PMID- 28427099
OWN - NLM
STAT- MEDLINE
DCOM- 20171211
LR  - 20171211
IS  - 1439-4286 (Electronic)
IS  - 0018-5043 (Linking)
VI  - 49
IP  - 4
DP  - 2017 Apr
TI  - Role of Phosphodiesterases on the Function of Aryl Hydrocarbon 
      Receptor-Interacting Protein (AIP) in the Pituitary Gland and on the Evaluation 
      of AIP Gene Variants.
PG  - 286-295
LID - 10.1055/s-0043-104700 [doi]
AB  - Familial isolated pituitary adenoma (FIPA) is caused in about 20% of cases by 
      loss-of-function germline mutations in the AIP gene. Patients harboring AIP 
      mutations usually present with somatotropinomas resulting either in gigantism or 
      young-onset acromegaly. AIP encodes for a co-chaperone protein endowed with tumor 
      suppressor properties in somatotroph cells. Among other mechanisms proposed to 
      explain this function, a regulatory effect over the 3',5'-cyclic adenosine 
      monophosphate (cAMP) signaling pathway seems to play a prominent role. In this 
      setting, the well-known interaction between AIP and 2 different isoforms of 
      phosphodiesterases (PDEs), PDE2A3 and PDE4A5, is of particular interest. While 
      the interaction with over-expressed AIP does not seem to affect PDE2A3 function, 
      the reported effect on PDE4A5 is, in contrast, reduced enzymatic activity. In 
      this review, we explore the possible implications of these molecular interactions 
      for the function of somatotroph cells. In particular, we discuss how both PDEs 
      and AIP could act as negative regulators of the cAMP pathway in the pituitary, 
      probably both by shared and independent mechanisms. Moreover, we describe how the 
      evaluation of the AIP-PDE4A5 interaction has proven to be a useful tool for 
      testing AIP mutations, complementing other in silico, in vitro, and in vivo 
      analyses. Improved assessment of the pathogenicity of AIP mutations is indeed 
      paramount to provide adequate guidance for genetic counseling and clinical 
      screening in AIP mutation carriers, which can lead to prospective diagnosis of 
      pituitary adenomas.
CI  - (c) Georg Thieme Verlag KG Stuttgart . New York.
FAU - Hernandez-Ramirez, Laura C
AU  - Hernandez-Ramirez LC
AD  - Section on Endocrinology and Genetics (SEGEN), Eunice Kennedy Shriver National 
      Institute of Child Health and Human Development (NICHD), National Institutes of 
      Health (NIH), Bethesda, MD, USA.
FAU - Trivellin, Giampaolo
AU  - Trivellin G
AD  - Section on Endocrinology and Genetics (SEGEN), Eunice Kennedy Shriver National 
      Institute of Child Health and Human Development (NICHD), National Institutes of 
      Health (NIH), Bethesda, MD, USA.
FAU - Stratakis, Constantine A
AU  - Stratakis CA
AD  - Section on Endocrinology and Genetics (SEGEN), Eunice Kennedy Shriver National 
      Institute of Child Health and Human Development (NICHD), National Institutes of 
      Health (NIH), Bethesda, MD, USA.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20170420
PL  - Germany
TA  - Horm Metab Res
JT  - Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et 
      metabolisme
JID - 0177722
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Isoenzymes)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (aryl hydrocarbon receptor-interacting protein)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 3.1.4.17 (Cyclic Nucleotide Phosphodiesterases, Type 2)
RN  - EC 3.1.4.17 (Cyclic Nucleotide Phosphodiesterases, Type 4)
RN  - EC 3.1.4.17 (PDE2A protein, human)
RN  - EC 3.1.4.17 (PDE4A protein, human)
RN  - Pituitary Adenoma, Familial Isolated
SB  - IM
MH  - Animals
MH  - Cyclic AMP/genetics/metabolism
MH  - Cyclic Nucleotide Phosphodiesterases, Type 2/genetics/*metabolism
MH  - Cyclic Nucleotide Phosphodiesterases, Type 4/genetics/*metabolism
MH  - *Germ-Line Mutation
MH  - Growth Hormone-Secreting Pituitary Adenoma/genetics/*metabolism/pathology
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/genetics/*metabolism
MH  - Isoenzymes/genetics/metabolism
MH  - Neoplasm Proteins/*metabolism
MH  - Pituitary Gland/*metabolism/pathology
MH  - Second Messenger Systems/genetics
EDAT- 2017/04/21 06:00
MHDA- 2017/12/12 06:00
CRDT- 2017/04/21 06:00
PHST- 2017/04/21 06:00 [entrez]
PHST- 2017/04/21 06:00 [pubmed]
PHST- 2017/12/12 06:00 [medline]
AID - 10.1055/s-0043-104700 [doi]
PST - ppublish
SO  - Horm Metab Res. 2017 Apr;49(4):286-295. doi: 10.1055/s-0043-104700. Epub 2017 Apr 
      20.