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 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.
Tateno
Toru
T
Department of Clinical and Molecular Endocrinology, Tokyo Medical and Dental University Graduate School, Japan.
Izumiyama
Hajime
H
Doi
Masaru
M
Akashi
Takumi
T
Ohno
Kikuo
K
Hirata
Yukio
Y
D049913:ACTH-Secreting Pituitary Adenoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000236:Adenoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000328:Adult; D000368:Aged; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism; D045664:Proprotein Convertase 1 / Q000235:genetics* / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism
D020033:Protein Isoforms; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D045664:Proprotein Convertase 1