15-hydroxy-5-8-11-13-eicosatetraenoic-acid and Pituitary-Neoplasms

Pituitary adenoma accounts as a complex and multifactorial intracranial neoplasm with wide range of clinical symptoms which its underlying molecular mechanism has yet to be determined. The bioactive lipid mediators received attentions toward their contribution in cancer cell proliferation, progression and death. Amongst, 15-Lipoxygense (15-Lox) enzymes and products display appealing role in cancer pathogenesis which their possible effect in pituitary adenoma tumor genesis is perused in the current study.. The 15-Lipoxygenses isoforms expression level was evaluated in tumor tissues of prevalent functional and non-functional pituitary adenomas and normal pituitary tissues via Real-Time PCR. The circulating levels of 15(S) HETE and 13(S) HODE as 15-Lox main products were assessed in serum of patients and healthy subjects using enzyme immunoassay kits.. Our results revealed that 15-Lox-1 and 15-Lox-2 expression levels were elevated in tumor tissues of pituitary adenomas comparing to normal pituitary tissues. The elevated levels of both isoforms were accompanied with 15(S) HETE and 13(S) HODE elevation in the serum of patients. The 15-Lox-1 expression and activity was higher in invasive tumors as well as tumors with bigger size indicating the possible pro-tumorigenic role of 15-Lox-1, more than 15-Lox-2 in pituitary adenomas. The diagnostic value of 15-Lipoxygense isoforms and products were considerable between patients and healthy groups.. The possible involvement of 15-Lipoxygense pathway especially 15-Lox-1 in the regulation of pituitary tumor growth and progression may open up new molecular mechanism regarding pituitary adenoma pathogenesis and might shed light on its new therapeutic strategies.

Topics: Adenoma; Adult; Aged; Arachidonate 15-Lipoxygenase; Case-Control Studies; Female; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; Hydroxyeicosatetraenoic Acids; Linoleic Acids; Male; Middle Aged; Pituitary Neoplasms; Up-Regulation; Young Adult

We investigated the involvement of arachidonic acid metabolites in basal and thyrotropin releasing hormone (TRH) stimulated prolactin release by GH3 cells, a cloned strain of rat pituitary tumor cells. GH3 cells spontaneously released 9 and 15 HETEs and the 15 HETE release was greater than that of 9 HETE. When the cells were challenged by 10(-5) M AA, they were able to produce 5, 9, 12 and 15 HETEs. 10(-6) M TRH only stimulated the release of the two metabolites synthesized by the basal cells (15 and 9 HETEs). This release depended on the length of stimulation by TRH. When both AA and TRH were added, there was an increase in 15 and 9 HETE production. In all cases, more 15 HETE was released than other metabolites. In dose-response studies using TRH concentrations of 10(-6) M to 10(-12) M, the highest level of 9 HETE release was obtained at 10(-11) M TRH and the highest release of 15 HETE was at 10(-9) M TRH. PRL secretion by GH3 cells challenged by TRH showed the same pattern as 15 HETE release, and the correlation between PRL and 15 HETE was significant (p less than 0.001). These data indicate that 15 HETE is the lipoxygenase metabolite released in the largest amounts by GH3 cells and suggest some physiological interaction between 15 HETE and TRH in the control of PRL secretion.

Topics: Animals; Arachidonic Acid; Arachidonic Acids; Clone Cells; Dose-Response Relationship, Drug; Hydroxyeicosatetraenoic Acids; Kinetics; Pituitary Neoplasms; Prolactin; Rats; Thyrotropin-Releasing Hormone