Expression patterns of messenger ribonucleic acids encoding prohormone convertases (PC2 and PC3) in human pituitary adenomas

Hashimoto, Kunihiko; Koga, Masafumi; Kouhara, Haruhiko; Arita, Norio; Hayakawa, Tõru; Kishimoto, Tadamitsu; Sato, Bunzo

doi:10.1111/j.1365-2265.1994.tb02528.x

Cited by 11 publications

(6 citation statements)

References 31 publications

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“…Indeed, Righi et al, studying a series of functioning and silent CTs, reported that the three cases of silent CTs that evolved during follow-up to functioning ones showed an increase in PCSK1 and PC1/3 expression (9). Regarding ACTH post-translation regulation, most authors have reported a decrease in ACTH degradation in CT tumors compared with other PitNET subtypes, without differences between functioning and silent CTs (12,29). Our data agree with those previously reported, showing lower PCSK2 and PC2 expressions in functioning and silent CTs than in silent GTs.…”

Section: Intermediate State Between Micro-functioning and Silentsupporting

confidence: 92%

Why don’t corticotroph tumors always produce Cushing’s disease?

García‐Martínez

Cano

Flores-Martinez

et al. 2019

European Journal of Endocrinology

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Objective Silent corticotroph tumors are a pituitary neuroendocrine tumor subtype of corticotroph lineage that do not clinically express Cushing’s disease. The silencing of this type of tumor is not fully understood. The aim of the present study was to delve into the lack of secretory activity, studying the post-transcriptional and post-translational regulation of POMC/ACTH in a series of molecularly identified functioning and silent corticotroph tumors. Design We analyzed 24 silent corticotroph, 23 functioning corticotroph and 25 silent gonadotroph tumors. Methods We used Sanger sequencing, quantitative real-time PCR and Western blot to analyze genetic alterations in POMC, gene expression of TBX19, NEUROD1, POMC, PCSK1, PCSK2, CPE and PAM and protein expression of POMC, PC1/3, PC2, CPE and PAM. Results We found different polymorphisms in the POMC gene of corticotroph tumors, some of them related to deficiency of proopiomelanocortin. Silent corticotroph tumors showed lower PC1/3 gene and protein expression than functioning ones, especially compared to micro-functioning corticotroph tumors (all P < 0.05). Moreover, we found a positive correlation between PC2 and CPE gene and protein expression (rho ≥ 0.670, P < 0.009) in silent corticotroph tumors compared with functioning ones. Conclusions By studying the post-transcriptional and post-translational processing of POMC and ACTH, respectively, in a large series of silent and functioning corticotroph tumors, we found that the lack of secretory activity of these tumors is related to an impaired processing of POMC and a high degradation of ACTH, with the macro-functioning corticotroph tumor behaving as an intermediate state between micro-functioning and silent corticotroph tumors.

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Section: Intermediate State Between Micro-functioning and Silentsupporting

confidence: 92%

Why don’t corticotroph tumors always produce Cushing’s disease?

García‐Martínez

Cano

Flores-Martinez

et al. 2019

European Journal of Endocrinology

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“…In the present immunohistochemical study, we showed that expression of PC1/3 protein was negative in all 6 SCA tissues in contrast to the positive PC1/3 immunoreactivity in an ACTH-secreting pituitary tumor causing clinically overt Cushing's disease. PC1/3 is responsible for proper processing of POMC into mature ACTH(1-39) in a tissue-specific fashion [11,12,13], and highly expressed in ACTH-secreting adenomas [14,15]. However, there have been few studies on PC1/3 expression in SCA thus far reported; one case with negative PC1/3 expression [16], and another case with positive PC1/3 expression [8].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2007

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Abstract. 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.

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“…Prohormone convertase (PC) 3 was later indicated to be the same as PC 1 and now is designated as PC1/3. In endocrine tumors, the functions of PC1/3 and PC2, which are present in the neuroendocrine tissues, have been the subject of several investigations (Bloomquist et al 1991;Ohagi et al 1992;Seidah and Chretien 1992;Hashimoto et al 1994;Scopsi et al 1995;. Morphological studies have been done in pancreatic and pituitary tumors Otoh et al 1996).…”

Section: Processing Of Prohormonesmentioning

confidence: 99%

Contributions of Immunohistochemistry and In Situ Hybridization to the Functional Analysis of Pituitary Adenomas

Osamura

Tahara

Kurotani

et al. 2000

J Histochem Cytochem.

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S U M M A R Y Immunohistochemistry (IHC) and recently in situ hybridization (ISH) have elucidated various aspects of human pituitary adenomas, i.e., functional differentiation and classification, transcription factors and mechanism of hormone production, regulation of hormone secretion, and processing of prohormones. Recently, the use of tyramide (catalyzed signal amplification; TSA or CSA) and RT-PCR has been effective for detection of trivial amount of proteins (peptides) and mRNA, respectively. Immunomolecular histochemistry is expected to further clarify the function and biology of human pituitary adenomas.

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Expression patterns of messenger ribonucleic acids encoding prohormone convertases (PC2 and PC3) in human pituitary adenomas

Abstract: The expression of PC2 and PC3 mRNA in human pituitaries has been confirmed. However, their expression has been observed to vary quantitatively and not to be restricted to certain types of pituitary cells.

Cited by 11 publications

References 31 publications

Why don’t corticotroph tumors always produce Cushing’s disease?

Why don’t corticotroph tumors always produce Cushing’s disease?

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

Contributions of Immunohistochemistry and In Situ Hybridization to the Functional Analysis of Pituitary Adenomas

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