Defective Expression of Prohormone Convertase 1/3 in Silent Corticotroph Adenoma

Silent corticotroph adenoma (SCA) is defined as an ACTH-producing pituitary tumor not associated with clinical and endocrine feartures of Cushing's syndrome, but its underlying molecular mechanism(s) remains unknown thus far. We tested the hypothesis that reduced expression of prohormone conver...

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Bibliographic Details
Published in:ENDOCRINE JOURNAL 2007, Vol.54(5), pp.777-782
Main Authors: TATENO, Toru, IZUMIYAMA, Hajime, DOI, Masaru, AKASHI, Takumi, OHNO, Kikuo, HIRATA, Yukio
Format: Article
Language:English
Subjects:
ACTH-Secreting Pituitary Adenoma - genetics
ACTH-Secreting Pituitary Adenoma - metabolism
ACTH-Secreting Pituitary Adenoma - pathology
Adenoma - genetics
Adenoma - metabolism
Adenoma - pathology
Adrenocorticotropic Hormone - metabolism
Adult
Aged
Female
Gene Expression Regulation, Enzymologic
Gene Expression Regulation, Neoplastic
Humans
Immunohistochemistry
Male
Middle Aged
Pro-Opiomelanocortin - genetics
Pro-Opiomelanocortin - metabolism
Prohormone convertase (PC)
Proopiomelanocortin (POMC)
Proprotein Convertase 1 - genetics
Proprotein Convertase 1 - metabolism
Protein Isoforms - metabolism
Reverse transcriptase-polymerase chain reaction (RT-PCR)
Silent corticotroph adenoma (SCA)
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Summary:Silent corticotroph adenoma (SCA) is defined as an ACTH-producing pituitary tumor not associated with clinical and endocrine feartures of Cushing's syndrome, but its underlying molecular mechanism(s) remains unknown thus far. We tested the hypothesis that reduced expression of prohormone convertase (PC) 1/3 responsible for proteolytic processing of proopiomelanocortin (POMC) in SCA may lead to production of unprocessed, biologically inactive POMC and/or precursor of ACTH. Among 30 non-functioning pituitary macroadenomas (NFA) examined, we found 6 SCAs by immunohistochemical study using anti-ACTH antibody. Preoperative endocrine and diagnostic image tests did not reveal any differences between SCA and the remaining NFA except for the higher recurrence rate of SCA. While steady-state PC1/3 mRNA levels determined by RT-PCR were almost comparable between SCAs and NFAs, immunohistochemical study showed negative immunostaining for PC1/3 in all 6 SCAs. Our data suggest that defective PC1/3 expression may lead to preferential production of unprocessed, biologically inactive ACTH variants in SCA.
ISSN:0918-8959
1348-4540
DOI:10.1507/endocrj.K07-059