Cyclooxygenase enzyme and PGE2 expression in patients with functional and non-functional pituitary adenomas

Nasrin Akbari,Alimohammad Alimohammadi,Hamideh Akbari,S Fahimeh Taghavi,Vahid Salimi,Mohammad Ghorbani,Masoumeh Tavakoli-Yaraki,Alireza Sheikhi,Mohammad E Khamseh,Mitra Nourbakhsh

doi:10.1186/s12902-020-0515-8

Abstract

BackgroundPituitary adenomas as multifactorial intracranial neoplasms impose a massive burden of morbidity on patients and characterizing the molecular mechanism underlying their pathogenesis has received considerable attention. Despite the appealing role of cyclooxygenase enzymes and their bioactive lipid products in cancer pathogenesis, their relevance to pituitary adenoma pathogenesis is debated and yet to be determined. Thus, the current study perused this relevance.MethodsThe expression level of the isoforms of cyclooxygenase (COX-1 and COX-2) was evaluated in hormone-secreting and in-active pituitary adenoma tumors and normal pituitary tissues through Real-Time PCR. The level of PGE2, as the main product of enzymes, was assessed using enzyme immunoassay kits in patients and healthy subjects.ResultsThe results of the current study demonstrated that COX-1 and COX-2 expression levels were increased in pituitary tumors including non-functional pituitary adenoma (NFPA), acromegaly, Cushing’s disease and prolactinoma compared with normal pituitary tissues. A significant expression level of COX-2 was observed in NFPA compared with the other pituitary tumors. Furthermore, the COX-2 expression level was significantly increased in macroadenoma and invasive tumors. The level of PGE2 was consistent with COX enzymes enhanced in pituitary adenoma tumors compared with healthy pituitary tissue. A significant elevation in the PGE2 level was detected in NFPA compared with hormone-secreting pituitary tumors. Additionally, the PGE2 level was increased in macroadenoma compared with microadenoma and in invasive compared with non-invasive pituitary tumors. The diagnostic values of cyclooxygenase isoforms and PGE2 were considerable between patients and healthy groups; however, COX-2 revealed more value in distinguishing endocrinologically active and non-active pituitary tumors.ConclusionsData from the current study provides expression patterns of COX-1, COX-2 and PGE2 in prevalent pituitary tumors and their association with patients’ clinical features which may open up new molecular targets for early diagnosis/follow up of pituitary tumor growth.

Highlights

Pituitary adenomas as multifactorial intracranial neoplasms impose a massive burden of morbidity on patients and characterizing the molecular mechanism underlying their pathogenesis has received considerable attention
The COX-1 expression level enhanced in tumor tissues of different pituitary adenomas In order to determine the COX-1 expression status in pituitary adenomas, the COX-1 gene expression level was measured in 91 pituitary tissues including 71 pituitary adenoma tumor and 20 normal pituitary tissues using RealTime PCR
To address the status of COX-1 expression level in different types of pituitary adenomas, the tumor tissues of Functional pituitary adenoma (FPA) and non-functional pituitary adenoma (NFPA) were included in the study and it has been shown that COX-1 expression level increased in both FPA and NFPA compared with normal pituitary tissue; no significant difference was observed between FPA and NFPA groups (Fig. 1b)

Summary

Introduction

Pituitary adenomas as multifactorial intracranial neoplasms impose a massive burden of morbidity on patients and characterizing the molecular mechanism underlying their pathogenesis has received considerable attention. The prostaglandin E2 (PGE2) as the main product of COX-2 mediates its effects in cancer cell proliferation, invasion and death through activation of the PGE2 receptor (EP) and subsequent induction of cAMP and protein kinase K [16]. The up-regulation of COX-1 has been revealed in the cytoplasm of neoplastic cells in head and neck cancer [23] It seems that both isoforms influence cancer pathogenesis coordinately; this premise should be verified with further evidences. Despite few observations regarding the over expression of COX-2 in pituitary carcinomas, the expression patterns of both COX isoforms and PGE2 in different types of pituitary adenomas and their correlations with tumor types, size and behavior have yet to be determined; they were considered and investigated in the current study

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Discussion

Conclusion