease.

Keywords

Corticotrope adenoma 5-AZA-2′-deoxycytidine ACTH Methylation POMC Cushing’s disease 

Notes

Conflict of interest

The authors state that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Maria Francesca Cassarino
    • 1
  • Antonella Sesta
    • 1
  • Luca Pagliardini
    • 1
  • Marco Losa
    • 2
  • Giovanni Lasio
    • 3
  • Francesco Cavagnini
    • 1
  • Francesca Pecori Giraldi
    • 1
    • 4
    Email author
  1. 1.Neuroendocrinology Research LaboratoryIstituto Auxologico Italiano IRCCSMilanItaly
  2. 2.Department of NeurosurgeryOspedale San Raffaele IRCCSMilanItaly
  3. 3.Department of NeurosurgeryIstituto Clinico HumanitasRozzanoItaly
  4. 4.Department of Clinical Sciences and Community HealthUniversity of MilanMilanItaly

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