Related Experiment Video

Updated: Feb 11, 2026

Three-dimensional Alginate-bead Culture of Human Pituitary Adenoma Cells
08:31

Three-dimensional Alginate-bead Culture of Human Pituitary Adenoma Cells

Published on: February 18, 2016

10.5K

Reduced protein expression of the phosphodiesterases PDE4A4 and PDE4A8 in AIP mutation positive somatotroph adenomas

Mariana Ferreira Bizzi1, Sergio Veloso Brant Pinheiro2, Graeme B Bolger3

  • 1Department of Internal Medicine, The Federal University of Minas Gerais, Belo Horizonte/Minas Gerais, 30130-100, Brazil.

Molecular and Cellular Endocrinology
|May 6, 2018
PubMed

Insights

Type 4 phosphodiesterases (PDE4s) are crucial in somatotroph adenomas. AIP-mutated tumors show lower PDE4A4 and PDE4A8 expression, unlike sporadic adenomas, suggesting a unique cAMP-PDE pathway disturbance.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Oncology

Background:

  • Type 4 phosphodiesterases (PDE4s) regulate cyclic AMP (cAMP), a key signaling molecule implicated in somatotroph tumorigenesis.
  • Somatotroph adenomas often overexpress PDE4s, potentially as a compensatory mechanism to lower cAMP levels.
  • The aryl hydrocarbon receptor-interacting protein (AIP) tumor suppressor gene is mutated in familial isolated pituitary adenomas (FIPAs), and its interacting protein PDE4A4 is relevant.

Purpose of the Study:

  • To investigate the expression levels of PDE4A4 and PDE4A8 in Growth Hormone (GH)-secreting adenomas with AIP mutations.
  • To compare PDE4A4 and PDE4A8 expression in AIP-mutated adenomas with that in sporadic AIP-mutation negative GH-secreting adenomas.
  • To elucidate the role of AIP in regulating PDE4A4 and PDE4A8 expression in somatotroph tumors.

Main Methods:

  • Confocal immunofluorescence analysis was employed to quantify PDE4A4 and PDE4A8 expression.
  • Expression levels were compared between GH cells from AIP-mutated somatotropinomas and sporadic GH-secreting adenomas.
  • Statistical analysis was performed to determine the significance of expression differences.

Main Results:

  • Both PDE4A8 and PDE4A4 exhibited significantly lower expression in AIP-mutated somatotropinoma samples compared to sporadic GH-secreting tumors (P < 0.0001).
  • A strong association was observed between low PDE4A4 and PDE4A8 expression and the presence of germline AIP mutations.
  • These findings suggest that the absence or dysfunction of AIP hinders the upregulation of PDE4A8 and PDE4A4 proteins.

Conclusions:

  • AIP deficiency in somatotroph adenomas leads to reduced expression of PDE4A4 and PDE4A8, disrupting the cAMP-PDE pathway.
  • This unique cAMP-PDE pathway disturbance in AIP-mutation positive adenomas may explain their poor response to somatostatin analogues.
  • The study highlights a distinct molecular mechanism in AIP-mutated pituitary tumors, impacting therapeutic strategies.
Keywords:
AIPAcromegalyGH-Secreting tumourPhosphodiesterasePituitary

More Related Videos

Green Fluorescent Protein-based Expression Screening of Membrane Proteins in Escherichia coli08:46

Green Fluorescent Protein-based Expression Screening of Membrane Proteins in Escherichia coli

Published on: January 6, 2015

33.6K
Identifying the Effects of BRCA1 Mutations on Homologous Recombination using Cells that Express Endogenous Wild-type BRCA108:53

Identifying the Effects of BRCA1 Mutations on Homologous Recombination using Cells that Express Endogenous Wild-type BRCA1

Published on: February 17, 2011

15.1K

Related Concept Videos

Chromatin Position Affects Gene Expression02:35

Chromatin Position Affects Gene Expression

Chromatin is the massive complex of DNA and proteins packaged inside the nucleus. The complexity of chromatin folding and how it is packaged inside the nucleus greatly influences  access to genetic information. Generally, the nucleus' periphery is considered transcriptionally repressive, while the cell's interior is considered a transcriptionally active area. 
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the...
24.9K
Mutations01:39

Mutations

Overview
94.6K
Mutations01:35

Mutations

Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
44.6K
Viral Mutations00:36

Viral Mutations

A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
40.0K
Position-effect Variegation02:32

Position-effect Variegation

In 1928, a German botanist Emil Heitz observed the moss nuclei with a DNA binding dye. He observed that while some chromatin regions decondense and spread out in the interphase nucleus, others do not. He termed them euchromatin and heterochromatin, respectively. He proposed that the heterochromatin regions reflect a functionally inactive state of the genome. It was later confirmed that heterochromatin is transcriptionally repressed, and euchromatin is transcriptionally active chromatin.
7.1K
Treatment for Pulmonary Arterial Hypertension: Phosphodiesterase Inhibitors01:28

Treatment for Pulmonary Arterial Hypertension: Phosphodiesterase Inhibitors

Phosphodiesterase 5 (PDE5) inhibitors are potent enzymes that function to hydrolyze cyclic nucleotides to their corresponding 5' monophosphates. Their unique biochemical properties have been applied in treating Pulmonary Arterial Hypertension (PAH).
Among the PDE5 inhibitors, sildenafil (Revatio) stands out as a competitive and selective inhibitor. It operates by elevating cellular levels of cGMP and augmenting signaling through the cGMP-PKG pathway, promoting vasodilation. Upon oral...
621