Letrozole modulates tyrosine phosphorylation in liver and kidney of polycystic ovarian syndrome rats

Abstract

Letrozole (Letro), a non‐steroidal aromatase inhibitor, is commonly used to reduce estrogen level for breast cancer treatment and delay cancer cell metastasis. Recently, Letro is used to induce the polycystic ovarian syndrome (PCOS) in rat model. Protein phosphorylation on tyrosine residues is a posttranslational modification known to regulate biological processes and physiological functions including reproduction. Although the adverse effects of Letro have been reported, the alterations of tyrosine phosphorylation responsible for liver and kidney functions are not demonstrated. In present investigation, PCOS in rats was induced by daily oral administration of Letro (1 mg/kg BW) for consecutive 21 days. After induction, the effects of Letro on serum biochemical components, liver, and kidney functions were examined. In addition, both tissues were subjected for expression of protein tyrosine phosphorylation using Western blotting analysis. Histopathology of liver and kidney was performed by Masson’s trichrome staining. The results showed that Letro did not affect histological features but markedly increased the serum levels of urea nitrogen, cholesterol, triglyceride, high‐density lipoprotein (HDL), low‐density lipoprotein (LDL), alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP). Interestingly, expressions of tyrosine phosphorylation of 32 and 27 kDa in liver and of 55 and 43 kDa in kidney were increased in PCOS group. In contrast, such expression of a 26 kDa in PCOS kidney was decreased as compared to those of control. Our findings suggest that alterations of liver and kidney parameters in the Letro‐induced PCOS rat model may associate with modulation of the tyrosine phosphorylation.Support or Funding InformationKhon Kaen University