Differential gene expression in ACTH -secreting and non-functioning pituitary tumors.
OBJECTIVE
Differential expression of several genes between ACTH-secreting pituitary tumors causing Cushing' disease (CD), silent corticotroph adenoma (SCA), and non-functioning pituitary tumors (NFT) was investigated.


METHODS
We used tissue specimens from 35 pituitary tumors (12 CD, 8 SCA, and 15 NFT). Steady-state mRNA levels of the genes related to proopiomelanocortin (POMC) transcription, synthesis, processing, and secretion, such as neurogenic differentiation 1 (NeuroD1), T-box 19 (Tpit), corticotropin releasing hormone receptor (CRHR), vasopressin receptor 1b (V1bR), prohormone convertase (PC) 1/3 and PC2, 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 1 and type 2, glucocorticoid receptor alpha (GRalpha), annexin A1, histone deacetylase 2 (HDAC2), and BRM/SWI2-related gene 1, were determined by real-time RT-PCR.


CONCLUSIONS
POMC and Tpit mRNA levels were greater in CD and SCA than those in NFT. NeuroD1 mRNA levels were less in CD than those in NFT, but almost comparable between SCA and NFT. PC1/3 mRNA levels were greater in CD, but less in SCA than those in NFT. PC2 mRNA levels in CD and SCA were less than those in NFT. CRHR, V1bR, and 11beta-HSD2 mRNA levels in CD were greater than those in SCA and NFT. HDAC2 mRNA levels in CD and SCA were lower than those in NFT. In conclusion, our study demonstrated that the genes related to transcription, synthesis, processing, and secretion of POMC are differentially regulated in ACTH-secreting pituitary tumors causing CD and SCA compared with those in NFT. This may partly explain the development of clinically active and inactive CD.
Department of Clinical and Molecular Endocrinology, Tokyo Medical and Dental University Graduate School, 1-5-45, Yushima, Bunkyo-ku, Tokyo, Japan. ttateno.cme@tmd.ac.jp
Toru
T
Tateno
Hajime
H
Izumiyama
Masaru
M
Doi
Takanobu
T
Yoshimoto
Masayoshi
M
Shichiri
Naoko
N
Inoshita
Kenichi
K
Oyama
Shozo
S
Yamada
Yukio
Y
Hirata
D042842:11-beta-Hydroxysteroid Dehydrogenases / Q000235:genetics; D049913:ACTH-Secreting Pituitary Adenoma / Q000235:genetics / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D025461:Feedback, Physiological / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D047748:Pituitary ACTH Hypersecretion / Q000235:genetics / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000235:genetics / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis*; D045706:Proprotein Convertase 2 / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000235:genetics; D017483:Receptors, Vasopressin / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020825:T-Box Domain Proteins / Q000235:genetics; D000099052:CRF Receptor, Type 1
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000324:Adrenocorticotropic Hormone; D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D011333:Pro-Opiomelanocortin; D045706:Proprotein Convertase 2; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D011965:Receptors, Glucocorticoid; D017483:Receptors, Vasopressin; D020825:T-Box Domain Proteins; D000099052:CRF Receptor, Type 1; C093970:NEUROD1 protein, human; C486589:TBX19 protein, human; C411470:glucocorticoid receptor alpha